ABSTRACT
PURPOSE: Stereotactic body radiotherapy (SBRT) boost is a promising treatment for cervical cancer patients who are ineligible for intracavitary brachytherapy (ICBT). The aim of this multicenter, single-arm, phase I/II study was to prospectively evaluate the efficacy and toxicity of SBRT boost. MATERIALS AND METHODS: ICBT-ineligible patients with untreated cervical cancer were enrolled. Patients underwent whole-pelvic radiotherapy (45 Gy in 25 fractions) with SBRT boost to the primary lesion. In the phase I dose-escalation cohort (3 + 3 design), patients were treated with SBRT boost of 21 or 22.5 Gy in three fractions. Although dose-limiting toxicity was not confirmed, a dose of 21 Gy was selected for the phase II cohort because it was difficult to reproduce the pelvic organs position in two patients during the phase I trial. The primary endpoint was 2-year progression-free survival. RESULTS: Twenty-one patients (phase I, n = 3; phase II, n = 18) were enrolled between April 2016 and October 2020; 17 (81%) had clinical stage III-IV (with para-aortic lymph node metastases) disease. The median (range) follow-up was 40 (10-84) months. The initial response was complete response in 20 patients and partial response in one patient. The 2-year locoregional control, progression-free survival, and overall survival rates were 84%, 67%, and 81%, respectively. Grade ≥ 3 toxicity was confirmed in one patient each in the acute (diarrhea) and late (urinary tract obstruction) phases. CONCLUSION: These findings suggested that a SBRT boost is more effective than the conventional EBRT boost and can be an important treatment option for ICBT-ineligible patients with cervical cancer. STUDY REGISTRATION: This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000036845).
Subject(s)
Brachytherapy , Radiosurgery , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/radiotherapy , Radiosurgery/methods , Aged , Middle Aged , Brachytherapy/methods , Prospective Studies , Aged, 80 and over , Radiotherapy Dosage , Adult , Treatment OutcomeABSTRACT
Combined thoraco-laparoscopic resection can aid in precise resection of an invasive tumor of the diaphragm. A 44-year-old woman was referred to our department for resection of solitary peritoneal seeding from cervical cancer following systemic chemotherapy. The tumor was located in the right diaphragm with an ill-defined border of the liver. Combined thoraco-laparoscopic resection was proposed. Laparoscopy portrayed that the right diaphragm was partially attached to the liver, and the depth of tumor invasion to the diaphragm was ambiguous. Observation from the thoracic cavity indicated a white-colored distortion following the location of peritoneal seeding. Partial resection and repair of the diaphragm were made using the thoracoscopic-assisted approach, followed by laparoscopic hepatectomy. The postoperative course was uneventful, and pathological findings revealed that peritoneal metastases of the diaphragm and surgical margin was negative for cancer. Combined thoraco-laparoscopic resection can cover the drawbacks of each approach and is among the options for minimally invasive surgery for invasive tumor of the diaphragm.
Subject(s)
Laparoscopy , Liver Neoplasms , Uterine Cervical Neoplasms , Female , Humans , Adult , Diaphragm/surgery , Hepatectomy , Liver Neoplasms/surgery , Uterine Cervical Neoplasms/surgery , Peritoneum/surgeryABSTRACT
Uterine sarcomas have very poor prognoses and are sometimes difficult to distinguish from uterine leiomyomas on preoperative examinations. Herein, we investigated whether deep neural network (DNN) models can improve the accuracy of preoperative MRI-based diagnosis in patients with uterine sarcomas. Fifteen sequences of MRI for patients (uterine sarcoma group: n = 63; uterine leiomyoma: n = 200) were used to train the models. Six radiologists (three specialists, three practitioners) interpreted the same images for validation. The most important individual sequences for diagnosis were axial T2-weighted imaging (T2WI), sagittal T2WI, and diffusion-weighted imaging. These sequences also represented the most accurate combination (accuracy: 91.3%), achieving diagnostic ability comparable to that of specialists (accuracy: 88.3%) and superior to that of practitioners (accuracy: 80.1%). Moreover, radiologists' diagnostic accuracy improved when provided with DNN results (specialists: 89.6%; practitioners: 92.3%). Our DNN models are valuable to improve diagnostic accuracy, especially in filling the gap of clinical skills between interpreters. This method can be a universal model for the use of deep learning in the diagnostic imaging of rare tumors.
Subject(s)
Deep Learning , Leiomyoma , Pelvic Neoplasms , Sarcoma , Soft Tissue Neoplasms , Uterine Neoplasms , Female , Humans , Diagnosis, Differential , Sensitivity and Specificity , Uterine Neoplasms/diagnostic imaging , Uterine Neoplasms/pathology , Leiomyoma/pathology , Sarcoma/diagnostic imaging , Sarcoma/pathology , Soft Tissue Neoplasms/diagnosisABSTRACT
OBJECTIVE: To establish a quantitative method to evaluate the DNA methylation level of an immediate upstream region of major BRCA1 transcriptional start sites (TSSs), and to investigate whether methylation of the region is a prognostic factor in high-grade serous ovarian cancer patients after neoadjuvant chemotherapy. METHODS: Ninety-two FFPE samples of advanced high-grade serous ovarian cancers after neoadjuvant chemotherapy between 2011 and 2018 were used for mutation and methylation analysis. DNA methylation levels were assessed by pyrosequencing and DNA methylation microarray. An association between methylation level (or a mutation) and progression-free survival was assessed by Kaplan-Meier analysis. RESULT: Major BRCA1 transcripts and CpG sites immediately upstream of their TSSs were identified, and a pyrosequencing method was developed. BRCA1 methylation, BRCA1/2 mutations, and a RAD51C mutation were detected in 17/79 (21.5%), 17/92 (18.5%), and 1/92 (1.1%) high-grade serious ovarian cancer samples. In univariate analysis, BRCA1 methylation and no residual tumor were associated with progression-free survival (BRCA1 methylation: P = 0.025, no residual tumor: P = 0.0026). Multivariate analysis showed that both BRCA1 methylation (P = 0.038, HR = 0.47, 95% CI: 0.21-0.96) and no residual tumor (P = 0.012, HR = 0.49, 95% CI: 0.28-0.85) were significant favorable prognostic factors. CONCLUSION: A quantitative method to estimate the methylation level of the immediate upstream region of major BRCA1 TSSs was established. Methylation of the region of was an independent favorable prognostic factor in high-grade serous ovarian cancer patients.
Subject(s)
DNA Methylation , Ovarian Neoplasms , Humans , Female , Prognosis , Transcription Initiation Site , Germ-Line Mutation , Ovarian Neoplasms/pathology , BRCA1 Protein/geneticsABSTRACT
OBJECTIVE: To evaluate the diagnostic utility of conventional magnetic resonance imaging (MRI)-based characteristics and a texture analysis (TA) for discriminating between ovarian thecoma-fibroma groups (OTFGs) and ovarian granulosa cell tumors (OGCTs). METHODS: This retrospective multicenter study enrolled 52 patients with 32 OGCTs and 21 OTFGs, which were dissected and pathologically diagnosed between January 2008 and December 2019. MRI-based features (MBFs) and texture features (TFs) were evaluated and compared between OTFGs and OGCTs. A least absolute shrinkage and selection operator (LASSO) regression analysis was performed to select features and construct the discriminating model. ROC analyses were conducted on MBFs, TFs, and their combination to discriminate between the two diseases. RESULTS: We selected 3 features with the highest absolute value of the LASSO regression coefficient for each model: the apparent diffusion coefficient (ADC), peripheral cystic area, and contrast enhancement in the venous phase (VCE) for the MRI-based model; the 10th percentile, difference variance, and maximal correlation coefficient for the TA-based model; and ADC, VCE, and the difference variance for the combination model. The areas under the curves of the constructed models were 0.938, 0.817, and 0.941, respectively. The diagnostic performance of the MRI-based and combination models was similar (p = 0.38), but significantly better than that of the TA-based model (p < 0.05). CONCLUSIONS: The conventional MRI-based analysis has potential as a method to differentiate OTFGs from OGCTs. TA did not appear to be of any additional benefit. Further studies are needed on the use of these methods for a preoperative differential diagnosis of these two diseases.
Subject(s)
Fibroma , Granulosa Cell Tumor , Thecoma , Female , Fibroma/diagnostic imaging , Granulosa Cell Tumor/diagnostic imaging , Humans , Magnetic Resonance Imaging/methods , Ovarian Neoplasms , ROC Curve , Retrospective Studies , Thecoma/diagnostic imagingABSTRACT
Evaluation of a cancer cell fraction is important for accurate molecular analysis, and pathological analysis is the gold standard for evaluation. Despite the potential convenience, no established molecular markers for evaluation are available. In this study, we aimed to identify ovarian cancer cell fraction markers using DNA methylation highly specific to ovarian cancer cells. Using genome-wide DNA methylation data, we screened candidate marker genes methylated in 30 ovarian cancer FFPE samples and 12 high-grade serous ovarian cancer cell lines, and unmethylated in two female leucocytes and two normal fallopian epithelial cell samples. Methylation levels of two genes, SIM1, and ZNF154, showed high correlation with pathological cancer cell fractions among the 30 ovarian cancer FFPE samples (R = 0.61 for SIM1, 0.71 for ZNF154). For cost-effective analysis of FFPE samples, pyrosequencing primers were designed, and successfully established for SIM1 and ZNF154. Correlation between a pathological cancer cell fraction and methylation levels obtained by pyrosequencing was confirmed to be high (R = 0.53 for SIM1, 0.64 for ZNF154). Finally, an independent validation cohort of 29 ovarian cancer FFPE samples was analyzed. ZNF154 methylation showed a high correlation with the pathological cancer cell fraction (R = 0.77, P < 0.0001). Therefore, the ZNF154 methylation level was considered to be useful for the estimation of ovarian cancer cell fraction, and is expected to help accurate molecular analysis.
Subject(s)
Biomarkers, Tumor/genetics , DNA Methylation , DNA, Neoplasm/genetics , Genetic Markers , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Cell Line, Tumor , Female , Humans , Kruppel-Like Transcription Factors/geneticsABSTRACT
AIM: Patients with recurrent cervical cancer after radiotherapy have poor prognoses because of the lack of effective treatment options. Biomarkers to predict survival outcomes for recurrent cervical cancer are warranted because patients with limited life expectancy sometimes benefit from less aggressive treatment in combination with early palliative care. Therefore, we aimed to explore a predictive biomarker for the outcomes of patients with recurrent cervical cancer. METHODS: We retrospectively investigated 231 patients initially treated with radiation-based therapy between January 2004 and December 2015. The associations between clinicopathological features at the time of relapse and overall survival after relapse were assessed. As factors which reflect patients' conditions, we particularly focused on C-reactive protein-to-albumin ratio (CAR) and neutrophil-to-lymphocyte ratio (NLR) at the time of relapse. Additionally, we investigated biomarkers predictive of short-term survival. RESULTS: Among 231 patients, 91 patients experienced relapse and 74 patients died during the follow-up period. Multivariate analysis revealed that treatment after relapse, CAR, and NLR was significantly associated with overall survival. Among them, treatment after relapse significantly affected survival outcomes, and patients who received definitive local treatment had a better 3-year survival rate than those who received other treatments. Conversely, NLR was the most influential biomarker for short-term survival, and the prognosis of patients with high NLRs was much worse than those with low NLRs. CONCLUSIONS: This study thus demonstrated that, for the patients with recurrent cervical cancer who received radiation-based therapy, definitive local treatment can provide long-term survival and extremely high NLRs are predictive of short-term survival.
Subject(s)
Neutrophils , Uterine Cervical Neoplasms , Female , Humans , Lymphocyte Count , Lymphocytes , Neoplasm Recurrence, Local , Prognosis , Retrospective Studies , Uterine Cervical Neoplasms/radiotherapyABSTRACT
AIM: Skeletal muscle loss is often observed in advanced cancer patients. This study investigates whether skeletal muscle loss is associated with survival outcomes of advanced epithelial ovarian cancer (EOC) patients after induction chemotherapy (IC) in a Japanese cohort. Whether serum inflammatory markers are associated with skeletal muscle changes is also addressed. METHODS: We retrospectively reviewed 60 patients with stage III/IV EOC who underwent IC between 2010 and 2017. Skeletal muscle area (SMA) was measured at the third lumbar vertebrae level on a single axial computed tomography-scan image. Receiver operating curve analysis was used to determine cut-off values of pre- and post-IC SMA and SMA ratio (SMAR). Univariate and multivariate analyses of overall survival (OS) were conducted using the log-rank test and Cox proportional hazards regression model, respectively. RESULTS: The SMA decreased significantly after IC (P = 0.019). The cut-off value between low and high SMAR was 0.96. High or low SMAR was observed in 34 (57%) and 26 (43%) patients, respectively. Univariate analysis revealed that low SMAR was associated with poor OS (P = 0.025). Multivariate analysis showed that incomplete resection during interval debulking surgery (hazard ratio, 0.30; 95% CI, 0.11-0.80; P = 0.016) and a low SMAR (hazard ratio, 3.17; 95% CI, 1.18-9.06; P = 0.022) were independent predictors of poor OS. Of the serum inflammatory markers investigated, only post-IC absolute neutrophil count correlated significantly with SMAR (P = 0.012). CONCLUSION: Low SMAR can be used to predict poor prognosis in advanced EOC patients who have undergone IC.
ABSTRACT
Cervical intraepithelial neoplasia (CIN) has a natural history of bidirectional transition between different states. Therefore, conventional statistical models assuming a unidirectional disease progression may oversimplify CIN fate. We applied a continuous-time multistate Markov model to predict this CIN fate by addressing the probability of transitions between multiple states according to the genotypes of high-risk human papillomavirus (HPV). This retrospective cohort comprised 6022 observations in 737 patients (195 normal, 259 CIN1, and 283 CIN2 patients at the time of entry in the cohort). Patients were followed up or treated at the University of Tokyo Hospital between 2008 and 2015. Our model captured the prevalence trend satisfactory, particularly for up to two years. The estimated probabilities for 2-year transition to CIN3 or more were the highest in HPV 16-positive patients (13%, 30%, and 42% from normal, CIN1, and CIN2, respectively) compared with those in the other genotype-positive patients (3.1%-9.6%, 7.6%-16%, and 21%-32% from normal, CIN1, and CIN2, respectively). Approximately 40% of HPV 52- or 58-related CINs remained at CIN1 and CIN2. The Markov model highlights the differences in transition and progression patterns between high-risk HPV-related CINs. HPV genotype-based management may be desirable for patients with cervical lesions.
ABSTRACT
BACKGROUND: Radiotherapy (RT) is effective in cervical cancer; radiation-induced lymphopenia correlates with poor survival outcome in several cancer types. We investigated the association of total lymphocyte count (TLC) with survival outcomes in patients with cervical cancer. METHODS: We retrospectively reviewed 168 patients with cervical cancer initially treated with definitive RT. We obtained clinicopathological data and TLCs before RT and at the end and at 6 months after RT. Patient-, treatment-, and tumor-specific factors were evaluated to determine their predictive values for overall survival. The association of overall and progression-free survivals with lymphopenia at each point was evaluated. RESULTS: Median follow-up duration was 44 (interquartile range: 25-67) months. Median TLCs before RT and at the end and at 6 months after RT were 1625/mm3, 400/mm3, and 800/mm3 (interquartile range: 1270-1930/mm3, 290-550/mm3, and 600-1067/mm3), respectively. For overall survival, in addition to FIGO stage, body mass index, histology, treatment, and presence of para-aortic lymph node metastasis, lymphopenia at 6 months after RT was a poor prognostic factor in multivariate analysis (P = 0.0026; hazard ratio [HR], 3.06; 95% confidence interval [CI]: 1.48-6.33). For progression-free survival, TLCs before and at 6 months after RT were poor prognostic factors in univariate analysis (P = 0.0318 and 0.0081, respectively); however, the latter was the only independent prognostic factor in multivariate analysis (P = 0.0021; HR, 2.67; 95% CI: 1.43-4.99). CONCLUSION: Post-RT persistent lymphopenia could be a poor prognostic factor for patients with cervical cancer who receive RT.
Subject(s)
Lymphocyte Count , Lymphopenia/etiology , Uterine Cervical Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Lymph Nodes/pathology , Lymphatic Metastasis/radiotherapy , Lymphopenia/mortality , Lymphopenia/pathology , Middle Aged , Prognosis , Proportional Hazards Models , Radiation Injuries , Retrospective Studies , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathologyABSTRACT
OBJECTIVE: Some patients are ineligible for intracavitary brachytherapy (ICBT) for locally advanced cervical cancer. Stereotactic body radiotherapy (SBRT) could be a good treatment option for such patients. This phase I clinical trial aimed to determine the recommended SBRT boost dose for ICBT-ineligible cervical cancer patients. METHODS: Patients with untreated uterine cervical cancer (clinical stages IB1-IIIB) who were ineligible for ICBT were enrolled. Radiotherapy consisted of whole-pelvis radiotherapy (45 Gy in 25 fractions) followed by SBRT. Three dose levels of SBRT (19.5/21/22.5 Gy in three fractions) were set; the treatment protocol began at 21 Gy (level 2). The 'rolling-six' design study was used to establish the recommended dose of SBRT. Each dose level covered three or six patients. The primary endpoint included dose-limiting toxicity (DLT), defined as the occurrence of grade 3 (or worse) non-hematologic adverse effects within 6 months after SBRT. RESULTS: The median follow-up after registration was 17 (range, 8-32) months. Three patients were enrolled in study level 2 (SBRT of 21 Gy); none of the patients exhibited DLT within 6 months after treatment completion. In study level 3 (SBRT of 22.5 Gy), three patients did not exhibit DLT. Although all six patients achieved locoregional control during follow-up, one patient treated with level 2 SBRT experienced distant metastases 14 months after registration. CONCLUSIONS: The recommended dose of SBRT boost was 22.5 Gy in three fractions. We plan to conduct a phase II multi-center clinical trial using the methodology obtained from the current study.
Subject(s)
Radiosurgery/methods , Uterine Cervical Neoplasms/radiotherapy , Aged , Brachytherapy/adverse effects , Female , Humans , Middle Aged , Radiotherapy DosageABSTRACT
OBJECTIVE: We investigated whether the pretreatment albumin to globulin ratio, serum albumin level, and serum globulin level can be used to predict survival among cervical cancer patients treated with radiation based therapy and assessed globulin fractions. METHODS: We retrospectively enrolled 128 patients with cervical cancer treated with radiation based therapy at our institution between 2010 and 2015. The associations of the pretreatment albumin to globulin ratio, and serum albumin and globulin levels with overall survival were assessed. Additionally, the associations of the globulin fractions with the serum globulin levels and overall survival were evaluated. RESULTS: Median follow-up duration was 30 months (IQR 16-44 months). A low albumin to globulin ratio (< 1.53) was found to be an independent prognostic factor for overall survival (HR= 3.07; 95% CI, 1.03 to 13.3; P=0.044). On evaluating serum globulin and albumin separately, a high serum globulin level was significantly associated with overall survival (cut-off value 2.9 g/dL; HR=3.74; 95% CI 1.08 to 23.6; P=0.036) whereas a low serum albumin level was not associated with overall survival (cut-off value 3.6 g/dL; HR=1.77; 95% CI 0.57 to 4.54; P=0.29). Electrophoresis data of the serum proteins revealed that the γ-globulin fraction was most strongly correlated with the globulin levels (P<0.001). Furthermore, a high γ-globulin level (≥1.28 g/dL) was significantly associated with poor overall survival (log rank test, P=0.034). CONCLUSIONS: A pretreatment low albumin to globulin ratio, which might be attributable to a high serum globulin level, can be used to predict poor prognosis in cervical cancer patients treated with radiation based therapy.
Subject(s)
Biomarkers, Tumor/blood , Brachytherapy/mortality , Carcinoma, Squamous Cell/mortality , Serum Albumin/analysis , Serum Globulins/analysis , Uterine Cervical Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Uterine Cervical Neoplasms/blood , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/radiotherapyABSTRACT
BACKGROUND: Lymphopenia is associated with poor outcomes in patients with various cancers, but little is known about the prognostic impact of lymphopenia in patients with epithelial ovarian cancer (EOC) after induction chemotherapy (IC). This study investigated the prognostic significance of pre- and post-IC lymphopenia in patients with advanced EOC. METHODS: We reviewed medical records of 68 patients with stage III/IV ovarian, fallopian tube, or peritoneal cancer treated with IC at our institution between 2009 and 2017. We assessed the associations of pre- and post-IC inflammatory markers, including lymphocyte counts, with several oncological outcomes, such as the implementation of interval debulking surgery (IDS), complete resection, progression-free survival (PFS), and overall survival (OS). RESULTS: Lymphocyte counts increased significantly post-IC compared with the pre-IC values (P = 0.009). Pre-IC lymphopenia was observed in 27 patients (40%), whereas only 16 patients (24%) displayed lymphopenia post-IC (P = 0.020). Among several inflammatory markers, only post-IC lymphopenia was significantly associated with incomplete resection outcome during IDS (P = 0.012). Moreover, post-IC lymphopenia was significantly associated with poor PFS (log-rank test, P = 0.009), whereas pre-IC lymphopenia was associated with neither PFS nor OS. CONCLUSIONS: Post-IC lymphopenia may predict incomplete resection during IDS and poor prognosis in patients with advanced EOC.
Subject(s)
Carcinoma, Ovarian Epithelial/drug therapy , Induction Chemotherapy/adverse effects , Lymphopenia/chemically induced , Ovarian Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , Carcinoma, Ovarian Epithelial/mortality , Carcinoma, Ovarian Epithelial/surgery , Cytoreduction Surgical Procedures , Disease-Free Survival , Female , Humans , Inflammation/etiology , Lymphocyte Count , Lymphopenia/mortality , Middle Aged , Ovarian Neoplasms/mortality , Ovarian Neoplasms/surgery , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/surgery , Prognosis , Retrospective StudiesABSTRACT
The formation of gastrointestinal-type epithelium is found in 7-13% of mature cystic teratomas, which are the most common germ cell tumors of the ovary. Few cases harboring organized gastrointestinal tract formation have been reported, and a mucinous neoplasm arising in them is further rare. Here, we report a case of an ovarian mature cystic teratoma with intestinal structures harboring intestinal-type mucinous neoplasm, mimicking low-grade appendiceal mucinous cystadenoma. A 66-year-old female, with remarkably increased serum carcinoembryonic antigen (CEA) level, underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy due to the ovarian tumor. The immunoprofile of the tumor showed CK7-/CK20+. We review the past literatures, and then consider that the existence of mucinous neoplasm should be kept in mind if we find elevated level of serum CEA and the organized gastrointestinal development in an ovary. The immunoprofile of CK7/CK20 is useful to determine the origin of mucinous tumors associated with mature cystic teratomas.
ABSTRACT
BACKGROUND: Although many studies have already shown that lymph node metastasis is one of the major prognostic factors for cervical cancer, the therapeutic significance of para-aortic lymphadenectomy for the surgical treatment of cervical cancer remains controversial. METHODS: A total of 308 patients diagnosed with stage IB2, IIA2, or IIB cervical cancer and treated with radical hysterectomy were retrospectively investigated to assess the incidence of para-aortic lymph node metastasis and the clinicopathological factors linked to cervical cancer prognosis. RESULTS: Para-aortic lymph node metastases were pathologically confirmed in 13 of the 136 patients (9.6 %) who underwent para-aortic lymphadenectomy. The incidence of para-aortic lymph node metastasis was significantly higher in the patients who had common iliac lymph node metastases (odds ratio 31.5, p < 0.001) according to logistic regression analysis. Common iliac lymph node metastasis was related to risk of recurrence (hazard ratio 2.43, p = 0.003) and death (hazard ratio 2.62, p = 0.007) in Cox regression analysis. Kaplan-Meier analysis and Cox regression analysis showed that para-aortic lymphadenectomy did not have a positive impact on survival in 308 patients or 140 pN1 patients, but para-aortic lymphadenectomy was related to better overall survival with a marginal trend toward significance (p = 0.053) in 30 patients with common iliac lymph node metastasis. CONCLUSIONS: Indication for para-aortic lymphadenectomy in the surgical treatment of stage IB2, IIA2, or IIB cervical cancer needs to be individualized. Patients with common iliac lymph node metastasis are possible candidates, and a prospective study is needed to clarify this issue.
Subject(s)
Hysterectomy/mortality , Lymph Node Excision/mortality , Lymph Nodes/surgery , Neoplasm Recurrence, Local/surgery , Uterine Cervical Neoplasms/surgery , Adult , Aged , Female , Humans , Kaplan-Meier Estimate , Lymph Nodes/pathology , Lymphatic Metastasis , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Proportional Hazards Models , Retrospective Studies , Survival Rate , Uterine Cervical Neoplasms/pathologyABSTRACT
We investigated the role of human leukocyte antigen (HLA) class II alleles in multistage cervical carcinogenesis. Cross-sectional analysis for HLA association with cervical cancer included 1253 Japanese women: normal cytology (NL, n = 341), cervical intraepithelial neoplasia grade 1 (CIN1, n = 505), CIN grade 2 or 3 (CIN2/3, n = 96), or invasive cervical cancer (ICC, n = 311). The HLA class II allele frequencies were compared by Fisher's exact test or the χ(2) -test. The Bonferroni adjustment corrected for multiple comparisons. Among the study subjects, 454 women with low-grade squamous intraepithelial lesion cytology were prospectively monitored by cytology and colposcopy every 3-4 months to analyze cumulative risk of CIN3 within the next 10 years in relation to HLA class II alleles. HLA class II DRB1*1302 allele frequency was similar between women with NL (11.7%) and CIN1 (11.9%), but significantly decreased to 5.2% for CIN2/3 and 5.8% for ICC (P = 0.0003). Correction for multiple testing did not change this finding. In women with low-grade squamous intraepithelial lesion cytology, the cumulative risk of CIN3 diagnosed within 10 years was significantly reduced among DRB1*1302-positive women (3.2% vs. 23.7%, P = 0.03). In conclusion, the two different types of analysis in this single study showed the protective effect of the DRB1*1302 allele against progression from CIN1 to CIN2/3.
Subject(s)
Carcinogenesis/genetics , Disease Resistance/genetics , HLA-DRB1 Chains/genetics , Uterine Cervical Dysplasia/genetics , Uterine Cervical Neoplasms/genetics , Adolescent , Adult , Asian People , Cross-Sectional Studies , Female , Gene Frequency , Humans , Japan , Neoplasm Grading , Papillomaviridae/growth & development , Prospective Studies , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virology , Young Adult , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/virologyABSTRACT
We describe 9 tumors that resemble soft tissue myoepitheliomas but possess certain traits that do not fit perfectly into this category. These tumors, herein referred to as "myoepithelioma-like tumors of the vulvar region," occurred in the subcutis of the vulva and surrounding regions of adult women aged 24 to 65 years. Histologically, the tumors measured 2 to 7.7 cm and were well circumscribed, focally encapsulated, and lobulated. Tumor cells had an epithelioid to spindled shape, with fine amphophilic cytoplasm, and uniform nuclei with vesicular chromatin and nucleoli. The tumor stroma was relatively hypervascular, and comprised a mixture of myxoid and nonmyxoid components. Myxoid areas accounted for <5% to 95% of the tumor volume, wherein cells proliferated singly or in a loosely cohesive manner. In nonmyxoid areas, tumors cells grew in diffuse sheets or storiform arrangements. Immunohistochemically, all tested tumors were positive for vimentin, epithelial membrane antigen, and estrogen receptor; most tumors expressed actin. All tumors were negative for S100 protein, glial fibrillary acidic protein, and CD34. Cytokeratin expression was absent in all but 2 tumors, which showed rare positivity. SMARCB1 expression was deficient in all cases. EWSR1, FUS, and NR4A3 rearrangements were absent. All tumors were treated through surgery. Although 3 tumors regrew or recurred after intralesional excision, all 9 patients were alive without metastases at a mean follow-up of 66 months. Myoepithelioma-like tumors of the vulvar region constitute a distinct group of tumors, although future research is required to determine whether they are an unusual subtype of soft tissue myoepitheliomas or a separate disease.
Subject(s)
Biomarkers, Tumor/deficiency , Chromosomal Proteins, Non-Histone/deficiency , DNA-Binding Proteins/deficiency , Myoepithelioma/chemistry , Transcription Factors/deficiency , Vulvar Neoplasms/chemistry , Adult , Aged , Biomarkers, Tumor/genetics , Biopsy , Cell Proliferation , Female , Gene Rearrangement , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Middle Aged , Myoepithelioma/classification , Myoepithelioma/genetics , Myoepithelioma/pathology , Myoepithelioma/surgery , Predictive Value of Tests , SMARCB1 Protein , Time Factors , Treatment Outcome , Tumor Burden , Vulvar Neoplasms/classification , Vulvar Neoplasms/genetics , Vulvar Neoplasms/pathology , Vulvar Neoplasms/surgery , Young AdultABSTRACT
Few reports on malignant transformation of adenomyosis are available, and endometrioid adenocarcinoma arising from cystic adenomyosis is further rarely reported. We report a case of a 67-year-old asymptomatic woman who was referred to our hospital for evaluation of a cystic lesion in the pelvis, which had been diagnosed as cystic degeneration of leiomyoma for 3 years. Magnetic resonance imaging revealed a cystic mass measuring 11 cm in diameter, which was contiguous with uterine myometrium. The lesion contained solid areas enhanced on gadolinium-enhanced T1 -weighted imaging. Transabdominal simple total hysterectomy with bilateral salpingo-oophorectomy was performed. Pathological examination revealed endometrioid adenocarcinoma arising from cystic adenomyosis. The patient underwent six courses of adjuvant combination chemotherapy with paclitaxel and carboplatin. No metastasis or recurrence has been demonstrated for 16 months following surgery. Our case demonstrates that cystic adenomyoma possesses the risk of malignant transformation, indicating the importance of long-term follow-up with imaging examination.
Subject(s)
Adenomyoma/pathology , Carcinoma, Endometrioid/therapy , Endometrial Neoplasms/therapy , Aged , Carcinoma, Endometrioid/pathology , Cell Transformation, Neoplastic , Endometrial Neoplasms/pathology , Female , HumansABSTRACT
This is a retrospective study of fifteen cases of primary peritoneal carcinoma who were treated between 2001 and 2010 in our hospital. The median age at the time of diagnosis was 63 years(range, 40 to 79 years). Three patients had clinical stage II disease, eleven patients had stage III disease, and one patient was unstaged. The serum CA125 values at pretreatment were elevated in all patients, with a median value of 4,144. 8 U/mL(range, 102. 8 to 23, 611. 0 U/mL). Optimal debulking was possible in 9 of the 15 patients. All patients were treated with paclitaxel and carboplatin chemotherapy during the preoperative and/or postoperative period. All patients at stage II disease were alive without evidence of disease at the time of evaluation(2 patients>5 years, 1 patient>3 years). Four patients with stage III disease had died from the disease less than 3 years after the first treatment. The results of our study showed poor survival for the group with stage III disease, but good survival for the group with stage II disease.