Primary and recurrent regional metastases for lateralized oral cavity squamous cell carcinoma

ObjectivesMap regional lymph node metastases for lateralized oral cavity squamous cell carcinoma (OCSCC) and evaluate factors associated with regional metastases and recurrence.Materials and methodsRetrospective cohort study of 715 patients with lateralized OCSCC surgically treated in 1997–2011. Analysis was performed using log-rank, Kaplan-Meier, and multivariable logistic and Cox regression.ResultsRegional metastases were identified in ipsilateral levels IIA (24%), IB (18%), III (13%), V (9%), IV (7%), IA (2%) and IIB (1%) and the contralateral neck (3%). Lymphovascular invasion (LVI) (Hazard Ratio [HR] 2.2, 95% Confidence Interval [CI] 1.2–3.9) and T category (T3 vs. T1: HR 4.1, 95% CI 1.9–9.3; T4 vs. T1: HR 2.3, 95% CI 1.2–4.3) were associated with regional metastases. Most (71%) isolated regional metastatic recurrences were in undissected levels of the neck, including 58% in levels IV and V. Tumors of the hard palate (HR 4.3, 95% CI 1.2–16.1), upper alveolus (HR 3.2, 95% CI 1.0–4.7) or with LVI (HR 2.0, 95% CI 1.0–3.9) were associated with isolated regional recurrence. For upper alveolar/hard palate tumors, depth of invasion (DOI) ≥4 mm (P = .003) and LVI (P = .04) were associated with regional metastases.ConclusionsFor lateralized OCSCC, elective neck dissection of level IIB or the contralateral neck may rarely be needed, but additional surgical or radiation treatment of levels IV and V may be considered based on patient risk factors, including T category 3–4 or LVI. For upper alveolar/hard palate tumors, DOI ≥4 mm is an appropriate threshold for elective neck dissection.     

Direct detection of unamplified hepatoma upregulated protein RNA in urine using gold nanoparticles for bladder cancer diagnosis

ObjectiveTo develop a gold nanoparticle (AuNP) assay for direct detection of unamplified HURP RNA in urine.Design and methodsHURP RNA was extracted from urine samples (50 bladder carcinoma patients, 25 benign bladder lesions, and 25 controls) and further purified using magnetic nanoparticles (MNPs), functionalized with HURP RNA-specific oligonucleotides, and then detected by RT-PCR or gold nanoparticles.ResultsThe developed HURP RNA AuNP assay has a sensitivity and a specificity of 88.5% and 94%, respectively, and a detection limit of 2.4 nmol/L. The concordance between the HURP AuNP assay with RT-PCR after RNA purification using functionalized MNPs was 97%.ConclusionsThe developed colorimetric HURP RNA AuNP assay is sensitive, simple, and can aid noninvasive diagnosis of bladder cancer.     

FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer: A subset analysis of data from a nationwide multicenter observational study in Japan

BackgroundData on FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer are limited. In the JASPAC06 study—a nationwide, multicenter, observational study—FOLFIRINOX for patients with unresectable or recurrent pancreatic cancer as any line of treatment showed favorable efficacy and safety in Japanese clinical practice.MethodsWe performed exploratory analyses of patients with unresectable or recurrent pancreatic cancer who received FOLFIRINOX as the second-line chemotherapy in Japanese clinical settings.ResultsOf the 399 evaluable patients, 44 were eligible for inclusion in the analysis. The patients’ characteristics were as follows: median age, 62 years; men, 26 (59%); Eastern Cooperative Oncology Group-Performance status 0/1, 30 (68%)/14 (32%); disease status, recurrent/local/metastatic: 4 (9%)/8 (18%)/32 (73%). The initial dose was reduced in 28 (64%) patients. The median time to treatment failure and number of cycles were 4.5 (range, 0.2–19.1) months and 6 cycles (range, 1–13 or more), respectively. The major grade 3/4 adverse events were neutropenia in 29 (66%), leucopenia in 17 (39%), anorexia in 7 (16%), febrile neutropenia in 5 (11%), and anemia in 5 (11%) patients. The median overall survival, progression-free survival, and 1-year survival rates were 10.3 (95% confidence interval [CI], 7.2–13.3), 4.1 (95% CI, 2.6–5.5) months, and 30%, respectively.ConclusionOur findings suggest that FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer was effective in patients with a good performance status. It displayed toxicity similar to that observed with its use as a first-line treatment.     

Global Lung Oncology Branch trial 3 (GLOB3): final results of a randomised multinational phase III study alternating oral and i.v. vinorelbine plus cisplatin versus docetaxel plus cisplatin as first-line treatment of advanced non-small-cell lung cancer

Background: The study compared the efficacy of a first-line treatment with day 1 i.v. vinorelbine (NVBiv) and day 8 oral vinorelbine (NVBo) versus docetaxel (DCT) in a cisplatin-based combination in advanced non-small-cell lung cancer, in terms of time to treatment failure (TTF), overall response, progression-free survival (PFS), overall survival (OS), tolerance and quality of life (QoL).Methods: Patients were randomly assigned to receive cisplatin 80 mg/m² with NVBiv 30 mg/m² on day 1 and NVBo 80 mg/m² on day 8 every 3 weeks, after a first cycle of NVBiv 25 mg/m² on day 1 and NVBo 60 mg/m² on day 8 (arm A) or cisplatin 75 mg/m² and DCT 75 mg/m² on day 1 every 3 weeks (arm B), for a maximum of six cycles in both arms.Results: From 2 February 2004 to 1 January 2006, 390 patients were entered in a randomised study and 381 were treated. The patient characteristics are as follows (arms A/B): metastatic (%) 80.5/84.8; patients with three or more organs involved (%) 45.3/40.8; median age 59.4/62.1 years; male 139/146; squamous (%) 34.2/33.5; adenocarcinoma (%) 41.6/39.3; median TTF (arms A/B in months) [95% confidence interval (CI)]: 3.2 (3.0–4.2), 4.1 (3.4–4.5) (P = 0.19); overall response (arms A/B) (95% CI): 27.4% (21.2% to 34.2%), 27.2% (21.0% to 34.2%); median PFS (arms A/B in months) (95% CI): 4.9 (4.4–5.9), 5.1 (4.3–6.1) (P = 0.99) and median OS (arms A/B in months) (95% CI): 9.9 (8.4–11.6), 9.8 (8.8–11.5) (P = 0.58). The median survival for squamous histology was 8.87/9.82 months and for adenocarcinoma 11.73/11.60 months for arms A and B, respectively. Main haematological toxicity was grade 3–4 neutropenia: 24.4% (arm A) and 28.8% (arm B). QoL as measured by the Lung Cancer Symptom Scale was similar in both arms.Conclusions: Both arms provided similar efficacy in terms of response, time-related parameters and QoL, with an acceptable tolerance profile. In the current Global Lung Oncology Branch trial 3, NVBo was shown to be effective as a substitute for the i.v. formulation. This can relieve the burden of the i.v. injection on day 8 and can optimise the hospital's resources and improve patient convenience.     

Interference by adrenaline with chondrogenic differentiation through suppression of gene transactivation mediated by Sox9 family members

In contrast to osteoblasts, little attention has been paid to the functional expression of adrenergic signaling machineries in chondrocytes. Expression of mRNA was for the first time demonstrated for different adrenergic receptor (AdR) subtypes in chondrogenic ATDC5 cells and mouse metatarsals isolated before vascularization in culture, but not for other molecules related to adrenergic signaling. In neonatal mouse tibial sections, β₂AdR and α_2aAdR mRNA expression was found in chondrocytes at different developmental stages by in situ hybridization. Exposure to adrenaline significantly suppressed expression of several maturation markers through the cAMP/protein kinase A pathway activated by β₂AdR without affecting cellular proliferation in both cultured ATDC5 cells and metatarsals. Adrenaline also significantly inhibited gene transactivation by sry-type HMG box 9 (Sox9) family members essential for chondrogenic differentiation in a manner prevented by the general βAdR antagonist propranolol, with a concomitant significant decrease in the levels of Sox6 mRNA and corresponding protein, in ATDC5 cells and primary cultured mouse costal chondrocytes. Systemic administration of propranolol significantly promoted the increased expression of mRNA for collagen I and collagen X, but not for collagen II, in callus of fractured femur in mice. These results suggest that adrenaline may interfere with chondrogenic differentiation through downregulation of Sox6 expression for subsequent suppression of gene transactivation mediated by Sox9 family members after activation of β₂AdR expressed by chondrocytes.