Fat-suppressed 3D-T1-weighted-echo planar imaging: comparison with fat-suppressed 3D-T1-weighted-gradient echo in imaging the cartilage of the knee.

This study was conducted to compare a three-dimensional (3D) multi-shot echo-planar imaging (EPI) sequence with fat-suppression (FS) with the 3D-fat-suppressed gradient echo (GRE-FS) sequence in imaging the cartilage of the knee. One hundred sixty-nine patients were studied prospectively. The cartilage was imaged in the sagittal plane with: (a) 3D-T1-EPI-FS and (b) 3D-T1-GRE-FS sequences using a 1T MR scanner. The signal-to-noise ratio (SNR) of bone (b) and cartilage (c), and relative contrast (ReCon) between bone and cartilage and meniscus and cartilage were measured in 60 patients with arthroscopically normal cartilage. The imaging accuracy was assessed by comparing with linear regression analysis (length and depth) 32 defects in the cartilage of cadaveric (human and bovine) knees. The 3D-T1-EPI-FS provided better bone marrow signal suppression, better SNRc and better ReCon(bc) and ReCon(cm) (p<0.01). The 3D-T1-EPI-FS showed better accuracy concerning the depth of the defects and the 3D-T1-GRE-FS better accuracy concerning the length of the defects. In conclusion, the 3D-T1-EPI-FS pulse sequence could be included in the routine protocol in imaging the cartilage of the knee because it achieves high SNR of the cartilage and high ReCon compared to the surrounding structures, at a reduced scan time.     

Molecular networks in respiratory epithelium carcinomas

Current anti-cancer research is focused on cell surface receptors targeting, mainly epidermal growth factor receptor and vascular endothelial growth factor receptor, against which a few targeted agents are now available in clinical practice. Recent improvements of our understanding on the intracellular networks that participate in respiratory epithelium carcinogenesis have further elucidated the role of a variety of molecules that represent attractive targets for novel therapeutic strategies. The aim of this review is to explore the potential therapeutic opportunities of the manipulation of these pathways.     

Therapy and prognosis of testicular carcinomas in relation to tnm classification

Eight-hundred and thirty-one patients with testicular carcinomas, either teratocarcinoma (405), embryonal carcinoma (406) or pure choriocarcinoma (20), treated mainly at our center from 1950 to 1976, were clinicopathologically staged according to the TNM Classification. The cancer was confined to the body of testis alone (T₁ N₀ M₀) or extended to paratesticular structures (T_2–4 N₀ M₀) in 37% of all patients. Para-aortic lymph nodes were found involved (N_1–3)in 33% and juxtaregional lymph nodes (N₄) in 9% of patients; distant metastases were detected initially in the lung alone (M₁) and other distant organs (M₂) in 21 % of the patients. Postorchiectomy treatment was retroperitoneal lymphadenectomy with or without regional-juxtaregional irradiation and systemic chemotherapy in 470 patients; the other 361 patients received external irradiation and/or adjuvant chemotherapy. Survival determined at 5 years was 58 % in teratocarcinoma cases, 41 % in embryonal carcinoma cases and 0 % in pure choriocarcinoma cases. Rates of 5-year survival according to the TNM staging were 81 % for T₁ N₀ M₀ tumors, 58 % for T_2–4 N₀ M₀ tumors, 44% for N_1–3 M₀ tumors, 33% for N₄ M₀ tumors and 10% for N_0?4 M_{1 or 2} tumors. In patients who underwent lymphadenectomy with or without external irradiation, the 5-year survival rates with and without adjuvant chemotherapy, respectively, were 96% and 86% for T₁ N₀ M₀ tumors, 100% and 60% for T_2–4 N₀ M₀ tumors, 66% and 42% for N_1–3 M₀ tumors, 54% and 40% for N₄ M₀ tumors and 38% and 0 % for N_0?4 M₁ tumors. In patients treated by external irradiation alone or following lymphadenectomy the rates of 5-year survival with versus without adjuvant chemotherapy were 100% versus 66% for T_1–4 N₀ M₀ tumors, 44% versus 18% for N_1–3 M₀ tumors, 41 % versus 22 % for N₄ M₀ tumors and 3 % versus 4 % for N_0–4 M_1–2 tumors.     

Vinorelbine plus cisplatin versus docetaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III randomized trial.

PURPOSE To compare the activity and tolerability of docetaxel/gemcitabine (DG) and vinorelbine/cisplatin (VC) combinations in chemotherapy-naive non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS Patients with advanced NSCLC were randomly assigned to receive either DG (gemcitabine 1,000 mg/m(2) [days 1 and 8] plus docetaxel 100 mg/m(2) [day 8]) or VC (vinorelbine 30 mg/m(2) [days 1 and 8] plus cisplatin 80 mg/m(2) [day 8]) and prophylactic recombinant human granulocyte colony-stimulating factor (150 microg/m(2) subcutaneously [day 9 through 15]) every 3 weeks. Results A total of 413 randomly assigned patients were analyzed for response and toxicity (DG, n = 197; VC, n = 192). Median survival was 9.0 and 9.7 months (P = .965) for DG and VC arms, respectively; the corresponding 1-year survival rates were 34.3% and 40.8%, respectively. Overall response rate was 30% (95% CI, 23.9% to 36.3%) and 39.2% (95% CI, 32.5% to 45.9%; P = .053) for DG and VC, respectively. Toxicity was as follows (DG v VC): grade 2 to 4 anemia, 34% v 55% (P = .0001); grade 3 to 4 neutropenia, 16% v 37% (P = .0001); febrile neutropenia, 6% v 11% (P = .009); and grade 3 to 4 nausea and vomiting, 1% v 15% (P = .003). Nephrotoxicity occurred in 8% and ototoxicity in 2% of VC-treated patients. There were five and six treatment-related deaths in the DG and VC arms, respectively. Quality of life was improved in DG but not in VC patients. CONCLUSION Although the two regimens produced comparable overall survival, the DG regimen had a better toxicity profile. Therefore, DG could be used in the first-line setting of advanced NSCLC, especially for patients who cannot tolerate cisplatin.     

Incidence of chemotherapy-induced nausea and emesis after modern antiemetics

BACKGROUND: The authors determined the incidence of acute and delayed chemotherapy-induced nausea and emesis (vomiting) (CINV) among patients receiving highly (HEC) or moderately (MEC) emetogenic chemotherapy. They also assessed whether physicians and nurses accurately recognized the incidence of acute and delayed CINV in their own practices. METHODS: A prospective, observational study of adult patients receiving HEC or MEC for the first time was performed. Before patient enrollment, medical oncologists and oncology nurses estimated the incidence of acute (Day 1) and delayed (Days 2-5) CINV after first administration of HEC and MEC in their own practices. Eligible patients from their practices then completed a 6-day diary including emetic episodes, nausea assessment, and antiemetic medication use. Observed incidence rates of acute and delayed CINV were compared with physician/nurse predictions. RESULTS: Twenty-four physicians and nurses and 298 eligible patients (67 receiving HEC and 231 receiving MEC) were recruited from 14 oncology practices in 6 countries. Greater than 35% of patients overall experienced acute nausea, whereas 13% experienced acute emesis. Delayed nausea and emesis were observed in 60% and 50% of HEC patients, respectively, and in 52% and 28% of MEC patients, respectively. Delayed symptoms appeared without acute symptoms after HEC (emesis, 38%; nausea, 33%) and MEC (emesis, 19%; nausea, 21%). Physicians and nurses accurately predicted the incidence of acute CINV but underestimated the incidence of delayed nausea and emesis after HEC by 21 and 28 percentage points, respectively, and delayed nausea after MEC by 28 percentage points. Greater than 75% of physicians and nurses underestimated the incidence of delayed CINV after both HEC and MEC. CONCLUSIONS: Physicians and nurses markedly underestimated the incidence of delayed nausea and emesis after both HEC and MEC. Delayed nausea and emesis, which may appear even in the absence of acute nausea and emesis, remain important targets for improved therapeutic intervention.     

Mutant HRAS as novel target for MEK and mTOR inhibitors

HRAS is a frequently mutated oncogene in cancer. However, mutant HRAS as drug target has not been investigated so far. Here, we show that mutant HRAS hyperactivates the RAS and the mTOR pathway in various cancer cell lines including lung, bladder and esophageal cancer. HRAS mutation sensitized toward growth inhibition by the MEK inhibitors AZD6244, MEK162 and PD0325901. Further, we found that MEK inhibitors induce apoptosis in mutant HRAS cell lines but not in cell lines lacking RAS mutations. In addition, knockdown of HRAS by siRNA blocked cell growth in mutant HRAS cell lines. Inhibition of the PI3K pathway alone or in combination with MEK inhibitors did not alter signaling nor had an impact on viability. However, inhibition of mTOR or combined inhibition of MEK and mTOR reduced cell growth in a synergistic manner. Finally, Ba/F3 cells transformed with mutant HRAS isoforms Q61L, Q61R and G12V demonstrated equal sensitivity towards MEK and mTOR inhibition. Our results show that HRAS mutations in cancer activate the RAS and mTOR pathways which might serve as a therapeutic option for patients with HRAS mutant tumors.     

SDF-1/CXCR4 expression is an independent negative prognostic biomarker in patients with head and neck cancer after primary radiochemotherapy

Introduction

Preclinical and clinical data suggest that the chemokine pathway governed by SDF-1 and CXCR4 contributes to a resistant phenotype. This retrospective biomarker study aims to explore the specific prognostic value of SDF-1 and CXCR4 expression in locally advanced head and neck squamous cell carcinomas (HNSCC) treated with primary radiochemotherapy (RT-CT).

CK19 and CD10 expression in pancreatic neuroendocrine tumors diagnosed by endoscopic ultrasound‐guided fine‐needle aspiration cytology

BACKGROUND:

CK19 and CD10 are useful markers in the differential diagnosis of pancreatic tumors. The authors evaluated CK19 and CD10 expression in pancreatic neuroendocrine tumors (NETs) obtained by endoscopic ultrasound (EUS)‐guided fine‐needle aspiration (FNA).

METHODS:

Twenty‐eight patients diagnosed with pancreatic NETs based on EUS‐FNA cytology were studied retrospectively (2004‐2007) for immunohistochemical expression of CK19 and CD10. Immunohistochemistry was performed on cell blocks for each case. The pattern of expression for CD10 (cytoplasmic or membranous) and its intensity (0‐2) were noted. The staining of the stromal elements for CD10 was recorded as negative. Cytoplasmic staining in tumor cells and percentage distribution (1+ to 4+) for CK19 were regarded as positive.

RESULTS:

Twenty‐three of 28 (82.14%) NETs showed positive cytoplasmic and/or membranous staining for CD10, and 25 of 28 (89.29%) cases were positive for CK19.

CONCLUSIONS:

The findings demonstrate the high expression of CD10 and CK19 in pancreatic NETs. This indicates that CD10 and CK19 cannot reliably differentiate NETs from other tumors with similar cytomorphologic features (solid pseudopapillary tumors, which frequently stain with CD10, and pancreatic adenocarcinoma, which stains with CK19). Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group.

PURPOSE: To investigate whether docetaxel plus platinum regimens improve survival and affect quality of life (QoL) in advanced non-small-cell lung cancer (NSCLC) compared with vinorelbine plus cisplatin as first-line chemotherapy. PATIENTS AND METHODS: Patients (n = 1,218) with stage IIIB to IV NSCLC were randomly assigned to receive docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks (DC); docetaxel 75 mg/m2 and carboplatin area under the curve of 6 mg/mL * min every 3 weeks (DCb); or vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2 every 4 weeks (VC). RESULTS: Patients treated with DC had a median survival of 11.3 v 10.1 months for VC-treated patients (P =.044; hazard ratio, 1.183 [97.2% confidence interval, 0.989 to 1.416]). The 2-year survival rate was 21% for DC-treated patients and 14% for VC-treated patients. Overall response rate was 31.6% for DC-treated patients v 24.5% for VC-treated patients (P =.029). Median survival (9.4 v 9.9 months [for VC]; P =.657; hazard ratio, 1.048 [97.2 confidence interval, 0.877 to 1.253]) and response (23.9%) with DCb were similar to those results for VC. Neutropenia, thrombocytopenia, infection, and febrile neutropenia were similar with all three regimens. Grade 3 to 4 anemia, nausea, and vomiting were more common (P <.01) with VC than with DC or DCb. Patients treated with either docetaxel regimen had consistently improved QoL compared with VC-treated patients, who experienced deterioration in QoL. CONCLUSION: DC resulted in a more favorable overall response and survival rate than VC. Both DC and DCb were better tolerated and provided patients with consistently improved QoL compared with VC. These findings demonstrate that a docetaxel plus platinum combination is an effective treatment option with a favorable therapeutic index for first-line treatment of advanced or metastatic NSCLC.     

Toward the substitution of invasive electroencephalography in epilepsy surgery.

The authors compared the localization accuracy of interictal magnetoencephalography (MEG) with ictal and interictal invasive video electroencephalography (VEEG) in identifying the epileptogenic zone in epilepsy surgery candidates. Forty-one patients, 29 with temporal lobe epilepsy (TLE) and 12 with extratemporal lobe epilepsy (ETLE), participated. Only patients with interictal changes during the MEG recordings were included. A comparison of the accuracy of invasive VEEG and MEG seizure zone identification was based on the degree of overlap between the location of the actual surgical resection and the zone identified by each method, and the success of surgery in reducing seizure activity. No statistical differences were observed between the accuracy of invasive VEEG and MEG in determining the location of the seizure zone across TLE and ETLE cases. Invasive VEEG and MEG localization judgments were correct in 54% and 56% of the cases, respectively. Separate group analyses suggested that MEG may be less beneficial relative to invasive VEEG in ETLE than TLE cases. MEG is of statistically equivalent accuracy to invasive VEEG, despite the fact that its use has not reached optimal conditions. The authors predict the replacement of the more invasive procedure with MEG in the near future for TLE cases, subsequent to the optimization of the conditions under which preoperative MEG is performed.