Effect of chemo- or radiotherapy on sperm parameters of testicular cancer patients

BACKGROUND: The aims of our study were to investigate the short- and long-term effects of chemo- or radiotherapy on spermatogenesis in patients with testicular cancer and to establish any correlation between pre-therapy sperm parameters, histotype and treatment type/intensity and the progress of spermatogenesis during the post-therapy period. METHODS: We evaluated 166 patients affected by testicular cancer, who cryobanked about 1 month after the removal of the cancerous testis and before beginning chemo- (CH group; n = 71) or radiotherapy (RT group; n = 95). RESULTS: For the CH group, there was a statistically significant decrease in sperm parameters, which was most significant 3 months after the end of chemotherapy. For the RT group, this decrease was most relevant 6 months after the end of radiotherapy. Two years after therapy, 3% of the CH group and 6% of the RT group remained azoospermic. To evaluate whether spermatogenesis recovery is a function of baseline semen quality, we divided each group into two subgroups by pre-therapy total sperm count (A, <40 x 10(6)/ejaculate; B, >or=40 x 10(6)/ejaculate). At t(24), subgroup A of both the CH and RT groups showed improved sperm parameters over the baseline, whereas subgroup B for both CH and RT groups showed a return of sperm parameters to those of baseline values. CONCLUSIONS: In conclusion, the recovery of spermatogenesis after chemo- or radiotherapy in our group of testicular cancer patients was not a function of pre-therapy sperm parameter quality. Cryopreservation of sperm before performing such therapy is therefore imperative.     

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.     

Impact of therapy and androgen receptor polymorphism on sperm concentration in men treated for testicular germ cell cancer: a longitudinal study

BACKGROUND: Testicular cancer (TC) patients have a high survival rate, and the question of post-therapy recovery of sperm production and its dependence on genetic predisposition is of major interest. METHODS: Ejaculates were obtained from 112 TC patients at one or more of the following time points: post-orchidectomy, or 6, 12, 24, 36 and 60 months post-therapy. The lengths of the androgen receptor (AR) function modulating CAG and GGN repeats in leukocyte DNA were also analysed. RESULTS: No significant decrease in sperm concentration was seen in men who received 1-2 cycles of adjuvant chemotherapy (ACT). Radiotherapy (RT) or more than two cycles of chemotherapy (HCT) caused an initial decline in sperm concentration, which returned to pre-treatment levels 2-5 years after therapy. In the HCT group, sperm concentration 12-24 months post-treatment (T(12-24)) was inversely correlated with CAG length (rho = -0.72, P = 0.03). The type of treatment, but not the concentration at T(0), was an independent predictor of sperm concentration at T(6) (P < 0.0005) and T(12-24) (P = 0.004). CONCLUSION: ACT did not induce a significant decline in sperm concentration. After HCT and RT, a significant reduction of sperm concentration was observed, recovering to pre-treatment levels 2-5 years post-treatment. In HCT-treated patients, the AR CAG length influenced the recovery of spermatogenesis.     

Histological evidence of testicular dysgenesis in contralateral biopsies from 218 patients with testicular germ cell cancer

This study was prompted by a hypothesis that testicular germ cell cancer may be aetiologically linked to other male reproductive abnormalities as a part of the so-called 'testicular dysgenesis syndrome' (TDS). To corroborate the hypothesis of a common association of germ cell cancer with testicular dysgenesis, microscopic dysgenetic features were quantified in contralateral testicular biopsies in patients with a testicular germ cell tumour. Two hundred and eighty consecutive contralateral testicular biopsies from Danish patients with testicular cancer diagnosed in 1998-2001 were evaluated retrospectively. Two hundred and eighteen specimens were subsequently included in this study, after 63 patients who did not meet inclusion criteria had to be excluded. The presence of carcinoma in situ (which is believed to originate from transformed gonocytes) was detected in 8.7% of biopsies. The incidence of other dysgenetic features was immature tubules with undifferentiated Sertoli cells, 4.6%; microcalcifications (microliths), 6.0%; and the presence of a Sertoli-cell-only pattern in at least a few tubules, 13.8%. The cumulative incidence of one or more signs of testicular dysgenesis was 25.2%. In a few patients, areas with immature and morphologically distorted tubules were also noted. Spermatogenesis was qualitatively normal in 51.4%, whereas 11.5% had very poor or absent spermatogenesis. It is concluded that microscopic testicular dysgenesis is a frequent feature in contralateral biopsies from patients presenting with testicular germ cell neoplasms of the adolescent and young type. The findings therefore support the hypothesis that this cancer is part of a testicular dysgenesis syndrome. The presence of contralateral carcinoma in situ was higher in the present study than previously reported.     

贝伐单抗联合化疗治疗转移性结直肠癌的临床分析

目的分析贝伐单抗联合化疗治疗转移性结直肠癌的有效性与安全性,为结直肠癌的临床诊疗提供一定的理论依据。方法临床入选142例转移性结直肠癌患者,根据患者先后顺序,按照随机数字法分成观察组和对照组,每组71例,其中对照组患者给予IFL化疗方案（伊立替康、氟尿嘧啶、亚叶酸钙）治疗;而观察组患者均采用贝伐单抗联合IFL化疗方案治疗。治疗随访1年后,评价并分析上述两组患者的相关临床资料。结果经统计分析,两组之间的疾病控制率具有统计学差异（P〈0．05）,而在总有效率没有统计学差异。两组患者血清肿瘤标志物（CEA、TPS和CA242）在治疗前后均具有统计学差异,同时观察组在治疗后降低更显著（P〈0．05）。两组患者在药物毒副反应方面均无统计学差异。结论贝伐单抗联合化疗治疗转移性结直肠癌不仅提高了有效性,而且具有很好的安全性,是目前转移性结直肠癌患者较好的一种治疗选择。     

S-1 monotherapy as second line chemotherapy in advanced gastric cancer patients previously treated with cisplatin/infusional fluorouracil

The treatment choice of advanced gastric carcinoma after failure from first-line therapy is quite limited. To evaluate the efficacy and toxicity of S-1 monotherapy in patients with advanced gastric cancer after failure of first line cisplatin and fluorouracil combination (CF). S-1 monotherapy as a second line treatment was given to the patients who had failed to CF combination in SC-101 study. The efficacy and toxicity of S-1 monotherapy were evaluated exploratory. The results indicated that forty-one patients received S-1 as a second line therapy after disease progression. The overall response rate and disease control rate were 14.6% and 41.5%, respectively. The median progression free survival (PFS) was 5.1 months (ange: 2.9~6.2 month). The median overall survival time was 6.4 months. The survival rates at 6 month and 1 year were 56% and 7.3%, respectively. Grade 3/4 adverse events were uncommonly occurred, including anemia (2.4%), neutropenia (2.4%), thrombocytopenia (4.9%) and rash (2.4%). There were no unexpected or life-threatening toxicities. Only one patient experienced dose reduction due to grade 3 rash. In conclusion, S-1 monotherapy provided a mild response rate and overall survival, and a favorable toxicity profile in the second line setting after the first line failure to cisplatin and fluorouracil combination.     

S-1 monotherapy as second line chemotherapy in advanced gastric cancer patients previously treated with cisplatin/infusional fluorouracil

The treatment choice of advanced gastric carcinoma after failure from first-line therapy is quite limited. To evaluate the efficacy and toxicity of S-1 monotherapy in patients with advanced gastric cancer after failure of first line cisplatin and fluorouracil combination (CF). S-1 monotherapy as a second line treatment was given to the patients who had failed to CF combination in SC-101 study. The efficacy and toxicity of S-1 monotherapy were evaluated exploratory. The results indicated that forty-one patients received S-1 as a second line therapy after disease progression. The overall response rate and disease control rate were 14.6% and 41.5%, respectively. The median progression free survival (PFS) was 5.1 months (range: 2.9~6.2 month). The median overall survival time was 6.4 months. The survival rates at 6 month and 1 year were 56% and 7.3%, respectively. Grade 3/4 adverse events were uncommonly occurred, including anemia (2.4%), neutropenia (2.4%), thrombocytopenia (4.9%) and rash (2.4%). There were no unexpected or life-threatening toxicities. Only one patient experienced dose reduction due to grade 3 rash. In conclusion, S-1 monotherapy provided a mild response rate and overall survival, and a favorable toxicity profile in the second line setting after the first line failure to cisplatin and fluorouracil combination.     

Sperm aneuploidy frequencies analysed before and after chemotherapy in testicular cancer and Hodgkin's lymphoma patients

BACKGROUND Multicolour fluorescent in situ hybridization was utilized to detect sperm aneuploidy for chromosomes 13, 21, X and Y in testicular cancer and Hodgkin's lymphoma chemotherapy patients. METHODS Aneuploidy was assessed before, and 6, 12 and/or 18-24 months after, the initiation of chemotherapy, and compared with age matched controls. 635 396 sperm were scored blindly with 5000 sperm/patient/chromosome/ time point, where sperm was available. (First two phrases have been reversed). RESULTS Comparing testicular cancer and Hodgkin's lymphoma patients to each other and with controls, cancer-specific differences were identified. Hodgkin's lymphoma patients, particularly, exhibited significantly increased aneuploidy frequencies for all chromosomes throughout treatment. At 6 months, all cancer patients showed significantly increased frequencies of XY disomy and nullisomy for chromosomes 13 and 21. In general, aneuploidy frequencies declined to pretreatment levels 18 months after treatment initiation, but increased aneuploidy frequencies persisted in some chromosomes for up to 24 months. CONCLUSIONS Because of elevated aneuploidy frequencies prior to and up to 24 months from the start of chemotherapy, patients should receive genetic counselling about the potentially increased risk of an aneuploid conceptus from sperm cryopreserved prior to chemotherapy, and for conceptions up to 2 years after the initiation of treatment.     

Expression of reactive oxygen species-related proteins in metastatic breast cancer is dependent on the metastatic site

This study was performed to investigate the expression of reactive oxygen species (ROS)-related proteins and to analyze the implications for primary and metastatic breast cancer. We constructed a tissue microarray containing 143 metastatic breast cancers (52 lung metastases, 38 bone metastases, 37 brain metastases, and 16 liver metastases) and performed immunohistochemical staining for ROS-related proteins (catalase, GSTπ, TxNIP, and MnSOD). Analysis of ROS-related protein expression in metastatic breast cancers according to the metastatic sites revealed site-specific expression patterns. The expression of tumoral catalase was lower in bone metastases (P = 0.012), and stromal GSTπ expression was higher in bone and liver metastases (P < 0.001). The highest ROS activation status was observed for lung metastases, while non-activated ROS was observed for bone metastases (P = 0.001). Primary cancers were positive for stromal GSTπ, but a subset of lung metastases were negative (P = 0.021). Univariate analysis revealed that shorter overall survival (OS) was associated with negative catalase expression of the tumor (P = 0.026). Furthermore, univariate analyses according to the metastatic sites revealed that shorter OS was associated with TxNIP-positive tumors (P = 0.032) and the expression of stromal catalase (P = 0.032) in brain metastases. Tumors that were negative for MnSOD expression (P < 0.001) but positive for stromal catalase expression (P = 0.022) were associated with shorter OS in patients with liver metastases. In conclusion, cancer cells and stromal tissues showed different ROS-related protein expression patterns according to the metastatic site. In addition, the expression of ROS-related proteins is associated with patient prognosis.     

Maintenance hormonal treatment improves progression free survival after a first line chemotherapy in patients with metastatic breast cancer

The present study was conducted in patients with metastatic breast cancer. Its aim was to identify the factors which influence progression -free survival (PFS) and overall survival (OS) after the first line of chemotherapy in patients with positive tumour hormone receptor status. The patients with early disease progression during first-line chemotherapy were not included. In total, 560 patients who achieved a stable disease or a response to first-line chemotherapy were studied. The factors identified to improve the duration of PFS or OS in multivariate analysis were: number of metastatic sites (p = .01; p = .01), metastatic sites (p = .02; p = .04), Disease free interval (p = .001; p < .0001), previous hormonal therapy (p = .03; p = ns), response to first line chemotherapy (p < .0001; p = 0.0001) and an administration of maintenance hormonal therapy (p < .0001; p = .001). The major impact obtained by maintenance hormonal treatment after first-line chemotherapy in this study seems to indicate that this strategy should be recommended in patients with an ER or PgR positive tumour.     

Organic cation transporter 2 and tumor budding as independent prognostic factors in metastatic colorectal cancer patients treated with oxaliplatin-based chemotherapy

Oxaliplatin is currently approved for patients with metastatic colorectal cancer (mCRC). Its uptake and consequent cytotoxicity is determined by the levels of organic cation transporter 2 (OCT2). In addition, tumor budding (TB) is associated with high malignant potential. However, the impact of the levels of OCT2 and TB on clinicopathological findings and the prognosis of mCRC patients treated with oxaliplatin-based chemotherapy remains unclear. Here, 80 mCRC patients were retrospectively assessed. Immunohistochemistry was performed to determine the levels of OCT2 and TB. High levels of OCT2 (47/80, 59%) were detected at the invasion front and were associated with depth of invasion (P=0.03), whereas high levels of TB (40/80, 50%) were associated with extensive lymphatic invasion (P=0.03). In univariate analysis, high OCT2 levels were significantly correlated with longer progression-free survival (PFS) (P=0.02) whereas high TB levels were associated with shorter PFS (P=0.01). In combined analysis, patients with 2 favorable factors (high OCT2/low TB) had longer PFS than those with 1 (P=0.03) or 0 (P<0.001) favorable factors. Multivariate analysis confirmed that the OCT2 level (P=0.007), TB level (P=0.004), and combined OCT2/TB status (P=0.001) were independent predictors for PFS. These results suggest that high levels of OCT2 indicate severe invasion, but also better prognosis in mCRC patients treated with oxaliplatin-based chemotherapy, possibly because of its role in oxaliplatin susceptibility. Combined analysis of OCT2 and TB status may guide the selection of patients for successful oxaliplatin-based chemotherapy.     

Coping with chemotherapy for breast cancer

Relations among coping, physical symptoms, and affect were investigated in 43 women undergoing adjuvant chemotherapy for breast cancer. Patients were assessed at the same point in their treatment so that the time for which coping was reported would be equivalent across individuals. Patients were asked how they coped specifically with chemotherapy, rather than how they coped with cancer in general, to make the domain specific. Positive and negative affect were assessed separately, using a scale free of somatic content. Relations between coping and affect were consistent with prior studies that have employed a general approach to assessing coping. Coping correlates of positive and negative mood differed. When the relations between physical symptoms and affect were examined, physical symptoms were related to negative affect but not to positive affect. Findings are discussed in terms of their implications for coping with cancer as well as their implications for the general coping literature.     

计算机断层扫描纹理分析在预测联合靶向化疗后的结直肠癌肝转移灶治疗反应的价值研究

本研究旨在探讨治疗前计算机断层扫描(CT)纹理分析在预测联合靶向化疗后结直肠癌肝转移治疗疗效的价值。回顾性分析2011年3月–2017年10月在四川大学华西医院接受西妥昔单抗治疗且有完整资料的结直肠癌肝转移患者82例。参照RECIST1.1标准,将患者分为治疗有反应组和治疗无反应组。采用CT纹理分析软件,在门脉期对标记病灶进行3D纹理分析。对比治疗有反应组和治疗无反应组间的纹理参数差异,并对差异有统计学意义的参数行受试者工作曲线分析,得出其诊断效能参数。结果显示,治疗前病灶熵(Entropy)、能量(Energy)、方差(Variance)、标准差(std. Deviation)、95th分位数(Quantile95)以及熵和(sumEntropy)在治疗有反应组(n=44)和无反应组之间(n=38)有显著差异(P <0.05);较高的熵、熵和、方差、标准差以及较低的能量似乎预示着较好的治疗反应。当熵和> 0.867时,能够取得较好的诊断效能,敏感度和特异度分别为60.5%、79.5%。因此,CT纹理分析在预测联合靶向化疗的结直肠癌肝转移患者的治疗反应方面具有一定的价值,可作为潜在的疗效预测的生物学标志。     

Intensive short-term chemotherapy in patients with advanced breast cancer

Summary Aiming at a high complete remission rate with an intensive induction regimen, 27 patients with advanced breast cancer were given three cycles of VAC chemotherapy consisting of vinde-sine 3 mg/m² i.v. on days 1 and 12, adriamycin 40 mg/m² i.v. on days 1 and 12, and cyclophosphamide 200 mg/m² p.o. on days 3–6 and 14–17 together with medroxyprogesterone acetate (MPA) 1,500 mg p.o. daily during the induction phase and 1,000 mg p.o. thereafter until relapse. These VAC double cycles were repeated twice with 3-weekly intervals for a total induction period of 15 weeks. In responders, including no change, the chemotherapy was discontinued thereafter, and the patients were observed until relapse with a maintenance therapy of MPA 1,000 mg p.o. daily.A complete remission (CR) was achieved in 8 (29.6%) and a partial remission (PR) in 13 (48.2%) of the 27 patients (CR + PR 77.8%). A no change (NC) status was found in 6 patients (22.2%). There were no nonresponders. The median duration of the CR was 20 (5–42) months with two patients still in CR at 33 and 36 months, of the PR 8.3 (4–13.5) months, and of the NC 6.7 (2–13) months. The treatment was tolerated without life-threatening toxicity or interval prolongation by all patients. No dose-limiting cardiac toxicity was observed in these patients regularly controlled by left ventricular ejection fraction (LVEF). The high response rate of this intensive induction regimen warrants further investigation. Complete remission was achieved only in patients without previous chemotherapy, with marked tumor regression after the first chemotherapy cycle and when there was no extensive bone involvement.Abbreviations ADR Adriamycin - CK Creatinine kinase - CK-MB Cardiac muscle specific isoenzymes - CMF Cyclophosphamide, methotrexate, 5-FU - CNS Central nervous system - CR Complete remission - CYC Cyclophosphamide - DFI Disease-free interval - ECG Electrocardiogram - LMF Chlorambucil, methotrexate, 5-FU - LVEF Left ventricular ejection fraction - MPA Medroxyprogesterone acetate - NC No change - PD Progressive disease - PR Partial remission - VAC Vincristine, adriamycin, cyclophosphamide - VEC Vincristine, epirubicin, cyclophosphamide - VDS Vindesine - WBC White blood cell count     

脂质体紫杉醇联合顺铂对晚期宫颈癌术前化疗的疗效观察

目的探讨脂质体紫杉醇联合顺铂用于治疗局部晚期宫颈癌患者的临床疗效和不良反应。方法选择2005年5月至2009年5月我院收治的局部晚期宫颈癌患者78例,按就诊顺序将患者分为顺铂联合5-氟尿嘧啶组(PF组,39例)和脂质体紫杉醇联合顺铂组(Taoxl组,39例)。PF组患者采用顺铂联合5-氟尿嘧啶化疗方案,Taxol组患者采用脂质体紫杉醇联合顺铂化疗方案。2组患者化疗后均全麻下行广泛子宫切除术和盆腔淋巴结清扫术,评价并比较2组患者的临床疗效、不良反应和术后3年生存率。结果 PF组患者不良反应主要为消化道反应、口腔黏膜炎和骨髓抑制,Taxol组患者的不良反应主要有骨髓抑制、口腔黏膜炎和肾脏毒性。Taxol组患者的化疗后完全缓解率30.77%,高于PF组的10.26%(χ2=5.032,P=0.025)。Taxol组和PF组患者平均生存时间分别是33.5个月和34.7个月,3年生存率分别为59.6%和70.2%,差异无统计学意义(χ2=1.859,P=0.173)。结论 2种化疗方案患者不良反应差别较大,脂质体紫杉醇联合顺铂化疗方案临床疗效优于顺铂联合5-Fu化疗方案。     

新辅助化疗联合放疗治疗局限性晚期宫颈癌的临床疗效观察

目的分析新辅助化疗联合放疗治疗局限性晚期宫颈癌的有效性与安全性。方法临床收集84例局限性晚期宫颈癌患者,随机分成2组,对照组（44例）采用新辅助化疗方法治疗,治疗组（40例）均采用新辅助化疗联合放疗治疗,疗程结束后比较并评价两种治疗方法的有效性与安全性。结果治疗后临床观察结果显示,新辅助化疗联合放疗治疗局限性晚期宫颈癌近期观察是安全和有效的,有效率达到95%,与单纯新辅助化疗组相比具有显著的统计学差异（P〈0.05）。结论新辅助化疗联合放疗治疗局限性晚期宫颈癌是有效的,同时具有很好的耐受性。     

化疗对乳腺癌患者甲状腺功能或结构的影响

目的探讨化疗对乳腺癌患者甲状腺功能或结构的近期影响。方法选取蚌埠医学院第一附属医院于2017年3月至2018年12月收治的40例女性初治原发性乳腺癌患者,检测并比较化疗后2和4疗程与化疗前的甲状腺功能5项(包括T3、T4、FT3、FT4和TSH)及其结构的变化。结果乳腺癌患者化疗2和4疗程后T4、FT4水平明显低于化疗前(P<0.05);患者化疗4疗程后甲状腺TI-RADS分级及其结构异常的发生率较化疗前均明显升高(P<0.05)。结论化疗后近期可引起或加重乳腺癌患者甲状腺功能或结构的异常,适时进行检查并干预可防止病情进一步发展,具有重要的临床意义。     

Effects of taurolidine and octreotide on port site and liver metastasis after laparoscopy in an animal model of pancreatic cancer

Port site metastasis is a dreadful event following laparoscopy; however, the exact pathomechanism is still unknown. In order to prevent trocar metastasis we determined the effects of intraperitoneal lavage with either taurolidine or octreotide on port site and liver metastasis after laparoscopy in a chemically induced, solid pancreatic adenocarcinoma. Pancreatic adenocarcinoma was induced in 60 Syrian hamsters by weekly injection of 10 mg/kg body weight N-nitrosobis-2-oxopropylamine s.c. for 10 weeks. Six weeks later, a laparoscopic pancreatic biopsy was performed by the use of a pneumoperitoneum with carbon dioxide (12 mm Hg), followed by an abdominal irrigation with 5 ml normal saline (group 1, n=20), 5 ml 0.5% taurolidine (group 2, n=20) or 5 ml octreotide (20 mg/ml) (group 3, n=20). After 8 weeks, all hamsters were sacrificed and histopathologically examined. There was only one macroscopic visible primary tumor in the taurolidine group (5.9%), compared to 42.1% in the saline group and 62.5% in the octreotide group (P<0.05). The size of carcinomas was smaller in the saline group than after octreotide irrigation (median 6, range 2–25 vs. median 70, range 40–160 mm², P<0.05). The number of liver metastases per animal was increased after saline irrigation (median 4, range 2–6), compared to taurolidine (median 2, range 1–3) or octreotide (median 2.5, range 2–4) (P<0.05). Port site metastases were found in 36.8% after saline, in 37.5% after octreotide and in 0% after taurolidine irrigation (P<0.05). Thus port site metastasis was effectively prevented by taurolidine irrigation after staging-laparoscopy in pancreatic cancer. This revised version was published online in July 2006 with corrections to the Cover Date.     

Prevalence of anticipatory nausea and emesis in cancer chemotherapy patients

The prevalence of anticipatory nausea (AN) and anticipatory emesis (AE) in 71 cancer chemotherapy outpatients was measured by a self-report questionnaire. An 18.3% prevalence rate was found, with a mean onset of 5.12 hr prior to treatment. AN/AE most typically occurred at home or while traveling to the clinic and those who experienced it also reported a significantly higher frequency of posttreatment nausea, vomiting, constipation, and dry and itching skin.Questionnaire and further details of the study are available from the author upon request.