Short-term correlations between clinical and MR imaging findings in relapsing-remitting multiple sclerosis

BACKGROUND AND PURPOSE: Despite extensive use of MR imaging to provide markers of multiple sclerosis (MS) activity and accumulated disease burden, the magnitude of the relationship between clinical and MR findings is still debated. Using data from the European/Canadian glatiramer acetate (GA) trial, we investigated short-term correlations between clinical and MR measures of disease activity in patients with relapsing-remitting MS (RRMS). METHODS: In a 9-month, double-blinded, placebo-controlled study, 239 patients with RRMS were randomly assigned to receive 20 mg GA (n = 119) or placebo (n = 120). Clinical assessment included monthly neurologic examinations with Expanded Disability Status Scale scoring and visits for symptoms suggestive of relapse. Dual-echo T2-weighted and pre- and postcontrast T1-weighted brain MR images were obtained at baseline and monthly during follow-up. Contrast-enhancing and new T2-hyperintense lesions were counted, and total T2-hyperintense and T1-hypointense lesion volumes were measured. RESULTS: Significant univariate correlations were found between the number of relapses during the study period and the number of enhancing lesions at baseline (r = 0.25) and during follow-up (r = 0.30) in the study population as a whole. Multivariable analysis showed that two independent factors were more strongly correlated with relapse frequency: the number of relapses during the 2 years before entry and the number of on-trial enhancing lesions, in the whole study population and in the placebo group. CONCLUSION: In RRMS, MR imaging measures of inflammatory activity are modestly but significantly correlated with the occurrence of clinical attacks over the short term. Clinical and MR imaging assessment can provide complementary outcome measures for RRMS trials.     

Prevalence of patent foramen ovale in subjects with obstructive sleep apnea: a transcranial Doppler ultrasound study

BACKGROUND: Under particular conditions a patent foramen ovale (PFO) can potentially give rise to ischemic stroke by means of paradoxic embolization. In obstructive sleep apnea syndrome (OSAS) right to left shunting (RLSh) can occur through PFO during periods of nocturnal apnea. Our study aimed to evaluate the prevalence of PFO diagnosed by means of transcranial Doppler (TcD) in subjects with OSAS. METHODS: Seventy-eight consecutive subjects with OSAS (mean age 53+/-12 years) and 89 normal controls (mean age 48+/-9 years) underwent TcD with intravenous application of agitated physiological saline solution. The test was performed on patients at rest and during Valsalva maneuver. RESULTS: PFO was present in 21 out of 78 patients with OSA (27%) and in 13 out of 89 control patients (15%). Seventeen out of 21 patients with OSA showed PFO only during Valsalva maneuver (85%) with respect to 12 out of 13 subjects of the control group (92%). Prevalence of PFO in OSAS was statistically different with respect to the control group (P<0.05). However, no statistically significant differences could be found for the prevalence of provocative-only shunting PFO with respect to already at rest shunting PFO in patients with OSAS with respect to the control group. CONCLUSIONS: Prevalence of PFO in subjects with OSA is significantly higher than in normal controls. The shunt is frequently present only during Valsalva maneuver.     

Duct-to-mucosa versus end-to-side pancreaticojejunostomy reconstruction after pancreaticoduodenectomy: results of a prospective randomized trial

BACKGROUND: Anastomotic failure is still a significant problem that affects the outcome of pancreaticoduodenectomy. There have been many techniques proposed for the reconstruction of pancreatic digestive continuity, but there have been few prospective and randomized studies that compare their efficacy. METHODS: In the current work, 144 patients who underwent a pancreaticoduodenectomy with soft residual tissue were assigned randomly to receive either a duct-to-mucosa anastomosis (group A) or a 1-layer end-to-side pancreaticojejunostomy (group B). RESULTS: The 2 treatment groups were found not to have any differences in regards to vital statistics, underlying disease, or operative techniques. The postoperative course was complicated in 54% of the 144 patients, with a comprehensive incidence of abdominal complications in 36% (group A, 35%; group B, 38%; P=not significant). The principal complication was pancreatic fistulas, which occurred in 14% of patients (group A, 13%; group B, 15%; P=not significant). Two patients (2%) required reoperation; the postoperative mortality rate was 1%. CONCLUSION: The 2 methods that were studied revealed no significant difference the rate of complications.     

Gemcitabine and cisplatin versus vinorelbine and cisplatin versus ifosfamide+gemcitabine followed by vinorelbine and cisplatin versus vinorelbine and cisplatin followed by ifosfamide and gemcitabine in stage IIIB-IV non small cell lung carcinoma: a prospective randomized phase III trial of the Gruppo Oncologico Italia Meridionale

PURPOSE: we carried out a phase III randomized trial to compare vinorelbine-cisplatin regimen to gemcitabine-cisplatin regimen, and to a sequential administration of gemcitabine-ifosfamide followed by vinorelbine-cisplatin or the opposite sequence of vinorelbine-cisplatin followed by ifosfamide-gemcitabine according to the 'worst drug rule' hypothesis in patients with locally advanced unresectable stage IIIB or metastatic stage IV non-small cell lung cancer. The primary endpoint was survival parameters, while secondary endpoints included analysis of response rates and toxicity. PATIENTS AND METHODS: patients were randomized to receive: (a) gemcitabine 1000 mg/m(2) on days 1, 8 and 15 plus ifosfamide 1500 mg/m(2) on days 8-12 with mesna uroprotection (GI regimen) followed by vinorelbine 25 mg/m(2) on days 1 and 8 plus cisplatin 100 mg/m(2) on day 1 (GI --> VC regimen); (b) the opposite sequence (VC --> GI); (c) vinorelbine plus cisplatin as above described (VC regimen); or (d) gemcitabine 1400 mg/m(2) on days 1 and 8 plus cisplatin 100 mg/m(2) on day 8 (GC regimen). All regimens were given every 4 weeks. All patients were chemotherapy naive and had a ECOG PS 0-2. RESULTS: 400 patients were enrolled into the trial. Interim analysis after inclusion of 243 patients showed that ORR were 19% in the GI --> VC arm, 32% in the inverse sequence arm (CV --> GI), 42% in the VC arm, and 30% in the GC arm. The VC arm was statistically superior over the GI --> VC arm (p = 0.0074), but not over the other regimens. Median TTP was 3.1 months in the GI --> VC arm versus 5.0 months in the VC --> GI arm (p = 0.014). For these reasons the GI --> VC and VC --> GI arm were closed since the 'worst drug rule' hypothesis was rejected. Accrual in the VC and GC arms continued up to 140 and 138 patients respectively. Final ORR were 44% for the VC regimen (4 CR), and 34% for the GC regimen (1 CR). This difference was statistically significant (p = 0.032). OS was 9.0 and 8.2 months, respectively, with no statistically significant difference. The 1-year survival rate was 24 and 20%, respectively for VC and GC regimens. As expected the incidence of phlebitis was higher in the VC arm, while thrombocytopenia, flu-like syndrome and asthenia were more frequent in the GC arm. CONCLUSIONS: the results of this trial indicate that the combination of vinorelbine and cisplatin and that of gemcitabine and cisplatin are equivalent in terms of median TTP and OS, although the vinorelbine-cisplatin regimen is associated with a higher ORR. Both regimens may be considered as reference treatments for future studies. Moreover, our data reject the 'worst drug rule' hypothesis of sequential treatments in NSCCL at least with the combination used in this study.     

Cisplatin may be a valid alternative approach in ovarian carcinoma with carboplatin hypersensitivity. Report of three cases

Platinum-based therapy is considered the standard treatment for patients with advanced ovarian cancer. Carboplatin has a more favorable toxicity profile than cisplatin; however, hypersensitivity reactions to carboplatin have been reported occasionally. We reviewed 112 cases of ovarian cancer treated with carboplatin at our institute to identify the hypersensitivity reactions to this chemotherapeutic agent. Hypersensitivity reactions were documented in nine cases (8%). No deaths occurred, but the reactions were judged severe in three of the 112 patients (2.6%). In our own experience with patients showing idiosyncrasy to carboplatin we observed successful resolution after retreatment with cisplatin. Since patients who relapse after initial treatment with carboplatin often respond to it a second time, it is important to continue this treatment.     

Differences in transplant-related complications between hematologic malignancies and solid tumors receiving high-dose chemotherapy and autologous peripheral blood stem cell transplantation

Multiple factors contribute to transplant-related complications after high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation, including conditioning regimens, number of infused stem cells and clinical characteristics of patient at transplant. We compared the transplant-related complications of 141 patients affected with hematological malignancies with those of 109 patients with solid tumors. The total number of peripheral blood stem cell transplantations performed was 339. High-dose chemotherapy mainly consisted of melphalan-, busulphan- or thiotepa-based regimens. Despite the equal number of infused CD34+ cells, patients with a hematological malignancy showed a slower absolute neutrophil count (days to neutrophils > 0.5 x 10(9)/L, 10.6 +/- 3.6 for hematological malignancies versus 9.1 +/- 1.2 for solid tumors, P < 0.0001) and platelet recovery (days to platelets > 20 x 10(9)/L, 16.4 +/- 9.8 for hematological malignancies versus 12.3 +/- 4.1 for solid tumors, P < 0.0001) than patients with a solid tumor. A significantly higher requirement of red blood cell (3.3 +/- 4.1 versus 2.0 +/- 1.9, P < 0.0029) and platelet units (7.5 +/- 10.4 versus 4.2 +/- 3.4, P < 0.0001) was observed for hematological malignancies than for solid tumors. Five graft failures were documented exclusively in patients with a hematological malignancy. Moreover, such patients displayed a longer duration of mucositis (P < 0.0028) and hospital stay (P < 0.0001), but no difference was observed in terms of febrile episodes. Transplant-related mortality was similar between the two groups. In conclusion, patients with a hematological malignancy overall have more complications than those with a solid tumor.     

High-dose chemotherapy with mitoxantrone + melphalan and autologous stem cell rescue in metastatic breast cancer patients: a study of feasibility and tolerability

Hematological and extra-hematological toxicity of mitoxantrone-containing regimens with autologous stem cell rescue was evaluated in 32 metastatic breast cancer patients. The schedule was the final part of two high-dose chemotherapy programs, including an induction phase with three courses of conventional chemotherapy with epirubicin (120 mg/m2) and cyclophosphamide (600 mg/m2) plus three courses of docetaxel (100 mg/m2) and a first high-dose chemotherapy consisting of cyclophosphamide (6000 mg/m2), thiotepa (500 mg/m2) and carboplatin (800 mg/m2) or melphalan (160 mg/m2) plus thiotepa (600 mg/m2). The final second autograft phase included mitoxantrone (60 mg/m2) associated with melphalan (160 mg/m2) and autologous stem cell rescue infusion. The median duration of severe neutropenia and thrombocytopenia was 9 (range, 7-13) and 11.5 (range, 9-29) days. The median number of units of erythrocytes and platelets transfused was 1 (0-11) and 4 (1-9), respectively. Fever for a median of 2 (0-8) days developed in 71.8% of the patients. Mucositis was observed in 81.2% (WHO grade 3-4 in 25%). No acute or late cardiac toxicity was observed. One patient died because of a transplant-unrelated cause. The response according to the program phase showed an increased rate of complete response, from 12.5% at the end of conventional chemotherapy to 21.9% after the first high-dose chemotherapy course, to increase to 43.9% after the treatment with mitoxantrone-melphalan. We conclude that a conditioning regimen with high dose mitoxantrone-melphalan fits well within the high-dose chemotherapy program.     

Outbreak of infusion-related septicemia by Ralstonia pickettii in the Oncology Department

Hospital acquired blood stream infection by Ralstonia pickettii in 9 cancer patients related to the heparin solution contamination used to flush the central venous catheter.