Rameela Chandrasekhar

Delay to formalin fixation effect on breast biomarkers.

Delay to formalin fixation may invalidate hormone receptors and HER2 analyses. Invalid results of tumor markers could significantly alter the type of adjuvant therapy a patient receives and potentially impact outcome. The purpose of this study was to determine the effects of progressive delay to formalin fixation on breast cancer biomarkers. Ten palpable invasive breast cancers were resected and underwent immediate gross evaluation. For each case, the procured tumor was divided into eight parts and consecutively fixed after 0, 10, 30 min, 1, 2, 4, and 8 h; one section was kept in saline and stored overnight at 4°C. Two tissue microarray blocks were constructed. Estrogen and progesterone receptors and HER2 immunohistochemistry and fluorescence in situ hybridization were carried out. Statistical analyses including non-parametric sign test, exact McNemars test and Pages L test were used. All 10 cases were invasive ductal carcinomas. Q score ⩾6 was identified in five cases for estrogen receptor and four for progesterone receptor. Mean Q score started to decline at the 2 h mark for estrogen receptor and 1 h mark for progesterone receptor. Lowest score was at 8 h mark for estrogen receptor and overnight for progesterone receptor. HER2 fluorescence in situ hybridization started to be compromised for interpretation at the 1 h mark and became statistically significant at the 2 h mark (P<0.03). To avoid delay to formalin fixation as a factor negatively affecting on breast biomarkers, we recommend not to delay formalin fixation for more than 1 h and not to store specimens overnight.

The Learning Curve of Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium

BACKGROUND Robot-assisted radical cystectomy (RARC) has evolved as a minimally invasive alternative to open radical cystectomy for patients with invasive bladder cancer. OBJECTIVE We sought to define the learning curve for RARC by evaluating results from a multicenter, contemporary, consecutive series of patients who underwent this procedure. DESIGN, SETTING, AND PARTICIPANTS Utilizing the International Robotic Cystectomy Consortium database, a prospectively maintained and institutional review board-approved database, we identified 496 patients who underwent RARC by 21 surgeons at 14 institutions from 2003 to 2009. MEASUREMENTS Cut-off points for operative time, lymph node yield (LNY), estimated blood loss (EBL), and margin positivity were identified. Using specifically designed statistical mixed models, we were able to inversely predict the number of patients required for an institution to reach the predetermined cut-off points. RESULTS AND LIMITATIONS Mean operative time was 386 min, mean EBL was 408 ml, and mean LNY was 18. Overall, 34 of 482 patients (7%) had a positive surgical margin (PSM). Using statistical models, it was estimated that 21 patients were required for operative time to reach 6.5h and 8, 20, and 30 patients were required to reach an LNY of 12, 16, and 20, respectively. For all patients, PSM rates of <5% were achieved after 30 patients. For patients with pathologic stage higher than T2, PSM rates of <15% were achieved after 24 patients. CONCLUSIONS RARC is a challenging procedure but is a technique that is reproducible throughout multiple centers. This report helps to define the learning curve for RARC and demonstrates an acceptable level of proficiency by the 30th case for proxy measures of RARC quality.

Face Validation of a Novel Robotic Surgical Simulator

OBJECTIVES To assess the face validity of Robotic Surgery Simulator (RoSS), a novel virtual reality training platform for the da Vinci Surgical System (DVSS). METHODS Urologic surgeons, fellows, and residents attending the 2009 American Urologic Association Annual Meeting in April 2009 were invited to an orientation session with RoSS. Participants completed a questionnaire after orientation and two modules. RESULTS Thirty participants including 24 surgeons and fellows experienced with robotic surgery and 6 robotic surgery novices participated in the study. Eighty percent participants had at least 4 years of experience with robotic surgery and 77% had performed an average of 340 cases on the DVSS as primary console surgeons. Subjects indicated that RoSS was realistically close to the DVSS console in terms of virtual simulation and instrumentation. Fifty-two percent of subjects rated RoSS somewhat close and 45% rated RoSS very close to the DVSS console. Thirty-seven percent rated RoSS pinch device somewhat close, and 47% very close to the DVSS. With regard to movement of the arms, 43% rated it somewhat close, 40% rated it very close, and 7% felt that it was just like the DVSS. Camera movement and clutch functions were rated not close (11%), somewhat close (57%), and very close (32%) to the DVSS. Data were further analyzed in terms of surgical volume. Thirty-eight percent of subjects had also tried the Mimic dV-Trainer robotic surgery simulator. CONCLUSIONS RoSS provides opportunity for robot-assisted surgical training for future error-free surgery. Further validation will be necessary to assess RoSS and the application of specific modules for robot-assisted surgical training.

Content validation of a novel robotic surgical simulator.

Study Type – Therapy (case series)
Level of Evidence 4

Increasing pregnancy-related use of prescribed opioid analgesics.

PURPOSE To quantify the prevalence of prescribed opioid analgesics among pregnant women enrolled in Tennessee Medicaid from 1995 to 2009. METHODS Retrospective cohort study of 277,555 pregnancies identified from birth and fetal death certificates, and linked to previously validated, computerized pharmacy records. Poisson regression was used to estimate trends over time, rate ratios, and 95% confidence intervals (CI). RESULTS During the study period, 29% of pregnant women filled a prescription for an opioid analgesic. From 1995 to 2009, any pregnancy-related use increased 1.90-fold (95% CI, 1.83-1.98), first trimester use increased 2.27-fold (95% CI, 2.14-2.41), and second or third trimester use increased 2.02-fold (95% CI, 1.93-2.12), after adjusting for maternal characteristics. Any pregnancy-related, first trimester, and second or third trimester use were each more likely among mothers who were at least 21 years old, white, non-Hispanic, prima gravid, resided in nonurban areas, enrolled in Medicaid owing to disability, and who had less than a high school education. CONCLUSIONS Opioid analgesic use by Tennessee Medicaid-insured pregnant women increased nearly 2-fold from 1995 to 2009. Additional study is warranted to understand the implications of this increased use.

The Preschool Confusion Assessment Method for the ICU: Valid and Reliable Delirium Monitoring for Critically Ill Infants and Children.

Objectives:Delirium assessments in critically ill infants and young children pose unique challenges due to evolution of cognitive and language skills. The objectives of this study were to determine the validity and reliability of a fundamentally objective and developmentally appropriate delirium assessment tool for critically ill infants and preschool-aged children and to determine delirium prevalence. Design and Setting:Prospective, observational cohort validation study of the PreSchool Confusion Assessment Method for the ICU in a tertiary medical center PICU. Patients:Participants aged 6 months to 5 years and admitted to the PICU regardless of admission diagnosis were enrolled. Measurements and Main Results:An interdisciplinary team created the PreSchool Confusion Assessment Method for the ICU for pediatric delirium monitoring. To assess validity, patients were independently assessed for delirium daily by the research team using the PreSchool Confusion Assessment Method for the ICU and by a child psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders criteria. Reliability was assessed using blinded, concurrent PreSchool Confusion Assessment Method for the ICU evaluations by research staff. A total of 530-paired delirium assessments were completed among 300 patients, with a median age of 20 months (interquartile range, 11–37) and 43% requiring mechanical ventilation. The PreSchool Confusion Assessment Method for the ICU demonstrated a specificity of 91% (95% CI, 90–93), sensitivity of 75% (95% CI, 72–78), negative predictive value of 86% (95% CI, 84–88), positive predictive value of 84% (95% CI, 81–87), and a reliability &kgr;–statistic of 0.79 (0.76–0.83). Delirium prevalence was 44% using the PreSchool Confusion Assessment Method for the ICU and 47% by the reference rater. The rates of delirium were 53% versus 56% in patients younger than 2 years old and 33% versus 35% in patients 2–5 years old using the PreSchool Confusion Assessment Method for the ICU and reference rater, respectively. The short-form PreSchool Confusion Assessment Method for the ICU maintained a high specificity (87%) and sensitivity (78%) in post hoc analysis. Conclusions:The PreSchool Confusion Assessment Method for the ICU is a highly valid and reliable delirium instrument for critically ill infants and preschool-aged children, in whom delirium is extremely prevalent.

Robot-assisted Intracorporeal Ileal Conduit: Marionette Technique and Initial Experience at Roswell Park Cancer Institute

OBJECTIVES To present our technique and initial experience with patients who underwent robot-assisted intracorporeal creation of ileal conduit and to compare them with patients who underwent extracorporeal ileal diversion after robot-assisted radical cystectomy. METHODS Twenty-six patients diagnosed with invasive transitional cell carcinoma of the bladder underwent a robot-assisted radical cystectomy with bilateral extended pelvic lymphadenectomy with ileal conduit diversion. Total intracorporeal ileal conduit creation was performed in the last 13 patients. Operative data and short-term outcomes between the 2 groups were assessed. The novel surgical technique for intracorporeal ileal conduit will be presented. RESULTS The intracorporeal group (IC) included 2 female and 11 male patients (mean age 71 years). The extracorporeal group (EC) included 4 female and 9 male patients (mean age 66 years). No significant differences were noted between the groups in terms of patient age, BMI, sex, prior surgery, or pathologic stage. Overall operative time and intraoperative complications were similar. No significant differences were noted between the 2 groups in terms of diversion time or estimated blood loss. There were 4 complications recorded in IC patients, including nonspecific colitis, small bowel obstruction requiring exploratory laparotomy with lysis of adhesions, a urine leak that eventually resolved but required a temporary nephrostomy tube, and a fever of unknown origin that resolved without intervention. CONCLUSIONS Robot-assisted intracorporeal ileal conduit can be accomplished safely with acceptable operative times even during early experience. Larger series with favorable results will be required to add this new paradigm to minimally invasive surgery for bladder cancer.

Effect of delayed formalin fixation on estrogen and progesterone receptors in breast cancer: a study of three different clones.

We previously reported that delayed formalin fixation (DFF) has a negative effect on immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PR), and HER2. The primary aim of the study was to determine if DFF affected commonly used clones of the ER and PR differentially. The specific clones evaluated were ER clones 1D5, 6F11, and SP1 and PR clones 16, 1E2, and PgR636. Ten breast cancer cases were dissected and fixed at different times (0, 10, and 30 minutes; 1, 2, 4, and 8 hours; and overnight) and were then stained with anti-ER and anti-PR antibodies. The mean Q score for ER started to decline at 2 to 4 hours for clones 1D5 and 6F11 and at 1 hour for SP1. SP1 was superior to 1D5 at the 8-hour mark (P = .03). The Q score for PR started to decline at 1 hour for clones PgR636 and 16 and 4 to 8 hours for 1E2 (P = .03). Based on our findings, it appears that regardless of the antibody clones evaluated, DFF has a negative effect on hormone receptors.

Pleomorphic lobular carcinoma: a distinctive clinical and molecular breast cancer type

Monhollen L, Morrison C, Ademuyiwa F O, Chandrasekhar R, Khoury T 
(2012) Histopathology 61, 365–377

Frailty and Subsequent Disability and Mortality among Patients with Critical Illness

Rationale: The prevalence of frailty (diminished physiologic reserve) and its effect on outcomes for those aged 18 years and older with critical illness is unclear. Objectives: We hypothesized greater frailty would be associated with subsequent mortality, disability, and cognitive impairment, regardless of age. Methods: At enrollment, we measured frailty using the Clinical Frailty Scale (range, 1 [very fit] to 7 [severely frail]). At 3 and 12 months post‐discharge, we assessed vital status, instrumental activities of daily living, basic activities of daily living, and cognition. We used multivariable regression to analyze associations between Clinical Frailty Scale scores and outcomes, adjusting for age, sex, education, comorbidities, baseline disability, baseline cognition, severity of illness, delirium, coma, sepsis, mechanical ventilation, and sedatives/opiates. Measurements and Main Results: We enrolled 1,040 patients who were a median (interquartile range) of 62 (53‐72) years old and who had a median Clinical Frailty Scale score of 3 (3‐5). Half of those with clinical frailty (i.e., Clinical Frailty Scale score ≥5) were younger than 65 years old. Greater Clinical Frailty Scale scores were independently associated with greater mortality (P = 0.01 at 3 mo and P < 0.001 at 12 mo) and with greater odds of disability in instrumental activities of daily living (P = 0.04 at 3 mo and P = 0.002 at 12 mo). Clinical Frailty Scale scores were not associated with disability in basic activities of daily living or with cognition. Conclusions: Frailty is common in critically ill adults aged 18 years and older and is independently associated with increased mortality and greater disability. Future studies should explore routine screening for clinical frailty in critically ill patients of all ages. Interventions to reduce mortality and disability among patients with heightened vulnerability should be developed and tested. Clinical trial registered with www.clinicaltrials.gov (NCT 00392795 and NCT 00400062).