More problems, more money: Identifying and predicting high-cost rescue after colorectal surgery.

Background: Successful rescue after elective surgery is associated with increased healthcare costs, but costs vary widely. Treating all rescue events the same may overlook targeted opportunities for improvement. The purpose of this study was to predict high-cost rescue after elective colorectal surgery. Methods: We identified adult patients in the National Inpatient Sample (2016-2021) who underwent elective colectomy or proctectomy. Rescued patients were defined as those who underwent additional major procedures. Three groups were stratified: 1) uneventful recovery; 2) Low-cost rescue; 3) High-cost rescue. Multivariable Poisson regression was used to identify preoperative clinical predictors of high-cost versus low-cost rescue. Results: We identified 448,590 elective surgeries, and rescued patients composed 4.8 %(21,635) of the total sample. The median increase in costs in rescued patients was $25,544(p < 0.001). Median total inpatient costs were $95,926 in the most expensive rescued versus $34,811 in the less expensive rescued versus $16,751 in the uneventfully discharged(p < 0.001). When comparing the secondary procedures between the less expensive and most expensive rescued groups, the most expensive had an increased proportion of reoperation (73.4 % versus 53.0 %,p < 0.001). When controlling for other factors and stratification by congestive heart failure due to an interaction effect, a reoperation was independently associated with high-cost rescue (RR with CHF = 3.29,95%CI:2.69-4.04; RR without CHF = 2.29,95%CI:1.97-2.67). Conclusions: High-cost rescue after colorectal surgery is associated with disproportionately greater healthcare utilization and reoperation. For cost-conscious care, preemptive strategies that reduce reoperation-related complications can be prioritized.

How Far Is Too Far? Cost-Effectiveness Analysis of Regionalized Rectal Cancer Surgery.

BACKGROUND: Regionalized rectal cancer surgery may decrease postoperative and long-term cancer-related mortality. However, the regionalization of care may be an undue burden on patients. OBJECTIVE: This study aimed to assess the cost-effectiveness of regionalized rectal cancer surgery. DESIGN: Tree-based decision analysis. PATIENTS: Patients with stage II/III rectal cancer anatomically suitable for low anterior resection were included. SETTING: Rectal cancer surgery performed at a high-volume regional center rather than the closest hospital available. MAIN OUTCOME MEASURES: Incremental costs ($) and effectiveness (quality-adjusted life year) reflected a societal perspective and were time-discounted at 3%. Costs and benefits were combined to produce the incremental cost-effectiveness ratio ($ per quality-adjusted life year). Multivariable probabilistic sensitivity analysis modeled uncertainty in probabilities, costs, and effectiveness. RESULTS: Regionalized surgery economically dominated local surgery. Regionalized rectal cancer surgery was both less expensive on average ($50,406 versus $65,430 in present-day costs) and produced better long-term outcomes (10.36 versus 9.51 quality-adjusted life years). The total costs and inconvenience of traveling to a regional high-volume center would need to exceed $15,024 per patient to achieve economic breakeven alone or $112,476 per patient to satisfy conventional cost-effectiveness standards. These results were robust on sensitivity analysis and maintained in 94.6% of scenario testing. LIMITATIONS: Decision analysis models are limited to policy level rather than individualized decision-making. CONCLUSIONS: Regionalized rectal cancer surgery improves clinical outcomes and reduces total societal costs compared to local surgical care. Prescriptive measures and patient inducements may be needed to expand the role of regionalized surgery for rectal cancer. See Video Abstract at http://links.lww.com/DCR/C83 . QU TAN LEJOS ES DEMASIADO LEJOS ANLISIS DE COSTOEFECTIVIDAD DE LA CIRUGA DE CNCER DE RECTO REGIONALIZADO: ANTECEDENTES:La cirugía de cáncer de recto regionalizado puede disminuir la mortalidad posoperatoria y a largo plazo relacionada con el cáncer. Sin embargo, la regionalización de la atención puede ser una carga indebida para los pacientes.OBJETIVO:Evaluar la rentabilidad de la cirugía oncológica de recto regionalizada.DISEÑO:Análisis de decisiones basado en árboles.PACIENTES:Pacientes con cáncer de recto en estadio II/III anatómicamente aptos para resección anterior baja.AJUSTE:Cirugía de cáncer rectal realizada en un centro regional de alto volumen en lugar del hospital más cercano disponible.PRINCIPALES MEDIDAS DE RESULTADO:Los costos incrementales ($) y la efectividad (años de vida ajustados por calidad) reflejaron una perspectiva social y se descontaron en el tiempo al 3%. Los costos y los beneficios se combinaron para producir la relación costo-efectividad incremental ($ por año de vida ajustado por calidad). El análisis de sensibilidad probabilístico multivariable modeló la incertidumbre en las probabilidades, los costos y la efectividad.RESULTADOS:La cirugía regionalizada predominó económicamente la cirugía local. La cirugía de cáncer de recto regionalizado fue menos costosa en promedio ($50 406 versus $65 430 en costos actuales) y produjo mejores resultados a largo plazo (10,36 versus 9,51 años de vida ajustados por calidad). Los costos totales y la inconveniencia de viajar a un centro regional de alto volumen necesitarían superar los $15,024 por paciente para alcanzar el punto de equilibrio económico o $112,476 por paciente para satisfacer los estándares convencionales de rentabilidad. Estos resultados fueron sólidos en el análisis de sensibilidad y se mantuvieron en el 94,6% de las pruebas de escenarios.LIMITACIONES:Los modelos de análisis de decisiones se limitan al nivel de políticas en lugar de la toma de decisiones individualizada.CONCLUSIONES:La cirugía de cáncer de recto regionalizada mejora los resultados clínicos y reduce los costos sociales totales en comparación con la atención quirúrgica local. Es posible que se necesiten medidas prescriptivas e incentivos para los pacientes a fin de ampliar el papel de la cirugía regionalizada para el cáncer de recto. Consulte Video Resumen en http://links.lww.com/DCR/C83 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

Lower urinary tract symptoms, benign prostatic hyperplasia, and obesity.

Obesity has emerged as a global public health challenge. During the past 20 years, there has been a dramatic increase in obesity in the United States. In 2007, only one state had a prevalence of obesity less than 20%. In this growing epidemic of national concern is an emerging relationship between lower urinary tract symptoms (LUTS), benign prostatic hyperplasia (BPH), and obesity. BPH is the most common neoplastic condition afflicting men and constitutes a major factor impacting the health of the American male. Associations among obesity, physical inactivity, and BPH/LUTS resulting from epidemiological studies have not been explored via clinical trial methodology. A review of the available data appears to support a strong independent relationship between obesity and BPH/LUTS. This review also indicates that gene expression within the prostate varies with prostate size and can be affected by lifestyle modifications. Future studies may lead to office detection of a patient's particular polymorphisms, which may help guide individual treatment and lifestyle modifications that are more likely to succeed.

Variation in institutional review board responses to a standard protocol for a multicenter randomized, controlled surgical trial.

PURPOSE: The primary responsibility of institutional review boards is to protect human research subjects and, therefore, ensure that studies are performed in accordance with a standard set of ethical principles. A number of groups have compared the responses of institutional review boards in multicenter clinical trials involving medical therapies. To our knowledge no such studies have been performed to date of trials investigating surgical intervention. We investigated the consistency of the recommendations issued by various institutional review boards in the Minimally Invasive Surgical Therapies study for benign prostatic hyperplasia, a multicenter trial with a uniform consent and study protocol. MATERIALS AND METHODS: We obtained the institutional review board response from 6 of the 7 participating institutions after initial submission of the Minimally Invasive Surgical Therapies study protocol and classified the responses. We then redistributed the approved protocols to an institutional review board at another participating institution and analyzed that review of these protocols. RESULTS: We found that the number and type of responses required for institutional review board approval of an identical study protocol varied significantly among participating institutions. We also found that institutional review board responses were inconsistent in the second review, although all protocols were ultimately approved. CONCLUSIONS: The current system of local institutional review board review in the context of a multicenter surgical trial is inefficient in the review process and may not provide expertise for overseeing surgical trials. Based on these results a central surgical institutional review board may be needed to improve the ethical review process in multicenter trials.

Outcomes of radical prostatectomy for patients with clinical stage T1a and T1b disease.

OBJECTIVE: To compare the outcomes between patients with stage T1a/b with those of patients with T1c cancer of the prostate treated with radical retropubic prostatectomy (RRP), as the appropriate management of clinical stage T1a/b prostate cancer is subject to debate; although many patients are managed expectantly, some have adverse pathological features suggesting that more active treatment might be beneficial. PATIENTS AND METHODS: From 1983 to 2003, 3478 men had RRP by one surgeon. From this group, we retrospectively identified 29 men with clinical stage T1a and 83 with clinical stage T1b disease. Using statistical analysis we compared the treatment outcomes of these patients with those of 1774 men with clinical stage T1c disease. RESULTS: Men with T1a/b disease had a significantly lower preoperative prostate-specific antigen (PSA) level, a greater proportion with organ-confined disease, and a lower mean/median prostatectomy Gleason score than those with T1c disease. Also, men with T1a/b disease were less likely to be potent before surgery, although the frequency of recovery of potency was similar among all groups. On multivariate analysis with age, year of surgery, PSA level and Gleason score, there was no statistical difference in the rates of biochemical recurrence and the 10-year overall survival rates. However, patients with T1b disease had a significantly lower cancer-specific survival. CONCLUSIONS: T1a and T1b prostate cancer can be associated with aggressive pathological features and have a similar rate of progression as clinical stage T1c disease. That notwithstanding, most patients in the study were cured with RRP and had favourable long-term functional outcomes.

Organ cross talk modulates pelvic pain.

Interstitial cystitis (IC) is a chronic bladder inflammatory disease of unknown etiology that is often regarded as a neurogenic cystitis. IC is associated with urothelial lesions, voiding dysfunction, and pain in the pelvic/perineal area, and diet can exacerbate IC symptoms. In this study, we used a murine neurogenic cystitis model to investigate the development of pelvic pain behavior. Neurogenic cystitis was induced by the injection of Bartha's strain of pseudorabies virus (PRV) into the abductor caudalis dorsalis tail base muscle of female C57BL/6J mice. Infectious PRV virions were isolated only from the spinal cord, confirming the centrally mediated nature of this neurogenic cystitis model. Pelvic pain was assessed using von Frey filament stimulation to the pelvic region, and mice infected with PRV developed progressive pelvic pain. Pelvic pain was alleviated by 2% lidocaine instillation into either the bladder or the colon but not following lidocaine instillation into the uterus. The bladders of PRV-infected mice showed markers of inflammation and increased vascular permeability compared with controls. In contrast, colon histology was normal and vascular permeability was unchanged, suggesting that development of pelvic pain was due only to bladder inflammation. Bladder-induced pelvic pain was also exacerbated by colonic administration of a subthreshold dose of capsaicin. These data indicate organ cross talk in pelvic pain and modulation of pain responses by visceral inputs distinct from the inflamed site. Furthermore, these data suggest a mechanism by which dietary modification benefits pelvic pain symptoms.

Intermediate filament-membrane attachments function synergistically with actin-dependent contacts to regulate intercellular adhesive strength.

By tethering intermediate filaments (IFs) to sites of intercellular adhesion, desmosomes facilitate formation of a supercellular scaffold that imparts mechanical strength to a tissue. However, the role IF-membrane attachments play in strengthening adhesion has not been directly examined. To address this question, we generated Tet-On A431 cells inducibly expressing a desmoplakin (DP) mutant lacking the rod and IF-binding domains (DPNTP). DPNTP localized to the plasma membrane and led to dissociation of IFs from the junctional plaque, without altering total or cell surface distribution of adherens junction or desmosomal proteins. However, a specific decrease in the detergent-insoluble pool of desmoglein suggested a reduced association with the IF cytoskeleton. DPNTP-expressing cell aggregates in suspension or substrate-released cell sheets readily dissociated when subjected to mechanical stress whereas controls remained largely intact. Dissociation occurred without lactate dehydrogenase release, suggesting that loss of tissue integrity was due to reduced adhesion rather than increased cytolysis. JD-1 cells from a patient with a DP COOH-terminal truncation were also more weakly adherent compared with normal keratinocytes. When used in combination with DPNTP, latrunculin A, which disassembles actin filaments and disrupts adherens junctions, led to dissociation up to an order of magnitude greater than either treatment alone. These data provide direct in vitro evidence that IF-membrane attachments regulate adhesive strength and suggest furthermore that actin- and IF-based junctions act synergistically to strengthen adhesion.

Impaired urine concentration and absence of tissue ACE: involvement of medullary transport proteins.

ACE.2 mice lack all tissue angiotensin-converting enzyme (ACE) but have 33% of normal plasma ACE activity. They exhibit the urine-concentrating defect and hyperkalemia present in mice that lack all ACE, but in contrast to the complete knockout, ACE.2 mice have normal medullary histology and creatinine clearance. To explore the urine-concentrating defect in ACE.2 mice, renal medullary transport proteins were analyzed using Western blot analysis. In the inner medulla, UT-A1, ClC-K1, and aquaporin-1 (AQP1) were significantly reduced to 28 +/- 5, 6 +/- 6, and 39 +/- 5% of the level in wild-type mice, respectively, whereas AQP2 and UT-B were unchanged. In the outer medulla, Na(+)-K(+)-2Cl(-) cotransporter (NKCC2/BSC1) and AQP1 were significantly reduced to 56 +/- 11 and 29 +/- 6%, respectively, whereas Na(+)-K(+)-ATPase, UT-A2, UT-B, and AQP2 were unchanged, and renal outer medullary potassium channel was significantly increased to 711 +/- 187% of the level in wild-type mice. The abnormal expression of these transporters was similar in ACE.2 mice backcrossed onto a C57BL/6 or a Swiss background and was not rescued by ANG II infusion. We conclude that the urine-concentrating defect in ACE.2 mice is associated with, and may result from, downregulation of some or all of these key urea, salt, and water transport proteins.