Multidisciplinary total eradication therapy (TET) in men with newly diagnosed oligometastatic prostate cancer.

To evaluate the outcomes of total eradication therapy (TET), designed to eradicate all sites of visible cancer and micrometastases, in men with newly diagnosed oligometastatic prostate cancer (OMPCa). Men with ≤ 5 sites of metastases were enrolled in a prospective registry study, underwent neoadjuvant chemohormonal therapy, followed by radical prostatectomy, adjuvant radiation (RT) to prostate bed/pelvis, stereotactic body radiation therapy (SBRT) to oligometastases, and adjuvant hormonal therapy (HT). When possible, the prostate-specific membrane antigen targeted 18F-DCFPyL PET/CT (18F-DCFPyL) scan was obtained, and abiraterone was added to neoadjuvant HT. Twelve men, median 55 years, ECOG 0, median PSA 14.7 ng/dL, clinical stages M0-1/12 (8%), M1a-3/12 (25%) and M1b-8/12 (67%), were treated. 18F-DCFPyL scan was utilized in 58% of cases. Therapies included prostatectomy 12/12 (100%), neoadjuvant [docetaxel 11/12 (92%), LHRH agonist 12/12 (100%), abiraterone + prednisone 6/12 (50%)], adjuvant radiation [RT 2/12 (17%), RT + SBRT 4/12 (33%), SBRT 6/12 (50%)], and LHRH agonist 12/12 (100%)]. 2/5 (40%) initial patients developed neutropenic fever (NF), while 0/6 (0%) subsequent patients given modified docetaxel dosing developed NF. Otherwise, TET resulted in no additive toxicities. Median follow-up was 48.8 months. Overall survival was 12/12 (100%). 1-, 2-, and 3-year undetectable PSA's were 12/12 (100%), 10/12 (83%) and 8/12 (67%), respectively. Median time to biochemical recurrence was not reached. The outcomes suggest TET in men with newly diagnosed OMPCa is safe, does not appear to cause additive toxicities, and may result in an extended interval of undetectable PSA.

Cobalamin c deficiency associated with antifactor h antibody-associated hemolytic uremic syndrome in a young adult.

BACKGROUND: Thrombotic microangiopathy (TMA) syndromes are characterized by the association of hemolytic anemia, thrombocytopenia and organ injury due to arteriolar and capillary thrombosis. CASE PRESENTATION: We report the first case of adult onset cobalamin C (Cbl C) disease associated with anti-factor H antibody-associated hemolytic uremic syndrome (HUS). A 19-year-old woman was admitted to the nephrology department owing to acute kidney failure, proteinuria, and hemolytic anemia with schizocytes. TMA was diagnosed and plasma exchanges were started in emergency. Exhaustive analyses showed 1) circulating anti factor H antibody and 2) hyperhomocysteinemia, hypomethioninemia and high levels of methylmalonic aciduria pointing towards Clb C disease. Cbl C disease has been confirmed by methylmalonic aciduria and homocystinuria type C protein gene sequencing revealing two heterozygous pathogenic variants. The kidney biopsy showed 1) intraglomerular and intravascular thrombi 2) noticeable thickening of the capillary wall with a duplication aspect of the glomerular basement membrane and a glomerular capillary wall IgM associated with Cbl C disease related TMA. We initiated treatment including hydroxycobalamin, folinic acid, betaine and levocarnitine and Eculizumab. Rituximab infusions were performed allowing a high decrease in anti-factor H antibody rate. Six month after the disease onset, Eculizumab was weaning and vitaminotherapy continued. Outcome was favorable with a dramatic improvement in kidney function. CONCLUSION: TMA with renal involvement can have a complex combination of risk factors including anti-FH autoantibody in the presence of cblC deficiency.

End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation and androgen deprivation therapy for prostate cancer.

BACKGROUND: In men undergoing definitive radiation for prostate cancer, it is unclear whether early biochemical response can provide additional prognostic value beyond pre-treatment risk stratification. METHODS: Prostate cancer patients consecutively treated with definitive radiation at our institution by a single provider from 1993 to 2006 and who had an end-of-radiation (EOR) PSA (n=688, median follow-up 11.2 years). We analyzed the association of an EOR PSA level, obtained during the last week of radiation, with survival outcomes. Multivariable-adjusted cox proportional hazards models were constructed to assess associations between a detectable EOR PSA (defined as ⩾0.1 ng ml-1) and biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS) and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA. RESULTS: At the end of radiation, the PSA level was undetectable in 30% of patients. Men with a detectable EOR PSA experienced inferior 10-year BFFS (49.7% versus 64.4%, P<0.001), 10-year MFS (84.8% versus 92.0%, P=0.003), 10-year PCSS (94.3% versus 98.2%, P=0.007) and 10-year OS (75.8% versus 82.5%, P=0.01), as compared to men with an undetectable EOR PSA. Among National Comprehensive Care Network (NCCN) intermediate- and high-risk men who were treated with definitive radiation and androgen deprivation therapy (ADT), a detectable EOR PSA was more strongly associated with PCSS than initial NCCN risk level (EOR PSA: HR 5.89, 95% CI 2.37-14.65, P<0.001; NCCN risk level: HR 2.01, 95% CI 0.74-5.42, P=0.168). Main study limitations are retrospective study design and associated biases. CONCLUSIONS: EOR PSA was significantly associated with survival endpoints in men who received treatment with definitive radiation and ADT. Whether the EOR PSA can be used to modulate treatment intensity merits further investigation.

SU-E-J-153: Volumetric and Dosimetric Variations of Post-Prostatectomy Patients Treated with Radiation Therapy and Endorectal Ballon.

PURPOSE: Post-prostatectomy patients may be treated with endorectal balloon (ERB) placed during the radiation therapy. The objectives of this tudy are to investigate geometrical variation of organs at risk (OAR) and CTVs (based on RTOG and EORTC guidelines) throughout the course of radiation therapy and their dosimetric impact. METHODS: Six consecutive post-prostatectomy patients enrolled on a prospective IRB approved institutional study were analyzed. Patients underwent CT/MRI simulation and treatment with daily endorectal balloon (ERB). Six T2-MRI scans were performed during the treatment course. Bladder, rectum and two sets of CTVs according to the RTOG and EORTC guidelines were contoured by physician on each of the weekly MRI scans. The MRI scans were subsequently rigidly fused to the CT simulation images to simulate daily kV-kV patient alignment. RESULTS: 1. A consistent trend of decreasing bladder volume was found after the first week of treatment and therefore the V65Gy was found to increase after the second week of the treatment.2. The rectal volume with ERB was found to be relatively consistent during the treatment course. Displacements of rectal contours were within 2mm in all directions. The V60Gy<20% (our institutional rectal constraint) varied on average less than 2%.3. We found that the CTV volumes contoured per EORTC guideline exhibits a larger variation than those drawn according to the RTOG guidelines most likely due to the bladder exclusion imposed by it. While the average variation of RTOG based CTV volume was found within 5%, the variation of CTV-EROTC volumes was more then 10%) (p = 0.06). CONCLUSIONS: In post-prostatectomy patients undergoing radiotherapy with daily ERB had a consistent decrease in the bladder volume during the treatment leading to increased bladder irradiation and changes in the CTV volumes predominantly when EORTC guideline were followed.

[Bevacizumab/irinotecan. An active treatment for recurrent high grade gliomas: preliminary results of an ANOCEF Multicenter Study]. / Bevacizumab/irinotecan. Un nouveau traitement actif dans les gliomes de haut grade récidivants: résultats préliminaires d'une étude multicentrique de l'Anocef.

RATIONALE: Second-line chemotherapy is disappointing in recurrent high-grade gliomas. Dramatic responses in recurrent high-grade gliomas have been reported in a recent monocentric trial with a novel association combining bevacizumab (anti-VEGF monoclonal antibody agent) and irinitecan. OBJECTIVE: To report the experience of the ANOCEF group (French speaking neuro-oncology association) using the bevacizumab-irinotecan combination in recurrent high-grade gliomas. METHODS: Eight centers were involved in this retrospective multicenter study. Bevacizumab-irinotecan was delivered as previously described in a compassional setting to non-selected patients suffering from a high-grade glioma (WHO grade III and IV). Response rate at two months of the onset of the treatment was analyzed using the Macdonald criteria. The toxicity profile of the treatment was also investigated. RESULTS: From 2006 to 2007, 77 patients were treated (median age: 52 years; median Karnofsky score: 70) for a recurrent high-grade glioma (49 grade IV, 28 grade III). At two months, the response rates were objective response=36% (54% in grade III and 27% in grade IV); stable disease=39%; progressive disease=13%; patients not evaluable because of a rapid fatal clinical deterioration=12%. Improvement was noted in 49% of patients. Among the main toxicities, we noted; intratumoral hemorrage (n=5 with spontaneous regression in three) and thromboembolic complications including venous thrombophlebitis (n=4), pulmonary embolism (n=2), myocardial infarction (n=1), grade III-IV hematotoxicity (n=2), reversible leukoencephalopathy (n=1). CONCLUSION: This retrospective multicenter study adds further arguments in favor of the promising results of this new combination and its potential rapidity of action in recurrent high-grade gliomas. Antiangiogenic agents expose the patients to a well-known risk of thromboembolic and hemorragic complications, necessitating careful follow-up and patient selection in light of the cardiovascular contraindications.

Multiple aneurysm of saphenous vein graft with low symptoms 16 years after coronary artery bypass grafting.

Aneurysms of saphenous vein graft are a known but rare complication of coronary artery bypass grafting (CABG). In this report, we present a case of a 59-year-old man who presented 16 years after CABG, three aneurysms of the saphenous vein graft to the right coronary artery compressing right atrium but with low symptoms. Transoesophageal echocardiography and CT scan were used to identify the aneurysm which was confirmed by cardiac catheterization. A favourable course was obtained after surgical treatment. We also review the literature on saphenous vein graft aneurysms interesting symptoms, diagnosis, pathophysiology and treatments.

Mobile thrombus of the thoracic aorta: diagnosis and treatment in 9 cases.

Detection of mobile thrombus of the thoracic aorta has become increasingly common thanks to routine exploration using transesophageal echography (TEE) after any embolic event. Although the indication for treatment remains controversial, there is a growing interest in understanding this potential source of arterial emboli and in defining proper diagnostic and therapeutic approaches. The purpose of this study was to evaluate the utility of different diagnostic and therapeutic modalities used in our department over the last 6 years. Between 1995 and 2000, mobile thrombus of the thoracic aorta was diagnosed in 9 patients (5 men, 4 women) with a mean age of 49.2 years (range, 28 to 68 years). In all patients, aortic thrombus was suspected after a peripheral (n = 4) or cerebral (n = 5) vascular event. Treatment using intravenous heparin was attempted in all patients and allowed complete dissolution of thrombus in four. In the remaining five patients, repeat TEE demonstrated persistent thrombus and operative treatment was undertaken. In three patients with thrombosis in the aortic arch, thrombectomy was performed with cardiopulmonary bypass, and deep hypothermic circulatory arrest. In two patients presenting thrombosis in the descending thoracic aorta, thrombectomy was performed with an atriofemoral shunt. Thrombectomy was associated with repair of a wall defect in two patients and resection of atheromatous plaque in one patient. Postoperative recovery was uneventful but recurrence was noted in one patient because anticoagulation therapy was stopped too soon. On the basis of our experience and previous reports, we have defined the following therapeutic strategy. All patients are first treated with heparin. In case of failure, thrombectomy may be undertaken in young patients. Because of the highly invasive nature of the procedure, careful work-up including TEE should be performed to rule out any other cause of embolism and to determine that the lesion presents a high potential for embolism. Follow-up must include long-term coumadin therapy and routine surveillance using TEE or magnetic resonance imaging, since long-term outcome is unclear.

Surgery for post infarction ventricular septal defect (VSD): risk factors for hospital death and long term results.

OBJECTIVE: Repair of post infarction ventricular septal defect (VSD) is still a challenging procedure with a high risk of recurrence of the VSD and subsequent mortality. The aim of this retrospective study was to assess if technical change in the surgical procedure was followed by an improvement in recurrence of the VSD and operative results. METHOD: This retrospective study from 1971 to 2001 included 85 patients operated on early (<15 days) after the occurrence of a post infarction VSD. Double patch technique was introduced in 1986. A total of 44 variables were studied by a uni- and multivariate analysis. RESULTS: Hospital death occurred in 36 patients. Significant factors for hospital mortality included: preoperative and evolution of the clinical status, right ventricular function and type of repair (one or two patches). Moreover, no recurrence was observed in patients repaired with the double patch technique (P=0.09). None of the studied variables were significant for long term survival. Concomitant CABG was not associated with higher hospital mortality and long-term survival rate was similar in patients with or without concomitant CABG. CONCLUSION: The use of the double patch technique and glue by avoiding recurrence of the VSD played a role in the reduction of the hospital mortality. This technique has to be recommended in the early repair of post infarction VSD. Concomitant CABG can be done safely to control the added risk of an associated coronary artery lesion.

Endarteritis and false aneurysm complicating aortic coarctation.

We report a tricky case of endocarditis because of the localization, aortic coarctation, and the pathogenic bacteria Actinobacillus actinomycetemcomitans. Furthermore, we underline the leading role of transesophageal echocardiography in the diagnosis of aortic endarteritis. First, aortitis was treated with antibiotics and, second, successfully operated on.

Delayed left atrial wall dissection after mitral valve replacement.

We report two unusual cases of left atrial wall dissection creating a left atrial pseudoaneurysm associated with regurgitation a few months after mitral valve replacement. We emphasize the important role of transesophageal echocardiography in the diagnosis. The two patients successfully underwent surgery.

[Primitive leiomyosarcoma of the right atrium presenting with a pulmonary embolism]. / Léiomyosarcome primitif de l'oreillette droite révélé par une embolie pulmonaire.

Primary Cardiac leiomyosarcoma is a very rare condition. The authors report the case of a 64 year old woman admitted to hospital for suspected pulmonary embolism, confirmed by thoracic angio-CT scan. Despite thrombolytic therapy, a persistent poor haemodynamic condition associated with a superior vena cava syndrome led to a transoesophageal echocardiographic examination which demonstrated an abnormal intra-right atrial mass obstructing the tricuspid valve. At surgery, a leio-myosarcoma was successfully resected under good conditions. During systematic three-monthly clinical and echocardiographic follow-up, transoesophageal echocardiography detected an asymptomatic local recurrence at 15 months, for which surgery was repeated with adjuvant chemotherapy.

Early and long-term (one-year) effects of the association of aspirin and oral anticoagulant on thrombi and morbidity after replacement of the mitral valve with the St. Jude medical prosthesis: a clinical and transesophageal echocardiographic study.

OBJECTIVES: The aim of the study was to test the value of low dose aspirin associated with standard oral anticoagulants (OAC) after mechanical mitral valve replacement (MMRV) to reduce strands, thrombi and thromboembolic events. BACKGROUND: Strands and thrombi are thought to increase the risk of embolic events after MMVR, particularly in the immediate postoperative period. METHODS: Two hundred twenty-nine patients were prospectively recruited: 109 patients (group A+) were randomly assigned to aspirin (200 mg per day) with OAC and 120 patients (group A-) to OAC alone (international normalized ratio 2.5 to 3.5). All patients were subjected to multiplane transesophageal echocardiography at nine days and five months and were followed up for one year. RESULTS: At nine days and five months, there was a high and comparable incidence of strands in the two groups (group A+: 44%, 58%; group A-: 49%, 63%). However, the incidence of nonobstructive periprosthetic valve thrombi was significantly lower in group A+ at 9 days: 5% versus 13%, p = 0.03. Total thromboembolic events were reduced in group A+ (9% vs. 25%, p = 0.004) although there was an increased incidence of gastrointestinal hemorrhage (7% vs. 0%). Overall mortality was 9% in group A+ and 4% in group A-. Valve-related events were similar in both groups. Early thrombi, but not strands, were associated with higher morbidity, especially thromboembolic events (30% vs. 13%, p = 0.003). CONCLUSIONS: One year after MMVR, the association of aspirin with OAC reduced thrombi and thromboembolic events, but not morbidity, due to an increase in hemorrhagic complications.

Early and long term results of coronary artery bypass grafts in patients with dialysis dependent renal failure.

OBJECTIVE: Coronary artery disease is the main cause of mortality and morbidity in patients on renal therapy replacement. The aim of this study was to define peri-operative risk and long term results of coronary artery bypass grafts (CABG) in dialysis patients. METHODS: this retrospective study included 82 patients in chronic dialysis who underwent CABG between 1978 and 1997. The mean age was 61+/-10 years (range 28-81 years), 84% of the patients were male and the average duration of dialysis was 57 months (range 1-148 months). Combined procedures were carotid endarterectomy in one case, left ventricular aneurysm resection in one and valvular replacement in 10 (nine aortic and one mitral replacements). The operation was elective in 42 patients (51 %) and urgent in the others. Previous myocardial infarction was found in 37 patients (45%) and left ventricular ejection fraction (LVEF) at less than 45% in 15 patients (18%); 23 patients (28%) were in NYHA class III or IV and regarding angina functional status, 77% in CCS class 3 or 4. Follow-up was complete. Statistical analysis included 30 and pre and peri-operative data. Statistical analysis used Chi-square analysis or Fisher's exact test, and the Mann-Whitney test when appropriate. The estimated probability of survival, including postoperative mortality, was calculated by the method of Kaplan-Meyer, and the Log-Rank test used to compare the results. RESULTS: the hospital mortality was 14.6 % (n = 12). Ischemic time and ECC time were significantly lengthened in dead patients (P = 0.01). Moreover, use of internal mammary artery was directly related to lower hospital mortality (P = 0.02). For previous myocardial infarction, LVEF at less than 45%, diabetes and combined procedure, a P-value of < or = 0.1 was calculated. The follow-up ranged from 1 to 140 months (mean 36 months). There were 39 late deaths. The survival rates (included hospital mortality) were 71+/-5%, 56+/-6% and 39+/-6% at 1, 3 and 5 years, respectively. All surviving patients improved their functional status and had symptomatic relief. Statistical analysis showed significant difference in favor of long term survival for patients younger than 60 years, LVEF > 45% and NYHA class I or II. CONCLUSION: these data confirm that CABG in patients with renal replacement therapy is associated with an high operative and long term mortality. However it allows an improvement of functional status, and so, let possible duration of dialysis. It may be expected that more active prevention and detection of coronary disease might improve these results.

[Spontaneous rupture of the ascending aorta: a diagnostic and therapeutic emergency. Report of 2 cases]. / Rupture spontanée de l'aorte ascendante: une urgence diagnostique et thérapeutique. A propos de 2 cas.

The authors report two cases of spontaneous rupture of the ascending aorta complicating atheromatous disease but without traumatic or infectious factors. The clinical presentation is very similar to that of dissection of the aorta. The diagnosis is based on non-invasive and invasive investigations showing localised abnormalities of the aortic wall suggestive of localised dissection and haemopericardium. Surgery shows transverse tearing of the aortic wall without dissection of the media. It is a surgical emergency, the deceptive presentation of which should not be missed.

Infrarenal abdominal aortic aneurysm repair: detection and treatment of associated carotid and coronary lesions.

Management of carotid or coronary lesions associated with abdominal aortic aneurysm (AAA) remains controversial. To determine the influence of these lesions on the outcome of elective infrarenal AAA repair, we review our experience between January 1978 and December 1992. A total of 345 consecutive patients underwent infrarenal AAA repair. Procedures were performed under emergency conditions in 62 patients (18%) and electively in 283 patients (82%). Carotid and coronary risk was assessed in all 283 patients undergoing elective operations. There were 259 men (91.5%) with a mean age of 68 years (range: 45-88 years) and 24 women (8.5%) with a mean age of 76 years (range: 59-92 years). Previous cardiac manifestations included myocardial infarction in 57 patients (20%), angina in 50 patients (17.6%), coronary bypass grafting in 14 patients (14.9%), and coronary transluminal angioplasty in two patients. Cerebral ischemic attacks had been observed in 11 patients (3.8%) including transient events in two cases. Carotid endarterectomy had been performed in two patients. Assessment of carotid artery risk using Doppler ultrasonography led to selective carotid angiography in six patients and carotid endarterectomy in two patients. Assessment of coronary risk using a cardiac stress test was performed in 204 patients. Results were normal or subnormal in 132 patients (46.6%), abnormal in 21 patients (7.4%), and uninterpretable in 51 patients (18%). Coronary arteriography was performed in 151 patients (53.3%) for secondary assessment after the cardiac stress testing in 72 patients (25%) and for primary assessment in 79 patients (27.9%). Significant coronary lesions were demonstrated in 52 patients (18% of the overall population; 34% of coronary arteriography procedures). In 12 cases the lesions were not considered as threatening. In four cases the lesions were deemed inoperable. In the remaining 36 cases the lesions were treated either by aortocoronary bypass grafting (34 cases) or percutaneous transluminal angioplasty (two cases). In 11 of the 36 treated cases the patient was asymptomatic and had no history of coronary disease. In all cases AAA was treated by resection graft. Eight patients (2.8 +/- 1%) died during hospitalization including two deaths related to preexisting cardiac insufficiency. No death was attributed to preoperative work-up or treatment of associated lesions. With a mean follow-up of 62 months (range: 1-14 years), late mortality involved 96 patients (33.9 +/- 3%) including 16 deaths due to cardiac causes (16.7 +/- 4%) and 10 due to stroke (10.4 +/- 3%). Actuarial survival including deaths during hospitalization was 70.5 +/- 3% at 5 years and 41.4 +/- 5% at 10 years. Comparison of these results with those previously reported supports our policy of performing carotid or coronary angiography in patients selected by noninvasive tests.

[Surgical repair of postinfarction left ventricular lesion type I]. / Riparazione chirurgica della lesione postinfartuale di I tipo del ventricolo sinistro.

Left ventricular rupture is the most frequent cause of death following myocardial infarction after ventricular arrhytmias and cardiogenic shock. Under these circumstances, only a prompt diagnosis and urgent surgical treatment can be lifesaving. A review of the literature is made and a simple surgical technique with GRF glue application is presented.

[Description of a case of type I left ventricular rupture with formation of a false aneurysm following mitral and aortic valve replacement]. / Descrizione di un caso di rottura del I tipo del ventricolo sinistro con formazione di un falso aneurisma dopo intervento di sostituzione valvolare mitralica ed aortica.

A 65 year old patient underwent surgery for mitral and aortic valves replacement. Four months later, a type I left ventricular rupture with pseudoaneurysm was discovered. The formation and surgical reparation are described.

Intermediate-term results after en bloc double-lung transplantation with bronchial arterial revascularization. Bordeaux Lung and Heart-Lung Transplant Group.

OBJECTIVE: Between May 1990 and January 1994, 18 patients underwent en bloc double-lung transplantation with tracheal anastomosis and bronchial arterial revascularization. Because at that time it was already suggested that chronic ischemia could be a contributing factor in occurrence of obliterative bronchiolitis, the purpose of this study was to evaluate, with a follow-up ranging from 22 to 69 months, the midterm effects of bronchial arterial revascularization on development of obliterative bronchiolitis. RESULTS: Results were assessed according to tracheal healing, functional results, rejection, infection, and incidence of obliterative bronchiolitis. There were no intraoperative deaths or reexplorations for bleeding related to bronchial arterial revascularization, but there were three hospital deaths and five late deaths, two of them related to obliterative bronchiolitis. According to the criteria previously defined, tracheal healing was assessed as grade I, IIa, or IIb in 17 patients and grade IIIa in only one patient. Early angiography (postoperative days 20 to 40) demonstrated a patent graft in 11 of the 14 patients in whom follow-up information was obtained. Ten patients are currently alive with a 43-month mean follow-up. Among the 15 patients surviving more than 1 year, functional results have been excellent except in five in whom obliterative bronchiolitis has developed and who had an early or late graft thrombosis. Furthermore, those patients had a significantly higher incidence of late acute rejection (p < 0.02), cytomegalovirus disease (p < 0.006), and bronchitis episodes (p < 0.0008) than patients free from obliterative bronchiolitis. CONCLUSION: We conclude that besides its immediate beneficial effect on tracheal healing, long-lasting revascularization was, at least in this small series, associated with an absence of obliterative bronchiolitis, thus suggesting but not yet proving the possible role of chronic ischemia in this multifactorial disease.