Ileal pouch anal anastomosis in pediatric familial adenomatous polyposis: A 24-year review of operative technique and patient outcomes

Background

Total proctocolectomy with ileal pouch anal anastomosis (IPAA) is the operative procedure of choice for familial adenomatous polyposis (FAP) patients. We review 24 years of operative experience and outcomes in pediatric patients with FAP.

Methods

Patients with FAP, age < 20 years, presenting to a single institution between 1987 and 2011 were included. Operative technique and outcomes were reviewed retrospectively. Primary outcomes included postoperative complications (30 days), long-term bowel function, and polyp recurrence at the anal anastomosis.

Results

95 patients with FAP underwent IPAA. Mean age at IPAA was 15.5 years with a mean follow-up of 7.6 years. 29 patients underwent 1-stage IPAA, 65 patients had a two-stage IPAA, and 1 patient underwent a 3-stage procedure. 67 patients had an open procedure, 25 underwent a laparoscopic approach, and more recently 3 patients underwent single incision laparoscopic IPAA. Patients with 1-stage IPAA demonstrate better long term bowel control vs. 2-stage IPAA patients (10.7% vs. 36.0% occasional incontinence, p = 0.018). However, 1-stage IPAA patients suffered increased short-term complications, such as anastomotic leak (17.2% vs. 0%, p = 0.002) and reoperation (20.7% vs. 4.6%, p = 0.02) compared to 2-stage IPAA. Anal anastomosis polyp recurrence occurred in 22.7% of 1-stage patients and 10.0% of 2-stage patients. Short-term complications, polyp recurrence, or long-term continence were equivalent between open and laparoscopic cases.

Conclusion

Single-stage IPAA in children with FAP is associated with better bowel control but increased anastomotic leak, reoperative rate, and polyp recurrence. In experienced hands, laparoscopic IPAA is equivocal to open IPAA.     

Features Associated with Recurrence Beyond 5 Years After Nephrectomy and Nephron-Sparing Surgery for Renal Cell Carcinoma: Development and Internal Validation of a Risk Model (PRELANE score) to Predict Late Recurrence Based on a Large Multicenter Database (CORONA/SATURN Project)

Background

Approximately 10–20% of recurrences in patients treated with nephrectomy for renal cell carcinoma (RCC) develop beyond 5 yr after surgery (late recurrence).

Objective

To determine features associated with late recurrence.

Design, setting, and participants

A total of 5009 patients from a multicenter database comprising 13 107 RCC patients treated surgically had a minimum recurrence-free survival of 60 mo (median follow-up [FU]: 105 mo [range: 78–135]); at last FU, 4699 were disease free (median FU: 103 mo [range: 78–134]), and 310 patients (6.2%) experienced disease recurrence (median FU: 120 mo [range: 93–149]).

Interventions

Patients underwent radical nephrectomy or nephron-sparing surgery.

Outcome measurements and statistical analysis

Multivariable regression analyses identified features associated with late recurrence. Cox regression analyses evaluated the association of features with cancer-specific mortality (CSM).

Results and limitations

Lymphovascular invasion (LVI) (odds ratio [OR]: 3.07; p < 0.001), Fuhrman grade 3–4 (OR: 1.60; p = 0.001), and pT stage >pT1 (OR: 2.28; p < 0.001) were significantly associated with late recurrence. Based on accordant regression coefficients, these parameters were weighted with point values (LVI: 2 points; Fuhrman grade 3–4: 1 point, pT stage >1: 2 points), and a risk score was developed for the prediction of late recurrences. The calculated values (0 points: late recurrence risk 3.1%; 1–3 points: 8.4%; 4–5 points: 22.1%) resulted in a good-, intermediate- and poor-prognosis group (area under the curve value for the model: 70%; 95% confidence interval, 67–73). Multivariable Cox regression analysis showed LVI (HR: 2.75; p < 0.001), pT stage (HR: 1.24; p < 0.001), Fuhrman grade (HR: 2.40; p < 0.001), age (HR: 1.01; p < 0.001), and gender (HR: 0.71; p = 0.027) to influence CSM significantly. Limitations are based on the multicenter and retrospective study design.

Conclusions

LVI, Fuhrman grade 3/4, and a tumor stage >pT1 are independent predictors of late recurrence after at least 5 yr from surgery in patients with RCC. We developed a risk score that allows for prognostic stratification and individualized aftercare of patients with regard to counseling, follow-up scheduling, and clinical trial design.     

Outcome of CDH infants following fetoscopic tracheal occlusion — influence of premature delivery

Purpose

To evaluate the mortality and morbidity of infants with congenital diaphragmatic hernia who had undergone fetal endoscopic tracheal occlusion (FETO) and whether this was influenced by premature birth.

Methods

The gestational age at delivery, lung–head ratio (LHR) pre and post FETO, neonatal outcomes, and respiratory, gastro-intestinal, neurological, surgical, and musculoskeletal problems at follow up of consecutive infants who had undergone FETO were determined. Elective reversal of FETO was planned at 34 weeks of gestation.

Results

The survival rate of the 61 FETO infants was 48%, with 84% delivered prematurely. Thirty-one delivered < 35 weeks of gestation. Their survival rate was 18%. Twenty-three of 24 infants who had emergency balloon removal were born < 35 weeks of gestation. Survival was related to gestational age at delivery (OR 0.55, 95% CI 0.420, 0.77, p < 0.001) and the duration of FETO (OR 0.73, 95% CI 0.59, 0.91, p < 0.005). Infants born prior to 35 weeks of gestation compared to those born at ≥ 35 weeks required a longer duration of ventilation (median 45 days versus 12 days, p < 0.001), and a greater proportion had surgery for gastro-oesophageal reflux (50% versus 9%, p = 0.011).

Conclusion

These results emphasize the need to reduce premature delivery following FETO.     

Extranodal Extension Is a Powerful Prognostic Factor in Bladder Cancer Patients with Lymph Node Metastasis

Background

Lymph node metastasis (LNM) is the most powerful pathologic predictor of disease recurrence after radical cystectomy (RC). However, the outcomes of patients with LNM are highly variable.

Objective

To assess the prognostic value of extranodal extension (ENE) and other lymph node (LN) parameters.

Design, setting, and participants

A retrospective analysis of 748 patients with urothelial carcinoma of the bladder and LNM treated with RC and lymphadenectomy without neoadjuvant therapy at 10 European and North American centers (median follow-up: 27 mo).

Intervention

All subjects underwent RC and bilateral pelvic lymphadenectomy.

Outcome measurements and statistical analysis

Each LNM was microscopically evaluated for the presence of ENE. The number of LNs removed, number of positive LNs, and LN density were recorded and calculated. Univariable and multivariable analyses addressed time to disease recurrence and cancer-specific mortality after RC.

Results and limitations

A total of 375 patients (50.1%) had ENE. The median number of LNs removed, number of positive LNs, and LN density were 15, 2, and 15, respectively. The rate of ENE increased with advancing pT stage (p < 0.001). In multivariable Cox regression analyses that adjusted for the effects of established clinicopathologic features and LN parameters, ENE was associated with disease recurrence (hazard ratio [HR]: 1.89; 95% confidence interval [CI], 1.55–2.31; p < 0.001) and cancer-specific mortality (HR: 1.90; 95% CI, 1.52–2.37; p < 0.001). The addition of ENE to a multivariable model that included pT stage, tumor grade, age, gender, lymphovascular invasion, surgical margin status, LN density, number of LNs removed, number of positive LNs, and adjuvant chemotherapy improved predictive accuracy for disease recurrence and cancer-specific mortality from 70.3% to 77.8% (p < 0.001) and from 71.8% to 77.8% (p = 0.007), respectively. The main limitation of the study is its retrospective nature.

Conclusions

ENE is an independent predictor of both cancer recurrence and cancer-specific mortality in RC patients with LNM. Knowledge of ENE status could help with patient counseling, clinical decision making regarding inclusion in clinical trials of adjuvant therapy, and tailored follow-up scheduling after RC.     

Comparison of Oncologic Outcomes for Open and Laparoscopic Nephroureterectomy: A Multi-Institutional Analysis of 1249 Cases

Background

Data regarding the oncologic efficacy of laparoscopic nephroureterectomy (LNU) compared to open nephroureterectomy (ONU) are scarce.

Objective

We compared recurrence and cause-specific mortality rates of ONU and LNU.

Design, setting, and participants

Thirteen centers from three continents contributed data on 1249 patients with nonmetastatic upper tract urothelial carcinoma (UTUC).

Measurements

Univariable and multivariable survival models tested the effect of procedure type (ONU [n = 979] vs LNU [n = 270]) on cancer recurrence and cancer-specific mortality. Covariables consisted of institution, age, Eastern Cooperative Oncology Group (ECOG) performance status score, pT stage, pN stage, tumor grade, lymphovascular invasion, tumor location, concomitant carcinoma in situ, ureteral cuff management, previous urothelial bladder cancer, and previous endoscopic treatment.

Results and limitations

Median follow-up for censored cases was 49 mo (mean: 62). Relative to ONU, LNU patients had more favorable pathologic stages (pT0/Ta/Tis: 38.1% vs 20.8%, p < 0.001) and less lymphovascular invasion (14.8% vs 21.3%, p = 0.02) and less frequently had tumors located in the ureter (64.5 vs 71.1%, p = 0.04). In univariable recurrence and cancer-specific mortality models, ONU was associated with higher cancer recurrence and mortality rates compared to LNU (hazard ratio [HR]: 2.1 [p < 0.001] and 2.0 [p = 0.008], respectively). After adjustment for all covariates, ONU and LNU had no residual effect on cancer recurrence and mortality (p = 0.1 for both).

Conclusions

Short-term oncologic data on LNU are comparable to ONU. Since LNU was selectively performed in favorable-risk patients, we cannot state with certainty that ONU and LNU have the same oncologic efficacy in poor-risk patients. Long-term follow-up data and morbidity data are necessary before LNU can be considered as the standard of care in patients with muscle-invasive or high-grade UTUC.     

Transanal endorectal pull-through for classic segment Hirschsprung's disease: With or without laparoscopic mobilization of the rectosigmoid?

Background

It has been suggested that the outcome of transanal endorectal pull-through for classic Hirschprung's disease can be improved by laparoscopically mobilizing the colon before the pullthrough.

Methods

Charts of 43 patients (2005–2009) with proven recto-sigmoid aganglionosis were retrospectively analyzed with respect to postoperative outcomes. Twenty-one had been treated with the transanal endorectal pull through (TERPT) and 22 with the laparoscopically assisted TERPT (LTERPT).

Results

Gender ratio, congenital anomalies, preoperative enterostomy, and follow up did not differ between the groups. More colon was resected in the TERPT group: median 25 cm vs. 15 cm in the L-TERPT group (p < 0.001). The TERPT-procedure took less time: median 153 min. vs. L-TERPT 263 min (p < 0.001). Postoperatively, three patients showed colonic torsions after TERPT (p = 0.07). The long-term clinical outcomes did not differ significantly between both groups. There was a significant association between length of resection and obstructive symptoms (OR = 0.92, p = 0.01).

Conclusion

Postoperative and clinical outcomes are similar using the TERPT or L-TERPT to correct classic segment Hirschsprung's disease. Prevention of colonic torsion should be the prime concern during the TERPT procedure. L-TERPT requires laparoscopic equipment and takes more operation time, whereas TERPT leaves no visible scars. The positive relation between the larger length of resection and obstructive symptoms requires additional research.     

Prenatal MRI fetal lung volumes and percent liver herniation predict pulmonary morbidity in congenital diaphragmatic hernia (CDH)

Purpose

The purpose of this study was to determine whether prenatal imaging parameters are predictive of postnatal CDH-associated pulmonary morbidity.

Methods

The records of all neonates with CDH treated from 2004 to 2012 were reviewed. Patients requiring supplemental oxygen at 30 days of life (DOL) were classified as having chronic lung disease (CLD). Fetal MRI-measured observed/expected total fetal lung volume (O/E-TFLV) and percent liver herniation (%LH) were recorded. Receiver operating characteristic (ROC) curves and multivariate regression were applied to assess the prognostic value of O/E-TFLV and %LH for development of CLD.

Results

Of 172 neonates with CDH, 108 had fetal MRIs, and survival was 76%. 82% (89/108) were alive at DOL 30, 46 (52%) of whom had CLD. Neonates with CLD had lower mean O/E-TFLV (30vs.42%; p = 0.001) and higher %LH (21.3 ± 2.8 vs.7.1 ± 1.8%; p < 0.001) compared to neonates without CLD. Using ROC analysis, the best cutoffs in predicting CLD were an O/E-TFLV < 35% (AUC = 0.74; p < 0.001) and %LH > 20% (AUC =0.78; p < 0.001). On logistic regression, O/E-TFLV < 35% and a %LH > 20% were highly associated with indicators of long-term pulmonary sequelae. On multivariate analysis, %LH was the strongest predictor of CLD in patients with CDH (OR: 10.96, 95%CI: 2.5–48.9, p = 0.002).

Conclusion

Prenatal measurement of O/E-TFLV and %LH is predictive of CDH pulmonary morbidity and can aid in establishing parental expectations of postnatal outcomes.     

Fetal MRI lung volumes are predictive of perinatal outcomes in fetuses with congenital lung masses

Purpose

The purpose of this study was to evaluate fetal magnetic resonance imaging (MRI) as a modality for predicting perinatal outcomes and lung-related morbidity in fetuses with congenital lung masses (CLM).

Methods

The records of all patients treated for CLM from 2002 to 2012 were reviewed retrospectively. Fetal MRI-derived lung mass volume ratio (LMVR), observed/expected normal fetal lung volume (O/E-NFLV), and lesion-to-lung volume ratio (LLV) were calculated. Multivariate regression and receiver operating characteristic analyses were applied to determine the predictive accuracy of prenatal imaging.

Results

Of 128 fetuses with CLM, 93% (n = 118) survived. MRI data were available for 113 fetuses. In early gestation (< 26 weeks), MRI measurements of LMVR and LLV correlated with risk of fetal hydrops, mortality, and/or need for fetal intervention. In later gestation (> 26 weeks), LMVR, LLV, and O/E-NFLV correlated with neonatal respiratory distress, intubation, NICU admission and need for neonatal surgery. On multivariate regression, LMVR was the strongest predictor for development of fetal hydrops (OR: 6.97, 1.58–30.84; p = 0.01) and neonatal respiratory distress (OR: 12.38, 3.52–43.61; p ≤ 0.001). An LMVR > 2.0 predicted worse perinatal outcome with 83% sensitivity and 99% specificity (AUC = 0.94; p < 0.001).

Conclusion

Fetal MRI volumetric measurements of lung masses and residual normal lung are predictive of perinatal outcomes in fetuses with CLM. These data may assist in perinatal risk stratification, counseling, and resource utilization.     

Pretreatment Neutrophil-to-Lymphocyte Ratio Is Associated with Advanced Pathologic Tumor Stage and Increased Cancer-specific Mortality Among Patients with Urothelial Carcinoma of the Bladder Undergoing Radical Cystectomy

Background

Pretreatment neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been associated with adverse survival in a variety of malignancies. However, the relationship between NLR and oncologic outcomes following radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) has not been well studied.

Objective

To evaluate the association of preoperative NLR with clinicopathologic outcomes following RC.

Design, setting, and participants

We identified 899 patients who underwent RC without neoadjuvant therapy at our institution between 1994 and 2005 and who had a pretreatment NLR.

Outcome measurements and statistical analysis

Preoperative NLR (within 90 d prior to RC) was recorded. Recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox proportional hazard and logistic regression models were used to analyze the association of NLR with clinicopathologic outcomes.

Results and limitations

Median postoperative follow-up was 10.9 yr (interquartile range: 8.3–13.9 yr). Higher preoperative NLR was associated with significantly increased risks of pathologic, extravesical tumor extension (odds ratio [OR]: 1.07; p = 0.03) and lymph node involvement (OR: 1.09; p = 0.02). Univariately, 10-yr cancer-specific survival was significantly worse among patients with a preoperative NLR (≥2.7 [51%] vs <2.7 [64%]; p < 0.001). Moreover, on multivariate analysis, increased preoperative NLR was independently associated with greater risks of disease recurrence (hazard ratio [HR]: 1.04; p = 0.02), death from bladder cancer (HR: 1.04; p = 0.01), and all-cause mortality (HR: 1.03; p = 0.01).

Conclusions

Elevated preoperative NLR among patients undergoing RC is associated with significantly increased risk for locally advanced disease as well as subsequent disease recurrence, and cancer-specific and all-cause mortality. These data suggest that serum NLR may be a useful prognostic marker for preoperative patient risk stratification, including consideration for neoadjuvant therapy and clinical trial enrollment.     

Minimally invasive repair of congenital diaphragmatic hernia

Purpose

Operative approach, including minimally invasive surgery (MIS) in the repair of congenital diaphragmatic hernia (CDH), is variable among institutions. The short-term recurrent hernia rate is not well described. We evaluated the in-hospital recurrence rate of MIS repairs of infants with CDH from the Congenital Diaphragmatic Hernia Registry.

Methods

Prospectively collected data from infants with CDH were analyzed from the Congenital Diaphragmatic Hernia Registry from January 1995 to January 2010. Recurrent hernia was defined as reoperations during initial hospitalization. Operative approaches included abdominal, thoracic, laparoscopic, and thoracoscopic techniques.

Results

Five thousand four hundred eighty infants with CDH were identified, of which 4516 (82.4%) were repaired. Operative data were available in 4390 infants. One hundred fifty-one infants (3.4%) underwent MIS repairs with 12 reported recurrences (7.9%) compared with 114 for open techniques (2.7%, P < .05). Minimally invasive surgery demonstrated a significant increased odds for recurrence (odds ratio, 3.59; 95% confidence interval, 1.92-6.71) after adjusting for gestational age, birth weight, patch repair, and extracorporeal membrane oxygenation.

Conclusion

Minimally invasive techniques appear to have a significant higher recurrent hernia rate, with thoracoscopy being the highest. Although adjusted for patch repair, other factors with regard to disease severity may contribute to differences in outcomes among centers. This study is limited to short-term recurrence during initial hospitalization.     

Ureterovesical junction obstruction causes increment in smooth muscle contractility,and cholinergic and adrenergic activity in distal ureter of rabbits

Background/Purpose

The controversy in management of primary obstructed megaureter necessitates further elucidation of the underlying pathophysiology. We evaluated smooth muscle contractility, and cholinergic, adrenergic and serotonergic activity of rabbit distal ureters after ureterovesical junction (UVJ) obstruction.

Methods

Sham (SH) operation, partial obstruction (PO) and complete obstruction (CO) of the right UVJ were performed in rabbits. Three weeks later, distal ureters were isolated; spontaneous contractions (SC), contractile responses to electrical field stimulation (EFS), high KCl, carbachol, phenylephrine and serotonin were recorded.

Results

SC amplitudes increased in CO compared to PO and SH (p < 0.001). SC frequency was higher in CO (p < 0.05). EFS-induced contraction amplitudes were greater in CO than other groups (p < 0.05). High KCl-induced contractions were greater in CO (p < 0.001) and PO (p < 0.01). Carbachol-induced contractility was enhanced in CO and PO (p < 0.05). Contractile response to phenylephrine was greater in CO than other groups (p < 0.05). Serotonin induced contractile responses in CO and PO, greater in CO (p < 0.05). UVJ obstruction also increased spontaneous contractility in contralateral PO and CO ureters.

Conclusions

UVJ obstruction increased spontaneous and neurotransmitter-induced contractions in an obstruction grade-dependent manner. Obstruction also altered contractility of the contralateral ureters. Our findings may serve to provide further understanding of the pathophysiology of megaureter.     

Photodynamic Diagnosis of Non–muscle-invasive Bladder Cancer with Hexaminolevulinate Cystoscopy: A Meta-analysis of Detection and Recurrence Based on Raw Data

Background

Studies on hexaminolevulinate (HAL) cystoscopy report improved detection of bladder tumours. However, recent meta-analyses report conflicting effects on recurrence.

Objective

To assess available clinical data for blue light (BL) HAL cystoscopy on the detection of Ta/T1 and carcinoma in situ (CIS) tumours, and on tumour recurrence.

Design, setting, and participants

This meta-analysis reviewed raw data from prospective studies on 1345 patients with known or suspected non–muscle-invasive bladder cancer (NMIBC).

Intervention

A single application of HAL cystoscopy was used as an adjunct to white light (WL) cystoscopy.

Outcome measurements and statistical analysis

We studied the detection of NMIBC (intention to treat [ITT]: n = 831; six studies) and recurrence (per protocol: n = 634; three studies) up to 1 yr. DerSimonian and Laird's random-effects model was used to obtain pooled relative risks (RRs) and associated 95% confidence intervals (CIs) for outcomes for detection.

Results and limitations

BL cystoscopy detected significantly more Ta tumours (14.7%; p < 0.001; odds ratio [OR]: 4.898; 95% CI, 1.937–12.390) and CIS lesions (40.8%; p < 0.001; OR: 12.372; 95% CI, 6.343–24.133) than WL. There were 24.9% patients with at least one additional Ta/T1 tumour seen with BL (p < 0.001), significant also in patients with primary (20.7%; p < 0.001) and recurrent cancer (27.7%; p < 0.001), and in patients at high risk (27.0%; p < 0.001) and intermediate risk (35.7%; p = 0.004). In 26.7% of patients, CIS was detected only by BL (p < 0.001) and was also significant in patients with primary (28.0%; p < 0.001) and recurrent cancer (25.0%; p < 0.001). Recurrence rates up to 12 mo were significantly lower overall with BL, 34.5% versus 45.4% (p = 0.006; RR: 0.761 [0.627–0.924]), and lower in patients with T1 or CIS (p = 0.052; RR: 0.696 [0.482–1.003]), Ta (p = 0.040; RR: 0.804 [0.653–0.991]), and in high-risk (p = 0.050) and low-risk (p = 0.029) subgroups. Some subgroups had too few patients to allow statistically meaningful analysis. Heterogeneity was minimised by the statistical analysis method used.

Conclusions

This meta-analysis confirms that HAL BL cystoscopy significantly improves the detection of bladder tumours leading to a reduction of recurrence at 9–12 mo. The benefit is independent of the level of risk and is evident in patients with Ta, T1, CIS, primary, and recurrent cancer.     

Impact of Tumor Location on Prognosis for Patients with Upper Tract Urothelial Carcinoma Managed by Radical Nephroureterectomy

Background

There is a lack of consensus regarding the prognostic significance of ureteral versus renal pelvic upper tract urothelial carcinoma (UTUC).

Objective

To investigate the association of tumor location on outcomes for UTUC in an international cohort of patients managed by radical nephroureterectomy (RNU).

Design, setting, and participants

A retrospective review of institutional databases from 10 institutions worldwide identified patients with UTUC.

Intervention

The 1249 patients in the study underwent RNU with ipsilateral bladder cuff resection between 1987 and 2007.

Measurements

Data accrued included age, gender, race, surgical approach (open vs laparoscopic), tumor pathology (stage, grade, lymph node status), tumor location, use of perioperative chemotherapy, prior endoscopic therapy, urothelial carcinoma recurrence, and mortality from urothelial carcinoma. Tumor location was divided into two groups (renal pelvis and ureter) based on the location of the dominant tumor.

Results and limitations

The 5-yr recurrence-free and cancer-specific survival estimates for this cohort were 75% and 78%, respectively. On multivariate analysis, only pathologic tumor (pT) classification (p < 0.001), grade (p < 0.02), and lymph node status (p < 0.001) were associated with disease recurrence and cancer-specific survival. When adjusting for these variables, there was no difference in the probability of disease recurrence (hazard ratio [HR]: 1.22; p = 0.133) or cancer death (HR: 1.23; p = 0.25) between ureteral and renal pelvic tumors. Adding tumor location to a base prognostic model for disease recurrence and cancer death that included pT stage, tumor grade, and lymph node status only improved the predictive accuracy of this model by 0.1%. This study is limited by biases associated with its retrospective design.

Conclusions

There is no difference in outcomes between patients with renal pelvic tumors and with ureteral tumors following nephroureterectomy. These data support the current TNM staging system, whereby renal pelvic and ureteral carcinomas are classified as one integral group of tumors.     

Initial bladder closure of the cloacal exstrophy complex: Outcome related risk factors and keys to success

Purpose

This study examines a large single-institution experience with cloacal exstrophy patients, analyzing patient demographics and surgical strategies predictive of bladder closure outcomes.

Methods

One hundred patients with cloacal exstrophy were identified. Complete closure history including demographics, operative history, and outcomes was available on 60 patients. Twenty-six patients with a history of failed initial bladder closure were compared to 34 with a history of successful initial bladder closure. Univariate logistic regression analysis was used to compare the two groups.

Results

Median follow up time after initial closure was 9 years (range: 13 months-29 years). A 1 cm increase in pre-closure diastasis resulted in a 2.64 increase in the odds of initial closure failure (p = 0.004). Protective strategies against failure included delaying closure (per month) (OR = 0.894, p = 0.009), employing pelvic osteotomies (OR = 0.095, p < 0.001), and applying external fixation (OR = 0.024; p = 0.001). Among patients who underwent osteotomy (31% of patients in the failed group, 82% in the successful group), a longer delay between osteotomy and closure (OR = 0.033; p = 0.005) was also protective against failure.

Conclusion

Patients with a large diastasis are more likely to fail initial closure. Delaying initial closure for at least 3 months, performing pelvic osteotomy, and using an external fixation device post-operatively are strategies that improve closure success.     

Perioperative Blood Transfusion and Radical Cystectomy: Does Timing of Transfusion Affect Bladder Cancer Mortality?

Background

While perioperative blood transfusion (BT) has been associated with adverse outcomes in multiple malignancies, the importance of BT timing has not been established.

Objective

The objective of this study was to evaluate whether intraoperative BT is associated with worse cancer outcomes in bladder cancer patients treated with radical cystectomy (RC).

Design, setting, and participants

Outcomes from two independent cohorts of consecutive patients with bladder cancer treated with RC were analyzed.

Outcome measurements and statistical analysis

Recurrence-free survival, cancer-specific survival (CSS), and overall survival were estimated and multivariate analyses were performed to evaluate the association of BT timing with cancer outcomes.

Results and limitations

In the primary cohort of 360 patients, 241 (67%) received perioperative BT, including 162 intraoperatively and 79 postoperatively. Five-year CSS was 44% among patients who received an intraoperative BT versus 64% for patients who received postoperative BT (p = 0.0005). After multivariate analysis, intraoperative BT was associated with an increased risk of cancer mortality (hazard ratio [HR]: 1.93; p = 0.02), while receipt of postoperative BT was not (p = 0.60). In the validation cohort of 1770 patients, 1100 (62%) received perioperative BT with a median postoperative follow-up of 11 yr (interquartile range: 8.0–15.7). Five-year RFS (p < 0.001) and CSS (p < 0.001) were significantly worse among patients who received an intraoperative BT. Intraoperative BT was independently associated with recurrence (HR: 1.45; p = 0.001), cancer-specific mortality (HR: 1.55; p = 0.0001), and all-cause mortality (HR: 1.40; p < 0.0001). Postoperative BT was not associated with risk of disease recurrence or cancer death.

Conclusions

Intraoperative BT is associated with increased risk of bladder cancer recurrence and mortality.

Patient summary

In this study, the effects of blood transfusion on bladder cancer surgery outcomes were evaluated. Intraoperative blood transfusion, but not postoperative transfusion, was associated with higher rates of recurrence and cancer-specific mortality.     

Impact of Smoking and Smoking Cessation on Oncologic Outcomes in Primary Non–muscle-invasive Bladder Cancer

Background

Cigarette smoking is the best-established risk factor for urothelial carcinoma (UC) development, but the impact on oncologic outcomes remains poorly understood.

Objective

To analyse the effects of smoking status, cumulative exposure, and time from smoking cessation on the prognosis of patients with primary non–muscle-invasive bladder cancer (NMIBC).

Design, setting, and participants

We collected smoking data from 2043 patients with primary NMIBC. Smoking variables included smoking status, average number of cigarettes smoked per day (CPD), duration in years, and time since smoking cessation. Lifetime cumulative smoking exposure was categorised as light short term (≤19 CPD, ≤19.9 yr), light long term (≤19 CPD, ≥20 yr), heavy short term (≥20 CPD, ≤19.9 yr) and heavy long term (≥20 CPD, ≥20 yr). The median follow-up in this retrospective study was 49 mo.

Interventions

Transurethral resection of the bladder with or without intravesical instillation therapy.

Outcome measurements and statistical analysis

Univariable and multivariable logistic regression and competing risk regression analyses assessed the effects of smoking on outcomes.

Results and limitations

There was no difference in clinicopathologic factors among never (24%), former (47%), and current smokers (29%). Smoking status was associated with the cumulative incidence of disease progression in multivariable analysis (p = 0.003); current smokers had the highest cumulative incidences. Among current and former smokers, cumulative smoking exposure was associated with disease recurrence (p < 0.001), progression (p < 0.001), and overall survival (p < 0.001) in multivariable analyses that adjusted for the effects of standard clinicopathologic factors and smoking status; heavy long-term smokers had the worst outcomes, followed by light long-term, heavy short-term, and light short-term smokers. Smoking cessation >10 yr reduced the risk of disease recurrence (hazard ratio [HR]: 0.66; 95% confidence interval [CI], 0.52–0.84; p < 0.001) and progression (HR: 0.42; 95% CI, 0.22–0.83; p = 0.036) in multivariable analyses. The study is limited by its retrospective nature.

Conclusions

Smoking status and a higher cumulative smoking exposure are associated with worse prognosis in patients with NMIBC. Smoking cessation >10 yr abrogates this detrimental effect. These findings underscore the need for integrated smoking cessation and prevention programmes in the management of NMIBC patients.     

Dutasteride Treatment Over 2 Years Delays Prostate-specific Antigen Progression in Patients with Biochemical Failure After Radical Therapy for Prostate Cancer: Results from the Randomised,Placebo-controlled Avodart After Radical Therapy for Prostate Cancer Study (ARTS)

Background

Rising prostate-specific antigen (PSA) levels after radical therapy are indicative of recurrent or residual prostate cancer (PCa). This biochemical recurrence typically predates clinically detectable metastatic disease by several years. Management of patients with biochemical recurrence is controversial.

Objective

To assess the effect of dutasteride on progression of PCa in patients with biochemical failure after radical therapy.

Design, setting, and participants

Randomised, double-blind, placebo-controlled trial in 294 men from 64 centres across 9 European countries.

Intervention

The 5α-reductase inhibitor, dutasteride.

Outcome measurements and statistical analysis

The primary end point was time to PSA doubling from start of randomised treatment, analysed by log-rank test stratified by previous therapy and investigative-site cluster. Secondary end points included time to disease progression and the proportion of subjects with disease progression.

Results and limitations

Of the 294 subjects randomised (147 in each treatment group), 187 (64%) completed 24 mo of treatment and 107 discontinued treatment prematurely (71 [48%] of the placebo group, 36 [24%] of the dutasteride group). Dutasteride significantly delayed the time to PSA doubling compared with placebo after 24 mo of treatment (p < 0.001); the relative risk (RR) reduction was 66.1% (95% confidence interval [CI], 50.35–76.90) for the overall study period. Dutasteride also significantly delayed disease progression (which included PSA- and non-PSA-related outcomes) compared with placebo (p < 0.001); the overall RR reduction in favour of dutasteride was 59% (95% CI, 32.53–75.09). The incidence of adverse events (AEs), serious AEs, and AEs leading to study withdrawal were similar between the treatment groups. A limitation was that investigators were not blinded to PSA levels during the study.

Conclusions

Dutasteride delayed the biochemical progression of PCa in patients with biochemical failure after radical therapy for clinically localised disease. The safety and tolerability of dutasteride were generally consistent with previous experience.

Clinical trial registry

ClinicalTrials.gov, NCT00558363.     

The association of type of surgical closure on length of stay among infants with gastroschisis born ≥ 34 weeks’ gestation

Background/Purpose

The optimal surgical approach in infants with gastroschisis (GS) is unknown. The purpose of this study was to estimate the association between staged closure and length of stay (LOS) in infants with GS.

Design/Methods

We used the Children's Hospital Neonatal Database to identify surviving infants with GS born ≥ 34 weeks' gestation referred to participating NICUs. Infants with complex GS, bowel atresia, or referred after 2 days of age were excluded. The primary outcome was LOS; multivariable linear regression was used to quantify the relationship between staged closure and LOS.

Results

Among 442 eligible infants, staged closure occurred in 68.1% and was associated with an increased median LOS relative to odds ration (OR):primary closure (37 vs. 28 days, p < 0.001). This association persisted in the multivariable equation (β = 1.35, 95% CI: 1.21, 1.52, p < 0.001) after adjusting for the presence of necrotizing enterocolitis, short bowel syndrome, and central-line associated bloodstream infections.

Conclusions

In this large, multicenter cohort of infants with GS, staged closure was independently associated with increased LOS. These data can be used to enhance antenatal and pre-operative counseling and also suggest that some infants who receive staged closure may benefit from primary repair.     

Base deficit correlates with mortality in pediatric abusive head trauma

Background/purpose

Children suffering from abusive head trauma (AHT) have worse outcomes compared to non-AHT, but the reasons for this are unclear. We hypothesized that delayed medical care associated with AHT causes prolonged pre-hospital hypotension and hypoxia as measured by admission base deficit (BD), and that this would correlate with outcome.

Methods

We performed a 10-year retrospective chart review of children admitted for AHT at two academic level-I trauma centers. Statistics were performed using Student's t test, chi-square analysis, and multivariate logistic regression, and considered significant at p < 0.05.

Results

Four-hundred twelve children with AHT were identified, and admission BD was drawn for 148/412 (36%) children, including 104 survivors and 44 non-survivors. Non-survivors had significantly higher BD compared to survivors (12.6 ± 1.6 versus 5.3 ± 0.6, p < 0.001). Non-survivors were more likely to be intubated pre-hospital and get cardiopulmonary resuscitation (CPR) (p < 0.001). Mortality increased with rising BD, according to CPR status. There was no difference in patterns of brain injury between survivors and non-survivors (p > 0.05).

Conclusions

BD correlates with mortality in children suffering severe AHT. Non-survivors are also more likely to be intubated pre-hospital and require CPR, with no difference in pattern of brain injury, suggesting that secondary injury is a major determinant of outcome in severe AHT.     

Inter-rater reliability of surgical reviews for AREN03B2: A COG renal tumor committee study

Purpose

The Children's Oncology Group (COG) renal tumor study (AREN03B2) requires real-time central review of radiology, pathology, and the surgical procedure to determine appropriate risk-based therapy. The purpose of this study was to determine the inter-rater reliability of the surgical reviews.

Methods

Of the first 3200 enrolled AREN03B2 patients, a sample of 100 enriched for blood vessel involvement, spill, rupture, and lymph node involvement was selected for analysis. The surgical assessment was then performed independently by two blinded surgical reviewers and compared to the original assessment, which had been completed by another of the committee surgeons. Variables assessed included surgeon-determined local tumor stage, overall disease stage, type of renal procedure performed, presence of tumor rupture, occurrence of intraoperative tumor spill, blood vessel involvement, presence of peritoneal implants, and interpretation of residual disease. Inter-rater reliability was measured using the Fleiss' Kappa statistic two-sided hypothesis tests (Kappa, p-value).

Results

Local tumor stage correlated in all 3 reviews except in one case (Kappa = 0.9775, p < 0.001). Similarly, overall disease stage had excellent correlation (0.9422, p < 0.001). There was strong correlation for type of renal procedure (0.8357, p < 0.001), presence of tumor rupture (0.6858, p < 0.001), intraoperative tumor spill (0.6493, p < 0.001), and blood vessel involvement (0.6470, p < 0.001). Variables that had lower correlation were determination of the presence of peritoneal implants (0.2753, p < 0.001) and interpretation of residual disease status (0.5310, p < 0.001).

Conclusion

The inter-rater reliability of the surgical review is high based on the great consistency in the 3 independent review results. This analysis provides validation and establishes precedent for real-time central surgical review to determine treatment assignment in a risk-based stratagem for multimodal cancer therapy.