Amy L. Weaver

Early Exposure to Anesthesia and Learning Disabilities in a Population-based Birth Cohort

Background:Anesthetic drugs administered to immature animals may cause neurohistopathologic changes and alterations in behavior. The authors studied association between anesthetic exposure before age 4 yr and the development of reading, written language, and math learning disabilities (LD). Methods:This was a population-based, retrospective birth cohort study. The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota, from 1976 to 1982 and who remained in the community at 5 yr of age were reviewed to identify children with LD. Cox proportional hazards regression was used to calculate hazard ratios for anesthetic exposure as a predictor of LD, adjusting for gestational age at birth, sex, and birth weight. Results:Of the 5,357 children in this cohort, 593 received general anesthesia before age 4 yr. Compared with those not receiving anesthesia (n = 4,764), a single exposure to anesthesia (n = 449) was not associated with an increased risk of LD (hazard ratio = 1.0; 95% confidence interval, 0.79–1.27). However, children receiving two anesthetics (n = 100) or three or more anesthetics (n = 44) were at increased risk for LD (hazard ratio = 1.59; 95% confidence interval, 1.06–2.37, and hazard ratio = 2.60; 95% confidence interval, 1.60–4.24, respectively). The risk for LD increased with longer cumulative duration of anesthesia exposure (expressed as a continuous variable) (P = 0.016). Conclusion:Exposure to anesthesia was a significant risk factor for the later development of LD in children receiving multiple, but not single anesthetics. These data cannot reveal whether anesthesia itself may contribute to LD or whether the need for anesthesia is a marker for other unidentified factors that contribute to LD.

Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma.

&NA; Our objective was to compare cancer‐specific survival and to examine associations with outcome among the histologic subtypes of renal cell carcinoma (RCC). We studied 2385 patients whose first surgery between 1970 and 2000 was a radical nephrectomy for sporadic, unilateral RCC. All RCC tumors were classified following the 1997 Union Internationale Contre le Cancer and American Joint Committee on Cancer guidelines. There were 1985 (83.2%) patients with clear cell, 270 (11.3%) with papillary, 102 (4.3%) with chromophobe, 6 (0.3%) with collecting duct, 5 (0.3%) with purely sarcomatoid RCC and no underlying histologic subtype, and 17 (0.7%) with RCC, not otherwise specified. Cancer‐specific survival rates at 5 years for patients with clear cell, papillary, and chromophobe RCC were 68.9%, 87.4%, and 86.7%, respectively. Patients with clear cell RCC had a poorer prognosis compared with patients with papillary and chromophobe RCC (p <0.001). This difference in outcome was observed even after stratifying by 1997 tumor stage and nuclear grade. There was no significant difference in cancer‐specific survival between patients with papillary and chromophobe RCC (p = 0.918). The 1997 TNM stage, tumor size, presence of a sarcomatoid component, and nuclear grade were significantly associated with death from clear cell, papillary, and chromophobe RCC. Histologic tumor necrosis was significantly associated with death from clear cell and chromophobe RCC, but not with death from papillary RCC. Our results demonstrate that there are significant differences in outcome and associations with outcome for the different histologic subtypes of RCC, highlighting the need for accurate subtyping.

An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: The SSIGN score

PURPOSE Currently outcome prediction in renal cell carcinoma is largely based on pathological stage and tumor grade. We developed an outcome prediction model for patients treated with radical nephrectomy for clear cell renal cell carcinoma, which was based on all available clinical and pathological features significantly associated with death from renal cell carcinoma. MATERIALS AND METHODS We identified 1,801 adult patients with unilateral clear cell renal cell carcinoma treated with radical nephrectomy between 1970 and 1998. Clinical features examined included age, sex, smoking history, and signs and symptoms at presentation. Pathological features examined included 1997 TNM stage, tumor size, nuclear grade, histological tumor necrosis, sarcomatoid component, cystic architecture, multifocality and surgical margin status. Cancer specific survival was estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to test associations between features studied and outcome. The selection of features included in the multivariate model was validated using bootstrap methodology. RESULTS Mean followup was 9.7 years (range 0.1 to 31). Estimated cancer specific survival rates at 1, 3, 5, 7 and 10 years were 86.6%, 74.0%, 68.7%, 63.8% and 60.0%, respectively. Several features were multivariately associated with death from clear cell renal cell carcinoma, including 1997 TNM stage (p <0.001), tumor size 5 cm. or greater (p <0.001), nuclear grade (p <0.001) and histological tumor necrosis (p <0.001). CONCLUSIONS In patients with clear cell renal cell carcinoma 1997 TNM stage, tumor size, nuclear grade and histological tumor necrosis were significantly associated with cancer specific survival. We present a scoring system based on these features that can be used to predict outcome.

Matched Comparison of Radical Nephrectomy vs Nephron-Sparing Surgery in Patients With Unilateral Renal Cell Carcinoma and a Normal Contralateral Kidney

OBJECTIVE To report the long-term follow-up of a matched comparison of radical nephrectomy (RN) and nephron-sparing surgery (NSS) in patients with single unilateral renal cell carcinoma (RCC) and a normal contralateral kidney. PATIENTS AND METHODS Between August 1966 and March 1999, 1492 and 189 patients with unilateral RCC and a normal contralateral kidney underwent RN and NSS, respectively. Patients with renal impairment, previous nephrectomy, bilateral or multiple RCCs, metastasis, and familial cancer syndromes were excluded. A total 164 patients in each cohort were matched according to pathological grade, pathological T stage, size of tumor, age, sex, and year of surgery. The Kaplan-Meier method and stratified Cox proportional hazards model were used to estimate and compare overall, cancer-specific, local recurrence-free, and metastasis-free survival and survival free of chronic renal insufficiency. The 2 groups were evaluated for early (< or = 30 days) complications and proteinuria at last follow-up. RESULTS At last follow-up, 126 RN patients (77%) and 130 NSS patients (79%) were alive with no evidence of disease. There was no significant difference observed between patients who had RN and those who had NSS with respect to overall survival (risk ratio, 0.96; 95% confidence interval [CI], 0.52-1.74; P = .88) or cancer-specific survival (risk ratio, 1.33; 95% CI, 0.30-5.95; P = .71). At 10 years, similar rates of contralateral recurrence (0.9% for RN vs 1% for NSS) and metastasis (4.9% for RN vs 4.3% for NSS) were seen in each group, whereas the rate of ipsilateral local recurrence for patients who underwent RN and NSS was 0.8% and 5.4%, respectively (P = .18). There was no significant difference in the early complications between the RN and NSS groups. However, patients who underwent RN had a significantly higher risk for proteinuria as defined by a protein/osmolality ratio of 0.12 or higher (55.2% vs 34.5%; P = .01). At 10 years, the cumulative incidence of chronic renal insufficiency (creatinine > 2.0 mg/dL at least 30 days after surgery) was 22.4% and 11.6%, respectively, for the RN and NSS groups (risk ratio, 3.7; 95% CI, 1.2-11.2; P = .01). CONCLUSIONS This retrospective study of patients with unilateral RCC and a normal contralateral kidney suggests that NSS is as effective as RN for the treatment of RCC on long-term follow-up. The increased risk of chronic renal insufficiency and proteinuria after RN supports use of NSS.

Cognitive and Behavioral Outcomes After Early Exposure to Anesthesia and Surgery

BACKGROUND: Annually, millions of children are exposed to anesthetic agents that cause apoptotic neurodegeneration in immature animals. To explore the possible significance of these findings in children, we investigated the association between exposure to anesthesia and subsequent (1) learning disabilities (LDs), (2) receipt of an individualized education program for an emotional/behavior disorder (IEP-EBD), and (3) scores of group-administered achievement tests. METHODS: This was a matched cohort study in which children (N = 8548) born between January 1, 1976, and December 31, 1982, in Rochester, Minnesota, were the source of cases and controls. Those exposed to anesthesia (n = 350) before the age of 2 were matched to unexposed controls (n = 700) on the basis of known risk factors for LDs. Multivariable analysis adjusted for the burden of illness, and outcomes including LDs, receipt of an IEP-EBD, and the results of group-administered tests of cognition and achievement were outcomes. RESULTS: Exposure to multiple, but not single, anesthetic/surgery significantly increased the risk of developing LDs (hazard ratio: 2.12 [95% confidence interval: 1.26–3.54]), even when accounting for health status. A similar pattern was observed for decrements in group-administered tests of achievement and cognition. However, exposure did not affect the rate of children receiving an individualized education program. CONCLUSIONS: Repeated exposure to anesthesia and surgery before the age of 2 was a significant independent risk factor for the later development of LDs but not the need for educational interventions related to emotion/behavior. We cannot exclude the possibility that multiple exposures to anesthesia/surgery at an early age may adversely affect human neurodevelopment with lasting consequence.

A New Questionnaire for Gastroesophageal Reflux Disease

OBJECTIVE To develop a questionnaire to measure gastroesophageal reflux disease in the community and to test its reliability and validity. MATERIAL AND METHODS The reliability of the questionnaire was measured by a test-retest procedure in 38 outpatients and 77 community residents 25 to 74 years of age, whereas concurrent validity was evaluated by comparing findings from a physician interview with self-report data from 51 patients. For statistical analysis of the reliability of each question, the kappa statistic and the 95% confidence interval were calculated. RESULTS The questionnaire was easy to understand and well accepted. The reliability (median kappa for outpatients, 0.70 [interquartile range, 0.59 to 0.81]; median kappa for population sample, 0.70 [interquartile range, 0.60 to 0.81]) and validity (median kappa, 0.62 [interquartile range, 0.49 to 0.74]) were acceptable. CONCLUSION Our initial results suggest that this questionnaire is valid and should be applicable in population-based studies to assess gastroesophageal reflux disease.

PROSTATE CANCER DIAGNOSIS USING A SATURATION NEEDLE BIOPSY TECHNIQUE AFTER PREVIOUS NEGATIVE SEXTANT BIOPSIES

PURPOSE We hypothesized that markedly increasing the number of cores obtained during prostate needle biopsy may improve the cancer detection rate in men with persistent indications for repeat biopsy. MATERIALS AND METHODS We performed saturation ultrasound guided transrectal prostate needle biopsy in 224 men under anesthesia in an outpatient surgical setting in whom previous negative biopsies had been performed in the office. The mean number of previous sextant biopsy sessions plus or minus standard deviation before saturation biopsy was 1.8 (range 1 to 7). A mean of 23 saturation biopsy cores (range 14 to 45) were distributed throughout the whole prostate, including the peripheral, medial and anterior regions. Indications for repeat biopsy were persistent elevated serum prostate specific antigen (PSA) in 108 cases, persistent elevated PSA and abnormal rectal examination in 27, persistent abnormal rectal examination in 4, high grade prostatic intraepithelial neoplasia in the previous biopsy in 64 and atypia in the previous biopsy in 21. RESULTS Cancer was detected in 77 of 224 patients (34%). The number of previous negative sextant biopsies was not predictive of subsequent cancer detection by saturation biopsy. Median PSA was 8.7 ng./ml. and median PSA velocity was 0.63 ng./ml. yearly. Of the 77 patients in whom cancer was detected radical prostatectomy was performed in 52. Pathological stage was pT2 in 48 patients and pT3 in 4, while Gleason score was 4 to 5, 6 to 7 and 8 in 5, 46 and 1, respectively. At prostatectomy median cancer volume was 1.04 cc and 85.7% of removed tumors were clinically significant, assuming a 3-year doubling time. The overall complication rate for saturation needle biopsy was 12% and hematuria requiring hospital admission was the most common event. CONCLUSIONS Saturation needle biopsy of the prostate is a useful diagnostic technique in men at risk for prostate cancer with previous negative office biopsies. This technique allows adequate sampling of the whole prostate gland and has a detection rate of 34% in this cohort of patients.

Lack of discriminant value of dyspepsia subgroups in patients referred for upper endoscopy

BACKGROUND The subdivision of undiagnosed patients with dyspepsia into symptomatic subgroups (ulcerlike, dysmotilitylike, refluxlike, and nonspecific) may give a clue to the underlying cause; however, the value of this approach in practice is unclear. This study aimed to determine the discriminant value of dyspeptic symptoms and combinations of these symptoms. METHODS A consecutive sample of 820 outpatients (median age, 62 years; 47% male) completed, before endoscopy, a validated questionnaire that measured 46 gastrointestinal symptoms. RESULTS Of patients with functional dyspepsia (n = 162), 17% had ulcerlike, 9% dysmotilitylike, and 16% refluxlike dyspepsia alone; 31% fell into two or more symptom subgroups; and 27% had nonspecific symptoms. A similar distribution of the dyspepsia subgroups was observed in patients without functional dyspepsia. Younger age, female gender, frequent upper abdominal pain, no (or sometimes) pain relief with antacid use, and infrequent vomiting were predictive of functional dyspepsia vs. all other diagnoses (at a specificity of 80%, the sensitivity was 60%). The dyspepsia subgroups were poor discriminators in a separate model for functional dyspepsia vs. all other diagnoses (at a specificity of 80%, the sensitivity was only 43%). CONCLUSIONS The dyspepsia subgroups, as currently defined, appear to have little clinical utility and may be an inappropriate way of classifying dyspepsia.

Robotic radical hysterectomy: Comparison with laparoscopy and laparotomy

OBJECTIVE Comparison of perioperative results of patients undergoing radical hysterectomy by robotics, laparoscopy, and laparotomy. STUDY DESIGN Prospective analysis of 27 patients undergoing robotic radical hysterectomy between April 2003 and September 2006. Comparison was made with patients operated by laparoscopy and laparotomy matched by age, BMI, site and type of malignancy, FIGO staging, and type of radical hysterectomy. RESULTS The mean operating times for patients undergoing robotic, laparoscopy and laparotomy radical hysterectomy were 189.6, 220.4, and 166.8 min, respectively; the mean blood loss was 133.1, 208.4, and 443.6 ml, respectively; the mean rate of blood loss was 0.7, 0.9, and 2.6 ml/min, respectively; the mean number of removed lymph nodes was 25.9, 25.9, and 27.7, respectively; and the mean length of hospital stay was 1.7, 2.4, and 3.6 days, respectively. There were no significant differences in intra- or postoperative complications among the three groups, no fistula formation in any patient and no conversions in the robotic or laparoscopic groups. At a mean follow up of 31.1 months, none of the patients with cervical cancer has experienced recurrence. CONCLUSION Laparoscopy and robotics are preferable to laparotomy for patients requiring radical hysterectomy. Operating times for robotics and laparotomy were similar, and significantly shorter as compared to laparoscopy. Blood loss, rate of blood loss and length of hospital stay were similar for laparoscopy and robotics and significantly reduced as compared to laparotomy.

Sarcomatoid renal cell carcinoma: an examination of underlying histologic subtype and an analysis of associations with patient outcome.

A sarcomatoid component can occur in all histologic subtypes of renal cell carcinoma (RCC) and indicates an aggressive tumor. We studied 2381 patients treated with radical nephrectomy for RCC between 1970 and 2000. A urologic pathologist reviewed the microscopic slides from all tumor specimens for the presence of a sarcomatoid component, defined as a RCC with any malignant spindle cell component. All tumors with a sarcomatoid component were classified as nuclear grade 4. A total of 120 (5.0%) patients had RCC with a sarcomatoid component, including 94 who died of RCC at a mean of 1.4 years following nephrectomy (median 8 months; range 44 days to 10 years). Cancer-specific survival rates at 2 and 5 years following nephrectomy were 33.3% and 14.5%, respectively. The presence of distant metastases at the radical nephrectomy and histologic tumor necrosis were significantly associated with death from RCC among patients with sarcomatoid RCC. Patients with clear cell (conventional) RCC and chromophobe RCC were more likely to have tumors with a sarcomatoid component (5.2% and 8.7%, respectively) compared with patients with papillary RCC (1.9%). The presence of a sarcomatoid component was significantly associated with death from RCC for all three subtypes (P < 0.001). Even among patients with grade 4 clear cell RCC, the presence of a sarcomatoid component was significantly associated with outcome, both univariately (risk ratio 1.59; P = 0.010) and after adjusting for TNM stage, tumor size, and histologic tumor necrosis (risk ratio 1.46; P = 0.037).