An evolved AAV variant enables efficient genetic engineering of murine T cells.

Precise targeting of large transgenes to T cells using homology-directed repair has been transformative for adoptive cell therapies and T cell biology. Delivery of DNA templates via adeno-associated virus (AAV) has greatly improved knockin efficiencies, but the tropism of current AAV serotypes restricts their use to human T cells employed in immunodeficient mouse models. To enable targeted knockins in murine T cells, we evolved Ark313, a synthetic AAV that exhibits high transduction efficiency in murine T cells. We performed a genome-wide knockout screen and identified QA2 as an essential factor for Ark313 infection. We demonstrate that Ark313 can be used for nucleofection-free DNA delivery, CRISPR-Cas9-mediated knockouts, and targeted integration of large transgenes. Ark313 enables preclinical modeling of Trac-targeted CAR-T and transgenic TCR-T cells in immunocompetent models. Efficient gene targeting in murine T cells holds great potential for improved cell therapies and opens avenues in experimental T cell immunology.

Very long-term follow-up of autologous pubovaginal fascia slings in women with stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The objective was to report on the very long-term outcome of a published series of autologous pubovaginal slings (PVS) in women with stress urinary incontinence (SUI). METHODS: Following institutional review board approval, a cohort of well characterized, non-neurogenic women who underwent an autologous PVS (primary [PVS1] and secondary [PVS2]) for SUI was re-evaluated for their very long-term outcome status. Data collected included demographics, validated questionnaires (Urogenital Distress Inventory - short form [UDI-6], Incontinence Impact Questionnaire - short form 7, quality of life), SUI retreatment/operations, and subjective patient-reported SUI improvement (%) and symptom recurrence. The primary outcome was success defined as UDI-6 question 3 (SUI) ≤ 1 and no SUI retreatment/operation. Patients not seen in clinic for 2 years were contacted via a standardized phone interview. RESULTS: From 83 patients with 7-year intermediate follow-up data, 34 (PVS1 = 18, PVS2 = 16) had very long-term follow-up based on clinic visit (7) or phone interviews (27). Those lost to follow-up (49), including 5 deceased, did not differ in demographics and intermediate outcomes from the followed cohort, but lived further away (>75 miles). At a mean age of 74 years, and with a median follow-up of 14.5 years, 53% met the success criteria (PVS1 = 44%, PVS2 = 63%). Mean postoperative questionnaire scores did not differ significantly between intermediate and very long-term follow-ups, and long-term outcomes between PVS1 and PVS2 remained similar. CONCLUSIONS: A majority of women with long-term follow-up after PVS for primary and secondary SUI remained successful more than 14 years after their surgery. Both groups, PVS1 and PVS2, fared equally well, confirming the durability of PVS as a treatment alternative for SUI.

Lifestyle Counseling for Medication Adherence in Glaucoma.

BACKGROUND: Medication adherence in glaucoma patients remains sub-par despite proven benefits of regular administration. The objective was to analyze medication adherence before and after lifestyle counseling in patients with ocular hypertension (OHT) or primary open-angle glaucoma (POAG) (mild, moderate, severe). METHODS: Prospective cohort study from May to July 2018 at a single academic center. From 391 consecutive records, 247 were excluded based on exclusion criteria with 28 patients not meeting inclusion criteria resulting in the final sample of 116 patients (33 had OHT, 83 had POAG - 28 mild, 39 moderate, 16 severe). Scripted lifestyle counseling focusing on diet, exercise, vitamin intake, stress management, and medication adherence was administered by a team of trained medical students. Primary outcome measure was self-reported medication adherence, defined as not missing an eye drop administration in the past month. A 2-3 week follow-up with scripted telephone survey assessing medication adherence, diet, and exercise was collected. RESULTS: At baseline, in 116 patients, 59.5% were adherent to their medication with a breakdown of 42.4% OHT, 64.3% mild, 66.7% moderate, and 68.7% severe and an increasing trend in medication adherence was found across increasing disease severity (p=0.055). Of the 76 (65.5%) patients reached for follow-up, 17 (22.4%) became adherent following lifestyle counseling (p=0.02) increasing overall adherence to 78.9% from 62.5%. CONCLUSION: In our study, comprehensive lifestyle counseling succeeded in increasing medication adherence in patients with OHT and POAG.

Prospective performance of clear cell likelihood scores (ccLS) in renal masses evaluated with multiparametric magnetic resonance imaging.

OBJECTIVES: Solid renal masses have unknown malignant potential with commonly utilized imaging. Biopsy can offer a diagnosis of cancer but has a high non-diagnostic rate and complications. Reported use of multiparametric magnetic resonance imaging (mpMRI) to diagnose aggressive histology (i.e., clear cell renal cell carcinoma (ccRCC)) via a clear cell likelihood score (ccLS) was based on retrospective review of cT1a tumors. We aim to retrospectively assess the diagnostic performance of ccLS prospectively assigned to renal masses of all stages evaluated with mpMRI prior to histopathologic evaluation. METHODS: In this retrospective cohort study from June 2016 to November 2019, 434 patients with 454 renal masses from 2 institutions with heterogenous patient populations underwent mpMRI with prospective ccLS assignment and had pathologic diagnosis. ccLS performance was assessed by contingency table analysis. The association between ccLS and ccRCC was assessed with logistic regression. RESULTS: Mean age and tumor size were 60 ± 13 years and 5.4 ± 3.8 cm. Characteristics were similar between institutions except for patient age and race (both p < 0.001) and lesion laterality and histology (both p = 0.04). The PPV of ccLS increased with each increment in ccLS (ccLS1 5% [3/55], ccLS2 6% [3/47], ccLS3 35% [20/57], ccLS4 78% [85/109], ccLS5 93% [173/186]). Pooled analysis for ccRCC diagnosis revealed sensitivity 91% (258/284), PPV 87% (258/295) for ccLS ≥ 4, and specificity 56% (96/170), NPV 94% (96/102) for ccLS ≤ 2. Diagnostic performance was similar between institutions. CONCLUSIONS: We confirm the optimal diagnostic performance of mpMRI to identify ccRCC in all clinical stages. High PPV and NPV of ccLS can help inform clinical management decision-making. KEY POINTS: • The positive predictive value of the clear cell likelihood score (ccLS) for detecting clear cell renal cell carcinoma was 5% (ccLS1), 6% (ccLS2), 35% (ccLS3), 78% (ccLS4), and 93% (ccLS5). Sensitivity of ccLS ≥ 4 and specificity of ccLS ≤ 2 were 91% and 56%, respectively. • When controlling for confounding variables, ccLS is an independent risk factor for identifying clear cell renal cell carcinoma. • Utilization of the ccLS can help guide clinical care, including the decision for renal mass biopsy, reducing the morbidity and risk to patients.

Cost Analysis of Vaginal Anti-incontinence Procedures at a Tertiary Care Center.

OBJECTIVE: To compare the cost of 3 vaginal procedures used in the surgical management of stress urinary incontinence (SUI) at 1 tertiary institution. METHODS: The costs of autologous fascial sling (AFS), synthetic mid-urethral sling (MUS), and anterior vaginal wall suspension (AVWS) were analyzed from a prospective long-term database, with follow-up to 5 years after these procedures. Original costing data were obtained for operating room, medical and surgical supplies, pharmacy, anesthesia supplies, and room and bed over 2 consecutive years. Included were complete cost data provided by our institution from Medicare (2012) and private payer insurance. RESULTS: For the year 2013, the AVWS, AFS, and MUS had total median costs of $4513, $5721, and $3311, respectively. Total cost and all subcosts except for pharmacy costs were significantly different for each procedure. AVWS and MUS placement differed from each other regarding the cost of anesthesia and hospital stay, which was higher for AVWS. Compared to AFS, AVWS had significantly lower total costs due to decreased costs associated with operating time, hospital stay, and surgical supplies (P <.0001). At 5 years after these procedures, synthetic slings had less frequent follow-up visits. The most common revision for SUI failure was a bulking agent injection. CONCLUSION: Initial costs of vaginal SUI procedures at our institution fared favorably compared to SUI procedures reported in the contemporary US literature. Long-term costs can vary based on physician preference in follow-up routine and etiology of SUI.

Diagnostic performance of prospectively assigned clear cell Likelihood scores (ccLS) in small renal masses at multiparametric magnetic resonance imaging.

INTRODUCTION: Detection of small renal masses (SRM) is increasing with the use of cross-sectional imaging, although many incidental lesions have negligible metastatic potential. A method to identify this subtype would aid in risk stratification. A previously reported clear cell likelihood score (ccLS; 1-very unlikely, 2-unlikely, 3-equivocal, 4-likely, and 5-very likely), based on retrospective review of multiparametric magnetic resonance imaging (mpMRI), predicted the likelihood of encountering clear cell renal cell carcinoma (ccRCC) at surgery. Here, we assess the performance of ccLS prospectively assigned for prediction of ccRCC. METHODS: Patients with a known renal mass who underwent mpMRI at a single institution between June 2016 and April 2018 were prospectively assigned a ccLS as part of the clinical MRI report. These patients were retrospectively reviewed, and those with a cT1a lesion and available pathological tissue diagnosis (diagnostic biopsy or extirpative surgery) were selected for analysis. RESULTS: In total, 57 patients (mean age 61.7 ± 14.9 years) with 63 cT1a renal masses were identified. Mean tumor size was 2.7 ± 0.7 cm. Defining ccLS 4-5 lesions as positive demonstrated an overall accuracy of 84%, sensitivity of 89%, specificity of 79%, positive predictive value of 84%, and negative predictive value of 86%. A ccLS of 1-2 demonstrates an 86% accuracy and 100% sensitivity/positive predictive value of identifying non-ccRCC histology. CONCLUSIONS: Utilizing prospectively assigned ccLS, we confirm that mpMRI can reasonably identify ccRCC histology in cT1a renal masses. Standardization of imaging protocols and reporting criteria such as the ccLS can be used to aid in the diagnosis and management of small renal masses.

Age 80 years and over is not associated with increased morbidity and mortality following pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomy (PD) is associated with high morbidity, which is perceived to be increased in the elderly. To our knowledge there have been no Australian series that have compared outcomes of patients over the age of 80 undergoing PD to those who are younger. METHODS: Patients who underwent PD between January 2008 and November 2015 were identified from a prospectively maintained database. RESULTS: A total of 165 patients underwent PD of whom 17 (10.3%) were aged 80 or over. The pre-operative health status, according to American Society of Anesthesiologists class was similar between the groups (P = 0.420). The 90-day mortality rates (5.9% in the elderly and 2% in the younger group; P = 0.355) and the post-operative complication rates (64.7% in the elderly versus 62.8% in the younger group; P = 0.88) were similar. Overall median length of hospital stay was also similar between the groups, but older patients were far more likely to be discharged to a rehabilitation facility than younger patients (47.1 versus 12.8%; P < 0.0001). Older patients with pancreatic adenocarcinoma (n = 10) had significantly lower median survival than the younger group (n = 69) (16.6 versus 22.5 months; P = 0.048). CONCLUSION: No significant differences were seen in the rate of complications following PD in patients aged 80 or over compared to younger patients, although there appears to be a shorter survival in the elderly patients treated for pancreatic cancer. Careful selection of elderly patients and optimal peri-operative care, rather than age should be used to determine whether surgical intervention is indicated in this patient group.

The outcomes of pancreaticoduodenectomy in patients aged 80 or older: a systematic review and meta-analysis.

BACKGROUND: There is an increasing needed to consider pancreaticoduodenectomy (PD) for the treatment of pancreatic and periampullary malignancy in patients aged 80 and over, given the increasing aging population. METHODS: A systematic literature search was undertaken to identify selected studies that compared the outcomes of patients aged 80 years or over to those younger undergoing PD. RESULTS: In total 18 studies were included for evaluation. Octogenarian or older populations had significantly higher 30-day post-operative mortality rate (OR: 2.22, 95% CI = 1.48-3.31, p < 0.001) and length of hospital stay (OR: 2.23, 95% CI = 1.36-3.10, p < 0.001). The overall post-operative complication rate was higher in the older group compared to the younger population (OR: 1.51, 95% CI = 1.25-1.83, p < 0.001). Elderly patients were more likely to develop pneumonia (OR: 1.72, 95% CI = 1.39-2.13, p < 0.001) and experience delayed gastric emptying (DGE) (OR: 1.77, 95% CI = 1.35-2.31, p < 0.001). The incidence of post-operative pancreatic fistula and bile leak were not significantly different between the groups. Rehabilitation and home nursing care services was also more frequently required by the older patient group at the time of hospital discharge. CONCLUSION: Patients aged 80 years and older have approximately double the risk of 30-day post-operative mortality and 50% increased rate of complications following PD. Careful patient selection is required when offering surgery in this age group.

Perceptions of the care experience in critical care units enhanced by a tele-ICU.

The purpose of this study was to determine patients' and families' perceptions of care in 10 critical care units enhanced by a tele-intensive care unit (ICU) in a 5-hospital health care system. Patients and family members who had a critical care experience were approached for participation. An adapted version of the Schmidt Perception of Nursing Care Survey was administered. The Schmidt Perception of Nursing Care Survey factors--seeing the individual patient, explaining, responding, and watching over-were analyzed for 637 participants (263 before and 374 after the tele-ICU implementation). Analysis of data from patients and family members indicated significantly higher means for the following factors: seeing the individual patient (P =.004), responding (P =.002), and watching over (P =.006) only when there was an awareness by the patient and family members that the care team was at the bedside and at the tele-ICU command center. The perceptions of care in these cases may suggest an improved patient experience when a tele-ICU is part of the care team.

Clinical outcomes after telemedicine intensive care unit implementation.

OBJECTIVE: To examine clinical outcomes before and after implementation of a telemedicine program in the intensive care units of a five-hospital healthcare system. DESIGN: Observational study with the baseline period of 1 yr before the start of a telemedicine intensive care unit program implementation at each of 5 hospitals. The post periods are 1, 2, and 3 yrs after telemedicine intensive care unit program implementation at each hospital. SETTING: Ten adult intensive care units (114 beds) in five community hospitals in south Florida. A telemedicine intensive care unit program with remote 24/7 intensivist and critical care nurse electronic monitoring was implemented by a phased approach between December 2005 and July 2007. MEASUREMENTS AND MAIN RESULTS: Records from 24,656 adult intensive care unit patients were analyzed. Hospital length of stay, intensive care unit length of stay, hospital mortality, and Case Mix Index were measured. Severity of illness using All Patient Refined-Diagnosis Related Groups scores was used as a covariate. From the baseline year to year 3 postimplementation, the severity-adjusted hospital length of stay was lowered from 11.86 days (95% confidence interval [CI] 11.55-12.21) to 10.16 days (95% CI 9.80-10.53; p < .001), severity-adjusted intensive care unit length of stay was lowered from 4.35 days (95% CI 4.22-4.49) to 3.80 days (95% CI 3.65-3.94; p < .001), and the relative risk of hospital mortality decreased to 0.77 (95% CI 0.69-0.87; p < .001). CONCLUSIONS: After 3 yrs of deployment of a telemedicine intensive care unit program, this retrospective observational study of mortality and length of stay outcomes included all cases admitted to an adult intensive care unit and found statistically significant decreases in severity-adjusted hospital length of stay of 14.2%, intensive care unit length of stay of 12.6%, and relative risk of hospital mortality of 23%, respectively, in a multihospital healthcare system.

Induction of dsRNA-activated protein kinase links mitochondrial unfolded protein response to the pathogenesis of intestinal inflammation.

OBJECTIVE: Inflammatory bowel diseases (IBDs) feature multiple cellular stress responses, including endoplasmic reticulum (ER) unfolded protein responses (UPRs). UPRs represent autoregulatory pathways that adjust organelle capacity to cellular demand. A similar mechanism, mitochondrial UPR (mtUPR), has been described for mitochondria. ER UPR in intestinal epithelial cells (IECs) contributes to the development of intestinal inflammation, and since mitochondrial alterations and dysfunction are implicated in the pathogenesis of IBDs, the authors characterised mtUPR in the context of intestinal inflammation. METHODS: Truncated ornithine transcarbamylase was used to selectively induce mtUPR in a murine IEC line. Dextran sodium sulphate (DSS) was administered to PKR (double-stranded-RNA-activated protein kinase) knockout mice to induce IEC stress in vivo and to test for their susceptibility to DSS-induced colitis. Expression levels of the mitochondrial chaperone chaperonin 60 (CPN60) and PKR were quantified in IECs from patients with IBDs and from murine models of colitis using immunohistochemistry and Western blot analysis. RESULTS: Selective mtUPR induction by truncated ornithine transcarbamylase transfection triggered the phosphorylation of eukaryotic translation initiation factor (eIF) 2α and cJun through the recruitment of PKR. Using pharmacological inhibitors and small inhibitory RNA, the authors identified mtUPR-induced eIF2α phosphorylation and transcription factor activation (cJun/AP1) as being dependent on the activities of the mitochondrial protease ClpP and the cytoplasmic kinase PKR. Pkr(-/-) mice failed to induce CPN60 in IECs upon DSS treatment at early time points and subsequently showed an almost complete resistance to DSS-induced colitis. Under inflammatory conditions, primary IECs from patients with IBDs and two murine models of colitis exhibited a strong induction of the mtUPR marker protein CPN60 associated with enhanced expression of PKR. CONCLUSION: PKR integrates mtUPR into the disease-relevant ER UPR via eIF2α phosphorylation and AP1 activation. Induction of mtUPR and PKR was observed in IECs from murine models and patients with IBDs. The authors' results indicate that PKR might link mitochondrial stress to intestinal inflammation.

Radical cystectomy after bacillus Calmette-Guérin for high-risk Ta, T1, and carcinoma in situ: defining the risk of initial bladder preservation.

OBJECTIVES: To critically evaluate the survival of patients with high-grade Ta or T1 urothelial cancer (UC) or carcinoma in situ of the bladder who have received bacillus Calmette-Guérin (BCG) and who have undergone radical cystectomy. METHODS: We retrospectively reviewed our single-surgeon database of those patients who underwent cystectomy and previously received BCG. We evaluated the baseline characteristics, pathologic outcomes, and survival data. RESULTS: Of 313 patients who underwent cystectomy between January 1992 and March 2004, 90 (29%) received BCG before bladder removal. The mean time from the first BCG course to the date of cystectomy was 27.9 months. The mean duration of follow-up from cystectomy was 32.1 months. The risk of progression to muscle invasion for those who underwent cystectomy less than or more than 1 year from the time of their first BCG dose was 59% and 36%, respectively (P = 0.05). The disease-specific survival rate was 81% versus 80% for those who underwent early versus delayed cystectomy (P = 0.9). CONCLUSIONS: Patients with high-grade UC are at risk of dying from this cancer, even if they ultimately undergo cystectomy. Patients who receive BCG should be appropriately counseled that they remain at risk for disease progression and death from UC. It is difficult to ascertain the proper time to proceed with cystectomy if an initial bladder conservation approach is used.

Prostate specific antigen recurrence rates are low after radical retropubic prostatectomy and positive margins.

PURPOSE: Treatment in patients with a positive surgical margin after radical retropubic prostatectomy is controversial. Options are observation, radiation therapy and early hormone therapy. Making the appropriate choice should be based on an understanding of the risk of recurrence without treatment. MATERIALS AND METHODS: We reviewed the records of 1,383 patients after radical retropubic prostatectomy was performed by a single surgeon. All specimens were analyzed by a single pathologist. Of the patients 936 met criteria for analysis. RESULTS: Mean followup in these 936 patients was 45.8 months (minimum 12). The overall PSA biochemical recurrence rate was 11.5% (108 of 936 cases). Of the 936 patients 350 (37%) had tumor at an inked margin. These patients had a recurrence rate of 19% (67 of 350), while patients with negative margins had a recurrence rate of 7% (41 of 586). This difference was statistically significant (p <0.01). Multivariate HR analysis revealed that significant risk factors for recurrence in the 936 patients were PSA greater than 20 ng/ml, clinical stage T2 or greater, Gleason 7 or greater, seminal vesicle involvement, extraprostatic extension, a visual estimate of prostate cancer volume of greater than 9.1% and positive surgical margins. Statistically significant risk factors for recurrence in patients with a positive margin on multivariate HR analysis were PSA greater than 20 ng/ml, Gleason score 7 or greater and seminal vesicle involvement. CONCLUSIONS: Although the positive margin rate in this series was 37%, the recurrence rate in these patients was only 19%. It is important to consider other factors, such as PSA, Gleason score, seminal vesicle involvement and extraprostatic extension, when making treatment decisions.

Is adjuvant chemotherapy for bladder cancer safer in patients with an ileal conduit than a neobladder?

OBJECTIVE: To assess the safety of adjuvant chemotherapy in patients with neobladder reconstruction in comparison to ileal conduit, as radical cystectomy and urinary diversion is an effective curative surgical treatment for muscle-invasive and high-risk superficial bladder cancer, and adjuvant chemotherapy is usually considered for patients with clinical stage > T2 and nodal metastasis. PATIENTS AND METHODS: We analysed retrospectively patients who had had a radical cystectomy and urinary diversion between 1992 and 2004. Patients with high-risk disease who had adjuvant chemotherapy were identified and stratified based on the type of urinary diversion (ileal conduit or neobladder). The chemotherapy regimen, complications from the adjuvant chemotherapy and other relevant data were analysed. RESULTS: Overall, 343 patients had radical cystectomy, 40 had adjuvant chemotherapy; 25 had an ileal conduit and 15 had a neobladder. Patient characteristics including age, stage and follow-up were similar. In all, 55% of patients had grade 1 toxicity, 23% grade 2, 18% grade 3, and 13% grade 4. No patients had serious organ toxicity and none died. There were no significant differences in the toxicity among the two groups. CONCLUSIONS: Adjuvant chemotherapy appears to be safe in patients with a neobladder and equally safe in patients with an ileal conduit. Hence neobladder reconstruction should not be denied to patients with bladder cancer who are at high risk of recurrence and who might require adjuvant chemotherapy.

Transurethral bladder tumor resection: intraoperative and postoperative complications in a residency setting.

PURPOSE: We established a database on the incidence of intraoperative and postoperative complications associated with transurethral bladder tumor resection (TURBT) in an academic teaching setting, and we prospectively recorded all TURBTs performed by residents and fellows in our urology department. MATERIALS AND METHODS: : We prospectively evaluated all TURBTs performed between November 2003 and October 2004. All cases were performed at least in part by residents and fellows under direct attending supervision at a single academic medical center with 3 different teaching hospitals. Intraoperative complications were recorded by the resident and attending surgeon at the completion of the operative procedure. At patient discharge from the hospital the data sheet was reviewed, and length of stay, postoperative transfusions and any other complications were recorded. RESULTS: A total of 173 consecutive TURBTs were performed by residents and fellows at 3 different teaching hospitals. There were 10 (5.8%) complications, including 4 (2.3%) cases of hematuria that required blood transfusion and 6 (3.5%) cases of bladder perforation. Of these 6 perforations 4 were small extraperitoneal perforations requiring only prolonged catheter drainage. These perforations were caused by residents in their first or third year of urology training. Two perforations were intraperitoneal, caused by a senior resident or a fellow, 1 of which required abdominal exploration to control bleeding. CONCLUSIONS: TURBT is a reasonably safe procedure when performed by urologists in training under direct attending supervision. The complication rate was 5.8%, however only 1 case required surgical intervention. Contrary to expected findings, more senior residents were involved in the complications, likely secondary to their disproportionate roles in more difficult resections.

Venous thromboembolism in radical prostatectomy: is heparinoid prophylaxis warranted?

OBJECTIVE: To review the incidence of venous thromboembolism (VTE) after radical retropubic prostatectomy (RRP) and evaluate the need for heparinoid prophylaxis as opposed to mechanical compression devices after RRP. PATIENTS AND METHODS: RRP is classified as a category 1 (high risk) procedure for VTE by the American College of Chest Physicians and several international guidelines recommend subcutaneous heparinoids as the preferred prophylaxis. However, this regimen may be associated with a greater risk of bleeding. We have not used heparinoid prophylaxis but place a mechanical compression device for prophylaxis of VTE, and report our clinical experience over a 12-year period. Between 1992 and 2004, all RRPs carried out by one surgeon (M.S.S.) at our centre were retrospectively reviewed after obtaining institutional review board approval. The protocol for prophylaxis of VTE consisted of compression stockings and a sequential compression device from the time of entry into the operating room until complete ambulation (we encourage early ambulation). Patients were evaluated for VTE if they developed any clinical signs or symptoms. Patients were followed at 7 days, 6 weeks and 3 months after RRP in the first year and 6-monthly thereafter. All relevant clinical data and complications were entered in a database. RESULTS: In all there were 1364 RRPs; the mean (sd) age of the patients was 61 (7) years and the mean follow-up 44 (38) months. All patients had a mechanical compression device and ambulated on the first day after surgery. None received heparinoid prophylaxis. Three VTE events were identified (0.21%); two patients had a lower limb VTE and one an upper limb VTE. All were successfully treated with anticoagulation. No patient had a documented pulmonary embolus and none died from VTE. There was one death after RRP, from myocardial infarction. CONCLUSION: The incidence of VTE after RRP is low, possibly related to the use of a mechanical compression device and early aggressive mobilization. Despite the recommendations by some, we feel that routine heparinoid prophylaxis is questionable.

Intraoperative cell salvage during radical prostatectomy is not associated with greater biochemical recurrence rate.

OBJECTIVES: To evaluate the risk of long-term biochemical recurrence for patients who receive cell-salvaged blood. Radical retropubic prostatectomy (RRP) is historically associated with the potential for significant blood loss. Different blood management strategies include blood donation, hemodilution, preoperative erythropoietin, and intraoperative cell salvage (IOCS). Oncologic surgeons have been reluctant to use IOCS because of the potential risk of tumor dissemination. METHODS: We retrospectively analyzed an RRP database and compared those who did and did not receive cell-salvaged blood by baseline parameters, pathologic outcomes, and biochemical recurrence. We also stratified our patients according to the risk of recurrence. RESULTS: A total of 1038 patients underwent RRP between 1992 and 2003. Of these, 265 (25.5%) received cell-salvaged blood and 773 (74.5%) did not. The two groups had similar baseline characteristics. No differences were found between the two groups when compared by risk of seminal vesicle invasion or positive surgical margins. Those who received cell-salvaged blood had a lower risk of extraprostatic extension. The median follow-up for all patients was 40.2 months. The overall risk of biochemical recurrence at 5 years for those who did and did not receive cell-salvaged blood was 15% and 18%, respectively (P = 0.76). No significant differences were found in the risk of biochemical recurrence when patients were stratified according to low, intermediate, and high risk. CONCLUSIONS: IOCS is a safe and effective blood management strategy for patients undergoing RRP. The risk of biochemical recurrence was not increased for those who received cell-salvaged blood. Concerns about spreading tumor cells by way of IOCS would seem unwarranted.

Sexual, psychological and dyadic qualities of the prostate cancer 'couple'.

OBJECTIVES: To examine the levels of sexual, psychological and dyadic functioning of the prostate cancer 'couple' (as studies have shown that spouses/partners play an integral role in the patient's adjustment to prostate cancer treatment), to encourage the creation of innovative psychosexual interventions to be used in the outpatient setting, and to offer insights into a novel area of prostate cancer research. PATIENTS AND METHODS: In all, 103 men newly diagnosed with prostate cancer, and their partners, were assessed in an academic outpatient setting using instruments measuring sexual function, depressed mood, psychological distress and dyadic adjustment. RESULTS: The partners' mean scores on sexual function questions were 55.75, significantly higher than those of the patients (51.7, P = 0.018), showing that partners perceived their sexual performance at a better level. Partners' mean scores on the depression and distress measures were also significantly higher. On those items that monitored the accuracy of the patients' perceptions of their sexual function, partners rated the patients significantly lower in ability to gain erections (patient/partner means 2.67/4.52; P < 0.001) and to perform sexually (patient/partner means 1.38/4.68; P < 0.001) than they rated themselves. CONCLUSIONS: Information from this study could be useful in constructing interventions that allow the physician and the prostate cancer 'couple' to reflect on issues of sexual function and psychological distress that might once have been considered taboo. The results characterize the disparities between patients with prostate cancer and their partners on self-reported questionnaires, and underscore how important it is to hear the voice of the 'couple'.

Evaluation of analgesic requirements and postoperative recovery after radical retropubic prostatectomy using long-acting spinal anesthesia.

OBJECTIVES: To analyze the postoperative pain, analgesic requirements, and convalescence of patients undergoing radical retropubic prostatectomy (RRP) under spinal anesthesia using long-acting morphine sulfate as preemptive analgesia. METHODS: A total of 103 consecutive men underwent RRP by a single surgeon. The time to tolerate oral fluids, time to unassisted ambulation, postoperative pain levels (visual analog pain score of 0 to 10), and analgesic requirements expressed in morphine equivalents were evaluated. Baseline patient characteristics and intraoperative factors (operating room time, blood loss) were also evaluated. RESULTS: The mean time to tolerate oral fluids and unassisted ambulation was 11.3 +/- 7.6 hours and 20 +/- 6 hours, respectively. The mean narcotic requirements were 7.4 +/- 6.1 morphine equivalents before discharge and 28.5 +/- 25.9 morphine equivalents in the first week after discharge. The mean visual analog pain score was 4.5 +/- 2.1 at discharge and fell significantly to 1.5 +/- 1.0 by the time of Foley catheter removal on postoperative day 7 or 8. The analgesic requirements after discharge correlated with the pain score at discharge (P = 0.016). The mean time to resumption of normal preoperative activities was 19.4 +/- 9.4 days. Two patients developed postspinal anesthesia headache. No other complications attributable to the anesthetic occurred. CONCLUSIONS: RRP may be performed through a small modified Pfannenstiel incision under spinal anesthesia containing long-acting morphine with little postoperative pain, low narcotic requirements, and a short convalescence. A prospective, randomized study is needed to compare the early postoperative outcomes of RRP performed using general versus spinal anesthesia.