Clinical implications of circulating angiogenic factors in cancer patients.

PURPOSE: Angiogenesis, a process fundamental to tumor growth, is regulated by angiogenic factors. This article reviews prognostic and other clinical implications of circulating angiogenic factors in cancer patients. METHODS: A MEDLINE search of literature was performed using the names of various angiogenic factors as the key words. Studies pertaining to circulating angiogenic factors in cancer patients were reviewed. Pertinent literature regarding tumor expression of common angiogenic factors and their prognostic relevance in human cancers were also examined. RESULTS: A substantial number of studies have demonstrated a strong association between elevated tumor expression of vascular endothelial growth factor (VEGF) and advanced disease or poor prognosis in various cancers. This supports the pivotal role of VEGF in regulating tumor angiogenesis. More recently, there is mounting evidence that the level of circulating VEGF in patients with different types of cancer may be predictive of tumor status and prognosis. Preliminary data also suggest that circulating VEGF may be useful in predicting and monitoring tumor response to anticancer therapies and in follow-up surveillance for tumor relapse. There are reports supporting the prognostic value of other circulating angiogenic factors such as basic fibroblast growth factor, platelet-derived endothelial cell growth factor, transforming growth factor-beta, and angiogenin, but their clinical significance is less conclusive because of limited data. CONCLUSION: Circulating VEGF seems to be a reliable surrogate marker of angiogenic activity and tumor progression in cancer patients. Evaluation of circulating angiogenic factors is a promising novel approach of prognostication in cancer patients that has the advantages of being convenient and noninvasive, and it may provide new prognostic information that is not afforded by conventional clinicopathologic prognostic indicators.     

Clinical implications of fibroblast activation protein in patients with colon cancer.

PURPOSE: Human fibroblast activation protein (FAP)/seprase is a 97-kDa surface glycoprotein expressed on tumor associated fibroblasts in the majority of epithelial cancers including colon adenocarcinomas. FAP overexpression in human tumor cells has been shown to promote tumor growth in animal models, and clinical trials targeting FAP enzymatic activity have been initiated. The primary objective of this study was to evaluate the clinical significance of stromal FAP in human colon cancers by immunohistochemisty. EXPERIMENTAL DESIGN: Sections of paraffin-embedded resected primary human colon cancer specimens from 1996 through 2001 within the Fox Chase Cancer Center tumor bank were stained with D8 antibody directed against FAP/seprase. Xenotransplanted human colorectal tumors in mice were examined similarly for stromal FAP in tumors of different sizes. Overall percentage of stromal FAP staining of the primary tumor was assessed semiquantitatively (0, 1+, 2+, 3+) and staining intensity was also graded (none, weak, intermediate, strong). Survival time and time to recurrence data were analyzed using Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models. RESULTS: One hundred thirty-eight patients with resected specimens were available for study (mean follow-up, 1,050 days) with 6 (4%) stage I, 52 (38%) stage II, 43 (31%) stage III, and 37 (27%) stage IV patients. FAP was detected in >93% of specimens. Semiquantitative staining was scored as 1+ in 28 (20%), 2+ in 52 (38%), and 3+ in 49 (35%). FAP staining intensity was graded as weak in 45 (33%), intermediate in 48 (35%), and dark in 36 (26%). Stromal FAP was found to correlate inversely with tumor stage (semiquantitative, P = 0.01; intensity, P = 0.009) and with tumor size of the tumor xenograft model (correlation coefficient, -0.61; P = 0.047), suggesting that stromal FAP may have a greater role in the early development of tumors. Furthermore, greater stromal FAP for patients with known metastatic disease was associated with a decreased survival. CONCLUSION: Our data indicate that patients whose colon tumors have high levels of stromal FAP are more likely to have aggressive disease progression and potential development of metastases or recurrence. This study affirms the rationale for ongoing clinical investigations using FAP as a therapeutic target to disrupt FAP-driven tumor progression in patients with metastatic disease. It also suggests that the effects of FAP inhibition should be investigated in earlier-stage tumors, given its high levels and potential effect earlier in the course of the disease.     

肺癌患者术后合并肺部感染的临床特点及影响因素

目的探讨肺癌患者术后合并肺部感染的临床特点及其影响因素。方法选取2016年8月至2018年8月间青岛市市立医院东院区收治的89例肺癌手术患者,按照术后是否合并肺部感染分为肺部感染组(46例)与非肺部感染组(43例)。分析肺部感染组患者的病原菌感染情况,采用单因素及多因素Logistic回归分析,探究肺癌患者术后合并发生肺部感染的影响因素。结果46例肺部感染患者中,革兰阴性菌27例(58. 7%),革兰阳性菌16例(37. 8%),真菌3例(6. 5%)。两组患者年龄、糖尿病、侵入性操作、慢性阻塞性肺疾病、切口明显疼痛和手术时间比较,差异均有统计学意义(均P <0. 05);性别和预防性使用抗菌药比较,差异无统计学意义(P> 0. 05)。上述因素纳入多因素Logistic回归分析,高龄、切口疼痛明显、慢性阻塞性肺疾病和糖尿病为肺癌患者术后合并肺部感染的独立影响因素,差异均有统计学意义(均P <0. 05)。结论肺癌患者术后合并肺部感染时,病原菌以革兰阴性菌为主,配合积极有效的预防措施,防止术后肺部感染。     

肺癌患者条件致病性真菌感染的特征

目的：调查唐山市人民医院2005年至2009年住院肺癌患者感染条件致病性真菌的临床特点及种类,探讨条件致病性真菌感染的危险因素。方法：采用回顾性调查研究的方法,对2005年至2009年在唐山市人民医院住院并发生条件致病性真菌感染的肺癌患者进行研究。结果：住院肺癌患者送检标本的送检率和条件致病性真菌检出率均逐年增高,以念珠菌属为主,白色念珠菌是最常见的感染真菌,年龄≥60岁、住院时间长、吸烟、肿瘤恶性程度高、接受化疗及放疗、广谱抗生素和激素的大量使用、各种侵入性诊疗操作的应用等因素与肺癌患者发生条件致病性真菌感染有关。结论：控制危险因素,提高患者免疫力是预防肺癌患者条件致病性真菌感染的主要措施。     

Managements of urinary catheterization and urinary tract infection in cancer patients

Urinary tract infections(UTIs)are the most frequently seen bacterial infections. Recently, cancer has become a very common disease, havingthe highest mortality rate in Japan, and the number of patients requiringurinary indwellingcatheters has increased. Indwelling catheters are employed as drainage for various urinary tract obstructions as well as local care and general management. These catheters provide a niche for opportunistic pathogens to colonize and form bacterial biofilms, causing intractable complicated UTI. The disease concept of catheter-associated urinary tract infection(CAUTI)and efforts to prevent it have received general attention. More recently, the U. S. CDC updated the original guideline for prevention of CAUTI, published in 1981, and the Japanese guidelines for prevention of infections in the urological field were also published. Based on these new guidelines, we review practical ways to manage CAUTI in cancer patients, since infectious complications associated with CAUTI adversely affect cancer treatment.     

Clinical implications of chemotherapy-induced diarrhea in patients with cancer

Diarrhea is a common, often dose-limiting toxicity associated with cancer chemotherapy treatment. However, the problem is not well recognized and frequently is not managed appropriately. The primary objectives of the current study were to describe the sociodemographic and clinical characteristics of cancer patients with chemotherapy-induced diarrhea (CID) and describe the clinical consequences of CID on treatment changes. This was a retrospective review of medical records from 378 cancer patients who experienced diarrhea while receiving chemotherapy at 25 geographically dispersed US cancer clinics.Severe diarrhea (National Cancer Institute-Common Toxicity Criteria grades 3 or 4) was experienced by about one third of patients during their chemotherapy. Patients who experienced CID underwent changes in their chemotherapy treatment, including dose reductions (45%), delays in therapy (71%), reduction in dose intensity (64%), and discontinuation of therapy (3%). Dose reductions were statistically significant. Although the majority of diarrhea was grade 1, almost one half of all patients required dosing reductions, and more than one half of these patients experienced dosing delays. Changes to chemotherapy treatment resulting from CID may ultimately impact patient clinical outcomes.     

血液恶性肿瘤患者化疗后血流感染发生率、病原菌分布情况及其影响因素分析

目的 探讨血液恶性肿瘤患者化疗后血流感染发生率、病原菌分布情况及其影响因素.方法 将60例血液恶性肿瘤患者化疗后血流感染的发生情况和病原菌分布情况进行统计分析,并检测病原菌的耐药性,分析其相关影响因素.结果 60例血液恶性肿瘤患者化疗后,发生血流感染22例,感染发生率为36.67％,其中革兰阳性菌感染7例,占31.82％;革兰阴性菌感染14例,占64.63％;真菌感染1例,占4.55％.革兰阳性菌以粪肠球菌为主,对万古霉素最敏感,革兰阴性菌以大肠埃希菌和肺炎克雷博菌为主,对美罗培南、亚胺培南最为敏感.单因素分析结果显示,年龄、化疗周期、中心静脉置管时间、基础疾病、脏器功能衰竭数目、住院时间均可能是血液恶性肿瘤患者发生血流感染的影响因素(P﹤0.05);而不同性别、凝血功能障碍情况均可能不是血液恶性肿瘤患者发生血流感染的影响因素(P﹥0.05).进一步行多因素Logistic回归分析,结果显示,年龄≥60岁、化疗周期﹥5个、中心静脉置管时间﹥20天、有基础疾病、脏器功能衰竭数目≥2个、住院时间≥20天均是血液恶性肿瘤患者化疗后发生血流感染的独立危险因素(P﹤0.05).结论 血液恶性肿瘤患者化疗后易发生血流感染,主要以革兰阴性菌感染为主,血流感染的发生与多个因素相关,临床治疗时应针对性预防.     

大肠癌患者尿液层粘连蛋白检测及临床意义

目的:探讨检测尿液层粘连蛋白(LN)含量对大肠癌的诊断价值及手术前、后含量的变化,了解其对大肠癌预后的判断、监测肿瘤有无复发和转移的意义.方法: 应用放射免疫技术测定大肠癌患者手术前、后尿液层粘连蛋白(LN)含量.结果: 大肠癌患者尿液层粘连蛋白(LN)含量(98.7±16.3)高于良性病变组(50.2±9.3)和对照组(46.5±8.6)(P<0.05),而良性病变组与对照组之间尿液层粘连蛋白(LN)含量差异无显著性(P>0.05);DukesC D期组尿液层粘连蛋白(LN)含量高于DukesA B期组(P<0.05);尿液层粘连蛋白(LN)含量术后较术前降低(P<0.05).结论: 大肠癌患者尿液层粘连蛋白(LN)含量的检测对诊断、判断预后、指导临床治疗、与良性病变鉴别有一定参考价值.     

大肠癌患者尿液层粘连蛋白检测及临床意义

目的：探讨检测尿液层粘连蛋白（LN）含量对大肠癌的诊断价值及手术前、后含量的变化，了解其对大肠癌预后的判断、监测肿瘤有无复发和转移的意义。方法：应用放射免疫技术测定大肠癌患者手术前、后尿液层粘连蛋白（LN）含量。结果：大肠癌患者尿液层粘连蛋白（LN）含量（98．7±16．3）高于良性病变组（50．2±9．3）和对照组（46．5±8．6）（P〈0．05），而良性病变组与对照组之间尿液层粘连蛋白（LN）含量差异无显著性（P〉0．05）；DukesC＋D期组尿液层粘连蛋白（LN）含量高于DukesA＋B期组（P〈0．05）；尿液层粘连蛋白（LN）含量术后较术前降低（P〈0．05）。结论：大肠癌患者尿液层粘连蛋白（LN）含量的检测对诊断、判断预后、指导临床治疗、与良性病变鉴别有一定参考价值。     

Multi-drug-resistant Enterococcus faecalis among Egyptian patients with urinary tract infection

The prevalence of Enterococcus faecalis (E. faecalis) infections among Egyptians with urinary tract infection (UTI), their antimicrobial susceptibility and mechanisms of resistance are under investigated. In this study, 300 urine samples were collected from UTI patients to identify E. faecalis. Antimicrobial susceptibility to 18 antimicrobial agents was tested. The presence of aac(6)-Ie-aph(2)Ia, erm(B) and mef(A/E) genes was examined by PCR. Fifty-seven (19%) isolates were identified as E. faecalis. All isolates were sensitive to teicoplanin and were completely resistant to nalidixic acid, cefotaxime and cefadroxil. Multi-drug-resistant (MDR) was found to be 100% with 45 different antibiotypes. The aac(6)Ia-aph(2)Ia gene was found in 100 and 90% of the isolates resistant to gentamicin at concentrations of 120 and 10 μg, respectively. erm(B) and mef(A/E) genes were present in 92.5% (37/40) and 2.5% (1/40) of erythromycin-resistant isolates, respectively. We conclude that there is a high prevalence of E. faecalis in UTI cases with a 100% MDR rate indicating a serious problem in treating infections by this organism in Egypt.     

Clinical prognostic factors for patients with recurrent head and neck cancer: implications for randomized trials

The purpose of our study was to determine the clinical prognostic factors for the duration of the overall survival from recurrence (OSR) in patients with recurrent head and neck squamous-cell carcinoma. We performed a retrospective analysis on 496 patients treated between 1982 and 1993 at the Antoine Lacassagne Center. The significant favorable prognostic factors for the OSR were: initial T(1-2) (p = 0.008), no initial nodal involvement (p = 0.002), no initial chemotherapy exposure (p = 0.002), induction chemotherapy response (p = 0.001), duration of disease-free interval (DFI; p = 0.0001), performance status (PS) 0-1 (p = 0.004) and local-regional recurrence (p = 0.001). In the multivariate analysis, the apparent nonsignificance of all factors apart from the DFI suggested that relevant prognostic factors could be embedded in the DFI. Multivariate analysis was performed after excluding the DFI. The results indicated that local-regional recurrence, PS 0-1 and no initial chemotherapy exposure remained significant favorable prognostic factors for the OSR. The advantages of taking into account such prognostic factors are to eliminate the patient selection bias and to ensure a fairer comparative evaluation of new or already existing agents in recurrent head and neck cancer.     

Immunomodulatory properties of CNF1 toxin from E. coli: implications for colorectal carcinogenesis

Colorectal cancer (CRC) is a leading cause of cancer death worldwide. The risk of developing CRC is influenced by both environmental and genetic factors. Recently, chronic inflammation and gut microbiota modifications have been associated with increased CRC risk. Escherichia coli belongs to the commensal intestinal flora and can become highly pathogenic following the acquisition of genes coding for virulence factors, such as the cytotoxic necrotizing factor type 1 (CNF1). Numerous reports highlight that, besides exerting direct effects on epithelial cells, CNF1 can also act on immune cells, modulating their responses and possibly contributing to disease development. In the present review, we summarized the key studies addressing the immunomodulatory functions of CNF1 and discussed the contribution that CNF1 can bring about to CRC through the creation of a pro-inflammatory microenvironment.     

Clinical factors associated with suicidality in cancer patients

BACKGROUND: Previous epidemiological studies have indicated that the risk of suicide in cancer patients is higher than that of the general population. In addition, euthanasia and physician-assisted suicide (PAS) have recently become controversial medical, ethical and legal issues all over the world. Although suicide in cancer patients and appropriate management of cancer patients with suicidality are critical issues in clinical oncology practice, there have been very few studies to understand suicidality in cancer patients. The purpose of this study was to explore the clinical factors associated with suicidality in Japanese patients with cancer. METHODS: We investigated the clinical factors associated with suicidality in cancer patients by analyzing the consultation data of patients referred to the Psychiatry Division, National Cancer Centre Hospital and Hospital East, Japan. RESULTS: Of 1713 psychiatric referrals, 62 (3.6%) were related to suicidality, including 44 cases with suicidal ideation, 10 suicide attempts and eight cases who had requested euthanasia and/or continuous sedation. Most of the patients suffered from physical distress and/or psychiatric disorders. The results of a multivariate analysis comparing cancer patients with a psychiatric referral related to suicidality and those referred for other reasons indicated that impaired physical functioning and major depression were significant associated factors. CONCLUSIONS: Our findings suggest that early detection and appropriate management of major depression and comprehensive care improving physical functioning may help to prevent suicide and manage suicidality in Japanese cancer patients.     

恶性淋巴瘤患者血流感染情况及病原菌耐药性分析

目的 分析恶性淋巴瘤患者血流感染情况及病原菌耐药性.方法 选取310例恶性淋巴瘤患者,检测血流感染的病原菌分布情况,以纸片扩散法进行药敏反应试验.结果 310例恶性淋巴瘤患者中,发生血流感染29例,感染率为9.35％.29例发生血流感染的恶性淋巴瘤患者中共分离出25株病原菌,其中革兰阳性菌15株,占60.00％;革兰阴...     

Role of chronic E. coli infection in the process of bladder cancer- an experimental study

ABSTRACT: Bladder cancer is a common malignancy in Egypt. A history of urinary tract infection can be considered as a risk factor for bladder cancer. Escherichia coli (E. coli) infection is responsible for 70% of urinary tract infection. This study aimed to evaluate the role of chronic E. coli infection during bladder carcinogenesis. In order to achieve this aim, we investigated the histopathological changes in bladder tissue and measured the level of nuclear factor kappa p65 (NF-kappaBp65), Bcl-2 and interleukin 6 ( IL-6) in four groups each consisting of 25 male albino rats except of control group consisting of 20 rats .The first group was normal control group, second group was infected with E. coli, the third group was administered nitrosamine precursor, and the forth group was infected with E. coli and administered nitrosamine precursor.     

Clinical implications of angiogenic factors in patients with acute or chronic leukemia: hepatocyte growth factor levels have prognostic impact, especially in patients with acute myeloid leukemia.

The present study evaluated the serum levels of known angiogenic factors and analysed their prognostic significance in patients with acute or chronic leukemia. Enzyme-linked immunosorbent assays (ELISAs) were performed to quantify the basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), tumor necrosis factor-alpha (TNF-alpha), angiogenin, and matrix metalloproteinase-9 (MMP-9) in stored samples obtained before treatment from patients with acute myeloid leukemia (AML; 30 patients), acute lymphoblastic leukemia (ALL; 10 patients), and chronic myelogenous leukemia (CML; 14 patients). The levels of VEGF, HGF, angiogenin, and MMP-9 were all significantly higher in patients with CML than in healthy individuals. The HGF levels were also higher in patients with AML than in healthy individuals, plus there was a significant correlation between the HGF level and the white blood cell count, monocyte count, and serum level of lactate dehydrogenase (LDH) in patients with AML. In a univariate analysis, age and HGF level were both found to be significant parameters predictive for an achievement of complete remission (CR) in patients with AML. Meanwhile, in a multivariate analysis using a logistic regression model, the HGF level was the only parameter strongly predictive for CR (P=0.047). The leukemia-free survival (LFS) rate for AML patients with a lower HGF concentration was better than that for AML patients with a higher HGF concentration (1 year LFS rates=75.0% vs. 37.5%, P=0.065). The HGF concentration was an independent prognostic factor for an achievement of CR, plus higher HGF concentrations were associated with a lower survival in patients with AML.     

Clinical implications of learned food aversions in patients with cancer treated with chemotherapy or radiation therapy.

BACKGROUND. The nutritional implications of learned food aversions were evaluated in patients with newly diagnosed cancer receiving either chemotherapy (n = 53) or radiation therapy (n = 49). METHODS. Aversion incidence was determined by questionnaires and a food challenge. Measures of dietary and nutritional status included ratings of appetite and chemosensory function; reported shifts of food selection and measured body weight; lymphocyte count; hematocrit; and plasma albumin, transferrin, and hemoglobin levels. Quality of life was assessed by self-ratings of mood and well-being. RESULTS. Subsequent to the initiation of treatments, aversions formed in 56% and 62% of patients receiving chemotherapy and radiation therapy, respectively. The aversions were specific (two to four items per afflicted patient) and transient (mean duration, 0.25-2 months). All types of foods and beverages were targeted. No significant association was observed between food aversion incidence and any measure of dietary complications, nutritional status, or quality of life. CONCLUSIONS. Although food aversions are a common sequela of chemotherapy and radiation therapy, they generally have limited clinical significance.     

The incidence and risk factors of resistant E. coli infections after prostate biopsy under fluoroquinolone prophylaxis: a single-centre experience with 2215 patients

We evaluated the incidence and risk factors of resistant Escherichia coli infections after the prostate biopsy under flouroquinolone prophylaxis. From January 2003 to December 2012, we retrospectively evaluated the records of 2215 patients. The risk factors were described for infective complications and resistant E. coli in positive cultures was calculated. Of 2215 patients, 153 had positive urine cultures, such as 129 (84·3%) E. coli, 8 (5·2%) Enterococcus spp., 6 (3·9%) Enterobacter spp., 5 (3·2%) Pseudomonas spp., 3 (1·9%) MRCNS, and 2 (1·3%) Klebsiella spp. Of the positive urine cultures which yielded E. coli, 99 (76·7%) were evaluated for fluoroquinolone resistance. Of those, 83 (83·8%) were fluoroquinolone-resistant and composed of 51 (61·4%) extended-spectrum beta-lactamase (ESBL)-positive. Fluoroquinolone-resistant E. coli ratios were 73·4 and 95·9% before 2008 and after 2008, respectively (P?=?0·002). The most sensitive antibiotics for fluoroquinolone-resistant E. coli strains were imipenem (100%), amikacin (84%) and cefoperazone (83%). The use of quinolones in the last 6 months and a history of hospitalization in the last 30 days were found to be significant risk factors. We found that resistant E. coli strains might be a common microorganism in patients with this kind of complication. The risk factors for development of infection with these resistant strains were history of the use of fluoroquinolones and hospitalization     

437例淋巴瘤患者医院感染临床分析

目的探讨淋巴瘤医院感染的临床特征。方法回顾分析437例淋巴瘤患者发生医院感染的发生率、感染部位、病原菌特点、感染与疾病状态、中性粒细胞数的关系。结果淋巴瘤患者医院感染发生率16.3%、例次感染率20.6%;以呼吸道感染最多见,占42.2%,其次是口腔牙龈及泌尿生殖道;G-杆菌占46.7%、G 球菌占31.7%、真菌占21.7%,G-杆菌中以大肠埃希菌、肺炎克雷伯氏菌、铜绿假单胞菌等最常见;不同的疾病状态与医院感染发生率差异有显著性,尤其在复发时感染率高达29.4%;中性粒细胞数与感染发生率呈负相关。结论淋巴瘤患者易发生医院感染,应把呼吸道感染的预防放在首位,严格掌握抗生素使用指征,使用重组粒细胞集落刺激因子可有效地降低粒细胞减少感染发生率。