What is the impact of microbiota on dry eye: a literature review of the gut-eye axis.

BACKGROUND: Dry eye is a chronic and multifactorial ocular surface disease caused by tear film instability or imbalance in the microenvironment of the ocular surface. It can lead to various discomforts such as inflammation of the ocular surface and visual issues. However, the mechanism of dry eye is not clear, which results in dry eye being only relieved but not cured in clinical practice. Finding multiple environmental pathways for dry eye and exploring the pathogenesis of dry eye have become the focus of research. Studies have found that changes in microbiota may be related to the occurrence and development of dry eye disease. METHODS: Entered the keywords "Dry eye", "Microbiota", "Bacteria" through PUBMED, summarised the articles that meet the inclusion criteria and then filtered them while the publication time range of the literature was defined in the past 5 years, with a deadline of 2023.A total of 13 clinical and 1 animal-related research articles were screened out and included in the summary. RESULTS: Study found that different components of bacteria can induce ocular immune responses through different receptors present on the ocular surface, thereby leading to an imbalance in the ocular surface microenvironment. Changes in the ocular surface microbiota and gut microbiota were also found when dry eye syndrome occurs, including changes in diversity, an increase in pro-inflammatory bacteria, and a decrease in short-chain fatty acid-related bacterial genera that produce anti-inflammatory effects. Fecal microbiota transplantation or probiotic intervention can alleviate signs of inflammation on the ocular surface of dry eye animal models. CONCLUSIONS: By summarizing the changes in the ocular surface and intestinal microbiota when dry eye occurs, it is speculated and concluded that the intestine may affect the occurrence of eye diseases such as dry eye through several pathways and mechanisms, such as the occurrence of abnormal immune responses, microbiota metabolites- intervention of short-chain fatty acids, imbalance of pro-inflammatory and anti-inflammatory factors, and release of neurotransmitters, etc. Analyzing the correlation between the intestinal tract and the eyes from the perspective of microbiota can provide a theoretical basis and a new idea for relieving dry eyes in multiple ways in the future.

Research on Image Stitching Algorithm Based on Point-Line Consistency and Local Edge Feature Constraints.

Image stitching aims to synthesize a wider and more informative whole image, which has been widely used in various fields. This study focuses on improving the accuracy of image mosaic and proposes an image mosaic method based on local edge contour matching constraints. Because the accuracy and quantity of feature matching have a direct influence on the stitching result, it often leads to wrong image warpage model estimation when feature points are difficult to detect and match errors are easy to occur. To address this issue, the geometric invariance is used to expand the number of feature matching points, thus enriching the matching information. Based on Canny edge detection, significant local edge contour features are constructed through operations such as structure separation and edge contour merging to improve the image registration effect. The method also introduces the spatial variation warping method to ensure the local alignment of the overlapping area, maintains the line structure in the image without bending by the constraints of short and long lines, and eliminates the distortion of the non-overlapping area by the global line-guided warping method. The method proposed in this paper is compared with other research through experimental comparisons on multiple datasets, and excellent stitching results are obtained.

Characterization of neoantigen-specific T cells in cancer resistant to immune checkpoint therapies.

Neoantigen-specific T cells are strongly implicated as being critical for effective immune checkpoint blockade treatment (ICB) (e.g., anti-PD-1 and anti-CTLA-4) and are being targeted for vaccination-based therapies. However, ICB treatments show uneven responses between patients, and neoantigen vaccination efficiency has yet to be established. Here, we characterize neoantigen-specific CD8+ T cells in a tumor that is resistant to ICB and neoantigen vaccination. Leveraging the use of mass cytometry combined with multiplex major histocompatibility complex (MHC) class I tetramer staining, we screened and identified tumor neoantigen-specific CD8+ T cells in the Lewis Lung carcinoma (LLC) tumor model (mRiok1). We observed an expansion of mRiok1-specific CD8+ tumor-infiltrating lymphocytes (TILs) after ICB targeting PD-1 or CTLA-4 with no sign of tumor regression. The expanded neoantigen-specific CD8+ TILs remained phenotypically and functionally exhausted but displayed cytotoxic characteristics. When combining both ICB treatments, mRiok1-specific CD8+ TILs showed a stem-like phenotype and a higher capacity to produce cytokines, but tumors did not show signs of regression. Furthermore, combining both ICB treatments with neoantigen vaccination did not induce tumor regression either despite neoantigen-specific CD8+ TIL expansion. Overall, this work provides a model for studying neoantigens in an immunotherapy nonresponder model. We showed that a robust neoantigen-specific T-cell response in the LLC tumor model could fail in tumor response to ICB, which will have important implications in designing future immunotherapeutic strategies.

Nutritional evaluation of Japanese abalone (Haliotis discus hannai Ino) muscle: Mineral content, amino acid profile and protein digestibility.

The chemical compositions and nutritional values of the water-soluble fraction (WF), myofibrillar protein (MP), and stroma protein (SP) from abalone muscle were investigated. The protein, carbohydrate, lipid, and ash contents of abalone muscle were 15.87, 6.36, 0.22, and 1.36 g/100 g, respectively. Most of the carbohydrates in the abalone muscle were released easily into water, and potassium was the most abundant mineral. WF and SP were rich in essential and umami amino acids, and all three fractions had high arginine contents. The essential amino acid index and predicted biological value of WF were 75.84 and 90.96, respectively. These values were considerably higher than those of MP and SP. Meanwhile, the predicted protein efficiency ratio of MP was the highest. Lysine was the first limiting essential amino acid (EAA) in MP and SP, and the score of the first limiting EAA (tryptophan) in WF was more than 100%. The in vitro protein digestibility of WF and SP was approximately 92% higher than that of MP. The in vivo experiments showed that WF was the easiest to digest. The nutritional value and high digestibility of WF can be claimed as a high-quality protein source based on the current findings.

Identification of a CD8+ T-cell response to a predicted neoantigen in malignant mesothelioma.

Neoantigens present unique and specific targets for personalized cancer immunotherapy strategies. Given the low mutational burden yet immunotherapy responsiveness of malignant mesothelioma (MM) when compared to other carcinogen-induced malignancies, identifying candidate neoantigens and T cells that recognize them has been a challenge. We used pleural effusions to gain access to MM tumor cells as well as immune cells in order to characterize the tumor-immune interface in MM. We characterized the landscape of potential neoantigens from SNVs identified in 27 MM patients and performed whole transcriptome sequencing of cell populations from 18 patient-matched pleural effusions. IFNγ ELISpot was performed to detect a CD8+ T cell responses to predicted neoantigens in one patient. We detected a median of 68 (range 7-258) predicted neoantigens across the samples. Wild-type non-binding to mutant binding predicted neoantigens increased risk of death in a model adjusting for age, sex, smoking status, histology and treatment (HR: 33.22, CI: 2.55-433.02, p = .007). Gene expression analysis indicated a dynamic immune environment within the pleural effusions. TCR clonotypes increased with predicted neoantigen burden. A strong activated CD8+ T-cell response was identified for a predicted neoantigen produced by a spontaneous mutation in the ROBO3 gene. Despite the challenges associated with the identification of bonafide neoantigens, there is growing evidence that these molecular changes can provide an actionable target for personalized therapeutics in difficult to treat cancers. Our findings support the existence of candidate neoantigens in MM despite the low mutation burden of the tumor, and may present improved treatment opportunities for patients.

Pre-treatment tumor neo-antigen responses in draining lymph nodes are infrequent but predict checkpoint blockade therapy outcome.

Immune checkpoint blockade (ICPB) is a powerfully effective cancer therapy in some patients. Tumor neo-antigens are likely main targets for attack but it is not clear which and how many tumor mutations in individual cancers are actually antigenic, with or without ICPB therapy and their role as neo-antigen vaccines or as predictors of ICPB responses. To examine this, we interrogated the immune response to tumor neo-antigens in a murine model in which the tumor is induced by a natural human carcinogen (i.e. asbestos) and mimics its human counterpart (i.e. mesothelioma). We identified and screened 33 candidate neo-antigens, and found T cell responses against one candidate in tumor-bearing animals, mutant UQCRC2. Interestingly, we found a high degree of inter-animal variation in the magnitude of neo-antigen responses in otherwise identical mice. ICPB therapy with Cytotoxic T-lymphocyte-associated protein (CTLA-4) and α-glucocorticoid-induced TNFR family related gene (GITR) in doses that induced tumor regression, increased the magnitude of responses and unmasked functional T cell responses against another neo-antigen, UNC45a. Importantly, the magnitude of the pre-treatment draining lymph node (dLN) response to UNC45a closely corresponded to ICPB therapy outcomes. Surprisingly however, boosting pre-treatment UNC45a-specific T cell numbers did not improve response rates to ICPB. These observations suggest a novel biomarker approach to the clinical prediction of ICPB response and have important implications for the development of neo-antigen vaccines.

Long-Term Survival and Late Toxicity Associated With Pelvic Intensity Modulated Radiation Therapy (IMRT) for Cervical Cancer Involving CT-Based Positive Lymph Nodes.

The purpose of this study was to evaluate the outcomes and toxicity experienced by cervical cancer patients with positive lymph nodes (LNs) who were treated with intensity-modulated radiation therapy (IMRT) and intracavitary brachytherapy (ICBT) plus concurrent chemotherapy. We retrospectively evaluated 108 cervical cancer patients with computed tomography (CT)-based positive LNs treated with IMRT and ICBT plus concurrent chemotherapy between 2009 and 2011. IMRT plans were designed to deliver 50 Gy to 95% of the planning target volume (PTV; cervical tumor, pelvis, and parametrium), with daily doses of 1.6-1.8 and 60-70 Gy to 95% of the planning gross tumor volume (PGTV)-LN (pelvic or para-aortic LNs), with daily doses of 2.0-2.2 Gy. Overall survival (OS) and progression-free survival (PFS) Kaplan-Meier curves were plotted. Acute and late toxicities were evaluated according to the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer toxicity criteria. Of the 108 cases, 45 were stage IIB and 63 were stage IIIB. The median follow-up was 65 months (range 2-83). Overall, the 5 year cumulative incidences of pelvic failure alone, distant failure alone, and synchronous pelvic and distant failure were 8.3, 12.9, and 8.3%, respectively. The 5 year OS rate was 67.6%, and the 5 year PFS rate was 53.7%. The 5 year cumulative incidence was 9.2% for late gastrointestinal and genitourinary toxicities of Grade ≥3 and 51.8% for acute leukopenia of Grade ≥3. The clinical results suggest that IMRT and ICBT with concurrent chemotherapy is an effective treatment, with acceptable toxicity, for advanced cervical cancer involving positive LNs.

Immunotherapy strategies for mesothelioma - the role of tumor specific neoantigens in a new era of precision medicine.

INTRODUCTION: Immunotherapy has long been considered a potential therapy for malignant mesothelioma and is currently being pursued as such. Some of the early phase clinical trials involving immunomodulators have demonstrated encouraging results and numerous clinical trials are underway to further investigate this treatment approach in various treatment settings and larger patient cohorts. Areas covered: This review summarizes the current and emerging clinical evidence for checkpoint blockade and other immunotherapeutic strategies in mesothelioma. The mesothelioma tumor immune microenvironment and mutational landscape are also discussed, including their impact on treatment strategies. We also provide an evaluation of the current evidence for neoantigen targeted personalized immunotherapy. Expert opinion: Immune checkpoint inhibitors work by unleashing the host immune response against probable neoantigens. Despite impressive activity in a small subset of patients and the potential for prolonged responses, most patients experience treatment failure. Neoantigen vaccines provide a potential complementary therapeutic strategy by increasing the immunogenic antigen load, which can lead to an increased tumor specific immune response. Further research is needed explore this treatment option in mesothelioma and technological advances are required to translate this concept into clinical practice.

Transient Treg depletion enhances therapeutic anti-cancer vaccination.

INTRODUCTION: Regulatory T cells (Treg) play an important role in suppressing anti- immunity and their depletion has been linked to improved outcomes. To better understand the role of Treg in limiting the efficacy of anti-cancer immunity, we used a Diphtheria toxin (DTX) transgenic mouse model to specifically target and deplete Treg. METHODS: Tumor bearing BALB/c FoxP3.dtr transgenic mice were subjected to different treatment protocols, with or without Treg depletion and tumor growth and survival monitored. RESULTS: DTX specifically depleted Treg in a transient, dose-dependent manner. Treg depletion correlated with delayed tumor growth, increased effector T cell (Teff) activation, and enhanced survival in a range of solid tumors. Tumor regression was dependent on Teffs as depletion of both CD4 and CD8 T cells completely abrogated any survival benefit. Severe morbidity following Treg depletion was only observed, when consecutive doses of DTX were given during peak CD8 T cell activation, demonstrating that Treg can be depleted on multiple occasions, but only when CD8 T cell activation has returned to base line levels. Finally, we show that even minimal Treg depletion is sufficient to significantly improve the efficacy of tumor-peptide vaccination. CONCLUSIONS: BALB/c.FoxP3.dtr mice are an ideal model to investigate the full therapeutic potential of Treg depletion to boost anti-tumor immunity. DTX-mediated Treg depletion is transient, dose-dependent, and leads to strong anti-tumor immunity and complete tumor regression at high doses, while enhancing the efficacy of tumor-specific vaccination at low doses. Together this data highlight the importance of Treg manipulation as a useful strategy for enhancing current and future cancer immunotherapies.

[Clinical analysis of 32 cases with neuroendocrine carcinoma of the uterine cervix in early-stage disease].

OBJECTIVE: To investigate the survival and recurrence data after treatment in neuroendocrine carcinoma of the uterine cervix (NECUC) with stage Ib-IIa, and to analyse its prognostic factors. METHODS: Thirty-two cases of primary NECUC in early-stage disease treated from Jan. 2005 to Dec. 2013 at Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences were reviewed, and their data of clinicopathologic characteristics were collected and analysed. The median age was 37 years (range, 23-57 years). The distribution by International Federation of Gynecology and Obstetrics (FIGO) clinical stage: 19 cases stage Ib1, 10 cases stage Ib2, 1 case stage IIa1, 2 cases stage IIa2. Pathologic types: 22 cases of small cell carcinoma, 1 case of atypical carcinoid, 9 cases of mixed carcinoma. The diameter of cervical tumor: 12 cases ≥4 cm, 20 cases <4 cm. All patients underwent radical hysterectomy and pelvic ± para-aortic lymphadenectomy, and 15 cases of them were preserved unilateral or bilateral ovaries. Pathologic examination showed that 25 cases with cervical deep stromal invasion thickness ≥1/2, 21 cases with lymph-vascular space invasion (LVSI), and 18 cases with pelvic and (or) para-aortic lymph nodes involvement. Ten cases were performed neoadjuvant chemotherapy (range,1-3 cycles), all patients received postoperative chemotherapy (range,3-6 cycles), and 15 patients were treated with radiotherapy after surgery. The follow-up data were updated on Jul. 2014. The median follow-up time was 18 months (range, 7-71 months). A retrospective analysis was conducted to analyse the survival and recurrence data,and to explore the prognostic factors of NECUC. RESULTS: Thirteen patients died during the follow-up period. The cumulative progression-free survival (PFS) of 2 and 5 years were respectively 54.2% and 38.1%, and the estimated median PFS was 29 months. The cumulative overall survival (OS) of 2 and 5 years were respectively 56.1% and 44.9%, and the estimated median OS was 31 months. Fourteen cases had recurrence, and the median recurrence time was 9 months (range, 3-30 months). Recurrent or metastatic sites: 2 cases in pelvis, 4 cases in liver, 3 cases in lung, 3 cases in adrenal glands, 3 cases in bones, 2 cases in brain, 1 case in pancreas, 1 case in lymph nodes of para-aorta and neck, and 3 cases had metastasis in two or more organs. Thirteen cases with recurrence died of disease, and another one is alive with disease. The univariate analysis showed that lesion size of the cervix and FIGO stage were significant prognostic factors (P<0.01), while age, tumor components, deep invasion in cervical stromal, LVSI, pelvic and (or) para-aortic lymph nodes involvement, neoadjuvant chemotherapy, adjuvant radiotherapy and preserving ovaries were not significantly associated with prognosis (all P>0.05). CONCLUSION: The prognosis of NECUC in early-stage is poor and the lesion size of the cervix and FIGO stage are prognostic factors.

Strong spontaneous tumor neoantigen responses induced by a natural human carcinogen.

A key to improving cancer immunotherapy will be the identification of tumor-specific "neoantigens" that arise from mutations and augment the resultant host immune response. In this study we identified single nucleotide variants (SNVs) by RNA sequencing of asbestos-induced murine mesothelioma cell lines AB1 and AB1-HA. Using the NetMHCpan 2.8 algorithm, the theoretical binding affinity of predicted peptides arising from high-confidence, exonic, non-synonymous SNVs was determined for the BALB/c strain. The immunoreactivity to 20 candidate mutation-carrying peptides of increased affinity and the corresponding wild-type peptides was determined using interferon-γ ELISPOT assays and lymphoid organs of non-manipulated tumor-bearing mice. A strong endogenous immune response was demonstrated to one of the candidate neoantigens, Uqcrc2; this response was detected in the draining lymph node and spleen. Antigen reactive cells were not detected in non-tumor bearing mice. The magnitude of the response to the Uqcrc2 neoantigen was similar to that of the strong influenza hemagglutinin antigen, a model tumor neoantigen. This work confirms that the approach of RNAseq plus peptide prediction and ELISPOT testing is sufficient to identify natural tumor neoantigens.

[Effects of tillage mode and nitrogen application rate on nitrogen use efficiency of wheat in a farming-pasture zone of North China].

A field experiment was conducted in a farming-pasture zone in Chifeng City of Inner Mongolia Autonomous Region, North China to investigate the effects of different tillage modes and nitrogen (N) application rates on the grain yield and nitrogen use efficiency (NUE) of winter wheat. The results showed that long term conservation tillage increased the wheat NUE by 3% -4%, and decreased the environmental pollution by fertilizer N. Conservation tillage promoted the N absorption by wheat, and increased the grain yield. When the N application rate increased from 120 kg hm-2 to 360 kg . hm-2, the NUE decreased from 36. 5% to 26% , fertilizer N loss increased by about 5% , i. e. , the corresponding N loss was increased from 60 kg hm-2 to 200 kg hm-2, and the environmental N pollution increased markedly. The wheat NUE of the residual N in last season was less affected by tillage mode, but more affected by the N application rate in last season, with an overall tendency of the higher the N application rate in last season, the lower the NUE and the more the fertilizer N loss. After two seasons' wheat planting, the proportion of the total nitrogen recovery by the wheat-soil system was about 44% -50%, among which, the residual N in soil occupied about 13% -18% of applied N.

[Clinical analysis of 44 cases with malignant transformation of ovarian mature cystic teratoma].

OBJECTIVE: To analyze the clinicopathologic characteristics, treatment and prognostic factors in malignant transformation of mature cystic teratoma (MCT) of ovary. METHODS: The clinical data of 44 patients with MCT from January 1961 to June 2009 were reviewed. RESULTS: The median age of the 44 patients was 48 years (range, 16 - 84 years). Mean tumor size was (16 ± 6) cm. Thirty-two cases were diagnosed squamous cell carcinoma (73%, 32/44), and 5 of them with the elevated level of serumal squamous cell antigen (SCC-Ag). Three of 37 cases (8%, 3/37) were identified with malignant transformation in image examinations. Rapid frozen section examination and multiple-location biopsy were performed in 8 cases, and 5 of them were detected with malignant diseases. Twenty-two patients with disease confined within the unilateral ovary (10 with intact capsule, and 12 with ruptured capsule). Diseases extended extra ovaries in the others 22 patients. The median cumulative overall survivals were 126 and 10 months, respectively. The difference between the two groups was significant (P < 0.01). Twenty-seven patients had no residual tumor after primary surgery. The median cumulative overall survivals between the patients with and without residual tumor were 10 and 84 months respectively, and there were significant difference between two groups (P < 0.01). Seven selected patients with malignant disease confined within unilateral ovary underwent fertility-sparing surgery, and 2 cases of them had successful pregnancies and delivery, while other 4 cases with ruptured capsule recurred. CONCLUSIONS: The most common pathology type of malignant transformation in mature cystic teratoma of the ovary is squamous cell carcinoma. Comprehensive pre-operation image examination and tumor marker level detection might be of great help in diagnosis. Tumor extension extraovary and residual tumor after surgery are the most significant poor prognostic factors. Early stage patient with ruptured capsule should be very discreet to choose fertility-sparing surgery.

[Clinical review of 97 patients with endometrial stromal sarcoma].

OBJECTIVE: To review the survival outcomes in patients with endometrial stromal sarcoma (ESS) in Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, and to discuss prognostic factors and the role of post-operative adjuvant radiotherapy and chemotherapy. METHODS: Hospital records and pathology reports for 97 patients with ESS were reviewed. Among 97 patients, 69 had low-grade ESS (LGESS), 16 had high-grade ESS (HGESS) and 12 had unclear grade. The median age at diagnosis was 44.0 years. The median follow-up time was 62 months (5 - 277 months). Atypical vaginal bleeding (43%) and prolonged and increased menses (36%) were the main symptoms. RESULTS: Totally 2-year and 5-year cumulative survival rates were 93% and 84%, respectively. Cumulative survival curves were significantly different between LGESS and HGESS, and so did cumulative survival curves between stage I - II and stage III - IV (P < 0.05). Totally, 34 patients (37%) had local or distant recurrence. The median time-to-recurrence (TTR) was 27 months. The recurrence rates of the patients with or without preserve of ovary were 89% and 24%, respectively (P = 0.000). The local-control-rates of the patients who received or did not receive post-operative radiotherapy were 81% and 43%, respectively (P = 0.011). CONCLUSIONS: The prognosis of HGESS is obviously worse than that of LGESS. The risk of recurrence of patients with preserve of ovary was remarkably higher than that of patients without preserve of ovary. Postoperative radiotherapy could increase the local-control-rates.

[Impact of squamous cell carcinoma antigen in patients with recurrent squamous cell carcinoma of the uterine cervix].

OBJECTIVE: To investigate the impact of squamous cell carcinoma antigen (SCCAg) in patients with recurrent squamous cell carcinoma of the uterine cervix. METHODS: Totally 72 patients with recurrent squamous cell carcinoma of the uterine cervix treated at the Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, between 1999 and 2005 were retrospectively analyzed to investigate the impact of SCCAg on diagnosis and prognosis by univariate and multivariate analysis. RESULTS: This study included 30 patients with recurrent disease after primary radical surgery and 42 patients with recurrent cervical cancer after radio-chemotherapy. Sixty one patients (85%) had serum SCCAg elevated (>or=1.5 pg/L), and 20 of these (28%) had an increase of SCCAg before clinical manifestation of relapse. The median leading time was 3 months (range: 1-13 months). Forty five patients had no symptoms with only SCCAg elevation, and 15 patients experienced leg edema and (or) sciatic pain, 7 patients suffered from irregular bleeding and 5 patients had symptoms resulting from distant metastasis. Thirty three patients were diagnosed by histology biopsy and (or) cytology, 39 patients were diagnosed with SCCAg elevation and clinical and radiological examinations, 29 of these patients were diagnosed only by SCCAg elevation and CT or MRI. Fourteen patients recurred limited to the cervix or to the cervix and adjacent tissues (central recurrence), 31 cases recurred at pelvis, and 20 patients with distant metastasis and 7 patients suffered from pelvic recurrence and distant metastasis. Twenty three cases received salvage therapy including surgery for patients recurring after definitive radiotherapy and radiotherapy and or conform radiotherapy for patients after primary radical surgery, 46 patients were given palliative chemotherapy and or radiotherapy, and 3 patients refused any treatment. The median and mean survival time were 11 months and 23 months respectively (2-62 months). The 3-year, 5-year overall survival rate were 25% and 19% respectively. Univariate analysis showed SCCAg elevation before primary treatment, grade, recurrent site, treatment method, SCCAg>or=10 pg/L, SCCAg elevation during treatment, and SCCAg not within normal after treatment were correlated with 3-year survival rate. Twenty patients had an increase of SCCAg before clinical manifestation of relapse compared with other patients who did not, and the 3-year survival rate was not significantly different (22% vs 27%). Multivariate analysis revealed that only grade and treatment methods were independent risk factors. CONCLUSION: The impact of the SCCAg in recurrent squamous cell carcinoma of the uterine cervix needs further study.

[Synchronous primary cancers of the endometrium and ovary: review of 43 cases].

OBJECTIVE: To investigate the clinical and pathological characteristics, treatment methods, and prognosis of synchronous primary cancers of the endometrium and ovary. METHODS: The clinical data of 43 patients with synchronous primary cancers of the endometrium and ovary were retrospectively reviewed. The survival was calculated by Kaplan-Meier method and compared using the log-rank test. RESULTS: The median age at diagnosis was 49 years (range, 28-73 years). The most common symptoms were abnormal vaginal bleeding (69.8%) and abdominal or pelvic pain (44.2%).Pelvic masses were found in 39.5% of the patients and enlarged corpus in 27.9% at physical examination, while pelvic masses were found in 67.4% of the 43 patients (29 cases) and thickening or abnormal endometrium in 23.3% (10 cases) during ultrasound examination. Of 25 patients examined by CT/MRI, pelvic masses were found in 13 cases and enlarged uterus in 11 cases. All 15 patients who underwent endometrial biopsies were proven to have endometrial carcinomas. Serum CA125 level was found to be elevated in 22 of the 34 examined cases (64.7%) with a median value of 500 U/ml (range, 39-3439 U/ml). FIGO stages of endometrial carcinomas: IA 18 cases, IB 20 cases, IC 2 cases, IIA 3 cases; Stages of ovarian carcinomas: IA 19 cases, IB 4 cases, IC 7 cases, II 4 cases, III C 9 cases. Twenty-four patients (55.8%) were in stage I both endometrial and ovarian carcinomas. Thirty-one patients underwent total hysterectomy plus bilateral salpingo-oophorectomy with omentectomy and appendectomy, meanwhile, 12 patients had pelvic lymph node dissection. Thirty-eight of the 43 patients (88.4%) had a pathologically proven endometrial adenocarcinoma. The predominant ovarian histology was endometrioid or mixed tumor with endometrioid components (30/43, 69.8%). Postoperatively, 26 patients (60.5%) received adjuvant chemotherapy alone, 12 had chemotherapy plus radiotherapy, only one patient had radiation alone and the remaining 4 cases received no adjuvant treatment. The 3- and 5-year survival rates of the group were 87.4% and 71.1%, respectively. The 3- and 5-year survival rates of patients with both endometrioid and ovarian carcinomas were higher than that of those with non-endometrioid or mixed subtypes (93.8%, 82.0% vs. 79.7%, 69.0%). The 3-year and 5-year survival rates of patients with early stage disease were better than those of the other patients (93.3%, 93.3% vs. 69.7%, 36.7%). Recurrence developed in 15 patients (34.9%). It was showed by univariate analysis that lower CA125 level, early FIGO stage, and adjuvant chemotherapy plus radiotherapy significantly and positively affect the 5-year survival rates, while only early FIGO stage and chemotherapy plus radiotherapy were revealed by multivariate analysis as independent prognostic factors. CONCLUSION: Synchronous primary cancers of the endometrium and ovary are different from either primary endometrial carcinoma or ovarian cancer, while it can usually be detected in early stage and with a good prognosis. The impact of the CA125 level on prognosis needs to be further studied. Surgical treatment alone may be enough for early stage patients. Chemotherapy plus radiotherapy may be necessary for advanced stage patients.

Treatment options in stage I endometrial stromal sarcoma: a retrospective analysis of 53 cases.

OBJECTIVE: To discuss the optimal treatment options for stage I patients with endometrial stromal sarcoma (ESS). METHODS: We reviewed hospital records and pathology of 53 patients with ESS at stage I. Statistical analysis was performed using SPSS 12.0 software, and Chi-square test, t-test and log rank test were adopted. RESULTS: Among 53 patients, 37 had low-grade tumors, 11 had undifferentiated endometrial sarcoma (UES) and 5 had unclassified ESS. The median follow-up time was 66 months, and 48 cases were still alive. The overall 2-year and 5-year survival rates were 91.5% and 85.9%, respectively. The recurrence rate of the patients with preserved ovarian function was remarkably higher than that of patients without (100% vs. 22.7%, P<0.001). The patients who received adjuvant whole pelvic radiation (Dt 40 approximately 45 Gy) had obviously higher local control rate than the patients who did not (93.8% vs. 57.1%, P=0.007), but they had similar survival (P=0.963). Among 7 of the 11 UES patients without distant recurrence, 5 received the adjuvant chemotherapy with IAP (ifosfamide 1.0 g, d1-4; epirubicin 25 mg/m2, d1-2; cisplatin 20 mg, d1-5; mensa 0.2 g, 0, 4, 8 h from the application of ifosfamide, d1-4, q 28 days) or VAD (vincristine 1.2 mg/m2, d1; adriamycin 20 mg/m2, d1-3; dacarbazine 250 mg/m2, d1-5, q 28 days), and none of the other 4 cases recurring distantly received the chemotherapy with IAP or VAD. CONCLUSIONS: Surgeries not preserving ovarian function were helpful to decrease the risk of recurrence compared with those surgeries sparing ovarian function. Adjuvant radiotherapy could improve local control but not survival. Adjuvant chemotherapy with IAP or VAD seemed to be beneficial to UES patients.

[Efficiency and side effects of concurrent radiotherapy and chemotherapy for advanced cervical cancers].

OBJECTIVE: To investigate the efficiency of concurrent radiotherapy and chemotherapy for advanced cervical cancer. METHODS: Between Dec. 1999 and Dec. 2003, 158 women with cervical cancer were treated with concurrent radiotherapy and chemotherapy. The regimen was 45 Gy/25 fraction radiation to the pelvis, intracavitary after-loading 7-9 fractions, (42 +/- 7) Gy to point A and 10-30 Gy to cervical submucosa 0.5 cm for debulking; meanwhile, chemotherapy was given with cisplatin 60 mg/m2, d1-d4, and 5-Fu 2400 mg/m2, over a 96-hour period. RESULTS: The rate of local resistence and pelvic recurrence was 4.4% and 3.2%, respectively. The rate of distant metastasis was 17.1%. The overall 5-year survival rate was 66.3%, without statistically significant difference between concurrent chemoradiation group and radiation alone group during the same period. The adverse effect included grade 3 or grade 4 leukopenia in 12.7% of these patients, grade 3 thrombocytopenia in 1.3%, anemia in 3.2%, diarrhoea in 17.8%, cardiac toxicity in 10.1% and radiation- related rectitis in 13.3% and cystitis in 0.6%, but alopecia was rare. CONCLUSION: Concurrent chemotherapy and radiotherapy may not be able to improve survival for advanced cervical cancer, however, adverse effect is tolerable.

[Treatment and prognosis of low-grade malignant endometrial stromal sarcoma].

OBJECTIVE: To review the experience in the treatment of low-grade malignant endometrial stromal sarcoma. METHODS: The data of 41 patients with low-grade malignant endometrial stromal sarcoma surgically treated between 1982 and 2004 were reviewed. Statistical analysis was carried out using chi(2) and Kaplan-Meier life table. RESULTS: Of these 41 patients, 24 suffered from irregular vaginal bleeding, and 30 had been diagnosed to have leiomyoma before treatment. Thirty patients but 11 underwent surgical management with uterus removed. Thirty-three patients received postoperative adjuvant therapy including radiation and/or chemotherapy. The 5-year and 10-year actuarial survival was 87. 5% and 77. 8%, respectively. Eighteen patients (43. 9%) developed recurrent disease, most of which in the pelvis. The mean time to recurrence was 31 months (range 6 to 78 months) with the median time of 26 months. The recurrent rate was 66.7% for patients whose ovarian function was reserved versus 37. 5% for those without reservation. Patients who received adjuvant therapy had a lower recurrent rate (30. 3%) than those who did not (87. 5%). The recurrent rate of the patients treated with postoperative adjuvant radiation was 32. 3% (10/31) versus 80% (8/10) for those patients without. The 5-year actuarial survival rate of patients with recurrent disease was 71. 8%. CONCLUSION: Low-grade malignant endometrial stromal sarcoma has a good prognoses though dwarfed by higher late recurrence after initial treatment. Postoperative adjuvant radiation is helpful to reduce local recurrence. Endometrial stromal sarcoma;

[Prognostic analysis of 88 patients with ovarian clear cell carcinoma].

OBJECTIVE: To investigate the clinical characteristics of clear cell carcinoma of the ovary and to compare the survival of the patients treated by three different chemotherapy regimens. METHODS: Between 1984 and 2005, the clinical data of 88 surgically treated patients with clear cell carcinoma of the ovary were retrospectively analyzed. Of the 88 patients, 55 (62.5%) had tumor in stage I, 2 in stage II, 22 in stage II, 3 in stage IV and 6 in indefinite stage. These patients underwent either bilateral salpingo-oophorectomy with hysterectomy and omemtectomy or cytoreduction surgery. Of 55 stage I patients, 20 received pelvic lymohadenectomy. All patients were given postoperative chemotherapy, 43 patients received CAP/CP, 33 paclitaxel combination with carboplatinum/cisplatin (TC/TP) and 12 CPT-11 plus MMC. RESULTS: The response rate, recurrence rate, 3- and 5-year survival was 35.0%, 30.2% (13/43), 67.4% (29/43), 43.9% and 29.3%, respectively in patients treated with CAP/CP; 73.9%, 18.2% (6/33), 45.5% (15/33), 57.3% and 40.5%, respectively in the patients with TC/TP; 71.4%, 16.7% (2/12), 25.0% (3/12), 70.7% ( 3-yr survival, no available 5-yr survival), respectively in the patients with CPT-11 + MMC (P < 0.05). During follow-up, 47 (53.4%) patients were found to have recurrence, it was 45.4% (25/55) in stage I patients including 29.6% (8/27) in stage I a + I b and 60.7% (17/28) in stage I c, 75.0% (18/24) in stage II + III and 4/6 in the indefinite FIGO stage. The recurrences rate was 27.8% (5/18) in stage I patients with pelvic lymphadenectomy vs. 51.3% (19/37) in those without. It was 67.3% in 46 patients with elevated CA125, and 38.1% in the other 42 patients with normal or unavailable CA125 (P < 0.05). The overall 3- and 5-year survival rate of 88 patients was 48.7% and 40.9% , respectively, with 72.5% and 66.8% in stage I, 100.0% and 70.5% in stage Ia + Ib, 68.5% and 60.3% in stage Ic, 41.8% and 20.8% in stage II + III, 0 in stage IV (P < 0.05). The 3- and 5-year survival in stage I with pelvic lymphadenectomy was 88.5% and 75.8% vs. 70.3% and 65.1% in those without (P < 0.05). The 3- and 5-year survival of the patients with optimal (residual disease less than 2 cm) was 36.7% and 23.1% vs. 22.2% and 0 in those with suboptimal cytoreduction (P < 0.05), it was 46.8% and 38.8% in the patients with elevated CA125 vs. 46.7% and 43.5% in those with normal one (P > 0.05). CONCLUSION: Our data show that ovarian clear cell cancer patient have a poor response to CAP/CP and may have a better response to TC/TP, especially to CPT-11 plus MMC. However, the overall prognosis is still poor and further clinical investigations are needed to improve it.