Adjuvant dose-dense sequential chemotherapy with epirubicin, CMF, and weekly docetaxel is feasible and safe in patients with operable breast cancer

Currently, randomized phase III trials have demonstrated that docetaxel is an effective strategy in the adjuvant treatment of breast cancer. However, previous attempts to incorporate docetaxel with an anthracycline in a dose-dense regimen have been unsuccessful. Therefore, new schedules containing both drugs should be explored. Forty-four patients with high-risk operable breast cancer entered this feasibility study. They were treated with three cycles of epirubicin 110 mg/m2 every 2 wk with G-CSF followed by three cycles of "intensified" CMF (840 mg/m2 cyclophosphamide; 57 mg/m2 methotrexate; 840 mg/m2 fluorouracil) every 2 wk with G-CSF followed 3 wk later by nine weekly cycles of 35 mg/m2 docetaxel (E-CMF-doc). Totally, 39 patients (89%) received all cycles of chemotherapy. The vast majority (92%) of cycles were administered at full dose. Therefore, dose intensity was sufficiently maintained for all drugs. Toxicity was generally mild to moderate. Most frequently recorded side effects apart from alopecia were neutropenia (54%) and nausea/vomiting (89%). Infection developed in nine patients. Two cases of febrile neutropenia were reported. The E-CMF-doc regimen, as used in this study, is feasible and well tolerated. Its impact on survival should be evaluated in phase III trials.     

The combination of gemcitabine and carboplatin as first-line treatment in patients with advanced urothelial carcinoma. A Phase II study of the Hellenic Cooperative Oncology Group

BACKGROUND: The toxicity of platinum-based combinations represents a common problem for patients with advanced urothelial carcinoma. The authors previously reported encouraging efficacy for the combination of carboplatin and gemcitabine in patients considered to be unfit for cisplatin-based treatment. The objective of the current multicenter Phase II study was to evaluate the safety and efficacy of the combination of gemcitabine and carboplatin as first-line treatment in unselected patients with advanced urothelial carcinoma. METHODS: Patients with previously untreated, bidimensionally measurable, inoperable or metastatic urothelial carcinoma were treated with carboplatin, area under the concentration curve of 5 (Day 1) and gemcitabine at a dose of 1000 mg/m(2) (Days 1 and 8), every 21 days for a total of 6 cycles. RESULTS: Sixty patients (49 men and 11 women, with a median age of 69 yrs) were enrolled in the current study. Intent-to-treat analysis demonstrated an objective response rate (ORR) of 38.4% (95% confidence interval [95% CI], 26-51.8%) (11.7% complete responses and 26.7% partial responses). The median time to disease progression was 7.6 months (95% CI, 4.5-10.7 mos) and the median overall survival was 16.3 months (95% CI, 12-20.6 mos). The median survival was comparable to that reported for the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) according to the Memorial Sloan-Kettering Cancer Center prognostic model for patients with similar baseline prognostic features. Grade 3 or 4 toxicity (according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) included anemia (18%), thrombocytopenia (23%), and neutropenia (52%), with 7 episodes of febrile neutropenia (11%) reported. Nonhematologic toxicity was rare. One toxic death occurred during the study. CONCLUSIONS: The combination of gemcitabine and carboplatin appears to have considerable activity as the first-line treatment of unselected patients with advanced urothelial carcinoma with manageable toxicity, and deserves further evaluation in this setting.     

Application of the pedicled anterolateral thigh flap to defects from the pelvis to the knee

The blood flow and the blood perfusion of pedicled anterolateral thigh (ALT) flap was evaluated in 11 patients with skin and soft tissue defects by means of color Doppler ultrasonography and of near-infrared spectroscopy, respectively. Also, the authors assessed the ability of the pedicled perforator flap to cover the above defects. A proximally based flap was used to cover defects at the lower abdominal wall (two patients), the suprapubic area, the penis (two patients), the greater trochanter (two patients), the lateral gluteal area, and the ischial tuberosity. A distally based flap was used to cover the exposed knee joint (two patients). Near-infrared spectroscopy revealed excellent oxygen saturation and Doppler ultrasonography documented increased blood flow and decreased vascular resistance in the pedicled ALT flap, postoperatively. All flaps survived completely and the wounds healed uneventfully, resulting in excellent esthetic and functional results. The vascular anatomy of ALT flap facilitates the design of versatile pedicled flaps with tremendous vascularity, two pivot points and large arc of rotation, able to cover defects from the lower abdominal wall to the knee joint.     

Survival and prognostic factors in chondrosarcoma: results in 115 patients with long-term follow-up

Background and purpose

There have been few long-term studies on the outcome of chondrosarcoma and the findings regarding prognostic factors are controversial. We examined a homogeneous group of patients with primary central chondrosarcoma of bone who were treated according to a uniform surgical protocol at our institution, in order to determine the factors that influence survival and identify potential improvements to our therapeutic algorithm.

Patients and methods

We performed a retrospective analysis of 115 patients with primary central chondrosarcoma of bone who presented with localized disease and who had a minimum follow-up of 5 years after diagnosis. 68 tumors were localized in the extremities and 47 in the axial skeleton or pelvis. 59 patients had a high-grade (II and III) and 56 a low-grade (I) tumor. 94 patients underwent surgical resection with adequate (wide or radical) margins, while 21 patients had inadequate (marginal or intralesional) margins.

Results

Tumor grade and localization were found to be statistically significant independent predictors of disease-related deaths in multivariate analysis. The quality of surgical margins did not influence survival. The AJCC staging system was able to predict prognosis in patients with chondrosarcoma of the extremities, but not in those with tumors of the axial skeleton and pelvis. Long-term survival after secondary metastatic disease was only observed when metastases were resected with wide margins. Patients with metastases who received further treatment with conventional chemotherapy, radiotherapy, and/or further surgery had significantly better survival compared to those who received best supportive care.

Interpretation

The outcome in patients with primary central chondrosarcoma of bone who present with localized disease is mostly affected by tumor-related parameters.Chondrosarcoma is the second most common primary malignant solid tumor of bone, and accounts for approximately 25% of all bone sarcomas (Bertoni et al. 2002). It is largely considered to be resistant to conventional chemotherapy and radiotherapy (Healey and Lane 1986, Campanacci 1999, Gelderbloom et al. 2008). As such, surgical resection has been the cornerstone of treatment for over 50 years (Dahlin and Henderson 1956, Healey and Lane 1986, Gelderbloom et al. 2008). However, in recent years several novel therapeutic approaches have been evaluated in experimental studies (Morioka et al. 2003, Gouin et al. 2006, Klenke et al. 2007, Delaney et al. 2009, Schrage et al. 2009, 2010).There is no consensus on prognostic factors to determine which patients have a higher risk of treatment failure and disease-related deaths, although several papers have addressed this issue (Evans et al. 1977, Pritchard et al. 1980, Gitelis et al. 1981, Björnsson et al. 1998, Lee et al. 1999, Rizzo et al. 2001, Fiorenza et al. 2002). One reason may be that most studies have included patients treated over several decades, with no account for the different surgical criteria, indications, and methods applied over the years. Furthermore, most studies have included patients with short follow-up, despite the fact that a high rate of late recurrence and metastasis has been reported for chondrosarcoma patients compared to those with other primary bone sarcomas (Evans et al. 1977, Pritchard et al. 1980), as well as patients with rare histopathological subtypes that have a distinct biologic behavior (Lee et al. 1999, Bertoni et al. 2002, Gelderbloom et al. 2008) such as dedifferentiated chondrosarcoma, mesenchymal chondrosarcoma, and clear cell chondrosarcoma, thus reducing the validity of the results.The purpose of this long-term retrospective study was to examine a group of patients with primary central chondrosarcoma of bone who presented with localized disease and were treated with a uniform surgical protocol at our institution, in order to determine the factors that influence overall and event-free survival. We further aimed at identifying potential improvements to our therapeutic algorithm.     

Lanthanum carbonate versus sevelamer hydrochloride: improvement of metabolic acidosis and hyperkalemia in hemodialysis patients

Sevelamer hydrochloride (SH) has been reported to aggravate metabolic acidosis and hyperkalemia. This study was performed to evaluate acid-base status and serum potassium changes after replacing SH with lanthanum carbonate (LC) in hemodialysis patients. SH was prescribed for 24 weeks in 14 stable hemodialysis patients and replaced by LC in a similar treatment schedule. Laboratory tests, including indices of acid-base status, nutrition, bone/mineral metabolism, and dialysis adequacy, were performed monthly during the study. Dialysate bicarbonate, potassium and calcium concentrations remained constant. Serum bicarbonate and pH rose, and serum potassium dropped significantly under LC. Alkaline phosphatase also decreased significantly under LC. No significant differences were observed in the other studied parameters between the two treatment periods. Control of serum phosphate was similar under both phosphate-binders and no differences were observed in calcium, Ca × P product, CRP, or lipid levels. Dialysis adequacy was constantly kept within K/DOQI target-range. Although full compliance to treatment was reported, three patients on LC complained of gastrointestinal upset and/or a metallic taste, and four had difficulty chewing the LC tablet. LC improves metabolic acidosis and hyperkalemia in hemodialysis patients previously under SH. Although both medications are well-tolerated, the gastrointestinal side-effects appear to occur more frequently with LC; a fact that, together with difficulties in chewing the tablet, may result in decreased compliance.     

Reversal of Experimental Posthepatectomy Liver Failure in Pigs: A New Application of Hepatocyte Bioreactors

Postoperative liver failure remains a major cause of morbidity and mortality after extensive hepatectomies. This study aims to evaluate the effectiveness of a hepatocyte bioreactor in the treatment of experimental post‐hepatectomy liver failure. Our experimental model included a combination of a side‐to‐side portacaval shunt, occlusion of the hepatoduodenal ligament for 150 min, 70% hepatectomy, and reperfusion. Following the development of liver failure, 12 pigs were randomized into a control group (n = 6) and a treatment group (n = 6). Both groups underwent extracorporeal perfusion through a plasma separation device, a membrane oxygenator, and two parallel bioreactors. In the latter group, the bioreactors were loaded with 10 billion fresh hepatocytes, isolated from a donor pig. Following hepatocyte treatment, all animals were maintained for 24 h under mechanical ventilation, with intravenous fluid and glucose supplementation. Hemodynamic parameters, intracranial pressure, and biochemical parameters were measured. Liver biopsies were obtained during the 24‐h autopsy. The extracorporeal circuit was well‐tolerated hemodynamically. Treated animals had lower intracranial pressure compared with controls (at 24 h, 15 ± 3.1 vs. 22 ± 3.5 mm Hg, P = 0.006). Plasma ammonia in treated animals was lower compared with controls at 12 h (100 ± 29 vs. 244 ± 131 µmol, P = 0.026). Liver histological study showed decreased necrosis and increased regeneration activity in treated animals compared with controls. Treatment through an extracorporeal hepatocyte bioreactor attenuates brain edema and improves histological and functional parameters of the liver remnant of pigs with posthepatectomy liver failure.     

Changes in arterial blood flow of free flaps after the administration of sildenafil in swine

We evaluated blood flow changes after experimental free tissue transfer and the potential hemodynamic effect of sildenafil on the free flap. Sixteen swine were used for free transfer of a latissimus dorsi myocutaneous flap to the chest that was anastomosed to the internal mammary vessels, and were randomized into controls and study group. The latter received a single dose of sildenafil, 6 hours following flap revascularization. Doppler ultrasonography revealed that arterial flow was mainly systolic postoperatively. Diastolic flow patterns were gradually restored after the first postoperative day. Pulsatility index (PI) significantly increased and flow volume decreased in all animals postoperatively. In the sildenafil group, PI significantly decreased and flow volume increased, while diastolic flow patterns were restored earlier on compared to controls, postoperatively. In conclusion, the administration of sildenafil after free tissue transfer increases flow volume and facilitates the restoration of diastolic blood flow patterns in the early critical postoperative period.     

Real-time ultrasound-guided catheterisation of the internal jugular vein: a prospective comparison with the landmark technique in critical care patients

Introduction  

Central venous cannulation is crucial in the management of the critical care patient. This study was designed to evaluate whether real-time ultrasound-guided cannulation of the internal jugular vein is superior to the standard landmark method.     

Anomalous origin of right coronary artery: magnetic resonance angiography and viability study

OBJECTIVE: To detect origin and course and to evaluate viability in patients with anomalous RCA. DESIGN: 3D coronary MR angiography and viability study using gadolinium-enhanced magnetic resonance imaging (Gd-MRI) was performed. SETTING: A tertiary hospital center. PATIENTS: Four patients, selected from the catheter lab, were studied. RESULTS: Anomalous RCA from the left sinus of Valsalva was identified in all patients. Inferior myocardial infarction was documented in three patients. CONCLUSIONS: Magnetic resonance imaging can non-invasively identify anomalous RCA and perform viability study in the same examination.