Increased aneuploidy in spermatozoa from testicular tumour patients after chemotherapy with cisplatin, etoposide and bleomycin

Testicular cancer is the most common neoplasia occurring in the young male population. The PEB (cisplatin, etoposide and bleomycin) adjuvant chemotherapy usually proposed after orchidectomy in non seminomatous tumours, and in metastatic seminomas, has improved the long-term survival of these patients. Following an azoospermic period, sperm cell recovery is generally observed after treatment delivery, but little is known about the genetic consequences on these new spermatozoa. To estimate the chromosomal consequences of this chemotherapy on sperm cells during the period of recovery of spermatogenesis, sperm cell aneuploidy was studied in testicular cancer patients, at 6-18 months after PEB adjuvant chemotherapy delivery, using fluorescence in-situ hybridization (FISH) of chromosomes 7, 16, 18, X and Y with specific DNA probes. A significant increase in the frequency of diploidy and disomy for chromosomes 16, 18 and XY was observed in treated patients compared with a healthy control group. Spermatozoa aneuploidy occurring during the spermatogenesis recovery period might be a possible side effect of the PEB regimen. Thus, practitioners should be advised to provide counselling about the need for an appropriate duration of contraception. Moreover, genetic counselling should be offered in cases of pregnancy occurring soon after the end of chemotherapy.     

After chemotherapy,functional humoral response capacity is restored before complete restoration of lymphoid compartments

Chemotherapy has, besides the beneficial effects, several adverse effects. Suppression of the immune system is one of the most important problems. Infections caused by encapsulated bacteria like Streptococcus pneumoniae are responsible for a major part of infectious problems during and after treatment. The splenic marginal zone is essential in the initiation of an immune response to encapsulated bacteria. In this study, we analysed the effects of three different cytostatic agents on humoral immune responses. We found a reduced, but detectable immune response capacity at two days after treatment although the marginal zone B cell population is severely reduced at this time point. Twenty-four days after cessation of treatment, the immune response capacity was largely restored although lymphoid compartments were still not completely restored at that time point. Apparently, the presence of only few marginal zone B cells is sufficient to evoke a rise in antibody titres and although antibody titre increases are low, even small rises are most likely clinically relevant.     

Fluoropyrimidine chemotherapy in a rat model: comparison of fluorouracil metabolite profiles determined by high-field 19F-NMR spectroscopy of tissues ex vivo with therapy response and toxicity for locoregional vs systemic infusion protocols

A Sprague-Dawley rat model with DS sarcoma transplanted in the thigh was used to compare transcatheter locoregional i.a. and systemic i.v. administration of 5-fluorouracil (FU) at 12 dose-rate schedules: 25, 50 and 100 mg/kg; bolus, 1, 5 and 24 h infusions. In experiment A tumor (62/67 animals) as well as liver and kidney (56/67 animals) were excised 1 h after a single bolus or 1 h infusion or at the end of 5 and 24 h infusions. (19)F-NMR spectroscopy at 11.7 T was used to quantitate FU and its metabolites in ca. 1 g of tissue at 4 degrees C. In experiment B analogous FU treatments were repeated for 5 days (rats 80+11 controls). Tumor volumes vs time, various blood parameters and survival times were recorded, and a log growth rate parameter log GR, a response index RI, and a toxicity index TI were calculated. The i.a. vs i.v. ratios for tumor concentrations of FU and total anabolites (F-Nucl) were >1 for nearly all treatments and increased with infusion time at the higher doses. F-Nucl in tumor correlated linearly with total fluorine concentration (Tot. F range 30-1100 nmol/g) over all treatments (r=0.92, slope=0.45, p<0.0001). For non-bolus i.v. treatments [FU+F-Nucl] decreased linearly with decreasing FU dose rate (r(2)=0.74, zero intercept), while i.a. treatments showed non-linear behavior. For non-bolus treatments the mean log GR per treatment group showed a negative correlation (r=-0.87) with log[F-Nucl]. The most effective non-toxic treatments were 25 mg/kg over 5 or 24 h; the i.a. route was superior to i.v. on the basis of [FU+F-Nucl], RI, the reduction in log GR, and Kaplan-Meier survival statistics. For liver and kidney Tot. F (>83% FU catabolites) reached ca. 3-4 and 6-7 micromol/g, respectively, at the highest dose rates for either route; F-Nucl were detected only for Tot. F>500 nmol/g and increased exponentially as Tot. F increased (toxic treatments). The concentrations of the main catabolite (alpha-fluoro-beta-alanine, FBAL) in tumor did not correlate with Tot. F but rather with FBAL levels in kidney (r=0.90, all treatments), indicating that uptake of liver-derived FBAL from the circulation is the major source of FBAL in tumor.     

Mitoxantrone combined to vincristine,cyclophosphamide and fluorouracil in advanced breast cancer

Summary In our wide experience of treating advanced breast carcinoma with chemotherapy, the combination of doxorubicin (DOX), vincristine (VCR), cyclophosphamide (CPM) and fluorouracil (FU) gave a complete plus partial response rate of over 60%, with 100% alopecia and frequent cardiac toxicity depending on total dose.After the EORTC Clinical Screening Group phase II trial we have conducted an expected difference method comparative phase II trial using the combination DOX, VCR, CPM, FU and the combination of MTX (10mg/m²), VCR, CPM and FU on a population of 50 breast carcinoma patients similar to those taking part in the first study.The reasons for similarity of action will be presented and discussed.     

High resolution real-time B-mode echotomography in the diagnosis of extracranial carotid lesions. Comparison with traditional angiography

Summary Tumour growth essentially requires fibrin formation and fibrinopeptide A (FPA) is liberated into the circulation on fibrin formation. In the present study, a possible elevation of serum FPA level was examined in patients with metastatic brain tumour. A significant elevation of serum FPA level was shown in all 6 patients with metastatic brain tumour, when blood was drawn from the internal jugular vein. It was extremely high in 2 patients with rapidly growing tumour. However, such a significant elevation was not shown in 3 cancer patients without brain metastasis or in 1 patient with a huge meningioma. This suggests the possibility that the presence of metastatic brain tumour could be detected by measuring FPA in blood drawn form the internal jugular vein. This also suggests the tendency that elevation of serum FPA is higher in patients with more rapidly growing tumour.Infusion of urokinase into the internal carotid artery resulted in an elevation of serum fibrinopeptide B (1)15–42 (FPB) in 5 patients with metastatic brain tumour, when blood was drawn from the internal jugular vein. This suggests that urokinase could induce fibrinolysis in the tumour tissue, though this remains in conclusive because of the lack of complete controls.     

Selective effects of Lipiodolized antitumor agents

Lipiodol Ultra-Fluid (Lipiodol) remains selectively in the tumor for an extended time when applied through arteries feeding the tumor. Although lipophilic antitumor drugs are selective when combined with Lipiodol, wide application of common hydrophilic agents is limited, as these compounds are insoluble in oil. We propose "Lipiodolization" of water-soluble agents using as an intermediate Urografin, a water-soluble contrast medium. Thirteen patients with primary hepatocellular carcinoma were treated with this Lipiodol-Urografin system containing antitumor agents. Marked decrease in serum alpha-fetoprotein (AFP) levels, decrease in tumor size in the hepatic imaging, and histologic studies of the resected specimen revealed this mode of therapy to be effective in 10 of 13 patients (77%) with hepatocellular carcinoma. Lipiodolization of antitumor agents is a new approach to selective cancer chemotherapy.     

介入联合手术治疗膀胱癌32例疗效分析

目的观察髂内动脉灌注化疗联合手术治疗膀胱癌的疗效。方法对32例中晚期膀胱癌先行介入治疗,再手术切除。结果32例膀胱癌完全缓解(CR)率为71．9％。结论介入治疗中晚期膀胱的手术提供了良好基础,对一部分原本行扩大切除术甚至全切的患实行单纯部分切除术,从而保留了膀胱生理功能,有助于提高患生活质量,延长生命。     

舌癌术前化疗PCNA、bcl-2、Bax基因表达及临床意义

目的 :通过舌癌术前化疗增殖细胞核抗原 (PCNA )和细胞凋亡相关基因 bcl- 2、Bax表达的研究 ,探讨舌癌的化疗作用机制。 方法 :对舌乳头状瘤、舌癌和舌癌术前化疗标本共 34例 ,采用免疫组织化学染色技术——酶标链亲和素生物素法 (L SAB)染色并进行光镜下观察。结果:PCNA在舌癌中的表达最强 ,在舌癌术前化疗中的表达明显减弱 (P <0 .0 5 ) ,其与舌乳头状瘤表达相似 (P >0 .0 5 )。 bcl- 2在舌癌术前化疗及舌乳头状瘤中低表达(P >0 .0 5 ) ,舌癌中表达明显增强 (P <0 .0 5 )。Bax在舌癌组和乳头状瘤组中表达有明显差异 (P <0 .0 5 )。结论 :化疗药物抑制肿瘤生长的机制可能与抑制肿瘤细胞增殖和诱导肿瘤细胞程序性死亡有关 ,提示舌癌术前化疗对肿瘤的预后有重要意义。     

Do hospital type or caseload make a difference in chemotherapy treatment patterns for early breast cancer? Results from 104 German institutions, 2008–2017

BackgroundOver the past decade, chemotherapy has been used more selectively in early breast cancer (EBC) due to better risk stratification. Neoadjuvant chemotherapy (NACT) has evolved to the primary treatment option. The type and size of hospitals is known to have a substantial influence on the kinds of treatment they provide, and therefore on patient outcomes (e.g. rates for pathological complete response, pCR), but it is not yet known how this has affected delivery of chemotherapy for EBC in Germany.MethodsThis study analyzed chemotherapy use and pCR rates after NACT for EBC patients treated at 104 German institutions 2008–2017. Institutions were separated into associated hospital type (university hospital; teaching hospital; community hospital) and annual caseload (≤100; 101–250; >250 cases/year).ResultsOverall, 124,084 patients were included, of whom 11.6% were treated at university hospitals, 63.1% at teaching hospitals, and 25.3% at community hospitals. In total, 46,274 (37.3%) received chemotherapy, of whom 44,765 had information available about systemic treatment and surgery. From 2008 to 2017, chemotherapy use declined from 48.3% to 36.4% for university hospitals, from 40.7% to 30.3% for teaching hospitals, and from 42.4% to 33.7% for community hospitals. Furthermore, the proportion of NACT increased the most in university hospitals (from 32.0% to 68.1%); whereas, the rate of pCR (defined as ypT0 ypN0) increased irrespective of institutional type. Analyses regarding annual caseload did not show any differences.ConclusionsThe results from this large, nationwide cohort reflect a more selective use of chemotherapy in Germany, irrespective of institutional type or case load.