Radiation enterocolitis requiring surgery in patients with gynecological malignancies

PURPOSE: To identify the characteristics, risk factors, and clinical outcomes of radiation enterocolitis requiring surgery in patients with gynecologic malignancies. METHODS AND MATERIALS: The records of 1,349 patients treated with pelvic radiotherapy were retrospectively reviewed. The majority of the patients (88%) were treated with 50 Gy or 50.4 Gy pelvic irradiation in conventional fractionations with anteroposterior fields. RESULTS: Forty-eight patients (3.6%) developed radiation enterocolitis requiring surgery. Terminal ileum was the most frequent site (50%) and most of the lesions had stenosis or perforation. On univariate analysis, previous abdominopelvic surgery, diabetes mellitus (DM), smoking and primary site had an impact on the complications, and on multivariate analysis, abdominopelvic surgery, DM, and smoking were independent predictors of the complications requiring surgery. After the surgical intervention, the frequency of Grade 2 or more bleeding was significantly lower in patients treated with intestinal resection in addition to decompression than those treated with intestinal decompression alone. CONCLUSIONS: Severe radiation enterocolitis requiring surgery usually occurred at the terminal ileum and was strongly correlated with previous abdominopelvic surgery, DM, and smoking. Concerning the management, liberal resection of the affected bowel appears to be the preferable therapy.     

Home hospice care for the patients with gynecological malignancies

In order to clarify the clinical characteristics along with the practical care of home hospice care for gynecological cancer patients, we analyzed 37 terminally-ill gynecological cancer patients who died at home from July 1, 2003 through June 30, 2010, and these patients were compared with 762 non-gynecology cancer patients. The range of patients' ages with gynecological malignancies was statistically younger(p<0. 05)than that of the control patients, whereas the duration of home care and home death ratio did not show significant differences. As for medical treatment, the frequency of the management of nephrostomy was significantly higher in cases with gynecological malignancies. However, the frequencies of the usage of strong opioids, home oxygen therapy, home parenteral hyperalimentation, management of central venous port and indwelling bladder catheter showed no significant differences. There were patients, who needed special treatments by a gynecologist, with vesicovaginorectal fistula in one case, subcutaneous abscess probably caused by rectocutaneous fistula in one case, vaginal bleeding in one case and acute urinary retention treated by an emergent bladder puncture. By analyzing the focus problem lists of the total suffering at each clinical phase, in patients living longer than 15 days at home,(Kawagoe's classification in 1991)this did not show significant difference against the control group. In conclusion, gynecologic cancer patients were significantly younger than those with non-gynecologic malignancies, though not statistically significant, showing the tendency of short duration. Thus, in cases of gynecologic malignancies, it is important to take these characteristics into consideration.     

Evaluation of circulating tumor necrosis factor-alpha in patients with gynecological malignancies

TNF-alpha levels in sera from patients with gynecological cancers were evaluated by ELISA and compared with those of patients with benign ovarian cysts or of anonymous healthy donors. Patients with cervical and endometrial carcinoma and with benign ovarian cysts showed levels of TNF-alpha similar to those of healthy donors. In contrast, significantly increased levels of TNF-alpha were found in patients with ovarian carcinoma, regardless of the stage of disease.     

Sarcopenia (and sarcopenic obesity) in older patients with gynecological malignancies

Cancer is often complicated by the deterioration of both muscle mass and function, which may be more pronounced in older people. The prevalence of sarcopenia varies according to tumour type, stage and sarcopenia definition; in gynaecologic malignancies it ranges from 25 to 50%. Unfortunately, sarcopenia is often underdiagnosed especially in overweight and obese patients. The consequences of sarcopenia are serious: shorter time of tumour progression, increased chemotherapy-related toxicity, post-operative complications, poor functional status, hospitalisation, increased length of hospital stay, high 30-day readmission rate and mortality. Therefore, its precocious recognition and treatment is of paramount importance. We demonstrated that obesity can mask sarcopenia, taking into consideration a sample of older patient with cancer, unless body composition evaluation and comprehensive geriatric assessment, including measures of muscle strength and performance, is executed. Our work underlines the importance of a multidisciplinary approach to older patients with cancer to optimize their management.     

妇科恶性肿瘤患者心理因素对血清VEGF水平影响的研究

目的:探讨心理因素对妇科恶性肿瘤患者血清VEGF水平的影响.方法:采用对照研究的方法.运用临床心理评定量表(LES、CS、SSRS)对妇科恶性肿瘤患者组(n=80)、健康对照组(n=80)病前遭遇的生活事件、应付方式及社会支持进行问卷调查,同时用ELISA方法检测两组对象血清中的VEGF的水平,分析心理因素与血清VEGF水平的关系.结果:恶性肿瘤组患者负性生活事件频数及消极应对明显高于健康对照组,P<0.01;而积极应对、客观支持、主观支持以及对支持的利用度均低于健康对照组,P<0.01;妇科恶性肿瘤组患者血清VEGF值高于同期健康组,P<0.01.负性事件和消积应对与VEGF水平呈正相关,r值分别为0.618和0.432,P值均<0.01.而积极应对、客观支持以及主观支持均与VEGF呈负相关.结论:负性生活事件、不良应对方式及低的社会支持可促进妇科恶性肿瘤患者血清中VEGF水平的增高,与妇科恶性肿瘤的发生、发展密切相关.     

Effect of remission induction chemotherapy on blood coagulability in patients with gynecological malignancies

In 12 patients (38 courses) with gynecological malignancies who had been treated with remission induction chemotherapy, we measured the levels of ESR, Platelet, PT, APTT, Hepa T, AT III, alpha 2 PI, FDP and D-dimer, and we also measured such molecular markers as Fibrinopeptide A (FPA), Fibrinopeptide B beta 1-42 (FPB beta 1-42), and Fibrinopeptide B beta 15-42 (FPB beta 15-42) before and after chemotherapy. Then the relation between the post chemotherapeutic trends and prognosis for patient with gynecological malignancies were investigated. 1) Before chemotherapy, the levels of ESR, FDP, D-dimer and FPB beta 1-42 were increased, PT and APTT were shortened significantly in cases on groups IIIrd and IVth stage compared with in cases on groups Ist and IInd stage (p less than 0.05). The levels of FPA were also high, but there was no significant differences. The levels of FPB beta 15-42 were almost same in both groups. However, the each markers indicated the existence of chronic DIC in cases of group IIIrd and IVth stage. 2) One week after chemotherapy, the levels of ESR, fibrinogen, FDP and FPA were decreased, while FPB beta 1-42 and FPB beta 15-42 were increased, suggesting elevated fibrinolytic activity. Two weeks after chemotherapy, there was stronger tendency to coagulation dominant again, but it was only temporary. Three weeks after chemotherapy, the hemostatic balance was regained. 3) In patient with complete remission after effective chemotherapy, their coagulability data were showed within normal range, however, some cases with poor prognosis were not able to obtain the recovery of hemostatic balance, and the levels of molecular markers were significantly elevated. Coagulative activity was more enhanced than fibrinolytic activity in patients with progressive gynecological malignancies, but hemostatic balance was maintained clinically. The hemostatic balance was disrupted by the chemotherapy, but this balance was regained for the IIIrd week. Accordingly, the recovery of hemostatic balance with effective chemotherapy is related to the prognosis for patients with gynecological malignancies, and the levels of molecular markers may be able to expect the prognosis for patients.     

CA-125 in gynecological malignancies

CA-125 is an antigenic determinant that can be demonstrated in the majority of epithelial ovarian carcinomas. It can be measured in the serum with a radioimmunoassay by means of a monoclonal antibody. The tumor marker has a low specificity but high sensitivity for ovarian cancer, especially for serous cystadenocarcinoma. In our investigation we were interested in particular in the correlation between GA-125 and the histological findings at second-look operation. In 22 patients, second-look was performed after 6 cycles of chemotherapy; in 16 patients active tumor was demonstrated. In 6 patients with negative CA-125 values, residual tumor less than 1 cm was demonstrated. In order to verify a complete remission, a second-look operation has to be performed. No false-positive CA-125 levels were found. In all patients with elevated CA-125 serum values, residual tumor was histologically confirmed at second look.     

Procoagulant activity of mononuclear phagocytes from different anatomical sites in patients with gynecological malignancies

Mononuclear phagocytes exhibit complex interactions with cancer cells and might contribute to fibrin formation associated with malignancy through the production of procoagulant activity (PCA). We have studied the PCA of peritoneal macrophages in 8 patients with advanced (stages III or IV) ovarian cancer and of macrophages from regional lymph nodes in 14 patients with limited (stages I or II) uterine cancer; peritoneal and lymph-node macrophages from patients with benign gynecological tumors were used as reference cell populations. In all patients, PCA of blood monocytes was also studied. Peritoneal and lymph-node macrophages obtained from patients with ovarian and uterine cancer, respectively, expressed far higher levels of basal PCA than the corresponding cell populations from patients with benign tumors (p less than 0.001). PCA of blood mononuclear cells from patients with ovarian, but not with uterine cancer, was significantly higher (p less than 0.001) than that of control cells. High levels of D-dimer, a specific product derived from plasmin-induced degradation of stabilized fibrin, were found in all ascitic fluids and in all plasma samples but one from patients with ovarian cancer. In contrast, all controls and all uterine cancer patients but one had normal plasma D-dimer. Our findings suggest that local activation of host macrophages for PCA production might contribute to fibrin formation within the tumoral mass. In advanced cancer, blood monocytes may also be activated to produce PCA and thus contribute to activation of intravascular coagulation and, possibly, to thrombo-embolic complications frequently associated with disseminated malignancy.     

Positron emission tomography in gynecological malignancies

Positron emission tomography (PET) is a functional diagnostic imaging technique. F-18 fluoro-2-deoxy-d-glucose (FDG) is a commonly used radiopharmaceutical that is an analog of glucose. PET with FDG is now the standard of care in initial staging, monitoring the response to the therapy and management of various cancers. There is not sufficient data to support the use of PET in the initial diagnosis of cervical cancer; however, FDG-PET has a role in initial staging in the detection of distant metastases in patients with cervical cancer. PET has limited value in lesion localization in early stages of ovarian cancer, but plays a significant role in identifying recurrent tumors in patients with rising tumor markers. In this article, the clinical application of PET in gynecological malignancies is reviewed.     

Positron emission tomography in gynecological malignancies

Positron emission tomography (PET) is a functional diagnostic imaging technique. F-18 fluoro-2-deoxy-d-glucose (FDG) is a commonly used radiopharmaceutical that is an analog of glucose. PET with FDG is now the standard of care in initial staging, monitoring the response to the therapy and management of various cancers. There is not sufficient data to support the use of PET in the initial diagnosis of cervical cancer; however, FDG-PET has a role in initial staging in the detection of distant metastases in patients with cervical cancer. PET has limited value in lesion localization in early stages of ovarian cancer, but plays a significant role in identifying recurrent tumors in patients with rising tumor markers. In this article, the clinical application of PET in gynecological malignancies is reviewed.     

Serum soluble fas level as a prognostic factor in patients with gynecological malignancies.

The Fas-Fas ligand system is important in apoptosis mediated by CTLs and natural killer cells. The suppression of apoptosis contributes to carcinogenesis, as well as to a resistance to chemotherapy and radiotherapy. Circulating soluble Fas (sFas), which is generated by alternative mRNA splicing, can antagonize cell-surface Fas function. We investigated sFas levels in 64 patients with gynecological malignancies (28 cervical carcinomas, 18 endometrial carcinomas, and 18 ovarian carcinomas) and in 24 healthy female donors by using a Fas-specific ELISA. In each carcinoma group, serum sFas demonstrated a statistically significant elevation relative to levels in normal controls (P < 0.0001). Levels of serum sFas in patients with advanced cancer (FIGO stages III and IV) significantly exceeded those in patients with localized cancer (FIGO stages I and II) or those in normal control subjects (P < 0.0001). We divided the patients into two groups based on the level of serum sFas and examined the relationship between serum sFas levels and survival. No deaths occurred in the groups with cervical and endometrial cancer with a serum sFas level < 1.5 ng/ml. Survival rates in groups with cervical carcinoma, endometrial carcinoma, and ovarian carcinoma with a serum sFas level < 1.5 ng/ml exceeded those in groups with sFas levels of 21.5 ng/ml (P < 0.001, P = 0.128, and P = 0.012, respectively). Proportional hazard models demonstrated that serum sFas level was a statistically significant factor (P = 0.0196) for survival, as well as histological grade (P = 0.0168) in ovarian carcinoma.     

A dose-finding study of nedaplatin and cyclophosphamide for patients with gynecological malignancies.

BACKGROUND: Nedaplatin is a new analogue of cisplatin with similar efficacy but less renal toxicity. We investigated the appropriate dose of nedaplatin in combination with cyclophosphamide for patients with gynecological malignancies. METHODS: Nine patients (five with ovarian cancer and four with uterine cervical cancer) were studied. Three patients received 60 mg/m2 of nedaplatin combined with 500 mg/m2 of cyclophosphamide every 4 weeks. Another three patients were each administered 80 or 100 mg/m2 of nedaplatin with the same dose of cyclophosphamide. A total of 27 courses was given. RESULTS: No patient needed dose reduction due to myelosuppression and no severe adverse events were observed. CONCLUSIONS: Treatment with 100 mg/m2 of nedaplatin and 500 mg/m2 of cyclophosphamide is feasible for patients with gynecological malignancies. However, phase II studies are needed to clarify the efficacy of this combination chemotherapy.     

LMR与妇科恶性肿瘤预后的研究进展

大量医学研究已证实炎症与肿瘤的发生、发展密切相关。在近年来的医学临床研究中,也逐渐证实并阐述了肿瘤相关性炎症反应在肿瘤的预后中发挥着重要作用。而且,肿瘤相关性炎症反应可通过患者的中性粒细胞、淋巴细胞和单核细胞等多种外周血象指标反映出来,同时,肿瘤患者的外周血淋巴细胞与单核细胞的比值,即淋巴细胞/单核细胞(LMR),在妇科恶性肿瘤的诊断及预后中发挥着重要作用。在国内外很多研究中,已将LMR在消化、血液等多个系统发生的恶性肿瘤预后中的重要作用给予阐述,而其在妇科生殖系统的肿瘤领域的研究进展,国内外鲜有报道。因此,本文主要就LMR对妇科常见恶性肿瘤预后的研究进展进行综述。     

波形蛋白在妇科恶性肿瘤中的研究进展

波形蛋白（vimentin）是一种Ⅲ型中间丝蛋白,是间质细胞骨架的主要组成部分。大量研究表明vimentin在多种肿瘤组织中存在高表达,与肿瘤的发生、发展和侵袭转移密切相关,但在子宫颈癌、子宫内膜癌和卵巢癌组织中的相关研究起步相对较晚,且研究结论不一致,其相关作用机制还有待进一步研究。文章就vimentin在妇科三大恶性肿瘤组织中的表达及其临床意义进行综述。     

Development of PARP inhibitors in gynecological malignancies

PARP inhibitors demonstrate synthetic lethality in tumors with BRCA1/2 mutations and other homologous recombination repair deficiencies by interfering with DNA repair and causing direct toxicity to DNA through PARP trapping. PARP inhibitors have been shown to be beneficial in the treatment of BRCA1/2-mutated ovarian cancers, which has led to a shift in the treatment paradigm of this disease. Further studies to establish the role of PARP inhibitors during earlier stages of treatment are ongoing. The use of PARP inhibitors in other cancers with homologous recombination repair deficiencies, such as breast cancer and prostate cancer, is gradually evolving as well, including their use in the neoadjuvant and adjuvant settings. PARP inhibitor combination strategies with chemotherapy, targeted agents, radiotherapy, and immunotherapy are also being explored. The role of predictive biomarkers, including molecular signatures and homologous recombination deficiency scores based on loss of heterozygosity and other structural genomic aberrations, will be crucial to improved patient stratification to enhance the clinical utility of PARP inhibitors. This may also allow the use of PARP inhibitors to be extended beyond tumors with specific homologous recombination DNA repair gene mutations in the future. An improved understanding of the mechanisms underlying PARP inhibitor resistance will also be important to enable the development of new approaches to increase efficacy. This is a field rich in opportunity, and the coming years should see a better understanding of which patients we should be treating with PARP inhibitors and where these agents should come in over the course of treatment.     

DNA甲基转移酶1与妇科恶性肿瘤

DNA甲基转移酶1（DNMTl）作为DNA甲基转移酶（DNMT）家族的主要成员,对维持和调节肿瘤细胞全基因组和局部区域甲基化起着核心作用。DNMTl在妇科恶性肿瘤中高表达,引起基因DNA的甲基化异常,特别是抑癌基因的高甲基化,继而造成相关基因表达沉默,导致细胞的恶性生长。     

Duodenal complications of gynecological malignancies.

Isolated para-aortic lymph node metastasis leading to intestinal complications is uncommon and diagnosis may therefore be delayed. In the present report duodenal bleeding, obstruction and perforation due to isolated para-aortic lymph node metastasis from stage I uterine malignancies are described. Knowledge of these potential problems may lead to early recognition and planning of treatment.     

妇科肿瘤伴腹主动脉旁淋巴节转移IMRT靶区勾画探讨

目的 初步探讨妇科肿瘤伴腹主动脉旁淋巴节转移患者IMRT的CTV勾画范围。方法 回顾分析2010—2016年收治的56例妇科肿瘤伴腹主动脉旁淋巴结转移患者。通过影像学方法判断腹主动脉旁转移淋巴结数目和分布情况。结果 56例妇科肿瘤患者腹主动脉旁淋巴结转移共计108个,平均每位患者转移淋巴结数目为2个(1~4个),腹主动脉旁转移淋巴结平均直径为2.3 cm (1.2~4.0 cm)。20个(19%)淋巴结位于L₄水平,38个(35%)转移淋巴结位于L₃水平,44个(41%)转移淋巴结位于L₂水平,6个(5%)位于L₁水平。腹主动脉旁左侧组转移淋巴结共71个(66%)。腹主动脉-腔静脉间组转移淋巴结共20个(19%)。下腔静脉旁右侧组转移淋巴结共17个(15%)。结论 妇科肿瘤腹主动脉旁淋巴结勾画不应以血管周围外扩固定范围方式勾画,腹主动脉旁左侧应充分勾画在靶区范围内,靶区上界应至肾动脉水平,对肾动静脉旁有淋巴结转移者靶区上界应适当扩展。     

32例妇科恶性肿瘤术后调强适形放射治疗分析

目的 探讨调强适形放射治疗（IMRT）在妇科恶性肿瘤患者术后治疗中的效果及价值。方法 32例子宫颈癌、子宫内膜癌术后患者（KPS≥70）在放疗前均行1～3个周期的化疗,而后给予全程IMRT。其中17例为术后、化疗后预防性照射,15例为术后、放疗和（或）化疗后腹膜后淋巴结转移和（或）盆腔壁复发的放疗。结果 32例患者均完成全程放射治疗,预防性照射的计划靶区（PTV）中位剂量为56．8Gy;腹膜后淋巴结转移、盆壁复发的胛V中位剂量为60．6Gy,90％的等剂量曲线可以覆盖99％以上的肉眼肿瘤靶区（GTV）体积。小肠、膀胱、直肠、肾脏和脊髓的中位剂量分别为21．3Gy、37．8Gy、35．3Gy、8．5Gy和22．1Gy。14例患者出现Ⅰ～Ⅱ级消化道反应,其中Ⅱ级反应者3例,I级反应者11例;5例出现Ⅰ～Ⅱ度骨髓抑制;12例出现Ⅰ级皮肤反应。1年生存率为100％。预防性照射的2、3年生存率均为100％;腹膜后淋巴结转移和（或）盆腔壁复发患者的2、3年生存分别为5／7和3／6。结论 IMRT对妇科恶性肿瘤术后患者的预防性照射和复发患者的放疗均可获得理想的剂量分布,邻近危险器官得到保护,临床近期疗效满意。