Clinical evaluation of sizofiran combined with irradiation in patients with cervical cancer. A randomized controlled study; a five-year survival rate

Following a previous report we ascertained the effectiveness of sizofiran (Schizophyllan:SPG) to prolong the survival and time to recurrence of the patients with Stage II or III cervical cancer, as evaluated in a 5-year randomized controlled study conducted in 19 institutions in Japan. Of the overall patients with Stage II or III cancer, time to recurrence and survival rate in the group on SPG were significantly longer than in the control group. In the Stage II patients, there was significant difference in time to recurrence, and survival of SPG group tended to be longer than that of the control group. However, in the Stage III patients, there was no significant difference in either time to recurrence or survival rate.     

Effect of sizofiran on regional lymph nodes in patients with head and neck cancer

The immunomodulating effects of preoperative sizofiran (SPG) administration on regional lymph nodes were studied in patients with stage III or IV head and neck cancer, by comparing the immunofunction of peripheral blood. The regional lymph nodes were dissected surgically, and freshly obtained mononuclear cells were studied to investigate the interleukin-2 (IL-2) production, the LAK and NK activities, and the quantitative analysis of the surface phenotype of the mononuclear cells. The results indicated that SPG enhanced immunological activities in the regional lymph nodes, as shown by increased IL-2 production and cytotoxic activities of the effector cells (NK, LAK), and increased helper T lymphocytes (CD4⁺) in the tumor-uninvolved lymph nodes. The immunofunction following SPG administration was attenuated, but was still augmented in the regional lymph nodes with metastases. Therefore, SPG was found to be a biologic response modifier to enhance the immunofunctions of the regional lymph node in patients with head and neck cancer.     

The role of para-aortic nodal irradiation in cervical cancer

The current standard of care for locally advanced cervical cancer is whole pelvis and para-aortic radiation when indicated, delivered concomitantly with chemotherapy and brachytherapy. Para-aortic node involvement is a predictor of survival in locally advanced disease but presence of metastases is difficult to determine because the currently available imaging methods lack enough sensitivity to be able to detect accurately para-aortic metastases when surgical staging is not feasible. The objective of this review is to describe the current status of para-aortic lymph node irradiation in locally advanced cervical cancer. It includes analysis of the diagnostic imaging and surgical approaches for assessment of para-aortic lymph node dissemination, together with indications for radiotherapy and radiotherapeutic techniques.     

Clinical evaluation of the EA-rosette test in the early detection of cervical cancer

It was previously found that a negative EA-rosette test, showing EA-rosette-forming cells in a cervical cell suspension, excluded the presence of cells of invasive carcinoma (predictive value of 99.9%). This study on 2,462 patients confirmed the applicability of the EA-rosette test in screening for precancerous as well as cancerous lesions. In 98.6% of the cases of dysplasia, carcinoma in situ and invasive carcinoma, the cervical cell suspensions contained EA-rosette forming cells (the rosette test was positive). With a negative EA-rosette test, the probability of missing a specimen with class III cytology (mild/moderate dysplasia) was 1.4%, of missing one with class IV cytology (severe dysplasia/carcinoma in situ) was 0.8% and of missing one with class V cytology (invasive carcinoma) was 0.25%. The predictive value of a negative EA-rosette test was 98.6%. The false-negative rate for negative EA-rosette tests was 3.7% for invasive carcinoma, 17.5% for carcinoma in situ and severe dysplasia and 41.4% for mild to moderate dysplasia.     

Clinical management of patients with invasive cervical cancer following a negative Pap smear

Among 535 patients with invasive cervical carcinoma seen between January 1975 and June 1986, 26 were found to have developed the disease within six months (65 percent), 35 within 12 months (88 percent), 37 within 13 months (93 percent), and three developed the disease within 17 months after a negative Pap smear. Eighty-eight percent of these 40 patients were under age 40 at diagnosis. Rapidly progressive cancers are highly resistant to radiation therapy. Seven stage IB patients treated only with radiation died within nine to 29 months after initial therapy. By contrast, 15 patients treated by radical hysterectomy and four by radical hysterectomy and post-surgical radiation were alive with no evidence of disease from six to 109 months after surgery (median, 30 months). Six of nine patients with stage II to IV disease treated with radiation have died; the remaining three are alive. One patient is well 14 months after therapy, but two others have developed metastases seven and 12 months after treatment. Surprisingly, 37 of 40 patients had symptoms of pain, bleeding, and discharge at the initial diagnosis, but their physicians had a false sense of security because of a recent negative Pap smear. Early biopsy diagnosis and radical hysterectomy with bilateral pelvic lymphadenectomy is the most effective management for this cancer.     

Lymph flow guided irradiation of regional lymph nodes in patients with cervical cancer: Preliminary analysis of scintigraphic data

PurposeTo evaluate patterns of lymph flow from primary lesions in patients with cervical cancer and to determine how useful for radiotherapy planning this information can be.Materials and methodsSPECT–CT visualization of sentinel (SLN) lymph nodes (LNs) was performed in 36 primary patients with IB-IIB cervical cancer. The acquisition started 120–240 min after 4 peritumoral injections of 99mTc-radiocolloids (150–300 MBq in 0.4–1 ml). We determined localization of LN with uptake of radiocolloids, type of lymph flow (mono-, bi-lateral) and lymph flow patterns (supraureteral paracervical, infraureteral paracervical and directly to para-aortic LNs).ResultsSLNs were visualized in 31 of 36 women. Bilateral lymph-flow was detected in 22 (71%), monolateral – in the other 9 (29%) cases. The distribution of SLNs was as follows: external iliac – 64.5%, internal iliac – 54.8%, obturator – 32.2%, common iliac – 35.5% and pre-sacral 3.2%. Para-aortic LNs were visualized in 5 (16.1%) patients. The supraureteral paracervical pattern of lymph flow was identified in 22, infraureteral paracervical – in 4 and their combination – in the other 5 women.ConclusionVisualization of an individual pattern of lymph flow from primary cervical cancer can be considered as a promising tool for optimization of the volume of irradiated regional LNs.     

Urinary selenium excretion in patients with cervical uterine cancer

In this work, we report on a relationship between urinary selenium and the development of cervical uterine cancer. A simple chemical method was developed to concentrate trace amounts of selenium from relatively large urine samples by use of small activated carbon filters. When these filters are irradiated with thermal neutrons, selenium can be determined either by ^77mSe (t _1/2=17.5 s) or ⁷⁵Se (t _1/2=120 d). In this article, we report the results for 82 urine samples from women with cervical uterine cancer in several stages of development and from healthy controls. These results show a statistically significant increase of selenium excretion in cancer patients as compared to controls. Urinary selenium excretion is highest for patients in the intermediate stages of the disease.     

24例维吾尔族宫颈癌新辅助化疗临床疗效分析

目的:研究5-氟尿嘧啶、丝裂霉素加顺铂在局部晚期宫颈癌术前新辅助化疗中的作用.方法:应用5.氟尿嘧啶、丝裂霉素加铂类经股动脉插管,超选择性选择子宫动脉对局部晚期维族宫颈癌术前进行灌注化疗后栓塞,观察24例患者化疗前后局部肿瘤体积变化、手术切除率、盆腔淋巴结转移、脉管癌栓、病灶局部化疗反应.结果:作为术前新辅助化疗,肿瘤体积缩小总有效率87.5%,CR16.66%,手术切除率100%.结论:5-氟尿嘧啶、丝裂霉素加铂类方案联合化疗在局部晚期宫颈癌术前新辅助化疗方面疗效明显.     

宫颈癌癌前病变及宫颈癌患者阴道微生态失调相关因素

目的 探讨宫颈癌癌前病变及宫颈癌患者阴道微生态失调相关因素。 方法 选择2016年7月至2018年12月我院收治的200例宫颈癌和癌前病变患者为研究对象,其中宫颈癌患者100例(宫颈癌组),癌前病变患者100例(癌前组),另选50例健康女性为对照组。观察各组对象阴道微生态指标(菌群密集度、菌群多样性、pH和H2O2)水平、HPV感染情况及乳杆菌分布情况。分析患者阴道微生态变化与HPV感染的关系。 结果 癌前组和宫颈癌组阴道菌群密集度Ⅰ-Ⅳ级的患者分别占33.00%和42.00%,显著高于对照组的10.00%(χ2=15.762 9,P=0.000 1);菌群多样性Ⅰ-Ⅳ级的患者分别占35.00%和41.00%,同样高于对照组的6.00%(χ2=19.783 1,P4.5的患者分别占53.00%和56.00%,高于对照组的12.00%(χ2=29.267 3,P2O2阴性患者占比分别为63.00%和70.00%,显著高于对照组的18.00%(χ2=39.343 7,P2=63.624 2,P2=8.742 1,P结论 宫颈癌前病变和宫颈癌的发生与患者阴道微生态失调、HPV感染、乳杆菌减少密切相关;同时癌前病变的发展与阴道微生态失调具有相关性。     

爱杰特联合波姆光治疗宫颈糜烂的临床研究

目的:探讨爱杰特联合波姆光治疗宫颈糜烂的疗效。方法:将300例宫颈糜烂患者,随机分为A组:爱杰特治疗;B组:波姆光治疗;C组:爱杰特联合波姆光治疗。分别于术后1个月及3个月复查观察疗效。结果:A、B、C三组的总有效率分别为88.67%、88%、98-33%,C组的有效率显著高于A组及B组(P<0.01)。结论:波姆光与爱杰特联合治疗宫颈糜烂的有效率高、操作简单、是宫颈糜烂的一种理想治疗方法,值得临床推广应用。     

A novel dynamic field-matching technique for treatment of patients with para-aortic node-positive cervical cancer: Clinical experience

Aim

To report outcomes for patients with para-aortic lymph node positive cervical cancer treated with a dynamic field-matching technique.

Background

PET staging of cervical cancer has increased identification of patients with para-aortic lymph node metastasis. IMRT enables dose escalation in this area, but matching IMRT fields with traditional whole pelvis fields presents a challenge.

Materials and methods

From 2003 to 2012, 20 patients with cervical cancer and para-aortic lymph node metastasis were treated utilizing the dynamic field-matching technique. As opposed to single-isocenter half-beam junction techniques, this technique employs wedge-shaped dose junctions for the abutment of fields. We reviewed the records of all patients who completed treatment with the technique and abstracted treatment, toxicity, and disease-related outcome data for analysis.

Results

Median prescribed dose to the whole pelvis field was 45 Gy and para-aortic IMRT field 50.4 Gy. All but 3 patients underwent HDR (13 pts) or LDR (4 pts) brachytherapy. All patients developed lower GI toxicity; 10 grade 1, 9 grade 2, and 1 grade 4 (enterovaginal fistula). Median DFS was 12.4 months with 1 and 2-year DFS 60.0% and 38.1%. One-year OS was 83.7% and 2-year OS, 64.4%. A total of 10 patients developed recurrence; none occurred at the matched junction.

Conclusions

The dynamic field-matching technique provides a means for joining conventional whole pelvis fields and para-aortic IMRT fields that substantially reduces dose deviations at the junction due to field mismatch. Treatment with the dynamic matching technique is simple, effective, and tolerated with no apparent increase in toxicity.     

Post-irradiation cytology of cervical cancer patients

The accuracy of cervicovaginal cytology following radiotherapy for cervical cancer is compromised by the anatomical and tissue changes resulting from irradiation. Collection of representative samples may be more difficult, and benign radiation changes, post-irradiation dysplasia, and the frequent occurrence of repair cells and active stromal cells in post-irradiation smears may cause diagnostic problems. Nevertheless, cytology is a valuable tool for the detection of locally recurrent cervical cancer. It is simple and economical to perform at the time of clinical follow-up examination, and may detect occult tumour recurrence. Awareness of the cellular changes resulting from irradiation, and the varied composition of post-irradiation smears may lead to more accurate interpretation of the cytological findings.     

Clinical evaluation of CA 15.3 in the post-operative follow-up of breast cancer patients

In 265 patients operated for breast carcinoma the monoclonal antibody serum test CA 15.3 was predictive of metastatic diffusion of the disease. Its level increased in cases of distant metastasis with no significant difference between multiple and single sites (p = 0.014). The concentration of the marker was higher in 21 (23.8%) patients without nodal involvement and in 19 (27.5%) with nodal involvement (p = 0.193). Our study suggests that CA 15.3 may be an aid in the follow-up of patients with metastatic diffusion of breast cancer.     

Plasma cholinesterase activity in patients with uterine cervical cancer during radiotherapy

The objectives of this study were to investigate: 1) the activity of pseudocholinesterase (PChE) in patients with uterine cervical cancer in different stages (uterine cervical carcinoma in stages II b and III and recurrent cervical carcinoma in stages III and IV a,b) and to compare it to the enzyme activity in patients with benign tumour of the uterus, and 2) the effects of radiotherapy on enzyme activity in those patients with uterine cervical carcinoma for which the chosen treatment was radical radiotherapy. Thirty patients with uterine cervical carcinoma in stages II b and III (Group A), sixteen patients with recurrent cervical carcinoma in stages III and IV a,b (Group B) and thirty-eight patients with benign tumours of the uterus (control, Group C) were evaluated and their PChE activity was determined prior to any treatment (pre-therapy enzyme activity). All eighty-four patients were free of any liver disease. The results have shown that the patients of Group A had the pre-therapy PChE activity practically identical to those in group C, but patients of Group B had significantly lower values of PChE with respect to enzyme activities of Groups A and C (p < 0.001). That is to say, PChE activity was influenced by the extent to which the malignancy had spread. Radical radiotherapy (up to 8 weeks in doses higher than 50 Gy into point A; average 80 Gy) which was the chosen treatment only for patients from group A did not cause a significant inhibition of PChE activity in any patients in comparison with their control values. With regard to the role of PChE in hydrolysis of succinylcholine, our results about the influence of the malignant disease and the radiotherapy on PChE activity are clinically significant.     

Breast cancer cell survival signal is affected by bergapten combined with an ultraviolet irradiation

In this study we have reported that bergapten (B) and bergapten plus UV (PUVA) are able to significantly affect MCF-7, ZR-75 and SKBR-3 breast cancer cell proliferations.B induced a lowering of PI3K/AKT survival signal in MCF-7 cells even in presence of IGF-I stimulation. Furthermore, B and in a higher extent, PUVA up-regulated the p53 mRNA and the protein content. An increased co-association between p21 WAF and proliferating cell nuclear antigen (PCNA) has been observed in PUVA-treated MCF-7 cells, thus inhibiting DNA replication. These results highlight how B, and its photoactivated compound, exert antiproliferative effects and induce apoptotic responses in breast cancer cells.