The increase in the number of liver sinusoidal pit cells in four patients with primary or metastatic cancer of the liver

Four patients with liver carcinoma (case 1: hepatocellular carcinoma; cases 2 and 3: metastases; case 4: adenocarcinoma possibly of hepatic origin) underwent a wedge liver biopsy taken at some distance from the tumor. Liver histology was normal in cases 2 and 3. Sinusoids were dilated in case 4. Fibrosis formed bridges between portal tracts in case 1. In all 4 cases, sinusoids contained lymphocytic cells. By electron microscopy (perfusion-fixation with glutaraldehyde) numerous lymphocytes could be identified as pit cells with characteristic dense granules and occasional rod-cored vesicles. The majority of the pit cells were luminal cells in contact with endothelial or Kupffer cells; some were in the Disse space. It is now accepted that pit cells are resident large granular lymphocytes with natural killer activity. The increase in the number of pit cells in liver carcinoma compared to the number observed in the control group (uncomplicated gallbladder lithiasis) could be hypothetically interpreted as a defense mechanism against tumor extension.     

Hepatic functional reserve and tumor size as prognostic factors in patients with primary liver cancer undergoing non-surgical therapy

A prognostic study on 119 patients with primary liver cancer undergoing nonsurgical therapy was carried out to evaluate the relevance of hepatic functional reserve and tumor size to their cumulative survival rates. All patients were classified into the three groups of Child's classification (A, B and C) according to their hepatic functional reserve and were also divided into the five groups according to their tumor size. The cumulative survival rates of all patients at 1, 2, 3, 4 and 5 years after the diagnosis were 50.9, 28.3, 18.8, 13.5 and 6.7%, respectively. The cumulative survival rates of group V whose tumor occupied more than 40% of the liver area were significantly lower than those of the other tumor-size-groups. The survival rates of Child's group A were significantly higher than those of group B and C. But in those patients who were classified into group V according to their tumor size, there was no significant difference in their survival rates among the three groups of Child's classification. These results suggest that hepatic functional reserve as well as tumor size is an important prognostic factor in patients with primary liver cancer. But if the cancer once develops greater than 40% of the liver area, hepatic functional reserve diminishes in value as a prognostic factor.     

Correlation between KRAS,NRAS and BRAF mutations and tumor localizations in patients with primary and metastatic colorectal cancer

IntroductionDetection of abnormalities in the KRAS, NRAS and BRAF genes is extremely important for proper qualification of colorectal cancer (CRC) patients for therapy with anti-EGFR (epidermal growth factor receptor) monoclonal antibodies. However, data about prevalence of mutations in these genes, in different localizations of CRC tumors, are limited.Material and methodsWe examined the frequency of mutations in the KRAS, NRAS and BRAF genes in 500 Caucasian CRC patients (200 women and 300 men, median age 66 years). DNA was isolated from formalin-fixed, paraffin-embedded (FFPE) tissues using a Qiagen QIAamp DNA FFPE-kit. Analysis of mutations was carried out using the KRAS/BRAF, NRAS and BRAF Mutation Analysis Kit for Real-Time PCR (EntroGen) with the Cobas 480 real-time PCR apparatus (Roche Diagnostics).ResultsKRAS mutations were detected in 190 (38%) patients, NRAS mutations in 20 (4%) patients, and BRAF mutations in 24 (4.8%) patients. There were no associations between age of CRC patients and frequency of KRAS, NRAS and BRAF gene mutations. These mutations were significantly more often diagnosed in women (55.5%) than in men (41%, p < 0.005). Tumors of the rectum and sigmoideum were the most often observed in both groups of CRC patients – with and without KRAS, NRAS and BRAF gene mutations. However, transverse colon, ascending colon and cecum cancers were the most often affected by mutations.ConclusionsOur study showed that the occurrence of mutations in the KRAS, NRAS and BRAF genes is not accidental and depends on the location of CRC tumors.     

Osteosarcoma of the urinary bladder with a prostatic cancer as a 2d primary tumor

Osteosarcomas of the urinary bladder are exceedingly rare neoplasms. Post mortem findings of such a tumor are described in a 78 year old man who also had a primary prostate cancer. Diagnostic principles as well as differential diagnosis are discussed and the literature concerning this tumor is reviewed.     

The effect of serum from liver cancer patients on the growth and function of primary and immortalised hepatocytes.

A limiting factor in the efficacy of bioartificial liver (BAL) for the treatment of liver failure is the toxicity of the patients' serum to the hepatocytes in the device. This study investigates the interaction of liver cancer patient serum with primary and immortalised rat hepatocytes. Liver cancer serum increased the growth rate of immortalised hepatocytes, without affecting reduced glutathione levels. The activities of DT-diaphorase and pi glutathione-S-transferase (GST), enzymes associated with de-differentiation, were also increased. Exposure of primary hepatocytes to liver cancer serum resulted in a decrease in cytochrome P450 (CYP) content, and in P450 dependent metabolism of testosterone. Formation of 2-alpha- and 6-beta- hydroxy testosterone was decreased. These reactions are predominantly associated with CYP 2C11 and 3A1 respectively in normal rat liver. The activity of total GST was also decreased, although that of the pi isoenzyme of GST was not affected. Our results suggest that exposure of hepatocytes in a bioreactor to liver cancer patient serum will result in overgrowth of cells, if proliferating cells are being used, and in de-differentiation. The serum may have to be pretreated with adsorbants to remove toxins prior to BAL treatment.     

Surgical resection versus perfusion in the treatment of metastatic and primary liver tumors

The involvement of the liver by malignancy, whether it be primary or metastatic, carries a grave prognosis. At this time, chemotherapy is solely palliative, and no survival advantage has been established. Resection of metastatic or primary carcinoma of the liver in a select number of patients may provide a survival advantage and an occasional cure. However, studies are difficult to control, and claims of survival benefits have been based on historical data of untreated disease prior to 1978. Currently, clinical trials are underway combining modes of therapy in the hope of increasing patient survival. Reduction of operative mortality to below five percent for liver resection is attributable to a major advance in operative technique. Other advances are improved diagnostic techniques for detection of liver metastases and selection of patients for resection. Finally, newer strategies for chemotherapy made practicable continuous infusion by implantable or external pumps, redoubling response rates to fluorodeoxyuridine (FUDR) in regional and 5-fluorouracil (5-FU) in systemic chemotherapy. A review of the current literature is presented along with data accumulated over the three-year experience of the Moffitt Cancer Center, Tampa, Florida. The case material from Moffitt Cancer Center is included to illustrate progress and limitations of combined surgical, regional, and systemic chemotherapy for primary and metastatic liver cancers.     

CT引导下放射性粒子125I植入治疗原发性肝癌的近期疗效和安全性

目的 观察CT引导下放射性粒子125I植入治疗原发性肝癌的近期疗效和安全性.方法 收集2010年4月至2011年3月在中山大学附属第一医院及解放军第四五八医院收治的原发性肝癌病例63例,接受研究病灶75个（其中16个病灶长径小于5 cm,其余病灶长径大于5 cm）,均行CT引导下放射性粒子125I植入治疗.术后2个月分别行CT检查评价粒子植入治疗效果.分别记录术前、术后3d、1个月、2个月肝功能变化及术后6个月内并发症发生情况.结果 所有75个病灶术后2个月CT检查评价治疗效果完全缓解（CR）4个,部分缓解（PR）10个,稳定（SD）39个,进展（PD）22个,总有效率为18.7％.然而对于长径小于5 cm的16个病灶,治疗效果评价完全缓解（CR）4个,部分缓解（PR）8个,稳定（SD）3个,进展（PD）1个,总有效率为75％.术后1、2个月复查肝功能丙氨酸氨基转移酶（ALT）及天门冬氨酸氨基转移酶（AST）与术前比较差异具有统计学意义（P＜0.05）,均较术前升高;术后3 d ALT、AST与术前比较及术后各时间点间比较差异无统计学意义.术前、术后各时间血清总胆红素及白蛋白水平变化差异无统计学意义.术后6个月内共出现粒子移位24例,针道种植转移2例,气胸2例,1例出现恶心、呕吐、纳差.结论 对于失去外科手术机会的原发性肝癌患者,放射性粒子125I植入治疗对于长径小于5 cm肿瘤病灶,有效率较高.放射性粒子植入会引起一些不良反应和并发症,但未发现有致命性并发症发生.     

The ratio of prostate chips with cancer: a new measure of tumor extent and its relationship to grade and prognosis

The ratio of chips with cancer to the total number of chips was studied in 118 patients with prostate cancer who underwent transurethral prostatectomy. We found that this ratio is a prognosticator closely associated to the stage of tumor (local or extensive) and to the chance of death from prostate cancer. Stage, the ratio of positive chips and the Gleason histologic score are all closely tied one to another, and it is unclear from this initial study whether these variables provide independent or additive prognostic information. Nevertheless, the ratio of positive chips shows far better interobserver agreement than does the Gleason score, and in patients with the most common predominant score of three, it can separate most of those with localized disease from most of those with extensive disease. Thus the ratio shows promise as a reliable predictor of stage of disease and of long-term failure, and hence it may help in the choice of patients for curative surgery.     

第二原发癌为肺癌的多原发癌患者临床分析

目的:收集第二原发癌为肺癌的多原发癌(lung cancer as second primary malignancy,LCSPM)患者临床特点、肿瘤部位和生存预后等临床信息进行回顾性分析,以期为指导临床实践提供一定的研究证据.方法:回顾性收集上海交通大学附属胸科医院2012年1月至2016年2月LCSPM患者病例,采用卡方检验和Fisher精确概率法比较分类资料,Kaplan-Meier法进行生存分析,得到影响LCSPM患者生存的因素及生存率.结果:LCSPM患者第一原发癌最多见的是乳腺癌,其次是上呼吸消化道恶性肿瘤、甲状腺癌和结直肠癌;两原发癌的中位间隔时间是72个月,53.9％的患者超过5年;LCSPM患者2年生存率为71.2％,手术和分期可影响预后.结论:对于存在肿瘤史的病人,随访同一器官的同时其他器官的情况也不容忽视.及早发现、及早治疗并争取手术机会,LCSPM患者的生存期将显著延长.     

原发灶广泛切除术或截肢术对合并远处转移肢体软骨肉瘤患者总体生存时间的影响

目的 探讨采用原发灶广泛切除术或截肢术治疗的合并远处转移的肢体软骨肉瘤患者的总体生存时间。方法 搜集美国国立癌症研究院SEER数据库中1994—2013年在诊断时已发生远处转移的58例肢体软骨肉瘤患者的临床资料进行回顾性分析,根据原发灶的手术方式分为广泛切除组(43例)和截肢组(15例)。通过单因素Log-rank分析、多因素Cox比例风险模型比较不同手术方式对软骨肉瘤患者总体生存时间的影响。结果 58例合并远处转移的肢体软骨肉瘤患者中,男33例、女25例,中位年龄61(14~88岁)。肿瘤发生于上肢16例、下肢42例。单因素Log-rank分析结果表明,广泛切除或截肢对患者总体生存时间的影响差异无统计学意义(P=0.409)。手术方式和单因素Log-rank分析中P＜0.1的变量被纳入到多因素Cox分析中以校正混杂因素,结果仍显示广泛切除和截肢对患者总体生存时间的影响差异无统计学意义(相对于广泛切除术,截肢术危险度为1.646,95%可信区间为0.856~3.166, P＞0.05)。结论 针对原发灶进行广泛切除或截肢治疗对合并远处转移的肢体软骨肉瘤患者的总体生存时间没有显著差异。     

Intra-articular treatment of arthritis with microsphere formulations of paclitaxel: biocompatibility and efficacy determinations in rabbits

Objectives:To assess the biocompatibility of controlled release microspheres prepared from different polymeric biomaterials in various size ranges in rabbit synovial joints and based on these data, design and evaluate the efficacy of an intra-articular, paclitaxel-loaded microspheres formulation in rabbit models of arthritis. Methods:Paclitaxel-loaded microspheres of poly(lactide-co-glycolide) (PLGA), poly(L-lactic acid) (PLA) and poly(caprolactone) (PCL) were prepared in different size ranges and inflammatory responses monitored following injection into healthy rabbit joints. The efficacy of 20% paclitaxel-loaded PLA microspheres (35–105 m size range) injected intra-articularly into antigen and carrageenan induced rabbit models of arthritis was monitored. Results:Polymeric microspheres in the 35–105 m size range were biocompatible whereas smaller microspheres (1–20 m) produced an inflammatory response. Efficacy studies showed that injection of 20% paclitaxel-loaded PLA microspheres significantly reduced all measures of inflammation in the antigen arthritis rabbit model. Conclusions:Paclitaxel-loaded PLA microspheres in the 35–105 m size range, released paclitaxel in a controlled manner over several weeks, and may be a potential formulation for the intra-articular treatment of inflammation in arthritic conditions.Received 6 November 2003; returned for revision 12 January 2004; accepted by J. S. Skotnicki 8 March 2004     

Safety and efficacy of a monomeric, functionally intact intravenous IgG preparation in patients with primary immunodeficiency syndromes

Results of an open, phase II clinical trial on therapy with an iv IgG preparation in patients with primary antibody-deficiency syndromes are reported. Three hundred infusions of the product, an intact monomeric IgG preparation, were given to 16 patients for an average of 14 (+/- 0.7) months, the dose being 220 (+/- 26.9) mg/kg/month. Only two minor adverse reactions occurred. This preparation did not produce transient leukopenia on infusion. Preinfusion serum IgG levels increased continuously in the course of treatment (average values: 325 +/- 51 at the beginning of therapy, 438 +/- 59 at 6 months, 568 +/- 75 at 12 months, 631 +/- 52 at the end of treatment). The infusions were well accepted and well tolerated by the patients, and the clinical efficacy was highly superior to intramuscular immunoglobulin.     

Laser flow cytofluorometry as a supplementary method of determining the degree of tumor differentiation in breast cancer patients

Content of cell DNA and RNA was studied by method of laser flowing cytophotometry in 21 cases of pretumorous conditions and 64 tumours of mammary gland. A clear-cut difference in DNA and RNA histograms is shown in non-proliferative and proliferative forms of mastopathy, in mastopathy and infiltrating mammary gland carcinoma. Likewise, a clear-cut correlation between the degree of malignancy and a nucleic acid content in the carcinoma cells is established.     

Pre-intervention distress moderates the efficacy of psychosocial treatment for cancer patients: a meta-analysis

This meta-analysis examined whether effects of psychosocial interventions on psychological distress in cancer patients are conditional upon pre-intervention distress levels. Published articles and unpublished dissertations between 1980 and 2005 were searched for interventions reporting the Hospital Anxiety and Depression Scale (HADS) or the Spielberger State-Trait Anxiety Inventory (STAI). Multilevel mixed-effects modeling was used to meta-analyze effect-sizes separately for the HADS (27 trials, 2,424 patients) and STAI (34 trials, 2,029 patients). Pre-intervention distress significantly moderated intervention effects, explaining up to 50% of the between-study effect-size variance: effects on anxiety and depression were generally negligible when pre-intervention distress was low and pronounced when it was high. These results could not be explained by differences in intervention type, setting, dose, and whether intervention was targeted at distressed patients. Psychosocial interventions may be most beneficial for cancer patients with elevated distress. Future research should identify which treatment components are most effective for these patients to facilitate optimal treatment tailoring and cost-effective health care.     

The use of a tumor metastasis targeting peptide to deliver doxorubicin-containing liposomes to highly metastatic cancer

Tumor metastasis is responsible for 90% of cancer-associated deaths and highly metastatic cancers are more prone to form metastasis foci and acquire the drug resistance. Here, a nanocarrier system (TMT-LS) has been constructed by modification of stealth liposomes with a metastatic cancer specific peptide, using the unmodified stealth liposomes (LS) as the control. The active targeted nanocarriers presented satisfactory particle size (about 100?nm) and drug release characteristics in?vitro. Highly metastatic cancer cells (MDA-MB-435S and MDA-MB-231) and non-metastatic cancer cells (MCF-7) were applied as?tumor cell models. The highly metastatic cancer cells were found to endocytose more TMT-LS in a faster?way than TS, through a receptor-mediated pathway proved by specific receptor inhibition. Co-localization technique indicated the integrity of nanocarriers in cytoplasm. The significant targeting of TMT-LS to highly metastatic tumors was demonstrated in?vivo and ex?vivo in an orthotopic model as well as in a double tumor-bearing animal model with both metastatic and non-metastatic tumors in the same mouse. Importantly, the active targeted drug delivery system was found to penetrate deeper into tumor mass and have a longer retention within the malignant tissue. Further, TMT-LS greatly facilitated the efficacy of doxorubicin loaded in terms of inhibiting xenograft tumor growth and inducing cancer cell apoptosis, with only minor side effects. Together, the specific nanocarriers hold great potential in the development of nanomedicine for diagnosis and therapy of metastatic tumor.     

The biological significance of cancer: mitochondria as a cause of cancer and the inhibition of glycolysis with citrate as a cancer treatment

In this article, I present the hypothesis that cancer presents due to the domination of the cell by mitochondria, which, from an evolution viewpoint, appeared in multi-cellular living being with the incorporation of a bacteria into a primitive cell, the bacteria sustained itself as mitochondria and these conserved their identity and bacterial characteristics, based on this, the hypothesis is suggested of the biological competition between the cell and the mitochondria; the mitochondria, on establishing itself as an independent entity within the cell, created the need to permanently remain in the cytoplasm of the cell, thus, from an energy viewpoint, when a cell becomes malignant, the mitochondria are the sole beneficiaries, as there is an ideal environment at the cellular level for the mitochondria to sustain their functions, and from this hypothesis, the treatment for fighting cancer consists of inhibiting glycolysis, being the principal source of energy for the mitochondria, this is achieved by administering citrate to cancer patients, as the citrate inhibits the phosphofructokinase enzyme, the pyruvate dehydrogenase complex and the succinate dehydrogenase enzyme of Krebs cycle, thus, the mitochondria will be forced to limit their metabolism and, secondarily, will lower the reproduction capacity of the cell in general.