Predicting Pathological Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Using 18FDG-PET/CT

Background

Pathologic complete response (pCR) after neoadjuvant chemoradiation (CRT) has been observed in 15?C30% of patients with locally advanced rectal cancer (LARC). The objective of this study was to determine whether PET/CT can predict pCR and disease-free survival in patients receiving CRT with LARC.

Methods

This is a retrospective review of patients with EUS-staged T3?CT4, N?+?rectal tumors treated with CRT, who underwent pre/post-treatment PET/CT from 2002?C2009. All patients were treated with CRT and surgical resection. Standardized uptake value (SUV) of each tumor was recorded. Logistic regression was used to analyze the association of pre-CRT SUV, post-CRT SUV, %SUV change, and time between CRT and surgery, compared with pCR. Kaplan?CMeier estimation evaluated significant predictors of survival.

Results

Seventy patients (age 62?years; 42M:28F) with preoperative stage T3 (n?=?61) and T4 (n?=?9) underwent pre- and post-CRT PET/CT followed by surgery. The pCR rate was 26%. Median pre-CRT SUV was 10.8, whereas the median post-CRT SUV was 4 (P?=?0.001). Patients with pCR had a lower median post-CRT SUV compared with those without (2.7 vs. 4.5, P?=?0.01). Median SUV decrease was 63% (7.5?C95.5%) and predicted pCR (P?=?0.002). Patients with a pCR had a greater time interval between CRT and surgery (median, 58 vs. 50?days) than those without (P?=?0.02). Patients with post-CRT SUV?P?=?0.03). Patients with SUV decrease ??63% had improved overall survival at median follow-up of 40?months than those without (P?=?0.006).

Conclusions

PET/CT can predict response to CRT in patients with LARC. Posttreatment SUV, %SUV decrease, and greater time from CRT to surgery correlate with pCR. Post-CRT, SUV?相似文献   

The influence of flourodeoxyglucose positron emission tomography on the management of gastroesophageal junction carcinoma

Background

The influence of positron emission tomography (PET) scanning with flourodeoxyglucose (FDG) on decision making for the treatment of patients with esophagogastric junction (EGJ) carcinoma is unclear as is the utility of the maximum standardized uptake value (SUV) as a prognostic indicator.

Methods

This study was a retrospective review of EGJ carcinoma cases at a single institution during a 5-year period.

Results

FDG-PET altered treatment in 13 of 64 patients (20%). Of these, 21 patients had PET scans before and after undergoing neoadjuvant chemoradiation (CRT) as well as surgery. Patients who had a decrease in SUV >50% had a 12-month disease-free survival advantage over patients a decrease in SUV <50% (93% vs 43%, P = .025).

Conclusions

FDG-PET alters treatment in a significant number of patients with EGJ carcinoma. A >50% decrease in SUV after CRT is associated with an improved prognosis.     

Pelvic/retroperitoneal salvage lymph node dissection for patients treated with radical prostatectomy with biochemical recurrence and nodal recurrence detected by [11C]choline positron emission tomography/computed tomography

Background

The management of patients with clinical recurrence of prostate cancer after radical prostatectomy (RP) remains challenging.

Objective

To determine whether the removal of positive lymph nodes at [11C]choline positron emission tomography/computed tomography (PET/CT) scan may have an impact on the prognosis of patients with biochemical recurrence (BCR) and nodal recurrence after RP.

Design, setting, and participants

Prospective analysis of 72 patients affected by BCR after RP associated with a nodal pathologic [11C]choline PET/CT scan.

Intervention

Patients underwent salvage lymph node dissection (LND).

Measurements

Biochemical response (BR) to treatment was defined as prostate-specific antigen (PSA) <0.2 ng/ml at 40 d after salvage LND. Kaplan-Meier and Cox regression analyses addressed time to and predictors of clinical recurrence (CR) after salvage LND, respectively.

Results and limitations

Overall, 56.9% of patients achieved BR. Mean and median follow-up after LND were 39.4 and 39.8 mo, respectively. The 5-yr BCR-free survival rate was 19%. Preoperative PSA <4 ng/ml (hazard ratio [HR]: 0.12; p = 0.005), time to BCR <24 mo (HR: 7.52; p = 0.005), and negative lymph nodes at previous RP (HR: 0.19; p = 0.04) represented independent predictors of BR. Overall, 5-yr CR-free and cancer-specific survival were 34% and 75%, respectively. At multivariable analyses, only PSA >4 ng/ml (HR: 2.13; p = 0.03) and the presence of retroperitoneal uptake at PET/CT scan (HR = 2.92; p = 0.004) represented independent preoperative predictors of CR. Similarly, the presence of pathologic nodes in the retroperitoneum (HR: 2.78; p = 0.02), higher number of positive lymph nodes (HR: 1.04; p = 0.006), and complete BR to salvage LND (HR: 0.31; p = 0.002) represented postoperative independent predictors of CR. Main limitations consisted of the lack of a control group and the heterogeneity of patients included in the analyses.

Conclusions

Salvage LND is feasible in patients with BCR after RP and nodal pathologic uptake at [11C]choline PET/CT scan. Biochemical response after surgery can be achieved in a consistent proportion of patients. Although most patients invariably progressed to BCR after surgery at longer follow-up, 35% of patients showed the absence of CR at 5 yr.     

Prognostic Role of Carcinoembryonic Antigen Level after Preoperative Chemoradiotherapy in Patients with Rectal Cancer

Background

The prognostic role of post-chemoradiotherapy (CRT) carcinoembryonic antigen (CEA) level is not clear. We evaluated the prognostic significance of post-CRT CEA level in patients with rectal cancer after preoperative CRT.

Methods

We reviewed 659 consecutive patients who underwent preoperative CRT and total mesorectal excision for non-metastatic rectal cancer. Patients were categorized into two groups according to post-CRT serum CEA level: low CEA (<?5 ng/mL) and high CEA (≥?5 ng/mL).

Results

Median post-CRT CEA level was 1.7 ng/mL (range, 0.1–207.0). A high post-CRT level was significantly associated with ypStage, ypT category, tumor regression grade, and pre-CRT CEA level. The 5-year overall survival rate of the 659 patients was 87.8% with a median follow-up period of 57.0 months (range, 1.4–176.4). When the post-CRT CEA groups were divided into groups according to pre-CRT CEA level, the 5-year overall survival rates were significantly different (P?<?0.001 and P?=?0.001, respectively). Post-CRT CEA level was an independent prognostic factor for overall survival. Multivariate analysis revealed that operation method, differentiation, perineural invasion, postoperative chemotherapy, tumor regression grade, and post-CRT CEA level were independent prognostic factors for overall survival.

Conclusion

The level of serum CEA after preoperative CRT was an independent prognostic factor for overall survival in patients with rectal cancer.

     

Sunitinib in urothelial cancer: clinical, pharmacokinetic, and immunohistochemical study of predictors of response

Background

Sunitinib has activity in patients with metastatic urothelial cancer (UC), but most patients do not respond.

Objective

To identify predictors of response to sunitinib.

Design, setting, and participants

Seventy-seven patients with advanced UC received sunitinib on one of two schedules at a single institution. Blood pressure (BP), immunohistochemistry (IHC), and pharmacokinetic (PK) results were correlated with response to sunitinib.

Measurements

BP was assessed on day 1 and 28 of each cycle and on day 14 of cycle 1. IHC was performed on 55 samples from 38 cases using mammalian target of rapamycin and hypoxia-inducible factor (HIF) pathway marker antibodies. Blood samples for PK analysis were collected from 15 patients at three time points. Response was assessed using Response Evaluation Criteria in Solid Tumors criteria.

Results and limitations

Sunitinib-induced hypertension predicted improved response when hypertension was categorized as a discrete (p = 0.02) or continuous variable (p = 0.005 [systolic BP] and p = 0.007 [diastolic BP]). The odds ratio of response was 12.5 (95% confidence interval, 1.95-246.8) for grade 3/4 hypertension compared with grade 0. Response was associated with low HIF-1α expression in primary (p = 0.07) tissue. A nonstatistically significant trend was seen for an association between greater drug concentration and best response. A correlation between expression markers within the same pathways was identified, phosphorylated-4EBP1 and phosphorylated-S6 (p = 6.5 × 10⁻⁹), and vascular endothelial growth factor receptor 2 and HIF-1α (p = 0.008). Results are limited by small numbers.

Conclusions

Clinical and molecular biomarkers of response to sunitinib may have clinical relevance and require prospective validation. There is an urgent need for predictive biomarkers to guide the management of UC.     

Does the extent of lymphadenectomy in radical cystectomy for bladder cancer influence disease-free survival? A prospective single-center study

Background

Controversy exists regarding the optimal extent of lymphadenectomy and the number of lymph nodes to be retrieved at radical cystectomy (RC).

Objective

To compare the disease-free survival of patients with standard lymphadenectomy (endopelvic region composed of the internal, external iliac, and obturator groups of lymph nodes) versus extended lymphadenectomy (up to the level of origin of the inferior mesenteric artery) at RC in a prospective cohort of patients at a single, high-volume center.

Design, setting, and participants

Prospective data were collected from 400 consecutive patients treated with RC for bladder cancer by two high-volume surgeons at Mansoura Urology and Nephrology Center. Of the 400 patients, 200 (50%) received extended lymphadenectomy and the other 200 (50%) underwent standard lymphadenectomy at RC. The patients did not receive any neoadjuvant or adjuvant therapy.

Measurements

Patient characteristics and outcomes are evaluated.

Results and limitations

Median patient age for the entire group was 53.0 yr. Ninety-six patients (24.0%) had lymph node metastases. Median follow-up was 50.2 mo. Estimates of 5-yr disease-free survival in the extended lymphadenectomy group were 66.6% compared with 54.7% for patients with standard lymphadenectomy (p = 0.043). Extended lymphadenectomy was associated with better disease-free survival after adjusting for the effects of standard pathologic features (p = 0.02). When restricting the analyses to lymph node-positive patients, patients with extended lymphadenectomy had much better 5-yr disease-free survival compared with patients with standard lymphadenectomy (48.0% vs 28.2%; p = 0.029). The study was nonrandomized.

Conclusions

Extended lymphadenectomy is associated with better disease-free survival for bladder cancer patients with endopelvic lymph node involvement and should be considered in these patients.     

Acute neonatal arterial occlusion: is thrombolysis safe and effective?

Purpose

We report our experience of the management of arterial occlusion in the newborn.

Methods

A case note review was carried out after ethical approval. Doppler ultrasonography confirmed the occlusion. Thrombolysis was the primary intervention. Surgery was used selectively. A good outcome was one without tissue loss or functional impairment or minimal tissue loss without functional impairment. Data are presented as medians with ranges.

Results

Ten patients (9 male; median gestational age, 35.5 weeks [range, 28-39 weeks]) presented on day 1 (range, 1-8 days). Initial management included systemic tissue plasminogen activator (8 patients) and surgery (2 infants in whom thrombolysis was contraindicated). Improvement was noted in 7 of 8 infants treated medically and in both who underwent surgery. Three infants had significant tissue loss. Outcome at 29 months (range, 1.3-95.4 months) was good in the remaining 7.

Conclusions

A multidisciplinary approach, thrombolysis and selective surgery achieved tissue preservation and function in the majority while minimizing complications. Early referral to centers with multidisciplinary teams is recommended.     

Laparoscopic splenectomy in children--a multicenter experience

Purpose

Splenectomy is frequently required in children for various hematologic pathologic findings. Because of progress in minimally invasive techniques, laparoscopic splenectomy (LS) has become feasible. The objective of this report is to present a multicenter experience of 159 laparoscopic splenectomies.

Methods

Records of 159 children, who underwent LS in 3 pediatric surgery centers between 1996 and 2006, were reviewed retrospectively with a special questionnaire. The indication for splenectomy were hematologic disorders (147), esophageal varices (6), splenic cyst (5), and tumor of the tail of the pancreas (1). The LS was performed using standard laparoscopic technique and instrumentation.

Results

There were 75 boys and 84 girls. Median age was 12.5 years (range, 2-19.4 years). Laparoscopic splenectomy alone was performed in 118 cases and LS with cholecystectomy or cholecystotomy in 36. In 5 cases, LS was performed together with fundoplication. Eight LS required conversion to an open procedure for following reasons: severe bleeding (3), massive splenomegaly (1), anatomical (2), and technical aspects (2). Accessory spleens were identified in 20 cases (12.6%). There was no mortality. Complications consisted of 8 conversions and postoperatively of mild generalized infection in 3 children and abdominal bleeding that resulted in re-laparoscopy in 1 case.

Conclusions

Laparoscopic splenectomy can be safely and effectively performed in children.     

Value of 18-FDG-positron emission tomography/computed tomography before and after transarterial chemoembolization in patients with hepatocellular carcinoma undergoing liver transplantation: initial results

Introduction

Liver transplantation is the treatment of choice for various types of end-stage liver disease and the most appropriate alternative for the treatment of hepatocellular carcinoma (HCC)-associated liver cirrhosis. The aim of this study was to describe our initial experience with the use of 18-FDG positron emission tomography (PET)/computed tomography CT before and after transarterial chemoembolization (TACE) in HCC patients undergoing liver transplantation, seeking to predict the percentage of tumor necrosis achieved by TACE procedures.

Patients and Methods

From January 2007 through December 2009, 39 patients with HCC and liver cirrhosis were included in our liver transplantation program. We selected the 6 subjects who underwent 18-fluorodeoxyglucose PET/CT (18-FDG PET/CT) pre- and post-TACE.

Results

The median SUV (standarized uptake value) in the lesions studied were 4 (range, 2.79-6.95) before TACE with a median post-TACE SUV of 0 (range, 0-4). Among patients whose post-TACE SUV decreased to <3, the percentage of necrosis after studying the hepatectomy was >80%.

Conclusion

Performance of an 18-FDG PET/CT before and after TACE and comparison of SUV in patients with HCC awaiting liver transplantation provided valuable information regarding the effectiveness of TACE.     

Factors affecting postoperative course and survival after en bloc resection for esophageal carcinoma

Background

To identify factors affecting postoperative course and survival after esophagectomy for cancer and reasons for improved survival over time.

Methods

Complete esophageal resection was attempted for middle and lower third esophageal carcinomas in 386 consecutive patients between January 1982 and January 2002. Two study periods were analyzed: 1982 to 1993 and 1994 to 2002. Prognostic factors were identified by multivariate analysis and the two periods compared.

Results

Hospital mortality rate decreased from 5.4% to 2.9% (p = 0.245). Both anastomotic leakage and pulmonary complications rates decreased from 9.8% to 2.2% (p = 0.001) and 24.1% to 19.3% (p = 0.295), respectively. An increased proportion of patients had R0 resection in the latter period, 78.5% versus 67.0%, (p = 0.028). Five-year survival rate after R0 resection increased from 29% to 46% (p = 0.001), with a decreased recurrence rate from 65.8% to 44.3% (p = 0.002). Three favorable prognostic factors were identified: low pT stage, pN0 stage, and operation during the 1994 to 2002 study period.

Conclusions

Short-term outcome and survival of patients with resected esophageal cancer have improved over time. Advances in perioperative technique, staging methods, and surgical management combined with higher patient selection and use of neoadjuvant chemoradiation may be responsible for this progress.     

The accuracy of integrated PET-CT compared with dedicated PET alone for the staging of patients with nonsmall cell lung cancer

Background

The treatment of patients with nonsmall cell lung cancer (NSCLC) is determined by the stage. We evaluated the accuracy of staging using integrated positron emission tomography (PET) and computed tomography (CT) and compared it with dedicated PET visually correlated with CT scan.

Methods

A prospective blinded trial was performed on a consecutive series of patients with NSCLC. Patients underwent integrated PET-CT scanning with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG-18). A radiologist assigned the T, N and M status. No sooner than 2 weeks the same radiologist read the dedicated PET alone, without the integrated CT images and a T, N and M status was assigned again. The most recent CT scan was available and visually correlated with both studies. All patients underwent biopsies of suspicious N2 or N3 lymph node or distant metastases and if negative, pulmonary resection with lymphadenectomy was performed.

Results

There were 129 patients. Integrated PET-CT is a better predictor than PET for all stages of cancer and achieved statistical significance for stage I (52% versus 33%, p = 0.03) and for stage II (70% versus 36%, p = 0.04). It also is a better overall predictor for T status (70% versus 47%, p = 0.001) and the N status (78% versus 56%, p = 0.008). Nodal analysis shows that integrated PET-CT was more accurate for the total N2 nodes (96% versus 93%, p = 0.01) and for the total N1 nodes (90% versus 80%, p = 0.001). It was also more sensitive, specific, and had a higher positive predictive value for both N2 and N1 nodes (p < 0.05 for all). Integrated PET-CT is significantly more sensitive at the 4R, 5, 7, 10L and 11 stations and more accurate at the 7 and 11 lymph nodes stations than dedicated PET.

Conclusions

Integrated PET-CT using FDG-18 better predicts stage I and II disease as well as the T and N status of patients with NSCLC when compared with dedicated PET alone. It is more accurate at some nodal stations but still only achieves an accuracy of 96% and 90% for the N2 and N1 nodes, respectively.     

The predictive value of incidental PET/CT findings suspicious for breast cancer in women with non-breast malignancies

Background

On occasion, patients followed with positron emission tomographic (PET)/computed tomographic (CT) imaging for nonbreast malignancies will have incidental breast findings concerning for second primary breast cancers. The aim of this study was to determine the predictive value of PET/CT imaging to identify breast cancers in these patients.

Methods

Patients with primary nonbreast malignancies and findings concerning for second primary breast cancers were identified from a prospectively acquired nuclear medicine database from January 2005 to July 2008. Chart reviews were then performed.

Results

Nine hundred two women underwent PET/CT imaging to evaluate nonbreast malignancies. Nine women (1%) had concerning breast findings, and 5 (56%) had subsequent breast cancer diagnoses. The positive predictive value of PET/CT imaging in these patients was 63%. Evidence of compliance with current screening guidelines was present in only 22% of these patients.

Conclusions

The data suggest that findings concerning for an additional primary breast cancer should be evaluated and that age-appropriate screening tools should not be abandoned.     

Comparison of late results of basic transsternal and extended transsternal thymectomies in the treatment of myasthenia gravis

Background

The influence of the technique of thymectomy on late results in the treatment of myasthenia gravis remains controversial.

Methods

Results of 60 basic transsternal thymectomies and 58 extended transsternal thymectomies were compared. Both positive results (complete remissions or improvement) and negative results (no improvement, deterioration, or death from myasthenia) were analyzed.

Results

There were no differences between both groups according to patient's characteristics and postoperative complications rate. Ectopic foci of the thymic tissue were discovered in the fat of the neck and the mediastinum in 56.9% of patients from the extended thymectomy group. The foci occurred in all areas of dissection of the neck and the mediastinum. Complete remission rates in the basic thymectomy group were 8.3%, 11.7%, 15.0%, 16.7%, 20.0%, and 21.7% after 1, 2, 3, 4, 5, and 6 years of follow-up, respectively, and 29.3%, 37.9%, 41.4%. and 46.6% after 1, 2, 3, and 4 years, respectively, in the extended thymectomy group. The differences between both groups after 1, 2, 3, and 4 years were statistically significant (p = 0.0093, p = 0.0013, p = 0.0018, and p = 0.0007, respectively). Negative results were noted in 23.3% of patients in the basic thymectomy group and in 6.9% of patients in the extended thymectomy group (p = 0.0613). No other factors had any influence on the results.

Conclusions

Late results, both positive and negative, were considerably better in the extended thymectomy group. The difference can be explained by the removal of ectopic foci of the thymic tissue from the neck and the mediastinum in these patients.     

Multidisciplinary pediatric trauma team training using high-fidelity trauma simulation

Background

Trauma resuscitations require a high level of team performance. This study evaluated the impact of a comprehensive effort to improve trauma care through multidisciplinary education and the use of simulation training to reinforce training and evaluate performance.

Methods

For a 1-year period, expanded trauma education including monthly trauma simulation sessions using high-fidelity simulators was implemented. All members of the multidisciplinary trauma resuscitation team participated in education, including simulations. Each simulation session included 2 trauma scenarios that were videotaped for debriefing as well as subsequent analysis of team performance. Scored simulations were divided into early (initial 4 months) and late (final 4 months) for comparison.

Results

For the first year of the program, 160 members of our multidisciplinary team participated in the simulation. In the early group, the mean percentage of appropriately completed tasks was 65%, whereas in the late group, this increased to 75% (P < .05). Improvements were also observed in initial assessment, airway management, management of pelvic fractures, and cervical spine care.

Conclusions

Training of a multidisciplinary team in the care of pediatric trauma patients can be enhanced and evaluated through the use of high-fidelity simulation. Improvements in team performance using innovative technology can translate into more efficient care with fewer errors.     

Adjunctive transmyocardial revascularization: five-year follow-up of a prospective, randomized trial

Background

In a prospective, randomized trial involving 263 patients who would be incompletely revascularized by coronary artery bypass grafting (CABG) alone, CABG plus transmyocardial revascularization (CABG/TMR) provided an early mortality benefit with similar angina relief compared with CABG alone at 1 year. We evaluated the long-term outcome of patients randomized to CABG/TMR or CABG alone.

Methods

Thirteen centers that enrolled 83% (218/263) of the patients in the original trial participated in this longitudinal study. Between 1996 and 1998, these centers randomized 218 patients who would be incompletely revascularized by CABG alone because of diffusely diseased target vessels to either holmium:yttrium-aluminum-garnet (holmium:YAG) CABG/TMR (n = 110) or CABG alone (n = 108). Baseline demographics and operative characteristics were similar between groups. Follow-up (mean 5.0 ± 1.7 years) included survival and blinded angina class assessment.

Results

At this 5-year follow-up both groups experienced significant angina improvement from baseline, however, the CABG/TMR group had a lower mean angina score (0.4 ± 0.7 vs 0.7 ± 1.1, p = 0.05), a significantly lower proportion of patients with severe angina (class III/IV: 0% [0/68] vs 10% [6/60], p = 0.009), and a trend towards greater number of angina-free patients (78% [53/68] vs 63% [38/60], p = 0.08), compared with CABG alone patients. Kaplan-Meier survival at 6 years was similar between CABG/TMR and CABG alone patients (76% vs 80%, p = 0.90).

Conclusions

Five-year follow-up of prospectively randomized patients who would be incompletely revascularized because of diffuse coronary artery disease indicates that the addition of TMR to conventional CABG provides superior angina relief compared to CABG alone.     

Insulinlike growth factor I gene expression is increased in the fetal lung after tracheal ligation

Background/Purpose

The mortality and morbidity in congenital diaphragmatic hernia are mainly caused by pulmonary hypoplasia. To improve clinical results, further methods inducing lung growth may have to be used. The aim of this report was to evaluate the expression of insulinlike growth factor I (IGF-I), estrogen receptor α, estrogen receptor β, growth hormone receptor, and thioredoxin in a rat model of hypoplastic, hyperplastic, and normal fetal lungs to improve understanding of lung growth.

Methods

Hypoplastic diaphragmatic hernia lungs were created by giving nitrofen by gavage to pregnant rats on day 9.5. Hyperplastic lungs were achieved by intrauterine tracheal ligation of rat fetuses on day 19. All lungs were harvested on gestational day 21. Total nucleic acids were extracted by proteinase K digestion and extraction in phenol/chloroform. The total nucleic acids mixture was hybridized with radioactively labeled RNA probes, and the radioactivity of the hybrids was compared with the respective standard curve of known amounts of in vitro synthesized mRNA. Immunohistochemistry staining was performed for IGF-I.

Results

The IGF-I mRNA was significantly (P < .01) higher in hyperplastic lungs compared with control and hypoplastic lungs. The latter 2 did not differ. No difference was found between the other mRNA levels in the study groups.

Conclusions

IGF-I is involved in the accelerated lung growth seen after intrauterine tracheal ligation.     

Impact of pexelizumab, an anti-C5 complement antibody, on total mortality and adverse cardiovascular outcomes in cardiac surgical patients undergoing cardiopulmonary bypass

Background

During cardiac surgery requiring cardiopulmonary bypass, pro-inflammatory complement pathways are activated by exposure of blood to bio-incompatible surfaces of the extracorporeal circuit and reperfusion of ischemic organs. Complement activation promotes the generation of additional inflammatory mediators thereby exacerbating tissue injury. We examined the safety and efficacy of a C5 complement inhibitor for attenuating inflammation-mediated cardiovascular dysfunction in cardiac surgical patients undergoing cardiopulmonary bypass.

Methods

Pexelizumab (Alexion Pharmaceuticals, Inc, Cheshire, CT), a recombinant, single-chain, anti-C5 monoclonal antibody, was evaluated in a randomized, double-blinded, placebo-controlled, multicenter trial that involved 914 patients undergoing coronary artery bypass grafting with or without valve surgery requiring cardiopulmonary bypass.

Results

Pexelizumab was administered intravenously as a bolus (2.0 mg/kg) or bolus plus infusion (2.0 mg/kg plus 0.05 mg/kg/h for 24 hours), and inhibited complement activation. There were no statistically significant differences between placebo-treated and pexelizumab-treated patients in the primary endpoint (composite of death, or new Q-wave, or non-Q-wave [myocardial-specific isoform of creatine kinase > 60 ng/mL] myocardial infarction, or left ventricular dysfunction, or new central nervous system deficit). However, post hoc analysis revealed a reduction in the composite of death or myocardial infarction (myocardial-specific isoform of creatine kinase ≥ 100 ng/mL) for the isolated coronary artery bypass grafting, bolus plus infusion subgroup on POD 4 (p = 0.007) and on POD 30 (p = 0.004).

Conclusions

Pexelizumab had no statistically significant effect on the primary endpoint. However, the reduction in death or myocardial infarction (myocardial-specific isoform of creatine kinase ≥ 100 ng/mL) as revealed in the post hoc analysis in the isolated coronary artery bypass grafting bolus plus infusion subpopulation, suggests that further investigation of anti-C5 therapy for ameliorating complement-mediated inflammation and myocardial injury is warranted.     

Evaluation of progression prior to surgery after neoadjuvant chemoradiotherapy with computed tomography in esophageal cancer patients

Background

The risk of tumor progression during neoadjuvant chemoradiotherapy (CRT) in esophageal cancer (EC) is around 8% to 17%. We assessed the efficacy of computed tomography (CT) to identify these patients before esophagectomy.

Methods

Ninety-seven patients with locally advanced EC treated with Carboplatin/Paclitaxel and 41.4 Gy neoadjuvantly were restaged with CT. Two radiologists reviewed pre- and post-CRT CT images. The primary outcome was detection of clinically relevant progressive disease. Missed metastases were defined as metastatic disease found during surgery or within 3 months after post-CRT CT.

Results

Progressive disease was detected in 9 patients (9%). Both radiologists detected 5 patients with distant metastases (liver, n = 4; lung metastasis, n = 1), but missed progressive disease in 4 cases. One radiologist falsely assessed 2 metastatic lesions, but after agreement progressive disease was detected with sensitivity and specificity of 56% and 100%, respectively.

Conclusion

CT is effective in detecting clinically relevant progressive disease in EC patients, after neoadjuvant treatment.     

Influence of open chest conditions on pulse pressure variations

Objectives

Pulse pressure variations are used to assess fluid responsiveness in mechanically ventilated patients. The accuracy of this index in open chest conditions remained unclear. The aim of the study was to evaluate the effect of open chest conditions on pulse pressure variations.

Study design

Non-interventional prospective study.

Methods and patients

Twenty-eight mechanically ventilated patients scheduled for open-heart surgery were included. Pulse pressure variations, peak aortic velocity, and stroke volume were measured before and after thoracotomy with pericardotomy. Measurements were made at each step and compared.

Results

Neither pulse pressure variation nor peak aortic velocity and nor stroke volume variation were modified by open chest conditions (median = 5% [interquartile range = 6] vs 4% [6], p = NS), (20% [11] vs 17% [12], p = NS and 11% [7] vs 10% [3], p = NS) respectively. Pulse pressure variations were correlated to stroke volume before thoracotomy (r’ = −0.432; p = 0.02) and after thorocatomy (r’ = −0.433, p = 0.02).

Conclusion

In these studied patients, preload dependancy indices were not modified by open chest conditions. Pulse pressure variations remained correlated to stroke volume even after thoracotomy.     

Efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: a randomised, double-blind, placebo-controlled trial

Background

Neurogenic detrusor overactivity (NDO) frequently results in urinary incontinence (UI) which impairs quality of life (QOL) and puts the upper urinary tract at risk.

Objective

To assess the effects of onabotulinumtoxinA (BOTOX^®, Allergan, Inc.) on UI, urodynamic variables, and QOL in incontinent patients with NDO.

Design, setting, and participants

This multicentre, randomised, double-blind, placebo-controlled study enrolled patients with multiple sclerosis (MS; n = 154) or spinal cord injury (SCI; n = 121) with UI due to NDO (≥14 UI episodes per week).

Intervention

Patients received 30 intradetrusor injections of onabotulinumtoxinA 200 U (n = 92), 300 U (n = 91), or placebo (n = 92), avoiding the trigone.

Measurements

Primary end point was change from baseline in UI episodes per week (week 6). Secondary end points included urodynamics (maximum cystometric capacity [MCC], maximum detrusor pressure during first involuntary detrusor contraction [P_detmaxIDC]), and Incontinence Quality of Life (I-QOL) total score. Adverse events (AEs) were assessed.

Results and limitations

At baseline, mean UI episodes per week (33.5) were similar across groups. At week 6, onabotulinumtoxinA 200 U and 300 U significantly reduced UI episodes per week (−21.8 and −19.4, respectively) compared with placebo (−13.2; p < 0.01); onabotulinumtoxinA benefit was observed by the first posttreatment study visit at week 2. Improvements in MCC, P_detmaxIDC, and I-QOL at week 6 were significantly greater with both onabotulinumtoxinA doses than with placebo (p < 0.001). Benefits were observed in both the MS and SCI populations. The median time to patient request for retreatment was the same for both onabotulinumtoxinA doses (42.1 wk) and greater than placebo (13.1 wk; p < 0.001). Most frequent AEs were localised urologic events (urinary tract infections and urinary retention, which were dose related in patients not using clean intermittent catheterisation [CIC] at baseline). Significant increases in postvoid residual were observed in patients not using CIC prior to treatment, and 12%, 30%, and 42% of patients in the placebo, 200-U, and 300-U groups, respectively, initiated CIC posttreatment.

Conclusions

OnabotulinumtoxinA significantly reduced UI and improved urodynamics and QOL in MS and SCI patients with NDO. Both doses were well tolerated with no clinically relevant differences in efficacy or duration of effect between the two doses (http://www.clinicaltrials.gov; NCT00461292).