Outcomes in Advanced Stage Epithelial Ovarian, Fallopian Tubal, and Peritoneal Cancer after Primary Surgery and Adjuvant Chemotherapies: A Single-Institute Real-World Experience.

Debulking surgery followed by systemic chemotherapy-including three-weekly intravenous paclitaxel and carboplatin (GOG-158)-is the cornerstone for advanced epithelial ovarian, fallopian tubal, and peritoneal cancer (EOC) treatment. In this scenario, Federation of Gynecology and Obstetrics (FIGO) stage, cell types, completeness of surgery, lymph nodes (LN) status, adjuvant chemotherapy regimens, survival status, progression-free survival (PFS), and overall survival (OS) of 192 patients diagnosed as having stage IIIA1-IVB EOC over January 2008-December 2017 were analyzed retrospectively. Of them, 100 (52.1%) patients had been debulked optimally. Of all cases, 64.1% and 10.9% demonstrated serous and clear-cell carcinoma. Moreover, the FIGO stage, surgery completeness, and LN status affected recurrence/persistence and mortality (all p < 0.001). Clear cell carcinoma led to shorter survival than serous carcinoma (p = 0.002). Adjuvant chemotherapy regimens were divided into five main groups according to previous clinical trials. However, choice of chemotherapy failed to demonstrate significant differences in patient outcomes. Similar results were found in the sub-analysis of optimally debulked cases, except that intraperitoneal chemotherapy could reduce mortality risk when compared with GOG-158 (p = 0.042). Notably, retroperitoneal LN dissection in all cases or optimally debulked cases reduced risks of recurrence/persistence and mortality, and prolonged PFS and OS significantly (all p < 0.05). Without optimal debulking, LN dissection led to little improvement in outcomes. Various modified chemotherapy regimens did not prolong PFS and OS or reduce recurrence/persistence and mortality risks. LN dissection is strongly recommended to improve the completeness of surgery and patient outcome. Clear cell type has a poorer outcome than serous type, which requires more aggressive treatment and follow-up.

Muscle loss during primary debulking surgery and chemotherapy predicts poor survival in advanced-stage ovarian cancer.

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 <5% or gain (5.4 vs. 11.2 months, P = 0.01). Pre-treatment SMI (1 cm2 /m2 decrease; hazard ratio: 1.08, 95% confidence interval: 1.03-1.11; P = 0.002) and SMI change (1%/180 days decrease; hazard ratio: 1.04, 95% confidence interval: 1.01-1.08; P = 0.002) were independently associated with poorer overall survival. SMD, body mass index, and total adipose tissue index at baseline and changes were not associated with overall survival. CONCLUSIONS: Skeletal muscle index decreased significantly during treatment and was independently associated with poor overall survival in patients with stage III EOC treated with PDS and adjuvant platinum-based chemotherapy. The modified Glasgow prognostic score might be a predictor of SMI loss during treatment.

Effect of Chemotherapy, Laparoscopy, and Cytology on Stage IC Ovarian Clear Cell Carcinoma: A Long-Term, Single-Center Study.

Ovarian clear cell carcinoma (OCCC) is the second common histology of epithelial ovarian cancer in Taiwan. Stage IC is common, especially during minimally invasive surgery. Adjuvant chemotherapy in stage IC OCCC is unavoidable, and paclitaxel-based chemotherapy in Taiwan is self-paid. However, surgical spillage from minimally invasive surgery as a cause of unfavorable prognosis is still uncertain. The information of patients with stage IC OCCC, corresponding to a period of January 1995 to December 2016, was retrospectively collected following a chart and pathology review. Data regarding surgical methods, cytology status, regimens of adjuvant chemotherapy, survivorship, progression-free survival (PFS), and overall survival (OS) period were analyzed. In total, 88 patients were analyzed, and 64 and 24 patients were treated with paclitaxel- and nonpaclitaxel-based chemotherapy, respectively. Recurrence was identical between the two groups: PFS (47.5 ± 41.36 versus 54.0 ± 53.9 months, p = 0.157) and OS (53.5 ± 38.14 versus 79.0 ± 49.42 months, p = 0.070). Of the 88 patients, 12 had undergone laparoscopy for histological confirmation before complete open staging surgery; however, their PFS (49.5 ± 46.84 versus 49.0 ± 35.55 months, p = 0.719) and OS (56.5 ± 43.4 versus 51.0 ± 32.77 months, p = 0.600) were still comparable. Cytology results were only available for 51 patients, and positive washing cytology results seemed to worsen PFS (p = 0.026) but not OS (p = 0.446). In conclusion, adjuvant nonpaclitaxel chemotherapy and laparoscopic tumor spillage before the staging operation did not worsen the outcome in stage IC OCCC. Positive washing cytology has a negative effect on PFS but not on OS.

Replication of results from a cervical cancer genome-wide association study in Taiwanese women.

Genetic epidemiological studies show that genetic factors contribute significantly to cervical cancer carcinogenesis. Several genome-wide association studies (GWAS) have revealed novel genetic variants associated with cervical cancer susceptibility. We aim to replicate 4 GWAS-identified single nucleotide polymorphisms (SNPs), which were associated with invasive cervical cancer in Chinese women, in a Taiwanese population. The rs13117307 C/T, rs8067378 A/G, rs4282438 G/T, and rs9277952 A/G SNPs were genotyped in 507 women with cervical squamous cell carcinoma (CSCC) and 432 age/sex matched healthy controls by using TaqMan PCR Assay. Human papillomavirus (HPV) DNA test and typing were performed in CSCC patients. Only the rs4282438 SNP was found to be significantly associated (G allele, odds ratio [OR] = 0.67, P = 1.5 × 10-5). This protective association remained in HPV-16 positive CSCC subgroup (G allele, OR = 0.60, P = 1.2 × 10-5). In conclusion, our study confirms the association of rs4282438 SNP with CSCC in a Taiwanese population. However, larger sample sets of other ethnic groups are required to confirm these findings.

Enhanced anti-tumor therapeutic efficacy of DNA vaccine by fusing the E7 gene to BAFF in treating human papillomavirus-associated cancer.

B-cell-activating factor (BAFF) belongs to the tumor necrosis factor family that not only stimulates B and T cells but also counteracts immune tolerance. BAFF is also a type II membrane protein, which is secreted through the endoplasmic reticulum (ER)-Golgi apparatus pathway. Fusing an antigen to BAFF might enhance the presentation of major histocompatibility complex class I molecules. These characteristics represent an opportunity to enhance the antitumor effects of DNA vaccines. Therefore, we fused BAFF to human papillomavirus type 16 E7 as a DNA vaccine and evaluated its antitumor effects. We found that this vaccine increased E7-specific CD8+ T-cell immune responses, engendered major antitumor effects against E7-expressing tumors, and prolonged the survival of the immunized mice. Interestingly, vaccinating B-cell-deficient mice with BAFF-E7 revealed considerable E7-specific CD8+ T-cell immune responses, suggesting that B cells do not contribute to this immune response. Image analysis through confocal fluorescence microscopy revealed that fusing BAFF to E7 targeted the protein to the ER, but not BAFF lacking 128 N-terminal residues that generated a lower number of E7-specific CD8+ T cells in the vaccinated mice. Our data indicated that the ER-targeting characteristic of BAFF is the main factor improving the potency of DNA vaccines.

ITPR3 gene haplotype is associated with cervical squamous cell carcinoma risk in Taiwanese women.

Host immunogenetic background plays an important role in human papillomavirus (HPV) infection and cervical cancer development. Inositol 1,4,5-triphosphate receptor type 3 (ITPR3) is essential for both immune activation and cancer pathogenesis. We aim to investigate if ITPR3 genetic polymorphisms are associated with the risk of cervical cancer in Taiwanese women. ITPR3 rs3748079 A/G and rs2229634 C/T polymorphisms were genotyped in a hospital-based study of 462 women with cervical squamous cell carcinoma (CSCC) and 921 age-matched healthy control women. The presence and genotypes of HPV in CSCC was determined. No significant association of individual ITPR3 variants were found among controls, CSCC, and HPV-16 positive CSCC. However, we found a significant association of haplotype AT between CSCC and controls (OR = 2.28, 95% CI 1.31-3.97, P = 2.83 × 10-3) and the OR increased further in CSCC patients infected with HPV-16 (OR = 2.89, 95% CI 1.55-5.37, P = 4.54 × 10-4). The linkage disequilibrium analysis demonstrated that ITPR3 association with CSCC was independent of HLA-DRB1 alleles. In conclusion, these findings suggest that AT haplotype in the ITPR3 gene may serve as a potential marker for genetic susceptibility to CSCC.

Functional variant of the P2X7 receptor gene is associated with human papillomavirus-16 positive cervical squamous cell carcinoma.

Human papillomavirus (HPV) infection and the fate of HPV infected cervical epithelial cells are strictly associated with cervical cancer development. P2X7 receptor has been implicated in both the regulation of immune responses and apoptosis of cervical cancer cells. The study aims to investigate if polymorphisms in the P2RX7 gene are associated with the risk of cervical cancer in Taiwanese women. P2RX7 253 T/C, 835 G/A, and 1513 A/C loss-of-function polymorphisms were genotyped in a hospital-based study of 507 women with cervical squamous cell carcinoma (CSCC) and 1619 age-matched healthy control women. The presence and genotypes of HPV in CSCC was determined. The frequency of 253 C/C genotype was found to increase significantly in patients with HPV-16 positive CSCC compared with controls (odds ratio = 10.2, 95% confidence interval 1.39-87.8, Pc = 0.03). No significant associations were found for other 2 polymorphisms. Analysis of haplotypes also revealed no significant differences among women with CSCC, those with HPV-16 positive CSCC and controls. In conclusion, inheritance of the C/C genotype at position 253 in the P2RX7 gene may contribute to the risk of HPV-16 associated CSCC in Taiwanese women.

Possible surrogate marker for an effective dose-dense chemotherapy in treating ovarian cancer.

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.

Nanoparticle-induced intraperitoneal hyperthermia and targeted photoablation in treating ovarian cancer.

Hyperthermic intraperitoneal chemotherapy is effective in treating various intra-abdominal malignancies. However, this therapeutic modality can only be performed during surgical operations and cannot be used repeatedly. We propose repeatedly noninvasive hyperthermia mediated by pegylated silica-core gold nanoshells (pSGNs) in vivo with external near-infrared (NIR) laser irradiation. This study demonstrated that repeated photothermal treatment can effectively eliminate intraperitoneal tumors in mouse ovarian cancer models without damage of normal tissues. By conjugating pSGNs with anti-human CD47 monoclonal antibody, a significant photoablative effect can be achieved using lower amount of pSGNs and shorter NIR laser irradiation. Conjugated pSGNs specifically targeted and bound to cancer cells inside the peritoneal cavity. Our results indicate the possibility of a noninvasive method of repeated hyperthermia and photoablative therapies using nanoparticles. This has substantial clinical potential in treating ovarian and other intraperitoneal cancers.

Genetic susceptibility to cervical squamous cell carcinoma is associated with HLA-DPB1 polymorphisms in Taiwanese women.

Cervical cancer is a multifactorial disease, and increasing evidence suggests that host immunogenetic background may contribute to its pathogenesis. Genetic variations in human leukocyte antigen (HLA) genes may alter the efficiency of immune response to human papillomavirus (HPV) antigens and have been implicated in the risk of cervical cancer. We investigated whether polymorphisms in the HLA-DPB1 gene were associated with cervical cancer risk in a Taiwanese population. HLA-DPB1 alleles and +550 G/A polymorphism were genotyped in a case-control study of 473 women with cervical squamous cell carcinoma (CSCC) and 676 healthy controls. The presence and genotypes of HPV in CSCC were determined. We found that the DPB1*05:01 and +550 A alleles were associated with decreased and increased risk of CSCC, respectively [odds ratio (OR) = 0.72, Pc = 0.001; OR = 1.25, Pc = 0.03]. In subgroup analysis based on HPV type 16 positivity, significant associations were shown in the DPB1*05:01 and *13:01 alleles (OR = 0.65, Pc = 0.0007; OR = 1.83, Pc = 0.004). Furthermore, the DPB1*05:01-G and *13:01-G haplotypes conferred decreased and increased risk of both CSCC and HPV-16 positive CSCC women, respectively (OR = 0.72, Pc = 0.0009; OR = 0.63, Pc = 0.0004 for DPB1*05:01-G; OR = 1.55, Pc = 0.03; OR = 1.84, Pc = 0.004 for DPB1*13:01-G). A risk haplotype DPB1*02:01-A was also observed in the HPV-16 positive CSCC women (OR = 1.51, Pc = 0.05). These findings suggest that HLA-DPB1 gene is involved in the CSCC development.

A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women.

BACKGROUND: The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age. METHODS: We performed a randomized, international, double-blind, phase 2b-3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV. RESULTS: The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group. CONCLUSIONS: The 9vHPV vaccine prevented infection and disease related to HPV-31, 33, 45, 52, and 58 in a susceptible population and generated an antibody response to HPV-6, 11, 16, and 18 that was noninferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine. (Funded by Merck; ClinicalTrials.gov number, NCT00543543).

Spontaneous pneumothorax after intensive chemotherapy in endometrial cancer: a rare complication.

OBJECTIVE: Endometrial cancer with hematogenous metastases can be treated with chemotherapy. We present a case of spontaneous pneumothorax that occurred when a solitary pulmonary endometrial metastatic lesion was treated with paclitaxel plus carboplatin. CASE REPORT: A 38-year-old female had stage II endometrial endometrioid adenocarcinoma. Solitary bilateral pulmonary metastases developed after primary treatment. Complete remission accompanied by a right spontaneous pneumothorax occurred during chemotherapy with paclitaxel plus carboplatin. CONCLUSION: Rapid shrinkage of a pulmonary space-occupying tumor sometimes causes rare but life-threatening spontaneous pneumothoraces. We report the first case of a spontaneous pneumothorax after using paclitaxel plus carboplatin in the treatment of endometrial cancer.

Pegylated gold nanoparticles induce apoptosis in human chronic myeloid leukemia cells.

Gold nanoparticles (AuNPs) have several potential biological applications as well as excellent biocompatibility. AuNPs with surface modification using polyethylene glycol (PEG-AuNPs) can facilitate easy conjugation with various biological molecules of interest. To examine the anticancer bioactivity of PEG-AuNPs, we investigated their effect on human chronic myeloid leukemia K562 cells. The results indicated that PEG-AuNPs markedly inhibited the viability and impaired the cell membrane integrity of K562 cells. The particles caused morphological changes typical of cell death, and a marked increase in the sub-G1 population in DNA histogram, indicating apoptosis. In addition, PEG-AuNPs reduced the mitochondrial transmembrane potential, a hallmark of the involvement of intrinsic apoptotic pathway in K562 cells. Observation of ultrastructure under a transmission electron microscope revealed that the internalized PEG-AuNPs were distributed into cytoplasmic vacuoles and damaged mitochondria, and subsequently accumulated in areas surrounding the nuclear membrane. In conclusion, PEG-AuNPs may have the potential to inhibit growth and induce apoptosis in human chronic myeloid leukemia cells.

Human leucocyte antigen-G polymorphisms are associated with cervical squamous cell carcinoma risk in Taiwanese women.

BACKGROUND: The mere presence of human papillomavirus (HPV) is not enough for cervical cancer development and immunogenetic background may play an important role. Human leucocyte antigen (HLA)-G acts as a negative regulator of immune responses and its expression in tumour cells may enable them to avoid immune attack. We aim to study if polymorphisms in the HLA-G gene are associated with cervical cancer risk in Taiwanese women. METHODS: +1537 A/C, 14-bp deletion/insertion (Del/Ins), and +3142 G/C polymorphisms were genotyped in a hospital-based study of 317 women with cervical squamous cell carcinoma (CSCC) and 400 healthy control women frequency matched by age. The presence and genotypes of HPV in CSCC were determined. RESULTS: We found the +3142 C/C genotype and C allele were associated with increased risk for CSCC (adjusted odds ratio [OR]=1.78, P=0.004; adjusted OR=1.31, P=0.014, respectively). In subgroup analysis based on HPV type 16 positivity, significant associations with higher adjusted ORs were found in +3142 C/C genotype and C allele (adjusted OR=2.19, P=0.001; adjusted OR=1.48, P=0.003, respectively) and +1537 C/C genotype and C allele frequencies increased significantly (adjusted OR=2.88, P=0.004; adjusted OR=1.69, P=0.0005, respectively). Furthermore, the C-Del-C haplotype conferred increased risk of both CSCC and HPV-16 positive CSCC women (adjusted OR=1.41, P=0.009; adjusted OR=1.94, P=0.0001, respectively). CONCLUSION: These findings suggest that HLA-G gene is involved in the susceptibility to CSCC.

Is conization once following by simple hysterectomy sufficient for all clinical stage IA1 cervical squamous cell carcinoma?

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.

Intra-peritoneal hyperthermia combining α-galactosylceramide in the treatment of ovarian cancer.

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.

Genetic variants in interleukin-18 gene and risk for cervical squamous cell carcinoma.

Cervical cancer is strongly associated with infection of oncogenic types of human papillomavirus (HPV). However, HPV infection alone is not sufficient for progression to cervical cancer. It is now recognized that host immunogenetic background participates in the control of HPV infection and development of cervical cancer. Interleukin-18 (IL-18) is a multifunctional cytokine that induces interferon-gamma secretion and plays a central role in antitumor immunity. The aim of this study is to determine if potentially functional polymorphisms in IL-18 gene are associated with risk of HPV-induced cervical cancer in Taiwanese women. Pre-Developed TaqMan Allelic Discrimination Assay was used to genotype IL-18 -1297 T/C, -607 C/A, -380 C/G, -137 G/C, and +105 A/C polymorphisms in a hospital-based study of 470 women with cervical squamous cell carcinoma (CSCC) and 722 age-matched healthy control women. The presence and genotypes of HPV in CSCC was determined by PCR. None of the polymorphisms or any haplotype was found to have significant differences in distribution among all subjects with CSCC, those with HPV-16 positive CSCC, and controls. Our results suggest that the IL-18 -1297 T/C, -607 C/A, -380 C/G, -137 G/C, and +105 A/C polymorphisms are not associated with susceptibility to CSCC in Taiwanese women.

Survival analysis of Stage IIA1 and IIA2 cervical cancer patients.

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.

Dose-dense chemotherapy improves mechanisms of antitumor immune response.

Dose-dense (DD) regimens of combination chemotherapy may produce superior clinical outcomes, but the basis for these effects are not completely clear. In this study, we assessed whether a DD combinatorial regimen of low-dose cisplatin and paclitaxel produces superior immune-mediated efficacy when compared with a maximum tolerated dose (MTD) regimen in treating platinum-resistant ovarian cancer as modeled in mice. Immune responses generated by the DD regimen were identified with regard to the immune cell subset responsible for the antitumor effects observed. The DD regimen was less toxic to the immune system, reduced immunosuppression by the tumor microenvironment, and triggered recruitment of macrophages and tumor-specific CD8(+) T-cell responses to tumors [as determined by interleukin (IL)-2 and IFN-γ secretion]. In this model, we found that the DD regimen exerted greater therapeutic effects than the MTD regimen, justifying its further clinical investigation. Fourteen patients with platinum-resistant relapse of ovarian cancer received DD chemotherapy consisting of weekly carboplatin (AUC2) and paclitaxel (60-80 mg/m(2)) as the third- or fourth-line treatment. Serum was collected over the course of treatment, and serial IFN-γ and IL-2 levels were used to determine CD8(+) T-cell activation. Of the four patients with disease control, three had serum levels of IL-2 and IFN-γ associated with cytotoxic CD8(+) T-cell activity. The therapeutic effect of the DD chemotherapy relied on the preservation of the immune system and the treatment-mediated promotion of tumor-specific immunity, especially the antitumor CD8(+) T-cell response. Because the DD regimen controlled drug-resistant disease through a novel immune mechanism, it may offer a fine strategy for salvage treatment.

Aggressive angiomyxoma: a small palpable vulvar lesion with a huge mass in the pelvis.

Aggressive angiomyxoma (AAM) is a rare soft tissue tumor typically in the pelvis and perineum in women of reproductive age, which is easily misdiagnosed. We describe a woman with vulvar AAM, initially mismanaged as a Bartholin cyst. However, a huge pelvic mass is noted on the following imaging studies. The characteristics of AAM on computed tomography and magnetic resonance imaging have been specified in the literature, but we further point out the potential value of sonography in diagnosing AAM. Besides, excisional biopsy may cause tumor bleeding in a case of AAM.