放疗联合西妥昔单抗治疗局部中晚期头颈部肿瘤：五年生存期及疗效分析

2006年NEngl J Med报道了一项初始放疗联合西妥昔单抗治疗头颈部局部中晚期鳞状上皮细胞癌（LASCCHN）Ⅲ期随机试验,结果显示患者3年总生存率提高。最近Lancet发表了该试验的5年生存数据,以及西妥昔单抗所致皮疹与生存期的相关性分析。     

Theatre of paediatric surgery

In the 50 years since the first edition of this journal, operative paediatric surgery has undergone radical change. Many of the most common instruments are unchanged, both as a testament to their utility and in recognition of past surgeons remembered eponymously. Surrounding that basic core of instruments, theatre has changed radically as new tools and techniques have arisen. Surgeons have come down from their pedestals, recognising surgery as a team sport rather than a solo performance. More than half of the current paediatric surgical trainees are women, a higher proportion than in any other craft group of the Royal Australasian College of Surgeons. The appearance, and rapid development, of laparoscopy is to many observers the most notable change in surgery over the last 50 years. Placed in its context though, it is simply the most prominent example of a frameshift in surgical thinking. The patient as a whole is now the focus, rather than just the disease. Recent developments are as much about minimising harm to normal tissues as they are about extirpating pathology. As a surgical maxim, ‘Primum non nocere’ is even more in evidence in 2015 than it was in 1965.     

Consumption of vegetables and fruits and risk of subtypes of head–neck cancer in the Netherlands Cohort Study

There is limited prospective data on the relationship between consumption of vegetables and fruits and the risk of head–neck cancer (HNC) subtypes [i.e., oral cavity cancer (OCC), oro‐/hypopharyngeal cancer (OHPC) and laryngeal cancer (LC)]. Therefore, we investigated these associations within the Netherlands Cohort Study, in which 120,852 participants completed a 150‐item food frequency questionnaire at baseline in 1986. After 20.3 years of follow‐up, 415 cases of HNC (131 OCC, 88 OHPC, three oral cavity/pharynx unspecified or overlapping and 193 LC) and 3,898 subcohort members were available for case–cohort analysis using Cox proportional hazards models. Total vegetable and fruit consumption was inversely associated with risk of HNC overall [multivariable‐adjusted rate ratios for highest vs. lowest quartile: 0.61, 95% confidence interval (CI) 0.44–0.85, p trend 0.002] and all HNC subtypes, with the strongest associations for OCC. Total vegetable intake and total fruit intake were also associated with a decreased risk of HNC overall and HNC subtypes. No significant interaction was found between vegetable and fruit intake and alcohol consumption or cigarette smoking. In conclusion, in this large‐scale cohort study, consumption of vegetables and fruits was associated with a decreased risk of HNC overall and all subtypes. Consumption of vegetables and fruits (or of specific groups of them) may protect against HNC and its subtypes.     

Postural instability in cerebellar ataxia: Correlations of knee,arm and trunk movements to center of mass velocity

The aim of this study was to investigate the correlations between body segment movements and center of mass (COM) velocity during pathological balance corrections of spinocerebellar ataxia (SCA) patients compared with controls, and to relate correlations indicating instability to EMG activity differences.     

Human recombinant interferon-alpha2a and interferon-alphaA/D have different effects on bleomycin-induced lung injury

BACKGROUND: Bleomycin (Bleo)-induced lung injury in mice serves as an animal model of pulmonary fibrosis. The pathogenesis of pulmonary fibrosis remains unclear, but it comprises both inflammatory and fibrotic components. The cytokine interferon (IFN)-alpha is produced by macrophages and may modulate both fibrogenesis and the determination of T lymphocyte phenotype in pulmonary fibrosis. OBJECTIVE: To investigate the effect of two preparations of recombinant IFN-alpha (IFN-alphaA/D and IFN-alpha2a) on Bleo-induced lung injury in C57BL/6 mice. METHODS: Mice were treated by a single intratracheal (IT) instillation of 0.06 mg of Bleo in 0.1 ml of saline or saline alone. One of two different IFN-alpha preparations, IFN-alphaA/D or IFN-alpha2a in saline, or saline alone were administered by daily intraperitoneal injections starting 1 day prior to IT instillation. The treatment groups were as follows: IT Bleo and intraperitoneal saline; IT Bleo and intraperitoneal IFN-alpha2a; IT Bleo and intraperitoneal IFN-alphaA/D; IT saline and intraperitoneal IFN-alphaA/D or IFN-alpha2a; IT saline and intraperitoneal saline. The animals were sacrificed 14 days after IT instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage (BAL) fluid, by a semiquantitative morphological index of lung injury and a quantitative image analysis of cellularity and fibrosis fraction and by biochemical analysis of lung hydroxyproline content. RESULTS: In Bleo-treated mice, IFN-alpha2a treatment caused a significant rise in BAL lymphocytes and in cellularity and fibrosis fractions in lung tissue. In contrast, IFN-alphaA/D treatment had no effect on Bleo-induced lung injury. CONCLUSION: IFN-alpha may enhance Bleo-induced lung injury but this effect varies with different IFN preparations.     

B-cell chronic lymphocytic leukaemia cells express and release transforming growth factor-β

Summary Transforming growth factor-β (TGF-β) has been described as a potent inhibitor of various cell types, among others of primitive haematopoietic progenitors in vitro, and as a negative autocrine regulator of normal B lymphocyte growth and differentiation. In the present study we investigated TGF-β gene expression in peripheral blood mononuclear cells (PBMC) and in B cells from patients with B-cell chronic lymphocytic leukaemia (B-CLL) and from normal controls. Monocyte depleted B-CLL cells expressed constitutively mRNA for TGF-β1 and secreted low amounts of TGF-β activity into the culture medium. Stimulation of cells by phorbol ester noticeably enhanced mRNA levels as well as protein secretion in most cases. TGF-β activity was of the same magnitude as in normal controls. We next analysed TGF-β in highly enriched B lymphocytes from B-CLL (95100% CD19+), and found that TGF-β secretion was up to 3 times higher than in the original PBMC population. It is discussed that B-CLL cells might escape from negative regulation by TGF-β and, on the other hand, inhibit normal haematopoietic cell proliferation and thereby achieve a growth advantage in the haematopoietic tissues.     

Enhancement of chemotactic factor-stimulated neutrophil oxidative metabolism by leukotriene B4

Leukotriene B4 (LTB4) is a potent primary stimulator of neutrophil chemotaxis, aggregation, and degranulation and induces superoxide production at higher concentrations. In order to determine whether LTB4 modulates neutrophil responses to oxidative stimuli, human neutrophils (PMNs) were incubated with LTB4 prior to stimulation with f-Met-Leu-Phe (fMLP, 10(-7) mol/L), opsonized zymosan (OZ, 250 micrograms/mL), or phorbol myristate acetate (PMA, 32 nmol/L). Superoxide (O2-) production by stimulated PMNs was assessed by the superoxide dismutase-inhibitable reduction of cytochrome c. LTB4 alone did not stimulate O2- production in concentrations below 10(-7) mol/L and had no effect on the O2- assay. In the concentration range of 10(-12) to 10(-8) mol/L, LTB4 did not alter O2- release induced by OZ or PMA. In contrast, LTB4-treated cells demonstrated enhanced O2- production following exposure to fMLP, and in the presence of 10 nmol/LLTB4, generated 180% +/- 41% of O-2 quantities produced by control cells (n = 23). Enhancement was LTB4 dose-dependent, was maximal in the range of 1 to 10 nmol/L LTB4, was not reversed by removal of the lipid from the medium prior to fMLP stimulation, and was not dependent on the presence of Ca++ or Mg++ in the suspending medium. Chemiluminescence of fMLP-stimulated neutrophils was increased to 323% of controls in neutrophils preincubated with 10 nmol/L LTB4. Unlike augmentation of oxidative responses to fMLP seen with other degranulating stimuli, enhancement by LTB4 was not correlated with an increase in 3H-fMLP receptor binding. These results indicate that, in addition to its primary effects on neutrophil function, LTB4 modulates PMN oxidative responses to the chemotactic peptide and, thus, may amplify the release of oxygen metabolites at inflammatory foci.     

Primary (essential) thrombocythemia versus initial (hyperplastic) stages of agnogenic myeloid metaplasia with thrombocytosis--a critical evaluation of clinical and histomorphological data

In 40 patients (17 male, 23 female, median age 57 years) with the presumptive diagnosis of primary (essential) thrombocythemia (PTH) according to the diagnostic requirements of the Polycythemia-Vera-Study-Group (PVSG) a follow-up study and a histological evaluation of initial trephine biopsies of the bone marrow were performed. Thorough review of the hematological data during the lengthy course of disease (observation time ranging from 1.5-10.5 years) and the histomorphology of the bone marrow implied a discrimination into two groups of patients. Group I patients (n = 26; 10 male, 16 female) were compatible with PTH according to our follow-up studies. Group II patients consisted of 14 cases (7 male, 7 female) which suggested retrospectively early hyperplastic stages of agnogenic myeloid metaplasia (AMM) with concomitant thrombocytosis. In PTH (group I patients) there was a sustained elevation of the platelet count lasting for several years accompanied by stable other blood values. Early AMM (group II patients) was characterized by an insidious decline of the initially elevated thrombocyte count, starting in a few patients already 4-6 months after admission. In AMM there was further an increase in hepatosplenomegaly observable together with the level of LDH and the score of the leukocyte alkaline phosphatase, and finally an evolution of a leukoerythroblastic blood picture could be noticed. Initial histopathology of the bone marrow revealed a profound proliferation of a not severely dysplastic megakaryopoiesis in group I patients (PTH) and a normal content of reticulin fibers. In early thrombocythemic AMM (group II patients) conspicuous abnormalities of megakaryocytes were accompanied by a slight to moderate increase in argyrophilic fibers and a left-shifted neutrophilic granulocyto- as well as erythropoiesis. These differences of certain histomorphological features could be substantiated by morphometric analysis. Our findings suggest that even the rigid requirements for the diagnosis of PTH as proposed by the PVSG may not be sufficiently restrictive to exclude patients with early hyperplastic stages of thrombocythemic AMM.