Probability Of Freedom Research Articles

Oncologic Outcome after Laparoscopic Radical Prostatectomy: 10 Years of Experience

BackgroundWhile the published short-term oncologic outcomes after laparoscopic radical prostatectomy (LRP) are encouraging, intermediate and long-term data are lacking. ObjectiveWe analyzed the oncologic outcome after LRP based on 10 yr of experience. Design, setting, and participantsThis retrospective analysis of data prospectively collected from 1998 to 2007 studies 1564 consecutive patients with clinically localized prostate cancer (cT1c–cT3a) who underwent LRP. InterventionLRP was performed by two surgeons at either L’Institut Mutualiste Montsouris (IMM) in Paris, France, or Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City, USA. MeasurementsProgression of disease was defined as a prostate-specific antigen (PSA) of ≥0.1ng/ml with confirmatory rise or initiation of secondary therapy. Patients were stratified as low, intermediate, or high risk based on the pretreatment prostate cancer nomogram progression-free probability of >90%, 89–71%, and <70%, respectively. Results and limitationsThe overall 5-yr and 8-yr probability of freedom from progression (PFP) was 78% (95% confidence interval [CI], 74–82%) and 71% (95% CI, 63–78%), respectively. For low-, intermediate-, and high-risk cancer, the 5-yr PFP was 91% (95% CI, 85–95%), 77% (95% CI, 71–82%), and 53% (95% CI, 40–65%), respectively. Surgical margins (SMs) were positive in 13% of the cases. Nodal metastases were detected in 3% of the patients after limited pelvic lymph node dissection (PLND) and in 10% after a standard PLND (p<0.001). The 3-yr PFP for node-positive patients was 49%. There were 22 overall deaths and 2 deaths from prostate cancer. ConclusionsLRP provided 5- and 8-yr cancer control in 78% and 71% of patients, respectively, with clinically localized prostate cancer and in 53% of those with high-risk cancer at 5 yr. A PLND limited to the external iliac nodal group is inadequate for detecting nodal metastases.

Miniesternotomía para cirugía valvular aórtica: Experiencia inicial en un centro cardiovascular en Chile

Aortic valve surgery can be performed through a reduced mid sternotomy with excellent long term results.To report the initial results obtained with this technique.Descriptive study of 20 patients aged 48+/-11 years, subjected to valve replacement surgery for aortic valve disease between 2004 and 2007. Arterial and venous cannulation were performed with the usual method and extracorporeal circulation was performed with a mean perfusion of 4.5 L/min. Hypothermia and cardioplegia were performed infusing the hematic cardioplegic solution at 4 degrees C in the aortic root or coronary ostia.Sixteen patients were in functional class (FC) III. Fourteen patients had aortic insufficiency and six had predominant stenosis. There was no operative mortality One patient had a left hemothorax and was reoperated. All patients were discharged between 4 and 6 days after surgery. Mean follow-up was 21 +/- 4 months. All patients are in FC I and free from cardiac events. Echocardiographic assessment was done in 16 patients, showing a good motility of valve disks. Actuarial survival probability was 100% and probability of freedom from cardiac events was 100% at 42 months of follow-up.Ministernotomy is an excellent approach for aortic valve surgery providing good visualization of the ascending aorta, simplifying the surgical technique.

Encouraging survival with erlotinib in advanced papillary renal cell carcinoma (pRCC): Final results from Southwest Oncology Group study 0317

5051 Background: Historically, patients (pts) with advanced or metastatic pRCC have a median survival time of 7 to 17 months following systemic therapy (Motzer, et al. JCO 2002; Patard et al. JCO 2005). Pre-clinical studies showed greater activity for epidermal growth factor receptor (EGFR) inhibition in clear cell RCC with wild type von Hippel-Lindau (vHL) gene. In this trial, we evaluated the efficacy of erlotinib, an oral EGFR tyrosine kinase inhibitor in pts with advanced pRCC (usually associated with wild-type vHL). Methods: Pts with histologically confirmed locally advanced or metastatic pRCC were treated with erlotinib 150 mg PO QD until disease progression, patient refusal, unacceptable toxicity, or a treatment delay > 3 wks. The primary endpoint was RECIST response rate (RR). A RR of ≥ 20% was to be considered a promising outcome. Secondary endpoints included overall survival & 6-month probability of treatment failure. EGFR expression by IHC and vHL mutation status by PCR were assessed in tumor specimens. Results: Of 52 pts registered, 7 were ineligible due to insufficient pathology material submission. Of 45 evaluable pts, there were 33M/12F with a median age of 63.4 y (range 27.9 to 82.8). Median follow-up was 17.1 months (range 1.5 to 41.6). Overall RR was 11% (5/45, 95% CI: 3 - 24%). The disease control rate (DCR) was 64% (5 PR + 24 Stable). Median overall survival time was 27 months (95% CI: 13 to 36). Probability of freedom from treatment failure at 6 months was 29% (95% CI: 17–42%). There was one Grade 5 adverse event (AE) of pneumonitis, one Grade 4 thrombotic AE, and eight other Grade 3 AEs. There were two vHL mutations detected. The correlative study between EGFR expression and treatment outcomes will be presented at the meeting. Conclusions: Although the RECIST RR of 11% did not exceed pre-specified estimates for further study, single agent erlotinib yielded encouraging DCR and OS results in pts with pRCC with an expected toxicity profile. Further evaluation of the EGFR axis in pRCC should be considered. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech

Percutaneous pulmonary valve-in-valve implantation: a successful treatment concept for early device failure

Percutaneous pulmonary valve implantation (PPVI) is now an accepted treatment strategy for right ventricular (RV) outflow tract (RVOT) dysfunction in many European Heart Centres. We analysed the efficacy of repeat PPVI as a treatment modality for early device failure. Twenty patients underwent repeat PPVI for RVOT obstruction because of early device failure ('Hammock effect', 'Hammock-like effect', stent fracture, residual stenosis). Repeat PPVI was feasible in all patients with no procedural complications. Following implantation of a second device, catheter-measured RVOT gradient and RV systolic pressure fell significantly (RVOT gradient: 46.1 +/- 3.9 to 18.1 +/- 2.4 mmHg, P < 0.001; RVSP: 70.9 +/- 4.8 to 46.1 +/- 2.6 mmHg, P < 0.001), in all but one patient (15 years, male, common arterial trunk, 11.5 mm homograft). During follow-up, four of 20 required re-intervention [third PPVI for stent fracture (n = 2), device explantation: external compression by the sternum (n = 1), endocarditis (n = 1)], and one of the 20 is awaiting surgical management. In the remainder, second PPVI resulted in a sustained improvement in haemodynamics with a mean follow-up of 10.9 +/- 3.0 months. In this series, the probability of freedom from re-intervention at 2 years was higher after second PPVI when compared with the index procedure (89.4 vs. 20.0%, P < 0.001). Repeat PPVI is an effective treatment for early device failure in defined conditions and leads to improved freedom from re-intervention.

Secondary Therapy, Metastatic Progression, and Cancer-Specific Mortality in Men with Clinically High-Risk Prostate Cancer Treated with Radical Prostatectomy

ObjectivesCommonly used definitions for high-risk prostate cancer identify men at increased risk of PSA relapse after radical prostatectomy (RP). We assessed how accurately these definitions identify patients likely to receive secondary cancer therapy, experience metastatic progression, or die of prostate cancer. Materials and methodsAmong 5960 men with clinically localized or locally advanced prostate cancer who underwent RP, we identified eight different high-risk subsets, each comprising 4–40% of the study population. Estimates of freedom from radiation therapy, hormonal therapy, and metastatic progression after surgery were generated for each high-risk cohort with the Kaplan-Meier method, and hazard ratios (HR) were calculated with a Cox proportional hazards regression. The cumulative incidence and HR for prostate cancer–specific mortality (PCSM) were estimated with competing risk analysis. ResultsEach of the studied high-risk criteria was associated with increased hazard of secondary cancer therapy (HR=1.3–5.2, p<0.05) and metastatic progression (HR=2.1–6.9, p<0.05). However, depending on the definition, the probability of freedom from additional therapy 10 yr after surgery ranged from 35% to 76%. The 10-yr cumulative incidence of PCSM in high-risk patients ranged from 3% to 11% (HR=3.2–10.4, p<0.0005). ConclusionsCommonly used definitions for high-risk prostate cancer identify men at increased risk of secondary cancer therapy, metastatic progression, and PCSM following RP. However, a substantial proportion of high-risk patients remain free from additional therapy or metastatic disease many years after surgery. The risk of PCSM within 10 yr of treatment is remarkably low, even for patients at the highest risk of recurrent disease.

Phase II trial of the epidermal growth factor receptor (EGFR) inhibitor erlotinib (E) in patients (pts) with advanced papillary renal cell carcinoma (pRCC)—SWOG S0317

15516 Background: Clear cell RCC often has mutations of the von Hippel-Lindau (vHL) gene and over expression of vascular endothelial growth factor (VEGF). pRCC has mutations of c-met and not vHL. Pre-clinically, normal vHL expression is associated with greater activity of EGFR inhibitors in clear cell RCC (Clin Can Res 6:1518, 2000). PRCC has no effective treatment. Given the absence of vHL mutations we undertook a study of E in pts with pRCC. Methods: Pts with histologically confirmed advanced or metastatic pRCC with measurable disease received E 150 mg PO QD from day 1 to disease progression, pt refusal, unacceptable toxicity, or a delay of therapy &gt;3 wks. Central path review and tissue submission for vHL gene analysis were required. The primary endpoint was response. Further study of this regimen would be considered if the observed response rate (RR) was =20% (i.e. 5+ observed responses). Results: 52 pts from 27 SWOG and 2 ECOG institutions were registered. 7 pts were ineligible (no path submission-3; incorrect histology-1; no measurable disease-2; scans outside timeframe-1). Central path review is ongoing for 7 pts, leaving 39 pts evaluable for response including 30M/9F with a median age of 60.2 y (range 27.9 to 82.3). Median follow-up was 12.8 months (range 1.5 to 35.4 m). 4 pts had confirmed PRs for a RR of 10% (95% CI: 3 - 24%). Five evaluable patients with inadequate response assessment were assumed to be non-responders. Median OS was 26.9 months (95% CI lower limit 12.8 m, upper limit not yet estimable). Probability of freedom from treatment failure at 6 m is 30% (95% CI: 15–45%). There was one Grade 5 adverse event (AE) of pneumonitis thought to be possibly drug-related and one Grade 4 thrombotic AE. 8 pts experienced Grade 3 AEs common to E including rash, anorexia, diarrhea and fatigue. vHL mutation was observed in two patients with stable disease. Conclusions: Though the observed RR in pts with pRCC receiving E is similar to pts with clear cell RCC we did not see enough responses to warrant further study. As this is the first phase II trial reported (to our knowledge) for the subset of pts with pRCC we have demonstrated that less common and distinct histological subtypes can be independently studied in the cooperative group setting. [Table: see text]

Prediction models in urology

Predicting risk is an inherent feature of clinical practice. How likely is a man with a given PSA level to have prostate cancer? Can lymph node dissection be safely avoided in a patient with testicular cancer? Should chemotherapy be given after cystectomy for bladder cancer? Traditionally, physicians use clinical judgment to estimate risks, relying on rules of thumb (heuristics) or assigning patients to simple risk groups. In the March issue of Nature Clinical Practice Urology, Novara et al. described a series of nomograms (or models) that can be used to predict whether a man with penile cancer has lymph node metastases and the likelihood that he will survive his cancer for 5 years (Novara et al. [2007] Nat Clin Pract Urol 4: 140–146). Risk stratification schemes have already been published that classify such patients into risk groups, and guidelines are available for the management of men with penile cancer. So why do we need nomograms? Nomograms are graphical representations of mathematical algorithms that incorporate multiple prognostic factors into optimized statistical models to predict a particular outcome. Since the first report of a nomogram for a urological disease (Kattan MW et al. [1998] J Natl Cancer Inst 90: 766–771), these models have come into widespread use, made easier to use in digital formats (www.nomograms.org). Despite their complexity, nomograms routinely provide more accurate predictions than risk group assignment or expert judgment (Kattan MW [2005] Nat Clin Pract Urol 2: 183–190). Risk groups are popular but their accuracy is limited, in that they combine individuals with similar but not identical risk factors into a single group and categorize variables, such as PSA (0–4 ng/ml, 4.1–10 ng/ml, etc.), which give more information when analyzed as continuous variables. D’Amico’s ‘low-risk’ prognostic group of prostate cancer patients (Stage T1c or T2a, Gleason score <7, PSA level <10 ng/ml) includes patients with a uniformly favorable prognosis, but many patients in his intermediate-risk and high-risk groups actually have an excellent prognosis as well (Kattan MW [2003] Curr Opin Urol 12: 111–116). Erroneous assignment to a high-risk group might lead to an inappropriate treatment decision, such as the pessimistic recommendation to avoid radical prostatectomy in a patient with a Gleason score 8, clinical stage T1c prostate cancer, whose PSA level is 4.5 ng/ml. This ‘high-risk’ patient actually has a 65% probability of freedom from biochemical recurrence 10 years after surgery alone (Stephenson et al. [2005] J Clin Oncol 23: 7005–7012). Nomograms sometimes seem counterintuitive, especially when they include prognostic factors that have not been found to be statistically significant as independent predictors of outcome in multivariable analyses or if they weigh the values of a risk factor nonlinearly. Nevertheless, the prediction is usually more accurate than if fewer factors are included or the results are weighted linearly. Novara et al. have made a valuable contribution by refining the accuracy of predicting nodal stage and survival in men with penile cancer. These nomograms, which incorporate standard, readily available, clinical and pathological variables are remarkably accurate (Ficarra V et al. [2006] J Urol 175: 1700–1705; Kattan MW et al. [2006] J Urol 175: 2103–2108). Before nomograms can be accepted in practice, or used to stratify patients in clinical trials, they should be validated in large, independent cohorts. Such nomograms provide patients with what they surely wish for: to know their own prognosis, not that of a risk group to which they might be assigned.

Long-Term Follow-Up of Patients with Non-Hodgkin Lymphoma Following Myeloablative Therapy and Autologous Transplantation of CD34+-Selected Peripheral Blood Progenitor Cells

Graft engineering by CD34(+) selection of peripheral blood progenitor cells (PBPC) has been used in non-Hodgkin lymphoma (NHL) with the aim to reduce relapse related to tumor cells within the graft. From September 1995 to January 2000, 39 patients with newly diagnosed (n = 31) or relapsed (n = 8) NHL were treated in our institution with myeloablative therapy followed by CD34(+) selected autologous PBPC transplantation. Thirty-one patients were diagnosed with follicular lymphoma, and eight patients with mantle-cell lymphoma. All patients had advanced disease (26% of patients stage III and 74% stage IV, Ann Arbor classification). Induction therapy resulted in a complete remission in 17 patients and a partial remission in 22 patients. PBPC were mobilized after cytotoxic chemotherapy with granulocyte colony-stimulating factor support. CD34(+) selection was performed using immunomagnetic beads (Baxter Isolex 300SA or 300i Magnetic Cell Separation System). Most patients (85%) received total body irradiation and high-dose cyclophosphamide as myeloablative regimen. Twelve patients also received rituximab 375 mg/m(2) before radiation and before the start of the cyclophosphamide treatment. The mean CD34(+) cell number for transplantation was 6.5 x 10(6) CD34(+) cells/kg of body weight. Platelet recovery (>20,000/microl median on day 13) and leukocyte recovery (>1,000/microl median on day 12) were within expected range. The estimated median follow-up was 47 months. The probabilities of freedom from progression, overall survival, and event-free survival 4 years after transplantation were 96%, 90%, and 87%, respectively, for patients with follicular lymphoma and 42%, 63%, and 33%, respectively, for patients with mantle-cell lymphoma. Risk factors for relapse were age and extranodal manifestation of disease. The rate of lethal infections in the 12-month follow-up period was 8%. We conclude that CD34(+) selection of autologous transplants following myeloablative therapy is feasible and results in long-term remission in the majority of patients, but the procedure is probably related to a higher rate of lethal infections.

Predicting recurrence following post-chemotherapy retroperitoneal lymph node dissection for residual fibrosis or teratoma

4551 Background: The current recommendation for the management of patients with the histologic finding of fibrosis or teratoma at PC-RPLND is surveillance. We evaluated men at our institution who underwent PC-RPLND for metastatic non-seminomatous germ cell tumor (NSGCT) to determine predictors of disease recurrence. Methods: From 1989 through 2003, a total of 532 men underwent PC-RPLND for metastatic NSGCT at our institution. Of these, 473 (89%) had either fibrosis or teratoma present in the RPLND specimen. Following IRB approval, clinical and pathologic data were obtained from our prospective surgical database. A Cox regression model was constructed to evaluate variables that may predict for recurrence of viable NSGCT following PC-RPLND and a prognostic index was developed. Freedom from disease recurrence was analyzed using the Kaplan Meier method. Results: Of the 473 patients with fibrosis or teratoma, all patients underwent complete resection of all residual retroperitoneal masses, however 35 (7%) did not undergo a full PC-RPLND. With a median follow-up of 41 months, 47 (10%) patients relapsed with viable NSGCT. The 2- and 5- year probability of freedom from recurrent viable GCT for the entire cohort was 90% and 89%, respectively. In our multivariable model only post-chemotherapy nodal size &gt; 5cm (p = 0.008), clinical stage III (p = 0.002), and absence of a full PC-RPLND (p = 0.002) were independent predictors for recurrence with viable NSGCT. Based on these three adverse predictors, a prognostic index was developed with favorable patients having no risk factors, intermediate prognosis patients with one risk factor, and poor prognosis patients having 2 or more risk factors. Favorable, intermediate, and poor prognosis patients had a 2-year progression free probability of 97% (95% CI 95–99%), 90% (95% CI 85–95%), and 66% (95% CI 54–78%), respectively (p &lt; 0.001). Conclusions: This data suggests that patients who have a high risk of reucrrence with viable GCT should undergo more frequent follow-up during the first 2-years with serum tumor markers and imaging. Additionally, this data suggests that an incomlete RPLND is not sufficient surgery for men with metastatic NSGCT. These men should undergo a bilateral RPLND. No significant financial relationships to disclose.

Automatic Implantable Cardioverter‐Defibrillators in Chagas' Heart Disease Patients with Malignant Ventricular Arrhythmias

A total of 46 consecutive Chagas' disease patients had an automatic cardioverter defibrillator implanted at our institution from October 1998 to January 2004. A retrospective longitudinal study was carried out to identity type of life-threatening ventricular arrhythmias as well as type of therapy delivered. Of these, 41 (91%) had been recovered from cardiac arrest. Five (15%) of 33 patients in whom echocardiography was done had no left ventricular function. Antiarrhythmic therapy was delivered to 37 (80%) patients during postimplant follow-up. Thirty-one of 37 (84%) patients received both shock and antitachycardia pacing, five (13%) only antitachycardia pacing, and one (3%) patient only shock. Median time to first shock was 16 days, varying from 1 to 576 days. Ventricular fibrillation was the cause of first shock in 12 patients (32%), ventricular tachycardia in 11 (29%), and ventricular tachycardia not responding to antitachycardia pacing degenerating into ventricular fibrillation in nine (24%). Five patients with ventricular tachycardia were treated with antitachycardia pacing. Probability of freedom from device discharged was 47% at 90 days, 34% at 180 days, and 9% at 360 days in the postimplant follow-up. Thus, patients with chronic Chagas' heart disease recovered from cardiac arrest have a peculiar arrhythmogenic profile characterized by a high frequency of ventricular fibrillation and no left ventricular systolic dysfunction and a short period of time for first shock.

Lymphoproliferative disorders after paediatric heart transplantation: a multi-institutional study

Post-transplant lymphoproliferative disorders (PTLD) are an important cause of morbidity and mortality after organ transplantation. We sought to better define the prevalence, pathology, current therapeutic approaches, and outcomes of PTLD in a large group of children who had received heart transplants. We assessed data on patients followed up at 19 centres in the Pediatric Heart Transplant Study (PHTS) from 1993 to 2002. Probability of freedom from PTLD was assessed along with details of presentation, pathology, treatment, and outcomes. Risk factors for survival and event-free survival were investigated. Of 1184 primary transplant recipients, 56 (5%) developed PTLD. Probability of freedom from PTLD was 98% at 1 year, 94% at 3 years, and 92% at 5 years. Mean time to PTLD was 23.8 months. Most common sites of disease were gastrointestinal tract (n=22, 39%) and respiratory system (n=14, 25%). Histology was polymorphic in 35 (65%) and monomorphic in 19 (35%). 47 of 48 cases were of B-cell origin, 39 of 45 (87%) were Epstein-Barr virus positive. Probability of survival was 75% at 1 year, 68% at 3 years, and 67% at 5 years after diagnosis. Death from graft loss was as frequent as death from PTLD. About 5% of paediatric heart-transplant recipients develop PTLD, almost always of B-cell lineage and driven by Epstein-Barr virus. Although many achieve satisfactory outcomes, mortality remains substantial with death due to progressive disease and allograft loss. Advances in management should focus on strategies to protect the allograft as well as improved therapies for PTLD.

Long term follow-up of 100 patients with portal hypertension treated by a modified splenorenal shunt.

One hundred consecutive Child's A or B patients with portal hypertension who survived the index episode of variceal bleeding were electively treated by a distal splenorenal shunt modified by a retroperitoneal approach. The operative mortality of the whole series was 11 per cent, but fell from 16 per cent in the first 50 patients to 6 per cent in the second half of the series. The median survival probability (68 months) and the 5 year survival rate (52 per cent) of Child's A patients differed significantly from those of Child's B patients (8 months and 15 per cent respectively; P less than 0.001). The probabilities of freedom from rebleeding and hepatic encephalopathy at 5 years were also significantly greater in Child's A patients (70 per cent and 70 per cent respectively) than Child's B patients (25 per cent and 30 per cent respectively). These results suggest that the modified distal splenorenal shunt is an effective and relatively safe procedure for the elective treatment of variceal bleeding in Child-Campbell 'A' patients but that patients in group B should be considered for other forms of therapy.

Revascularización miocárdica de la arteria descendente anterior con arteria mamaria interna izquierda con circulación extracorpórea: seguimiento a 10 años

The use of left internal mammary artery (LIMA) as a graft to anterior descending artery (LAD) has been associated with better long term results in coronary surgery. To assess and report the long-term results of LIMA to LAD bypass grafting for isolated LDA lesions. Retrospective analysis of the medical records and surgical protocols of 40 patients (aged 60+/-10 years, 28 male) subjected to coronary surgery between 1992 and 2002. Thirty-four patients presented with unstable angina. On angiography, the LAD had a proximal obstruction in 35 patients. Sixteen presented with a myocardial infarction of the LAD territory. Six were managed previously with angioplasty; four had a new critical obstruction, 1 was catalogued as a procedure failure, and one was totally occluded. There was no operative mortality, myocardial infarction, stroke or need for re operation. There were two late deaths, caused by an advanced cardiac failure at 120 months in one patient, and chronic renal failure at 61 months of follow-up in another. Actuarial survival probability was 100%, 93% and 75% at 1, 5 and 10 years. Probability of freedom from angina was 98%, and freedom of suffering a new myocardial infarction was 100% at more than 10 years. The probability of no need for a new coronary procedure (angioplasty or surgery) also was 100% at more than 10 years. The use of LIMA as a coronary bypass graft to LAD is a safe surgical technique, with an excellent duration and permeability and also provides a prolonged time free from cardiac events as mortality, angina, myocardial infarction, and the need of a new coronary procedure.

Prevention of acquired infections in intubated patients with the combination of two decontamination regimens

The use of topical polymyxin and tobramycin to prevent intensive care infections is controversial. Moreover, these antibiotics are ineffective against methicillin-resistant Staphylococcus aureus. A decontamination regimen using mupirocin and chlorhexidine could prevent acquired infections, including those involving S. aureus. Because these two regimens could have a complementary role, we evaluated their effects when given both alone and combined. The authors conducted a multiple-center, placebo-controlled, randomized, double-blind study performed according to a 2 x 2 factorial design. The study was conducted at three polyvalent medical intensive care units at university-affiliated hospitals in France. Adult patients (age, > or =18 yrs) intubated for <48 hrs who were likely to be ventilated for >48 hrs. Two regimens were used: topical administration of polymyxin/tobramycin (or placebo) and nasal mupirocin with chlorhexidine body washing (or nasal placebo with liquid soap). The patients (n = 515) received polymyxin/tobramycin alone (n = 130), mupirocin/chlorhexidine alone (n = 130), both regimens (n = 129), or all placebos (n = 126) for the period of mechanical ventilation plus 24 hrs. The incidence of total infections acquired from the date of randomization until the termination date of study treatments plus 48 hrs was assessed. There were fewer acquired infections with both regimens than with polymyxin/tobramycin alone (odds ratio, 0.44; 95% confidence interval, 0.26-0.75; p = .003), mupirocin/chlorhexidine alone (0.43; 0.25-0.73; p = .002), or all placebos (0.42; 0.25-0.72; p = .001). There were no differences between polymyxin/tobramycin alone (0.95; 0.59-1.54; p = .84) and mupirocin/chlorhexidine alone (0.98; 0.60-1.58; p = .92) vs. all placebos. The probability of freedom from infection was higher with both regimens than with polymyxin/tobramycin alone (p = .002), mupirocin/chlorhexidine alone (p < .001), or all placebos (p < .001). Infection rates were also significantly lower with both regimens than with polymyxin/tobramycin alone (p = .017), mupirocin/chlorhexidine alone (p < .001), or all placebos (p < .001). Acquired infections were substantially reduced by mupirocin/chlorhexidine plus polymyxin/tobramycin, whereas each regimen given alone was ineffective. Whether both regimens could increase Candida infections deserves further investigation.

Long-Term Predictors of Aortic Root Dilation and Aortic Regurgitation After Arterial Switch Operation

Neo-aortic root dilation (ARD) and neo-aortic regurgitation (AR) may be progressive after arterial switch operation (ASO) for d-loop transposition of the great arteries (dTGA). We sought to identify predictors of ARD and AR after ASO. 335 patients were identified who underwent ASO for dTGA with intact ventricular septum or ventricular septal defect (VSD), including double-outlet right ventricle (DORV), before 2001 with at least 1 postoperative echocardiogram at our institution, at least 1 year after ASO, and no previous atrial switch procedure (median follow-up of 5.0 years). Probability of freedom from ARD was 97%, 92%, 82%, and 51%, from at least moderate AR was 98%, 97%, 96%, and 93%, and from neo-aortic valve or root surgery was 100%, 100%, 99%, and 95%, at 1, 2, 5, and 10 years, respectively. For patients in whom ARD developed, progressive dilation was not observed during late follow-up. By Kaplan-Meier method, independent predictors of ARD, with neo-aortic root z-score of > or =3.0, were previous pulmonary artery band (PAB) (P=0.002, hazard ratio [HR]=2.4) and later time period when ASO was performed (P<0.002, HR=19.0). Risk factor for at least moderate AR was age > or =1 year at ASO (P=0.002, HR=5.8), which was closely related to VSD repair at ASO (P<0.001) and previous PAB. Significant ARD and AR continue to develop over time after ASO, but ARD does not tend to be progressive during late follow-up. Previous PAB was a significant risk factor for ARD. Older age at time of ASO, presence of VSD, and previous PAB were risk factors for AR.

Uveal melanoma recurrent after fractionated proton beam therapy: Comparison of survival in patients treated with re-irradiation or with enucleation

Uveal melanoma recurrent after fractionated proton beam therapy: Comparison of survival in patients treated with re-irradiation or with enucleation

Uveal melanoma recurrent after fractionated proton beam therapy: Comparison of survival in patients treated with re-irradiation or with enucleation

Uveal melanoma recurrent after fractionated proton beam therapy: Comparison of survival in patients treated with re-irradiation or with enucleation

Radiotherapy-induced supra-aortic trunk disease: early and long-term results of surgical and endovascular reconstruction

Purpose Few articles have dealt specifically with management of radiotherapy-induced supra-aortic trunk disease. We investigated the results of surgical and endovascular treatment of these lesions, and present our findings in a large series of patients. Methods The study was conducted at 11 centers. Over 10 years 64 patients with radiotherapy-induced supra-aortic trunk disease underwent surgical or endovascular treatment. Data were collected retrospectively in a consecutive cohort of patients, and were analyzed with the Kaplan-Meier method. Results Mean patient age was 64.4 years. The indications for radiotherapy included breast cancer (30%), head and neck malignancies (50%), and lymphomas (19%). The mean interval between irradiation and arterial revascularization was 15.2 years. Thirteen of the 64 patients (20%) had asymptomatic disease, and 51 patients (80%) had symptomatic disease. Ninety-two stenotic or occlusive lesions were observed, which involved the common carotid artery (n = 62), the subclavian artery (n = 26), or the innominate artery (n = 4). Twenty-three patients (36%) had multiple supra-aortic trunk lesions, but only 8 patients underwent reconstruction of multiple supra-aortic trunks. Five patients (8%) underwent sternotomy for revascularization from the ascending aorta. Forty-seven patients required revascularization of a common carotid artery; procedures included bypass grafting (n = 30), angioplasty with stent placement (n = 13), carotid-carotid transposition (n = 2), and endarterectomy (n = 2). Fifteen patients underwent restoration of a subclavian artery. One patient died on postoperative day 5, of stroke after early occlusion of an intercarotid crossover bypass graft. Mean follow-up was 37 months (range, 2-120 months). Ten late deaths occurred during follow-up. The probability of survival at 4 years was 78.1% ± 8.6%. During follow-up, 6 patients had stroke, 4 bypass occlusions occurred and 3 stenoses occurred in the revascularized arteries. At 4 years the probability of freedom from stroke was 85% ± 8.8%. At 4 years the primary patency rate was 79.3% ± 8.5% and the secondary patency rate was 87.9% ± 7.2%. Conclusions In light of the context, the results of arterial revascularization to treat radiation-induced arterial lesions of the supra-aortic trunk are satisfactory.

Early and late clinical outcomes after primary stenting of the unprotected left main coronary artery stenosis in the setting of acute myocardial infarction

Background: Acute left main coronary artery occlusion is a dramatic condition with very high mortality. The study was aimed to evaluate the effect of primary stenting in patients with left main coronary artery (LMCA) disease in the setting of acute myocardial infarction (AMI). Methods: Between June 1997 and April 2002, primary stenting for left main coronary artery disease was performed in 18 patients with acute myocardial infarction. We evaluated early and late clinical outcomes, and prognostic determinants in this clinical setting. Results: Mean ages of patients were 59±12 years. Fourteen patients had cardiogenic shock on admission. Angiographic success (TIMI flow ≥2 and diameter stenosis <30% after stenting) was achieved in 17 patients (94%). In-hospital death occurred in eight patients (44%). Two patients (11%) received emergent bypass surgery because of hemodynamic instability after primary stenting. On univariate analysis, good pre-intervention TIMI flow (grade ≥2) was identified as a good prognostic determinant of in-hospital survival. During mean follow-up of 39±22 months, there was no late death and one patient received bypass surgery. Probability of freedom from death at 3-year was 56±12%. Conclusion: Primary stenting is a valuable therapeutic strategy for left main coronary disease in the setting of acute myocardial infarction, and it might save the life especially in patients with good pre-intervention TIMI flow (grade ≥2). Long-term clinical outcome of patients surviving to hospital discharge is favorable.

Late abdominal aortic aneurysm enlargement after endovascular repair with the excluder device

Objectives Behavior of the abdominal aortic aneurysm (AAA) sac after endovascular abdominal aortic aneurysm repair (EVAR) is graft-dependent. The Excluder endograft has been associated with less sac regression than some other stent grafts. Long-term follow-up has not been reported. Methods Between May 1999 and July 2002, 50 patients underwent EVAR with the Excluder bifurcated endoprosthesis. These patients were followed up prospectively with computed tomography (CT) at 1, 6, and 12 months and yearly thereafter. One immediate conversion to open surgery and three deaths occurred within 6 months. One additional patient was lost to follow-up. The remaining 45 patients, 35 men and 10 women, were followed up for at least 1 year, and form the basis for this report. Their mean age was 73 ± 5.5 years. The minor axis diameter at the largest area of the AAA on CT examination was compared with the baseline measurement at 1 month and to the smallest size previously recorded during follow-up. Change in sac size of 5 mm or greater was considered significant. Mean follow-up was 2.7 ± 1.2 years (range, 1-4 years). Nominal variables were compared with the χ 2 test, and continuous variables with the Student t test. Results A significant decrease in average AAA sac diameter was observed at 6-month, 1-year, and 2-year follow-up. These differences were lost by the 3-year evaluation, because of delayed sac growth (n = 9) and re-expansion of once shrunken aneurysms (n = 3). The probability of freedom from sac growth or re-expansion at 4 years was only 43%. At last follow-up, sac expansion occurred in the absence of active endoleak in nine patients. Type II endoleak was associated with sac expansion in three patients ( P = .003), resulting in one conversion to open surgery after the 4-year follow-up. No graft migrations, AAA ruptures, or aneurysm-related deaths were noted. Conclusions Late aneurysm sac growth or re-expansion after EVAR with the Excluder device is common, even in the absence of endoleak. Although the incidence of important clinical sequelae is low at this point, the incidence of aneurysm expansion should be taken into consideration during the risk-benefit assessment before EVAR repair with the Excluder device.