Overview of breast cancer staging and surgical treatment options

Following diagnosis of breast cancer, patients undergo assessment for local and systemic treatment. Establishing a relationship and communication with the patient is critical to this assessment, as are history-taking, clinical breast examination, review of imaging studies, and interactive discussion with the patient of treatment options and possible breast reconstruction. Some type of surgical therapy is indicated in virtually all women with breast cancer, generally as the first part of a multicomponent treatment plan. The main goal of surgical therapy is to remove the cancer and accurately define the stage of disease. Surgical options broadly consist of breast conservation therapy, generally followed by radiation therapy, or mastectomy. The surgical procedure also includes assessment of regional lymph nodes for metastasis, either by axillary lymph node dissection or by the less-invasive sentinel lymph node biopsy, for the purpose of cancer staging and guiding adjuvant therapy.     

Ear,Nose and Throat Day-Case Surgery at a District General Hospital

INTRODUCTION

In 2000, The NHS Plan in the UK set a target of 75% for all surgical activity to be performed as day-cases. We aim to assess day-case turnover for ENT procedures and, in particular, day-case rates for adult and paediatric otological procedures together with re-admissions within 72 h as a proxy measure of safety.

PATIENTS AND METHODS

Retrospective collection of data (procedure and length of stay) from the computerised theatre system (Galaxy) and Patient Information Management System (PIMS) of all elective patients operated over one calendar year. The setting was a district general hospital ENT department in South East England. All ENT operations are performed with the exception of oncological head and neck procedures and complex skull-base surgery.

RESULTS

Overall, 2538 elective operations were performed during the study period. A total of 1535 elective adult procedures were performed with 74% (1137 of 1535) performed as day-cases. Of 1003 paediatric operations, 73% (730 of 1003) were day-cases. Concerning otological procedures, 93.4% (311 of 333) of paediatric procedures were day-cases. For adults, we divided the procedures into major and minor, achieving day-case rates of 88% (93 of 101) and 91% (85 of 93), respectively. The overall day-case rate for otological procedures was 91% (528 of 580). Re-admission rates overall were 0.7% (11 of 1535) for adults and 0.9% (9 of 1003) for paediatric procedures. The most common procedure for re-admission was tonsillectomy accounting for 56% of all adult re-admissions and 78% of paediatric re-admissions. The were no deaths following day-case procedures.

DISCUSSION

ENT surgery is well-suited to a day-case approach. UK Government targets are attainable when considering routine ENT surgery. Day-case rates for otology in excess of targets are possible even when considering major ear surgery.     

单倍型异基因造血干细胞-脐带间充质干细胞联合移植治疗1例急性白血病

目的研究急性粒细胞白血病异基因造血干细胞-人脐带源间充质干细胞（hUG—MSC）联合移植效果。方法急性髓性白血病-M2,供者为其胞兄,HLA单倍型相合,移植物为经粒细胞集落刺激因子（Granulocyte Clony—Stimulating Factor,G—CSF）动员的骨髓以及外周血造血干细胞,加入分离、扩增的hUC—MSC。移植物抗宿主病（Graft—Versus—Host Disease,GVHD）预防采用环孢菌素A＋ATG^＋霉酚酸酯＋短程甲氨喋呤和CD25单抗。结果输注供者的MSC总数和CD34细胞数分别为7．92×10^8/L和3．78×10^6／L。中性粒细胞大于0．5×10^9／L和血小板大于20×10^9／L的时间分别为14d和15d。24d嵌合体100％,40d左右出现Ⅰ度aGVHD,治疗后好转,未出现其他严重并发症。结论异基因造血干细胞-人脐带源间充质干细胞（hUC—MSC）联合移植安全简便,可加速造血功能恢复。     

联合脐血或脐带间充质干细胞异基因移植术后观察

目的观察联合脐血或脐带间充质干细胞（MesenchymalStemCell,MSC）的异基因造血干细胞移植的安全性、有效性及相关并发症发生情况。方法15例联合脐血或脐带MSC的异基因造血干细胞移植患者与15例未联合脐血或脐带MSC的异基因造血干细胞移植患者进行造血免疫重建、骨髓植入水平、骨髓恢复及移植相关并发症比较。结果实验组平均回输脐血或脐带间充质干细胞数为1．077×10^7／kg,移植过程顺利,血象恢复白细胞〉0．5×10^7／L平均13．07d,血小板〉20×10^9/L平均13．6d,较对照组血象恢复快（P〈0．05）。实验组较对照组严重广泛性慢性移植物抗宿主病（cGVHD）发生率低（P〈0．05）,但两组之间aGVHD、肺部及病毒感染、1年复发率、死亡率比较无统计学意义（P〉0．05）。结论联合脐血或脐带MSC的异基因造血干细胞移植成功率高,如何提高1年总生存率值得进一步研究。     

二甲基三十六烷基铵及卡介苗多糖核酸佐剂在结核亚单位疫苗加强BCG免疫中的效应研究

Objective To investigate the adjuvant effect of dimo-thylidioctyl ammonium bromide (DDA) and/or DDA-BCG polysaccharide nucleic acid( BCG-PSN), which was combined with a Mycobacterium tuberculosis fusion protein AMM ( Ag 8 5 B - MPT64190-198 - Mtb8.4 ) to boost BCG primed immunization. Methods DDA with or without BCG PSN was mixed with the fusion protein AMM to construct the boosting vaccine. Mice were immunized with BCG and then boosted twice with AMM formulated with the adjuvant DDA with or without BCG-PSN. PBS or BCG vaccination without boosting was used as control. The humoral and cell-mediated immune responses were analyzed by ELISA and ELISPOT. Moreover, the protective efficacy of BCG prime-AMM subunit vaccine boosting against Mycobacterium tuberculosis infection was analyzed. Results With in vitro stimulation of Ag85B and PPD( purified protein derivative) antigen, the number of IFN-γ secreting cells from the mice boosted twice by AMM/DDA/BCG-PSN and AMM/DDA were higher than BCG and PBS group (P <0.05). The CFU in lungs of mice boosted with AMM/DDA/BCG-PSN was less than that of PBS group(P <0.05), while the CFU of AMM/DDA-boosted mice was less than that of BCG and PBS group(P < 0.05).However, fewer lesions were seen in lungs of mice immunized with BCG alone or BCG-prime-AMM/DDA/BCG-PSN boosting than the other groups. Conclusion DDA is an idea adjuvant for tuberculosis subunit vaccine;BCG-PSN might play a role in alleviating the immunity-mediated pathology.     

Rotavirus-specific CD5+ B cells in young children exhibit a distinct antibody repertoire compared with CD5- B cells

Antiviral antibody responses in infants are limited in quality. One reason for this finding could be that the majority of B cells in infants are CD5+ cells, a subset of B cells that is thought to contain cells expressing polyreactive, low-affinity B cell receptors. We analyzed the rotavirus (RV)-specific antibody heavy chain variable region (VH) repertoire in CD5+ and CD5- B cells of four RV-infected children between 10 and 19 months of age. We found that the RV-specific B cell repertoire in CD5+ cells was VH3 family biased, in contrast to the VH1/VH4 dominance seen in CD5- B cells. The immunodominant RV-specific gene segment in CD5- B cells was VH1-46, which is the dominant segment used in RV-specific peripheral blood B cells from infants and adults. In contrast, the immunodominant gene segment was VH3-23 in RV-specific CD5+ B cells, which is the dominant gene segment in randomly selected B cells. Both RV-specific CD5+ and RV-specific CD5- B cells from all children studied demonstrated very low frequencies of somatic mutations. In conclusion, CD5+ B cells in infants responding to RV use an antibody gene repertoire that differs from the virus-specific repertoire of CD5- B cells, and both CD5+ and CD5- RV-specific B cells exhibit a low frequency of somatic mutations.     

二甲基三十六烷基铵及卡介苗多糖核酸佐剂在结核亚单位疫苗加强BCG免疫中的效应研究

Objective To investigate the adjuvant effect of dimo-thylidioctyl ammonium bromide (DDA) and/or DDA-BCG polysaccharide nucleic acid( BCG-PSN), which was combined with a Mycobacterium tuberculosis fusion protein AMM ( Ag 8 5 B - MPT64190-198 - Mtb8.4 ) to boost BCG primed immunization. Methods DDA with or without BCG PSN was mixed with the fusion protein AMM to construct the boosting vaccine. Mice were immunized with BCG and then boosted twice with AMM formulated with the adjuvant DDA with or without BCG-PSN. PBS or BCG vaccination without boosting was used as control. The humoral and cell-mediated immune responses were analyzed by ELISA and ELISPOT. Moreover, the protective efficacy of BCG prime-AMM subunit vaccine boosting against Mycobacterium tuberculosis infection was analyzed. Results With in vitro stimulation of Ag85B and PPD( purified protein derivative) antigen, the number of IFN-γ secreting cells from the mice boosted twice by AMM/DDA/BCG-PSN and AMM/DDA were higher than BCG and PBS group (P <0.05). The CFU in lungs of mice boosted with AMM/DDA/BCG-PSN was less than that of PBS group(P <0.05), while the CFU of AMM/DDA-boosted mice was less than that of BCG and PBS group(P < 0.05).However, fewer lesions were seen in lungs of mice immunized with BCG alone or BCG-prime-AMM/DDA/BCG-PSN boosting than the other groups. Conclusion DDA is an idea adjuvant for tuberculosis subunit vaccine;BCG-PSN might play a role in alleviating the immunity-mediated pathology.     

Positron emission tomography imaging of tissue P-glycoprotein activity during pregnancy in the non-human primate

Background and purpose:

Changes in tissue P-glycoprotein (P-gp) activity during pregnancy could affect the pharmacokinetics and thus the efficacy and toxicity of many drugs. Therefore, using positron emission tomography (PET) imaging, we tested whether gestational age affects tissue P-gp activity in the pregnant non-human primate, Macaca nemestrina.

Experimental approach:

Mid-gestational (day 75 ± 13, n= 7) and late-gestational (day 150 ± 10, n= 5) age macaques were imaged after administration of a prototypic P-gp substrate, ¹¹C-verapamil (13.7–75.4 MBq·kg⁻¹), before and during intravenous infusion of a P-gp inhibitor, cyclosporin A (CsA) (12 or 24 mg·kg⁻¹·h⁻¹). Accumulation of radioactivity in the fetal liver served as a reporter of placental P-gp activity. P-gp activity was expressed as CsA-induced percent change in the ratio of the area (0–9 min) under the ¹¹C-radioactivity concentration–time curve in the tissue (AUC_tissue) to that in the maternal plasma (AUC_plasma).

Key results:

The CsA-induced change in AUC_{fetal liver}/AUC_{maternalplasma} of ¹¹C-radioactivity significantly increased from mid- (35 ± 25%) to late gestation (125 ± 66%). Likewise, the CsA-induced change in AUC_{maternal brain}/AUC_plasma increased from mid- (172 ± 80%) to late gestation (337 ± 148%). The AUC ratio for the other maternal tissues was not significantly affected. Neither the CsA blood concentrations nor the level of circulating ¹¹C-verapamil metabolites were significantly affected by gestational age.

Conclusions and implications:

P-gp activity at the blood–brain barrier and the placental barrier in the macaque increased with gestational age. If replicated in humans, the exposure of the fetus and maternal brain to P-gp substrate drugs, and therefore their efficacy and toxicity, will change during pregnancy.     

Med-19对结肠癌细胞增殖及凋亡的影响

背景与目的:Med-19目前被定义为肿瘤转移相关基因,但对其在结肠癌中的功能还知之甚少。本文旨在检测Med-19基因在结肠癌中的表达及其与临床病理参数间的相关性,观察Med-19对结肠癌细胞增殖和凋亡的影响。方法:利用免疫组化检测Med-19基因在115例结肠癌中的表达情况;构建Med-19-siRNA载体转染结肠癌caco-2细胞,MTT法检测癌细胞的增殖活性,流式细胞术分析细胞凋亡的变化。结果:Med-19基因在结肠癌中的表达阳性率为64.3%,远远高于相应癌旁组织的27.8%,差异有统计学意义(P<0.05)。深入分析发现Med-19基因的表达水平与Dukes分期、淋巴结转移密切相关,而与年龄、性别、分化程度无关。与空载体转染组相比,MTT结果表明,Med-19-siRNA载体转染的caco-2细胞生长明显受到抑制,差异有统计学意义(P<0.05),流式细胞术结果提示,Med-19-siRNA载体转染的caco-2细胞凋亡比例升高,差异有统计学意义(P<0.05)。结论:Med-19基因在结肠癌中高表达,下调Med-19基因的表达可抑制结肠癌细胞增殖,促进结肠癌细胞凋亡,提示Med-19基因可以作为结肠癌治疗的潜在基因靶点。     

Dietary intake of iron, heme-iron and magnesium and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

Several studies support a protective effect of dietary magnesium against type 2 diabetes, but a harmful effect for iron. As diabetes has been linked to pancreatic cancer, intake of these nutrients may be also associated with this cancer. We examined the association between dietary intake of magnesium, total iron and heme-iron and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. In total, 142,203 men and 334,999 women, recruited between 1992 and 2000, were included. After an average follow-up of 11.3 years, 396 men and 469 women developed exocrine pancreatic cancer. Hazard ratios and 95% confidence intervals (CIs) were obtained using Cox regression stratified by age and center, and adjusted for energy intake, smoking status, height, weight, and self-reported diabetes status. Neither intake of magnesium, total iron nor heme-iron was associated with pancreatic cancer risk. In stratified analyses, a borderline inverse association was observed among overweight men (body mass index, ≥ 25 kg/m(2) ) with magnesium (HR(per 100 mg/day increase) = 0.79, 95% CI = 0.63-1.01) although this was less apparent using calibrated intake. In female smokers, a higher intake of heme-iron was associated with a higher pancreatic cancer risk (HR (per 1 mg/day increase) = 1.38, 95% CI = 1.10-1.74). After calibration, this risk increased significantly to 2.5-fold (95% CI = 1.22-5.28). Overall, dietary magnesium, total iron and heme-iron were not associated with pancreatic cancer risk during the follow-up period. Our observation that heme-iron was associated with increased pancreatic cancer risk in female smokers warrants replication in additional study populations.