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Objective: Metastatic squamous cell carcinoma (SCC) of inguinal lymph node region with unknown origin is a rare condition. A patient was diagnosed to have vulvar SCC 7 years after the initial diagnosis of inguinal nodal metastatic SCC of unknown primary. Case report: A 59-year-old woman with metastatic SCC of unknown origin in the right inguinal lymph node underwent tumor resection and no evidence of residual disease or possible tumor origin was detected after the surgery and a comprehensive work-up. Seven years later, she was diagnosed to have invasive right vulvar SCC with right pelvic lymph node metastasis. We performed a series of tests to evaluate the relationship between these two events. Conclusion: According to our investigation, the possible relationship between the two events could not be ruled out. This case emphasizes the possibility of late recurrence and the importance of long-term follow up for patients with isolated nodal CUP.

Since government-provided annual cervical cytology testing for all Taiwanese women aged 30 years or older became available in 1995, both cervical cancer incidence and death have decreased significantly. However, with the 2018 introduction of the national immunization program for human papillomavirus (HPV) vaccination in all schoolgirls aged 13–15 years old, the positive predictive value of cytology testing is expected to decrease with rising vaccination rates, and therefore a transition to more sensitive HPV-based testing may be needed. This position paper, derived from discussions by a panel of experts in cervical cancer screening, provides short-, medium-, and long-term policy recommendations to manage the transition between cervical screening methods for Taiwan. The recommendations include concrete suggestions regarding testing procedures, standards, accreditation, monitoring, promotion, and implementation. It is hoped that comprehensive preparation and management of this transition will enable Taiwan to repeat the previous successes of the cervical cytology testing program.

Abstract Background Malignant ascites is prevalent in advanced‐stage ovarian cancer and may facilitate identification of the drivers of muscle loss. This study aimed to evaluate the association of ascites with changes in systemic inflammation and muscle after treatment of advanced‐stage ovarian cancer. Methods We evaluated 307 patients with advanced‐stage (III/IVA) ovarian cancer who underwent primary debulking surgery and adjuvant platinum‐based chemotherapy between 2010 and 2019. The changes in skeletal muscle index (SMI) and radiodensity (SMD) were measured using pre‐surgery and post‐chemotherapy portal‐venous phase contrast‐enhanced computed tomography scans at L3. Systemic inflammation was measured using albumin levels, prognostic nutritional index (PNI), neutrophil‐lymphocyte ratio (NLR), and platelet‐lymphocyte ratio (PLR). Primary endpoint was the changes in SMI and SMD after treatment. Linear regression analysis was used to test associations between muscle change and other covariates. Mediation analysis was used to determine the mediator. Results The median (range) age was 53 (23–83) years. The median duration (range) of follow‐up was 5.2 (1.1–11.3) years. Overall, 187 (60.9%) patients had ascites. The changes in muscle and systemic inflammatory markers after treatment were significantly different between patients with and without ascites (SMI: −3.9% vs. 2.2%, P

Abstract Background Skeletal muscle loss during treatment is associated with poor survival outcomes in patients with ovarian cancer. Although changes in muscle mass can be assessed on computed tomography (CT) scans, this labour‐intensive process can impair its utility in clinical practice. This study aimed to develop a machine learning (ML) model to predict muscle loss based on clinical data and to interpret the ML model by applying SHapley Additive exPlanations (SHAP) method. Methods This study included the data of 617 patients with ovarian cancer who underwent primary debulking surgery and platinum‐based chemotherapy at a tertiary centre between 2010 and 2019. The cohort data were split into training and test sets based on the treatment time. External validation was performed using 140 patients from a different tertiary centre. The skeletal muscle index (SMI) was measured from pre‐ and post‐treatment CT scans, and a decrease in SMI ≥ 5% was defined as muscle loss. We evaluated five ML models to predict muscle loss, and their performance was determined using the area under the receiver operating characteristic curve (AUC) and F1 score. The features for analysis included demographic and disease‐specific characteristics and relative changes in body mass index (BMI), albumin, neutrophil‐to‐lymphocyte ratio (NLR), and platelet‐to‐lymphocyte ratio (PLR). The SHAP method was applied to determine the importance of the features and interpret the ML models. Results The median (inter‐quartile range) age of the cohort was 52 (46–59) years. After treatment, 204 patients (33.1%) experienced muscle loss in the training and test datasets, while 44 (31.4%) patients experienced muscle loss in the external validation dataset. Among the five evaluated ML models, the random forest model achieved the highest AUC (0.856, 95% confidence interval: 0.854–0.859) and F1 score (0.726, 95% confidence interval: 0.722–0.730). In the external validation, the random forest model outperformed all ML models with an AUC of 0.874 and an F1 score of 0.741. The results of the SHAP method showed that the albumin change, BMI change, malignant ascites, NLR change, and PLR change were the most important factors in muscle loss. At the patient level, SHAP force plots demonstrated insightful interpretation of our random forest model to predict muscle loss. Conclusions Explainable ML model was developed using clinical data to identify patients experiencing muscle loss after treatment and provide information of feature contribution. Using the SHAP method, clinicians may better understand the contributors to muscle loss and target interventions to counteract muscle loss.

Objective: Post-menopausal bleeding is one of the most common reasons for attending the gynecology outpatient clinic. The major proportion of the symptoms is endometrial atrophy (about 60%) despite of the endometrial thickness is over 4 mm. Therefore, the aim of this study is to evaluate the endometrial thickness under sonogram in the women with atrophic endometrium, with or without post-menopausal vaginal bleeding. Materials and methods: This is a retrospective study and we enrolled 237 post-menopausal women with pathological evidence of atrophic endometrium from Jan. 2014 to Dec. 2018 in Mackay Memorial hospital. Patient's characteristics taken into account were age, vaginal bleeding status, the methods of obtaining endometrial tissue, hormonal replacement therapy and breast cancer history under tamoxifen treatment. Endometrial thickness was classified as ≤ 4 mm, >4 mm–10 mm and >10 mm. We calculated the proportion of the characteristic mentioned before. Results: In total, 237 patients were enrolled and 35 patients were excluded; therefore, the remaining 202 patients were analyzed. There were 42 (20.8%), 109 (54%) and 51 (25.2%) patients with endometrial thickness ≤4 mm, >4 mm–10 mm and >10 mm respectively. There was significant difference in the numbers of patients with post-menopausal bleeding (p = 0.002) and breast cancer history under tamoxifen therapy (p

Human papillomavirus (HPV) remains a global health concern because it contributes to the initiation of various HPV-associated cancers such as anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancer. In HPV-associated cancers, oncogenesis begins with an HPV infection, which is linked to the activation of the Janus protein tyrosine kinase (JAK)/STAT signaling pathway. Various STAT signaling pathways, such as STAT3 activation, have been well documented for their tumorigenic role, yet the role of STAT1 in tumor formation remains unclear. In the current study, STAT1−/− mice were used to investigate the role of STAT1 in the tumorigenesis of a spontaneous HPV E6/E7-expressing oral tumor model. Subsequently, our candidate HPV DNA vaccine CRT/E7 was administered to determine whether the STAT1−/− host preserves a therapeutic-responsive tumor microenvironment. The results indicated that STAT1−/− induces robust tumorigenesis, yet a controlled tumor response was attained upon CRT/E7 vaccination. Characterizing this treatment effect, immunological analysis found a higher percentage of circulating CD4+ and CD8+ T cells and tumor-specific cytotoxic T cells. In addition, a reduction in exhaustive lymphocyte activity was observed. Further analysis of a whole-cell tumor challenge affirmed these findings, as spontaneous tumor growth was more rapid in STAT1−/− mice. In conclusion, STAT1 deletion accelerates tumorigenesis, but STAT1−/− mice maintains immunocompetency in CRT/E7 treatments.

Objective: Breast cancer metastasis to the female genital tract is rare, and the ovaries are the most frequent site of extragenital cancer metastasis. The uterus and cervix have been rarely reported as the site of metastasis. Case report: A 57-year-old woman diagnosed with invasive lobular carcinoma of the left breast 2 years prior was undergoing tamoxifen treatment. She presented with a right breast mass and postmenopausal bleeding. Synchronous right breast invasive lobular carcinoma with endometrium metastasis was diagnosed. The metastasis tumor involved the endometrium, myometrium, cervix, ovaries, and fallopian tubes. Conclusion: We noted the rarity of massive metastasis of the female genital tract from breast cancer. Gynecological surveillance and prompt evaluation of the endometrium led to timely diagnosis and treatment.

Purpose We aimed to determine the effects and possible mechanisms of hyperthermic intraperitoneal chemotherapy (HIPEC) in targeting ovarian cancer stem-like cells (CSCs). Methods Murine ovarian cancer cell lines presenting CSC surface markers were grown intraperitoneally in both immunocompetent and immunodeficient mice, which were then treated by intraperitoneal hyperthermia with the chemotherapeutic agents: paclitaxel and cisplatin. Tumor growth was measured by non-invasive luminescent imaging. Intraperitoneal immune cells, such as CD4+, CD8+ T cells, macrophages, and dendritic cells, were evaluated through flow cytometry analysis. Results Combined hyperthermia and chemotherapy exhibited an efficient therapeutic effect in the immunocompetent mice. However, a similar effect was not observed in the immunodeficient mice. Intraperitoneal hyperthermia increased the number of Intraperitoneal macrophages and dendritic cells that were lost due to chemotherapy. Compared with ovarian cancer bulk cells, CSCs were more susceptible to phagocytosis by macrophages. Conclusion We demonstrated that the superior therapeutic efficacy and reduced proportion of CSCs associated with intraperitoneal hyperthermic chemotherapy were immune-related. Hyperthermia recruits the phagocytes that target surviving CSCs after chemotherapy. These results provide a novel mechanism for the efficacy of HIPEC in treating ovarian cancer.

Abstract Background Sarcopenia is commonly observed in patients with advanced‐stage epithelial ovarian cancer (EOC). However, the effect of body composition changes—during primary debulking surgery (PDS) and adjuvant platinum‐based chemotherapy—on outcomes of patients with advanced‐stage EOC is unknown. This study aimed to evaluate the association between body composition changes and outcomes of patients with stage III EOC treated with PDS and adjuvant platinum‐based chemotherapy. Methods Pre‐treatment and post‐treatment computed tomography (CT) images of 139 patients with stage III EOC were analysed. All CT images were contrast‐enhanced scans and were acquired according to a standardized protocol. The skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), and total adipose tissue index were measured using CT images obtained at the L3 vertebral level. Predictors of overall survival were identified using Cox regression models. Results The median follow‐up was 37.9 months. The median duration between pre‐treatment and post‐treatment CT was 182 days (interquartile range: 161–225 days). Patients experienced an average SMI loss of 1.8%/180 days (95% confidence interval: −3.1 to −0.4; P = 0.01) and SMD loss of 1.7%/180 days (95% confidence interval: −3.3 to −0.03; P = 0.046). SMI and SMD changes were weakly correlated with body mass index changes (Spearman ρ for SMI, 0.15, P = 0.07; ρ for SMD, 0.02, P = 0.82). The modified Glasgow prognostic score was associated with SMI loss (odds ratio: 2.42, 95% confidence interval: 1.03–5.69; P = 0.04). The median time to disease recurrence was significantly shorter in patients with SMI loss ≥5% after treatment than in those with SMI loss

Abstract Background Treatment‐related toxicities and decreased levels of patient performance during cancer therapy might contribute to body composition changes and thereby impact outcomes. However, the effect of longitudinal body composition changes on outcomes in patients with advanced endometrial cancer is unknown. This study investigated the association between body composition changes during staging surgery and adjuvant chemoradiotherapy and outcomes in patients with stage III endometrial cancer. Methods Pretreatment and post‐treatment computed tomography (CT) images of 131 patients with stage III endometrial cancer who were treated between 2008 and 2016 were analysed. All CT images were contrast enhanced and acquired according to the standardized protocol. The skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), and total adipose tissue index were measured from two sets of CT images obtained at the level of the third lumbar vertebra. The skeletal muscle gauge was calculated by multiplying SMI by SMD (SMI × SMD). Predictors of overall survival and progression‐free survival were identified using Cox regression models. Results The median follow‐up was 50.6 (range 12.1–117.0) months. Overall, body mass index (BMI) changes during treatment were 0.4% per 210 days (95% confidence interval: −0.6 to 1.4; P = 0.41), and patients experienced an average SMD loss of 2.1% per 210 days (95% confidence interval: −4.0 to −0.2; P = 0.03). Weight loss and SMD loss ≥5% were observed in 23 (17.6%) and 54 (41.2%) patients, respectively. The changes in SMD did not correlate with those in BMI (Spearman's ρ for SMD, −0.13; P = 0.13). SMD change (per 1 Hounsfield unit/210 days decrease) was independently associated with poorer overall survival (hazard ratio: 1.32, 95% confidence interval: 1.14–1.52; P < 0.001) and progression‐free survival (hazard ratio: 1.28, 95% confidence interval: 1.12–1.43; P < 0.001). Our results did not show association between survival and pretreatment myosteatosis and sarcopenia or changes in SMI and total adipose tissue index during treatment. The pretreatment skeletal muscle gauge was associated with treatment modifications such as delays, dose reductions, and discontinuation of chemotherapy. Conclusions Skeletal muscle radiodensity decreased significantly during treatment and was independently associated with poorer survival in patients with stage III endometrial cancer who underwent staging surgery and adjuvant chemoradiotherapy. SMD loss was occult and occurred independently of BMI change.

Purpose: Intraperitoneal (IP) chemotherapy has several benefits but also can have severe hematologic side effects. We compared the effects of hyperthermic intraperitoneal chemotherapy (HIPEC) and conventional IP chemotherapy on bone marrow suppression and evaluated whether HIPEC increased neutrophil recovery. Methods: HIPEC or IP chemotherapy was administered to ovarian cancer–bearing mice. Bone marrow progenitor cell colony-forming unit (CFU) count, serum cytokine levels, and peripheral leukocyte count after HIPEC and IP chemotherapy were compared. Results: Peripheral neutrophil count, cytokine (G-CSF and CXCL1/KC) levels, and bone marrow progenitor cell CFU count were significantly higher after HIPEC than after IP chemotherapy. Conclusions: Hyperthermia increased the serum neutrophil-recruiting cytokine levels and reduced the magnitude of chemotherapy-induced neutropenia. Thus, HIPEC improved neutrophil and bone marrow recovery compared with conventional IP chemotherapy.

Objective: Tyrosine-protein kinase MET (c-MET) has been reported to be a prognostic marker and suitable therapeutic target for ovarian cancer. BMS-777607, a small molecule, can inhibit MET and other protein kinase activities. The present study was conducted to investigate the mechanism of action and antitumor effect of BMS-777607 on ovarian cancer cells with constitutively activated c-MET. Materials and methods: Ovarian cancer cells with constitutively activated c-MET were first identified through Western blot analysis. Bio-behaviors, including signal transduction, proliferation, apoptosis, and migration, of the cells with constitutively activated c-MET were evaluated after BMS-777607 treatment. Liu's stain and immunological staining of α-tubuline were performed to evaluate the ploidy of the cells. A xenograft mouse model was also used to evaluate the antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-MET. Results: BMS-777607 could induce the highest inhibition of cell growth in ovarian cancer cells constitutively expressing c-MET. Treating SKOV3 cells with BMS-777607 could reduce c-MET activation and inhibit downstream cell signaling, thus causing cell apoptosis and polyploidy as well as cell cycle and cell migration inhibition. This molecule also inhibited tumor growth in a mouse xenograft model of SKOV3 ovarian cancer cells in vivo. Conclusion: BMS-777607 exhibits antitumor effects on ovarian cancer cells that constitutively express c-MET through c-MET signaling blockade and the inhibition of Aurora B activity. Combination treatments to enhance the effects of BMS-777607 warrant investigation in the future. Keywords: Ovarian cancer, Tyrosine kinase, c-MET

Objective: Mucosal-associated invariant T cells (MAITs) are important for immune defense against infectious pathogens and regulation of various inflammatory diseases. However, their roles in cancer are rarely reported. Since cervical cancer is one of the diseases involving mucosal tissue, we try to investigate the association between circulating MAITs and cervical cancer. Materials and methods: Blood samples were obtained from patients with cervical cancer (n = 47) and healthy individuals (n = 39). We determined phenotypic MAITs in peripheral blood mononuclear cells (PBMCs) and evaluated the percentage of MAITs in CD3+ cells by flow cytometry. The percentage of MAITs was stratified according to Federation of Gynecology and Obstetrics (FIGO) staging system in patients with cervical cancer. Progression-free survival (PFS) with respect to the amount of MAITs was also analyzed. Results: The percentage of circulating MAITs in patients with cervical cancer was significantly lower than in healthy group (0.987% vs. 4.008%, p

Objective: c-Met is expressed in human ovarian cancer tissues, and its phosphorylation activates signaling cascades that might affect the behavior of cancer cells. In this study, we evaluated the association of c-Met and phosphorylated c-Met (phospho-c-Met) expressions with the clinical outcomes of ovarian cancer patients. Materials and methods: Archived tissue from surgical specimens of 269 ovarian cancer patients who underwent a debulking operation in MacKay Memorial Hospital between 2004 and 2012 were collected. Tissue microarrays were stained with anti-Met and anti-phospho-Met (Tyr1234/1235) monoclonal antibodies. Immunostaining intensity was scored on a scale of 0–3+. High expression was defined as more than 50% of moderate and intense staining. Patients’ clinical data were reviewed until April 2017 for analysis. Results: The proportion of high c-Met expression was significantly higher in patients with cancer in early stages (Federation of Gynecology and Obstetrics stages I and II) and low histologic grades (grades 1 and 2) (79.70%, p = 0.0008 and 80.15%, p ≤ 0.0001, respectively). However, no association was found between phospho-c-Met and FIGO stage or the histologic grade. Ovarian clear cell carcinoma and mucinous carcinoma had much higher c-Met expression (95.16% and 87.10%, p ≤ 0.0001 and p = 0.0292, respectively). Although the overall survival did not differ significantly, low expressions of c-Met and phospho-c-Met were obviously associated with poor progression-free survival respectively (p = 0.0034, HR: 0.5264, 95% CI: 0.3326–0.8330 and p = 0.0136, HR: 0.5626, 95% CI: 0.3709–0.8535). Conclusion: Low c-Met expression was associated with poor clinical outcomes. Keywords: c-Met, phospho-c-Met, Ovarian cancer

Recurrence of advanced epithelial ovarian cancer is common despite optimal surgical debulking and initial favorable responses to chemotherapy. Evidences suggest that cancer stem cells (CSCs) have inherent resistance to conventional therapies such as chemotherapy and play a decisive role in cancer recurrence. Cancer stem cells are also believed to be able to evade immunological attack. However, this study showed a different scenario in which cancer stem-like cells are more vulnerable to immunosurveillance. Our study demonstrated that isolated murine cancer stem-like cells, stem cell antigen (SCA)-1+ ID8 and CD133+ HM-1 cells, were susceptible to phagocytosis by macrophages and consequent CD8+ T cell immunity. The increased phagocytosis of these stem cell-like cells is attributed to low CD47 protein expression. SCA-1+ ID8 cells were able to grow in syngeneic mice but were soon rejected. Restoring CD47 expression delayed this immune-mediated rejection. SCA-1+ ID8 cells showed rapid growth by mixing with bulk ID8 cells. These results suggest that stem-like cells could be protected by surrounding non-stem cancer cells from immune attack. Similarly, both isolated human CD24−/low SKOV3 stem-like cells and spheroid OVCAR3 cells expressed lower CD47 levels. Our study provided novel insights into the immune characteristics of CSCs within a tumor microenvironment. The results might lead to the design of more effective treatment strategies for ovarian cancer.

Uterine sarcoma is a very aggressive and highly lethal disease. Even after a comprehensive staging surgery or en block cytoreduction surgery followed by multimodality therapy (often chemotherapy and/or radiation therapy), many patients relapse or present with distant metastases, and finally die of diseases. The worst outcome of uterine sarcomas is partly because of their rarity, unknown etiology, and highly divergent genetic aberration. Uterine sarcomas are often classified into four distinct subtypes, including uterine leiomyosarcoma, low-grade uterine endometrial stromal sarcoma, high-grade uterine endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Currently, evidence from tumor biology found that these tumors showed alternation and/or mutation of genomes and the intracellular signal pathway. In addition, some preclinical studies showed promising results for targeting receptor tyrosine kinase signaling, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, various kinds of growth factor pathways, Wnt/beta-catenin signaling pathway, transforming growth factor β/bone morphogenetic protein signal pathway, aurora kinase A, MDM2 proto-oncogene, histone deacetylases, sex hormone receptors, certain types of oncoproteins, and/or loss of tumor suppressor genes. The current review is attempted to summarize the recurrent advance of targeted therapy for uterine sarcomas.

Uterine sarcomas account for 3–7% of all uterine cancers. Because of their rarity, unknown etiology, and highly divergent genetic aberration, there is a lack of consensus on risk factors for occurrence and predictive poor outcomes as well as optimal therapeutic choices. Tumor types according to the World Health Organization classification include leiomyosarcoma, endometrial stroma sarcoma, and undifferentiated sarcoma. Staging is done using the 2014 Federation International Gynecology and Obstetrics and 2010 American Joint Committee on Cancer tumor, lymph node, and metastases systems. Tumor grade can be classified based on the French Federation of Cancer Centers Sarcoma Group system or the Broder’s system that incorporates tumor differentiation, mitotic count, and tumor necrosis. This review is a series of articles discussing uterine sarcoma, and this is Part I, which focuses on one of the subtypes of uterine sarcomas—uterine leiomyosarcoma. The clinical characteristics, diagnosis, outcome, and recent advances are summarized in this article.

Endometrial stromal tumors are rare uterine tumors (

Objective: To dissect the correlated hematologic markers that reflect the clinical outcome or treatment response in patients receiving dose-dense chemotherapy with a combination of platinum (cisplatin or carboplatin) and paclitaxel. Materials and Methods: From 2009 to 2014, we enrolled 55 ovarian cancer patients (total 67 courses) including first-line, persistent, platinum-sensitive, or platinum-resistant disease in MacKay Memorial Hospital, Taipei, Taiwan. Weekly pretreatment complete blood counts and calculated ratios [platelet/neutrophil ratio, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), neutrophil/monocyte ratio, platelet/monocyte ratio, lymphocyte/monocyte ratio] during dose-dense chemotherapy were collected. By grouping these hematologic biomarkers into three different response subgroups (responsive, stable, and nonresponsive) according to CA125 trend, the data were analyzed using one-way analysis of variance, and using post hoc-Tukey test for comparing each other. A p value < 0.05 was considered to be statistically significant. Results: Absolute counts of lymphocytes and platelets, PLR, platelet/neutrophil ratio, platelet/monocyte ratio (all p < 0.001), and NLR (p=0.013) had statistically significant differences. Moreover, using box-and-whisker plot, absolute count of lymphocyte, PLR, and NLR showed most remarkable discrepancy in responsive, stable, and nonresponsive patients. Subgroup analysis for primary, platinum-sensitive, and platinum-resistant patients further revealed that PLR and NLR were significantly correlated to the outcome of dose-dense chemotherapy. Conclusion: Lower PLR or lower NLR had better treatment response for dose-dense chemotherapy and are possible markers for representing treatment response in dose-dense chemotherapy. For a clinician, this is useful for timing when to switch to another chemotherapy regimen.

Purpose : Radiotherapy with concurrent chemotherapy has been recommended as standard treatment for locally advanced cervical cancer. To validate the main tumor location before each high-precision helical tomotherapy (HT) fraction, the development of a more reliable marker or indicator is of clinical importance to avoid inadequate coverage of the main tumor. Material and methods: A 61-year-old woman with cervical cancer, TMN stage cT2b2N1M1, FIGO stage IVB was presented. Extended field external beam radiotherapy (EBRT) with concurrent chemotherapy and the interdigitated delivery of intracavitary brachytherapy was performed. Helical tomotherapy equipped with megavoltage cone beam computed tomography (MV-CBCT) was used for image-guided radiotherapy. For the insertion of tandem of brachytherapy applicator, a silicone sleeve with a central hollow canal was placed into the endocervical canal with the caudal end stopping at the outer surface of the cervical os, and making contact with the distal boundary of the cervical tumor during the entire brachytherapy course. Results : In the remaining EBRT fractions, we found that the air cavity inside the central hollow canal of the sleeve could be clearly identified in daily CBCT images. The radiation oncologists matched the bony markers to adjust the daily setup errors because the megavoltage of the CBCT images could not provide a precise boundary between the soft tissue and the tumor, but the sleeve air cavity, with a clear boundary, could be used as a surrogate and reliable marker to guide the daily setup errors, and to demonstrate the primary tumor location before delivery of each HT fraction. Conclusions : The application of the sleeve during the interdigitated course of HT and brachytherapy in this patient provided information for the feasibility of using the sleeve air cavity as a surrogate marker for the localization of the main primary tumor before the daily delivery of image-guided HT.

Objective: Herein, we report a case of ovarian serous carcinoma with paraneoplastic cerebellar degeneration. Case report: A 44-year-old female presented to our hospital with dizziness, slurred speech, and ataxic gait. Brain magnetic resonance imaging was normal. A lumbar puncture revealed a normal cell count in the cerebrospinal fluid, but slightly elevated protein. Her serum cancer antigen -125 level was high (2126.4 U/mL), and abdominal computed tomography disclosed a pelvic mass measuring 11 cm in diameter. Exploratory laparotomy was then performed, and a frozen section of the tumor revealed serous carcinoma. Conclusion: According to the surgical findings and pathological report, The International Federation of Gynecology and Obstetrics (FIGO) Stage IIIC, Grade 3, serous-type ovarian cancer was diagnosed. Due to the abovementioned symptoms and signs, we performed a serial test to document the presence of anti-Yo antibody in this patient.

Objective: The goal of this study is to assess the feasibility of simple extrafascial hysterectomy for patients with clinical stage IA1 cervical squamous cell carcinoma (SCC) after once conization regardless of any pathologic risk factor. Materials and Methods: All cases with T1a1, SCC lesion in their cervical cone specimen were retrospectively collected after chart and pathology review for the period between January 2002 and December 2009. All cases underwent subsequent hysterectomies within a month of diagnosis. Pathologic risk factors of conization, surgical scale of hysterectomy, residual lesion of the uterus, necessity of adjuvant radiation therapy, complications, and survival were analyzed in this study. Results: Eighty-one cases were identified from the registry. Most were managed by simple hysterectomy (SH; 60/81, 74%), and the remaining 21 cases underwent modified radical hysterectomy (MRH). All cases without any risk factors in their cone specimens demonstrated residual lesion ≤T1a1 in both SH and MRH groups, whereas those with existing risk factor were confirmed positive for residual lesions ≤T1a1 [SH, 95.8% (46/48) vs. MRH, 75% (15/20)]. Only two cases in the SH group received adjuvant radiation for residual lesions >T1a1. On the contrary, 15 cases in the MRH group can receive smaller scale surgery than MRH. All cases were recurrence-free without any permanent treatment-related complication by the end of the study. Conclusion: Extrafascial simple hysterectomy may be recommended for clinical T1a1 cervical SCC regardless of the pathologic risk factor.

Objective: The aim of this study was to assess the benefits of the 2009 International Federation of Gynecology and Obstetrics (FIGO) staging system for survival of patients with Stage IIA1 and IIA2 cervical cancer (Cx Ca). Materials and Methods: A study cohort of 51 patients with Stage IIA Cx Ca was retrospectively collected from the 2004–2009 hospital-based, long-form Cx Ca data registry at Mackay Memorial Hospital (Taipei, Taiwan). The survivorship and overall survival were compared between these two groups (Stages IIA1 and IIA2) using log-rank test. Results: Thirty-six and 15 patients were classified into Stages IIA1 and IIA2, respectively. Stage IIA2 patients were younger than those with Stage IIA1 disease (mean age, 47.4 vs. 55.1 years, p = 0.008), but no significant difference was observed in confirmed pelvic lymph node status (21.4% vs. 38.5%, p = 0.280) between them. Although the 2-year and 5-year overall survival was better among Stage IIA1 patients, there was no significant difference in survival between Stage IIA1 and IIA2 groups (2-year, 90.6% vs. 77.8%; 5-year, 86.3% vs. 51.9%, p = 0.218). Conclusion: Although there was a trend in survival difference between Stage IIA1 and IIA2 patients, the difference was not statistically significant. The revised FIGO 2009 staging system for Cx Ca defines a group of Stage IIA patients with bulky tumor (Stage IIA2) that are generally younger than Stage IIA1 patients. It is sensible to investigate an alternate or enhanced treatment scheme for Stage IIA2 patients. Ideally, the treatment scheme should prevent unnecessary radical surgery if a patient can be exposed to either chemotherapy or radiotherapy, alone or in combination.

Background: Surgical staging using transperitoneal laparoscopic para-aortic lymph node dissection is an option for the pretreatment evaluation of locally advanced cervical cancer; however, its role for elderly patients (≥ 65 years) remains unclear. Methods: Elderly patients with stage IIB–IVA cervical squamous cell carcinoma who underwent transperitoneal laparoscopic para-aortic lymph node dissection (TLSPAD) before radiation therapy (RT) or concurrent chemoradiation therapy (CCRT) during 1993–2001 were included in this retrospective study. The control group included elderly patients with the same clinical conditions, except they did not undergo TLSPAD. Survival and major bowel complications were compared between these two groups. Results: The TLSPAD group consisted of 19 patients (median age: 72 years; range: 65–78 years), and the control group consisted of 37 patients (median age: 73 years; range: 65–86 years). In the TLSPAD group, para-aortic lymph node metastasis was noted in 15.8% of patients and another 15.8% were unable to have their lymph node laparoscopically retrieved. Although patients in the TLSPAD group demonstrated a higher rate of receiving CCRT than the control group, neither failure-free survival nor overall survival were statistically different between these two groups. Subsequent major bowel complications (e.g., fistula, bowel obstruction) were more frequent in the TLSPAD group (36.8%) than the control group (10.8%; p=0.032). Conclusion: In elderly patients with locally advanced cervical squamous cell carcinoma, pretreatment TLSPAD might not improve survival and might be associated with an increased risk of subsequent major bowel complications. Extraperitoneal laparoscopic para-aortic lymphadenectomy might be a better method for the pretreatment surgical staging of elderly patients because it could potentially result in fewer bowel complications.

Response to platinum retreatment in recurrent epithelial ovarian cancer is related to the platinum-free interval (PFI). The recommended and most accepted chemotherapy in the treatment of platinum-sensitive (PFI > 6 months) recurrence is platinum-based combination regimens. Patients with a PFI of 6–12 months are often considered partially platinum-sensitive (PPS) because lower response rates to subsequent platinum retreatment have been identified. Controversies and uncertainties still exist in this population of patients regarding the best treatment and the most effective therapeutic agents. It is proposed that extending the PFI with non-platinum agents may enhance the response to and the outcome of subsequent rechallenge with platinum. In this review, we discuss the treatment for PPS recurrent ovarian cancer and the possible clinical significance of extending PFI with intent to improve the medical care of PPS recurrence.

Objective: To report five cases of major congenital malformations associated with common aneuploidies detected by rapid aneuploidy diagnosis. Case Reports: The fetus in the first case presented cebocephaly, semilobar holoprosencephaly, and tetralogy of Fallot on ultrasound at 25 gestational weeks. Cordocentesis using multiplex ligation-dependent probe amplification to detect aneuploidies of chromosomes X, Y, 13, 18, and 21 in uncultured cord blood revealed three copies of all targets on chromosome 13 consistent with the diagnosis of trisomy 13. The fetus in the second case presented bilateral choroid plexus cysts, congenital diaphragmatic hernia, and club foot on ultrasound at 18 gestational weeks. Amniocentesis using array-based comparative genomic hybridization (aCGH) in uncultured amniocytes revealed a gain in the DNA dosage of chromosome 18 consistent with the diagnosis of trisomy 18. The fetus in the third case presented aortic stenosis and nuchal edema on ultrasound at 22 gestational weeks. Amniocentesis using aCGH in uncultured amniocytes revealed a result of monosomy X and Turner syndrome. The fetus in the fourth case presented nuchal cystic hygroma and ventriculomegaly on ultrasound at 17 gestational weeks. Amniocentesis using aCGH in uncultured amniocytes revealed a gain in the DNA dosage of chromosome 21 consistent with the diagnosis of trisomy 21. The fetus in the fifth case presented holoprosencephaly, omphalocele, and hydronephrosis on ultrasound at 17 gestational weeks. Amniocentesis using aCGH in uncultured amniocytes revealed a gain in the DNA dosage of chromosome 13 consistent with the diagnosis of trisomy 13. Conclusions: Prenatal diagnosis of major congenital malformations should alert one to the possibility of chromosomal abnormalities. Multiplex ligation-dependent probe amplification and aCGH have the advantage of rapid aneuploidy diagnosis of common aneuploidies in cases with major congenital malformations.

Objective: To evaluate the relevant factors for cervical cancer among young women in Taiwan. Materials and Methods: A case-control study was conducted between 1986 and 1992. The cases included 45 women younger than 36 years with histologically confirmed invasive cervical cancer. The controls were 54 women younger than 36 years with non-neoplastic conditions judged to be unrelated to any of the risk factors for cervical cancer. Questions were asked about demography, contraception, reproductive history, sexual history, diet, cigarette smoking, and cooking practices. Results: Cross tabulation and Pearson's Chi-squared test showed that monthly income, age at first birth, parity, numbers of vaginal deliveries, age at first intercourse, history of sexually transmitted disease, husband visiting prostitutes, and cooking practice were significantly different between the case and control groups. However, after conditional logistic regression analysis, only cooking practice remained associated with cervical cancer among young women. Among young women reporting to cook on a daily basis, the risk for cervical cancer tended to increase among those who fried five times or more per month (OR = 7.4) compared with women who fried less often. Conclusion: The results from this study indicated that cooking practice may be a risk factor for the development of cervical cancer among young women in Taiwan.

The purpose of this study was to investigate the anti-tumor effect and potential mechanisms of i.p. hyperthermia in combination with α-galactosylceramide (α-GalCer) for the treatment of ovarian cancer. In this study, immuno-competent tumor models were established using murine ovarian cancer cell lines and treated with i.p. hyperthermia combining α-GalCer. Th1/Th2 cytokine expression profiles in the serum, NK cell cytotoxicity and phagocytic activities of dendritic cells (DCs) were assayed. We also analyzed the number of CD8(+)/IFN-γ(+) tumor specific cytotoxic T cells, as well as the tumor growth based on depletion of lymphocyte sub-population. Therapeutic effect on those ovarian tumors was monitored by a non-invasive luminescent imaging system. Intra-peritoneal hyperthermia induced significant pro-inflammatory cytokines expression, and sustained the response of NK and DCs induced by α-GalCer treatment. The combination treatment enhanced the cytotoxic T lymphocyte (CTL) immune response in two mouse ovarian cancer models. This novel treatment modality by combination of hyperthermia and glycolipid provides a pronounced anti-tumor immune response and better survival. In conclusion, intra-peritoneal hyperthermia enhanced the pro-inflammatory cytokine secretion and phagocytic activity of DCs stimulated by α-GalCer. The subsequent CTL immune response induced by α-GalCer was further strengthened by combining with i.p. hyperthermia. Both innate and adaptive immunities were involved and resulted in a superior therapeutic effect in treating the ovarian cancer.