Depth Of Cervical Stromal Invasion Research Articles

Value of postoperative radiotherapy and analysis of prognostic factors in early-stage neuroendocrine carcinoma of cervix

Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.

The Prognostic Significance of the Depth of Cervical Stromal Invasion in Women With FIGO Stage II Uterine Endometrioid Carcinoma.

The objective of this study was to investigate the prognostic significance of the depth of cervical stromal invasion (CSI) in women with FIGO stage II uterine endometrioid adenocarcinoma (EC). Our database of women with EC was quired for patients with stage II EC. Pathologic slides were retrieved and reviewed by gynecologic pathologists to determine cervical stromal thickness and depth of CSI as a percentage of stromal thickness (%CSI). Kaplan-Meier, univariate, and multivariate analyses were used to compare recurrence-free, disease-specific (DSS), and overall survival (OS) between women who had<50% versus ≥50% CSI. Univariate and multivariate analyses were used to assess other prognostic variables associated with survival endpoints. A total of 117 patients were included in our study who had hysterectomy between 1/1990 and 8/2021. Seventy-nine patients (68%) with <50% and 38 (32w%) with ≥50% CSI. After a median follow-up of 131 months, 5-year DSS was significantly worse for women with ≥50% CSI (78% vs. 91%; P =0.04). However, %CSI was not an independent predictor for any of the studied survival endpoints. Independent predictors of worse 5-year recurrence-free survival and DSS included FIGO grade 3 tumors ( P =0.02) and the presence of lymphovascular space invasion ( P =0.03). Grade 3 tumors were the only independent predictor of worse 5-year OS ( P =0.02). Our results suggest that deep CSI is not an independent prognostic factor for survival endpoints in women with stage II uterine endometroid adenocarcinoma. The lack of independent prognostic significance of the depth CSI needs to be validated in a multi-institutional analysis.

Risk factors for lymph node metastasis and clinical outcomes in cervical cancer patients following primary radical hysterectomy: A single-center analysis of 1495 patients.

e17525 Background: Histopathological information obtained from surgical specimen is important to identify patients at increased risk for disease relapse and mortality. Lymph node metastasis (LNM) carries the highest impact on decreased survival in suspected early-stage cervical cancer. To further identify risk factors for LNM and prognosis in early stage cervical cancer patients is definitely necessary owing to the findings from different centers are inconsistent. Methods: A total 1495 cervical cancer patients were diagnosed with stage IA2-IIA cervical cancer according to clinical stage and underwent radical hysterectomy between April 2009 and December 2020. The stage of all the patients were reclassified after surgery according to FIGO 2018. We analyzed their clinicopathologic data to identify the risk factors for LNM. Among all the patients, the progression-free survival (PFS) and overall survival (OS) of 1109 patients between 2015 and 2020 were collected and analyzed. Results: The incidence of LNM is 18.8% in all 1495 patients, which increases with depth of cervical stromal invasion, tumor size, lymphovascular space involvement (LVSI) and vaginal wall invasion in univariate analysis. Multivariable analysis shows only stromal invasion (OR, 3.0; 95% CI, 1.7–5.3; P &lt; 0.001) and LVSI (OR, 4.9; 95% CI, 3.6-6.7; P&lt;0.001) are to be independent risk factors for LNM. In addition, the clinical parameters age is a protective factor against LNM in both univariate and multivariable analysis(P&lt;0.001). Among the 1109 patients, the median follow-up time is 49.7 months. Multivariate analyses using the Cox proportional hazards model show that LNM (HR, 8.5; 95% CI, 3.0-23.9; P&lt;0.001), stromal invasion (HR, 3.4; 95% CI, 2.2-5.4;P&lt;0.001) and special histologic type (HR, 3.2; 95% CI, 1.4-7.6; P=0.006) are independent prognostic factors for OS as well as PFS in early stage cervical cancer. Conclusions: The pattern of cervical stromal invasion and presence LVSI, but not the primary tumor size, predict risk of nodal metastasis. Cervical stromal invasion, LNM and special histologic type (non-squamous cell carcinoma; non-Adenocarcinoma) are independent prognostic factors for OS as well as PFS in early stage cervical cancer. [Table: see text]

Effects of colpotomic approaches on prognosis and recurrence sites of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy

Objective: To investigate the factors affecting the prognosis of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy (LRH), and to compare the prognosis and recurrence sites of patients with different colpotomy paths. Methods: The clinical data of 965 patients with stage Ⅰa2-Ⅱa2 cervical cancer who underwent LRH in the First Affiliated Hospital of Army Medical University from January 2015 to December 2018 were collected. The median age was 47.0 years of all patients with a median follow-up of 62 months (48-74 months). Cox regression was used to perform the univariate and multivariate analysis of the clinicopathological factors associated with the prognosis that included disease-free survival (DFS) and overall survival (OS). Patients were categorized into LRH through vaginal colpotomy (VC group, n=475) and LRH through intracorporeal colpotomy (IC group, n=490) according to the colpotomic approaches. The prognosis and recurrence sites of patients in each group were compared. Results: (1) During the follow-up period, 137 cases recurred (14.2%, 137/965) and 98 cases died (10.2%, 98/965). The 5-year DFS and OS were 85.8% and 89.9%, respectively. In univariate analysis, positive vaginal margin (PVM) was significantly affected the 5-year OS of patients with cervical cancer (P=0.023), while clinical stage, maximum diameter of tumor, degree of pathological differentiation, lymph node metastasis (LNM), depth of cervical stromal invasion, parametrium involvement, and uterine corpus invasion (UCI) were significantly associated with 5-year DFS and OS in patients with cervical cancer (all P<0.05). In multivariate analysis, clinical stage (HR=1.882, 95%CI: 1.305-2.716), LNM (HR=2.178, 95%CI: 1.483-3.200) and UCI (HR=3.650, 95%CI: 1.906-6.988) were independent risk factors of 5-year DFS (all P<0.001). Clinical stage (HR=2.500, 95%CI: 1.580-3.956), LNM (HR=2.053, 95%CI: 1.309-3.218), UCI (HR=3.984, 95%CI: 1.917-8.280), PVM (HR=3.235, 95%CI: 1.021-10.244) were independent risk factors of 5-year OS (all P<0.05). (2) Different colpotomy paths did not significantly affect the 5-year DFS and OS of patients with stage Ⅰa2-Ⅱa2 cervical cancer. The 5-year DFS in VC group and IC group were 85.9% and 85.6% (P=0.794), and the 5-year OS were 90.8% and 89.3% (P=0.966), respectively. Recurrence patterns consisted of intraperitoneal recurrence, pelvic recurrence, vaginal stump recurrence, and lymph node and distant metastasis. The intraperitoneal recurrence rate of VC group was significantly lower than that of IC group [0.6%(3/468) vs 2.3% (11/485), P=0.037], while the rates of pelvic recurrence, vaginal stump recurrence, lymph node and distant metastasis and overall recurrence were not significantly different between two groups (all P>0.05). Subgroup analysis of patients with different clinical stages, LNM and UCI showed that statistical differences of the intraperitoneal recurrence rates between two groups were only in patients without LNM (0.5% vs 2.3%, P=0.030) or without UCI (0.7% vs 2.3%, P=0.037). Conclusions: Clinical stage, LNM, PVM and UCI are independent risk factors for the prognosis of patients with stage Ⅰa2-Ⅱa2 cervical cancer. For patients without LNM or UCI, LRH through VC could reduce the intraperitoneal recurrence rate, while it is not enough to improve 5-year DFS and OS of patients. Low proportion of intraperitoneal recurrence, intra-operative tumor cells spillage to vagina stump and pelvic cavity might be the explanation.

Oncologic outcome in patients with 2018 FIGO stage IB cervical cancer: Is tumor size important?

To evaluate the prognostic factors and oncologic outcome in patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical cancer (CC) after radical hysterectomy and lymphadenectomy. This study included 290 patients with type II or III radical hysterectomy + pelvic ± para-aortic lymphadenectomy and 2018 FIGO stage IB1-3 epithelial CC. Disease-free survival (DFS) estimates were determinate by using the Kaplan-Meier method. Survival curves were compared using the log-rank test. Multivariate analysis was performed using a Cox proportional hazards models. The mean age of study cohort was 52 ± 10.25 years. Five-year DFS was 93% in entire cohort. On univariate analysis, surgical border involvement (p=0.007), lymphovascular space invasion (LVSI) (p=0.040), uterine involvement (p=0.040), and depth of cervical stromal invasion (p=0.007) were found to have statistical significance for DFS. However, none of them were independent prognostic factors for the risk of recurrence. Tumor size according to 2018 FIGO staging criteria was not related with recurrence. Surgical border involvement, LVSI, depth of cervical stromal invasion, and uterine involvement were predictors for DFS on univariate analysis. Tumor size was not predicting to recurrence in patient with 2018 FIGO stage IB1-3 CC.

The Prognostic Significance of the Depth of Cervical Stromal Invasion in Women with FIGO Stage II Uterine Endometrioid Carcinoma

<h3>Purpose/Objective(s)</h3> To explore the prognostic significance of the depth of cervical stromal invasion (CSI) on survival endpoints in women with FIGO stage II uterine endometrioid adenocarcinoma. <h3>Materials/Methods</h3> A total of 117 patients were included in this retrospective review. Between 1990 and 2021, all patients with FIGO stage II endometrial cancer (EC) underwent hysterectomy and oophorectomy at our institution, with or without lymph node dissection. Patients with synchronous ovarian or breast cancer, as well as those who had undergone adjuvant systemic chemotherapy for EC, were excluded from the study. Pathologic slides were retrieved for these patients and were reviewed by a gynecologic pathologist to determine stromal thickness and the depth of CSI. The depth of CSI was then measured as a percentage of invasion (% CSI) and used in the analysis as a continuous or dichotomous variable (< 50% vs > = 50%). Patients' demographics, pathologic, and treatment characteristics were analyzed using univariate and multivariate analysis to calculate recurrence-free (RFS) and disease-specific (DSS) rates. <h3>Results</h3> The median age for the study cohort was 65 years (range, 34–96), and the median follow-up was 131 months (range, 9–334). A total of 90 patients (77%) had lymph node dissection, with a median of 8 examined lymph nodes (range 0-18). Adjuvant radiation therapy (RT) with pelvic or vaginal cuff HDR brachytherapy, or a combination of the two, was completed in 92 patients (79 percent). The median % CSI was 27% (range, 1-100) with 68% of patients having ≥ 50% CSI. While there was a trend for a worse 5-year RFS and DSS for women with ≥ 50% CSI (69% vs. 83%, p = 0.093) and (78% vs. 91%, p = 0.034), respectively, the depth of CSI was not statistically significant as an independent predictor of 5-year RFS, DSS, or OS. The depth of CSI was not associated with a difference in the recurrence pattern (vaginal cuff, pelvic, paraaortic, or distant). In multivariate analysis, FIGO grade was the only predictor of 5-year OS. FIGO grade and the presence of lympho-vascular space invasion (LVSI) were independent predictors of 5-year RFS and DSS. <h3>Conclusion</h3> Deep cervical stromal invasion does not appear to be an independent predictive factor for survival endpoints in women with stage II uterine endometroid cancer, according to our findings. The presence of LVSI and tumor grade were both independent predictors of recurrence-free and disease-specific survival. Pooled data analysis may be needed to validate our study findings.

MRI-based radiomics analysis improves preoperative diagnostic performance for the depth of stromal invasion in patients with early stage cervical cancer

BackgroundThe depth of cervical stromal invasion is one of the important prognostic factors affecting decision-making for early stage cervical cancer (CC). This study aimed to develop and validate a T2-weighted imaging (T2WI)-based radiomics model and explore independent risk factors (factors with statistical significance in both univariate and multivariate analyses) of middle or deep stromal invasion in early stage CC.MethodsBetween March 2017 and March 2021, a total of 234 International Federation of Gynecology and Obstetrics IB1-IIA1 CC patients were enrolled and randomly divided into a training cohort (n = 188) and a validation cohort (n = 46). The radiomics features of each patient were extracted from preoperative sagittal T2WI, and key features were selected. After independent risk factors were identified, a combined model and nomogram incorporating radiomics signature and independent risk factors were developed. Diagnostic accuracy of radiologists was also evaluated.ResultsThe maximal tumor diameter (MTD) on magnetic resonance imaging was identified as an independent risk factor. In the validation cohort, the radiomics model, MTD, and combined model showed areas under the curve of 0.879, 0.844, and 0.886. The radiomics model and combined model showed the same sensitivity and specificity of 87.9% and 84.6%, which were better than radiologists (sensitivity, senior = 75.7%, junior = 63.6%; specificity, senior = 69.2%, junior = 53.8%) and MTD (sensitivity = 69.7%, specificity = 76.9%).ConclusionMRI-based radiomics analysis outperformed radiologists for the preoperative diagnosis of middle or deep stromal invasion in early stage CC, and the probability can be individually evaluated by a nomogram.

Vaginal brachytherapy alone for patients with Stage II endometrial cancer with inner half cervical stromal invasion

PurposeThe purpose of this study was to review outcomes of women with Stage II endometrial carcinoma with inner half cervical stromal invasion treated with adjuvant vaginal brachytherapy (VB) alone. Methods and MaterialsA single-institution retrospective chart review identified consecutive patients with Stage II endometrial cancer and inner half cervical stromal invasion treated with VB alone from 2011 to 2015. Patients who received chemotherapy or external beam radiotherapy were excluded. Patient and disease characteristics were collected. Association between variables and outcomes were assessed using Fisher's exact or Wilcoxon rank sum test. ResultsFifty-seven patients were identified over 5 years with a median followup of 46.8 months. Carcinoma was endometrioid Grade 1 (43.9%), 2 (36.8%), 3 (5.3%), or serous (14.0%). Depth of myometrial invasion was inner half in 75.4%. Lymphovascular invasion was seen in 28.1%, and lymph node assessment was performed in 43.9% of patients. The median depth of cervical stromal invasion was 1.25 mm (n = 48 patients). The median percentage of the cervical stromal wall invaded by tumor (obtained in 40 patients) was 16.7%. Seven (12.3%) patients recurred at a median of 16.9 months. Five-year estimates of progression-free survival and overall survival were 81.5% and 78.5%, respectively. The only factor associated with recurrence, progression-free survival or overall survival on bivariate analysis was high-grade (Grade 3 or serous) disease (p = 0.031). ConclusionsVB alone can be considered for Stage II patients with inner half cervical stromal invasion and Grade 1–2 disease. Systemic therapy may be required for patients with Grade 3 and serous histology as 75% (3/4) of these recurrences were outside the pelvis.

Clinical significance of serum squamous cell carcinoma antigen in patients with early cervical squamous cell carcinoma

Objective: To explore the clinical significance of serum squamous cell carcinoma antigen (SCC-Ag) in early cervical squamous cell carcinoma. Methods: The clinicopathological data and follow-up information of 1435 patients with stage ⅠA2-ⅡA cervical squamous cell carcinoma were collected. The correlation between serum SCC-Ag level and clinicopathological feature and prognosis were analyzed. The best cut-off of serum SCC-Ag for predicting pelvic lymph node metastasis and survival of cervical squamous cell carcinoma patients were also identified. Results: The result of univariate analysis showed that The International Federation of Gynecology and Obstetrics (FIGO) staging, tumor size, depth of cervical stromal invasion, lymphovascular space involvement, pelvic lymph node metastasis, common iliac lymph node metastasis and para-aortic lymph node metastasis were significantly related with serum SCC-Ag level (all P<0.05). The result of multivariate logistic regression analysis showed that tumor size, depth of cervical stromal invasion, pelvic lymph node metastasis and common iliac lymph node metastasis were the independent risk factors of preoperative serum SCC-Ag>2.65 ng/ml (all P<0.001). Multivariate Cox regression analysis showed that lymphovascular space involvement, SCC-Ag>3.15 ng/ml, common iliac lymph node metastasis and tumor size >4 cm were the independent prognostic risk factors (all P<0.05). The univariate analysis showed that, the tumor size, FIGO stage, depth of cervical stromal invasion and SCC-Ag level were significantly related with the recurrence of 1 096 patients without postoperative high risk factors (all P<0.05). Multivariate logistic regression analysis showed that FIGO stage (OR=1.671) and SCC-Ag>2.65 ng/ml (OR=4.490) were the independent risk factors for recurrence (both P<0.05). The best cut off of SCC-Ag for predicting early postoperative cervical lymph node metastasis of cervical squamous cell carcinoma was 2.65 ng/ml, the sensitivity was 60.8%, the specificity was 71.8%. The best cut off of SCC-Ag for predicting prognosis of cervical squamous cell carcinoma was 3.15 ng/ml, the sensitivity was 53.5%, the specificity was 71.1%. Conclusions: Preoperative serum squamous cell carcinoma antigen is an independent prognostic risk factor of survival of patients with early cervical squamous cell carcinoma, and is significantly related with recurrence of patients without postoperative high-risk factors. It can be used as a reference factor for postoperative adjuvant radiotherapy.

The effect of HMGB1 on the clinicopathological and prognostic features of cervical cancer.

Cervical cancer is the third leading cause of cancer death among women in less-developed regions. Because of the poor survivorship of patients with advanced disease, finding new biomarkers for prognostic prediction is of great importance. In the current study, mRNA datasets (GSE9750 and GSE63514) were retrieved from Gene Expression Omnibus and was used to identify differentially expressed genes. The underlying molecular mechanisms associated with high-mobility group box 1 protein (HMGB1) were investigated using bioinformatics analysis. Immunohistochemical analysis of HMGB1 was performed on 239 cases of cervical cancer samples to investigate its possible correlation with clinicopathological characteristics and outcomes. A preliminary validation has been made to explore the possible correlation factors with HMGB1 that promote migration of cervical cancer cells. Bioinformatics analysis showed that adherens junction was significant for both P-value and enrichment scores, which was consistent with the clinical study. The underlying molecular mechanisms might be the interaction among HMGB1, RAC1, and CDC42. HMGB1 expression was significantly associated with tumor size, parametrial infiltration, the depth of cervical stromal invasion, and FIGO stage (P=0.003, 0.019, 0.013, and 0.003, respectively). FIGO stage, lymph mode metastasis, and HMGB1 expression were independent predictors of a poorer prognosis of patients with cervical cancer. Knockdown of HMGB1 inhibits migration of Siha and C33A cells in vitro. Western blot and quantitative real-time PCR (qRT-PCR) showed that the expression of RAC1 and CDC42 was positively correlated with HMGB1. HMGB1 is a useful prognostic indicator and a potential biomarker of cervical cancer. RAC1 and CDC42 may be involved in the progression of cervical cancer migration induced by HMGB1.

Relationship of 18F-FDG PET/CT metabolic, clinical and pathological characteristics of primary squamous cell carcinoma of the cervix

The objectives of this retrospective study were to use preoperative 18fluoro-d-glucose (18FDG) PET/CT in patients with primary cervical squamous cell carcinoma to explore the relationship between clinical, pathological and metabolic...

Clinical and pathological characteristics related to parametrial involvement in clinical early-stage cervical cancer.

Since parametrial involvement is believed to be a crucial factor in the management of cervical cancer, our study was designed to investigate the clinical and pathological features which predicted parametrial involvement in patients with clinical early-stage cervical cancer. The study included patients with clinical early-stage cervical cancer who underwent radical hys-terectomy with pelvic and para-aortic lymphadenectomy between December 2001 and August 2014, at the Hacettepe University Hospital. The clinical and pathological characteristics of the affected patients were evaluated, including age, histologic subtype, tumor size, depth of cervical stromal invasion, lympho-vascular space invasion (LVSI), and lymph node metastasis. Univariate and multivariate analyses were performed to reveal factors associated with parametrial involvement. The study group consisted of 126 patients (mean age: 52.7 years; range: 29-83), including 101 (80.2%) with squamous, 19 (15.1%) with adenocarcinoma, and 6 (4.8%) with adenosquamous histological subtype of cervical cancer. Parametrial involvement and lymph node metastasis were detected in 41 (32.5%) and 46 (36.5%) women, respectively. Univariate analysis showed that deep cervical stromal invasion, LVSI, tumor size > 2 cm and lymph node metastasis were associated with parametrial involvement. Multivariate logistic regression analysis identified the independent risk factors associated with parametrial involvement as LVSI (OR 8.93, 95% CI 1.1-73.5, p = 0.042) and lymph node metastasis (OR 8.8, 95% CI 1.5-9.3, p = 0.004). LVSI, deep cervical stromal invasion, lymph node metastasis and tumor size are significantly associated with parametrial involvement in patients with clinical early-stage cervical cancer.

An Audit of 204 Histopathology Reports Over Three Years of Carcinoma of Cervix: Experience from a Tertiary Referral Centre

The aim was to see compliance to minimum data set information in carcinoma cervix histopathology reports from a team of 13 pathologists; and also to analyse the distribution of parameters like tumor size, grade, depth of cervical stromal invasion, lymph node yield and pTNM stage. All pathology reports of radical hysterectomy for carcinoma cervix operated in house within a three year duration (2010-2012), (n=204) were retrieved from medical records and analyzed for the above parameters. In 2010- 59 cases, in 2011- 67 cases and in 2012- 78 cases of carcinoma cervix underwent operations in our hospital. The median age was 50.5 years and the maximum T diameter was 2.8 cms in the reports of three years. Squamous carcinoma was the commonest subtype amongst all the tumors. It was noted that 60.8% of cases had cervical stromal involvement more than half the thickness of the cervical stroma. Parametrial involvement was seen in 4.82% of cases. pTNM Staging was not mentioned in 65.06% of the cases. The mean bilateral pelvic lymph node yield count in our study was 16.6 inclusive of all the three years. Compliance with provision of a minimum dataset in our team of 13 pathologists was generally good. Lymph node yield in our hands is reasonable, but constant striving for greater numbers should be made. pTNM staging should be more meticulously documented. Use of proformas /checklists is recommended.

The Number of Positive Pelvic Lymph Nodes and Multiple Groups of Pelvic Lymph Node Metastasis Influence Prognosis in Stage IA-IIB Cervical Squamous Cell Carcinoma.

Background:Pelvic lymph node metastasis (LNM) is an important prognostic factor in cervical cancer. Cervical squamous cell carcinoma accounts for approximately 75–80% of all cervical cancers. Analyses of the effects of the number of positive lymph nodes (LNs), unilateral versus bilateral pelvic LNM and a single group versus multiple groups of pelvic LNM on survival and recurrence of cervical squamous cell carcinoma are still lacking. The study aimed to analyze the effects of the number of positive pelvic LNs and a single group versus multiple groups of pelvic LNM on survival and recurrence.Methods:We performed a retrospective review of 296 patients diagnosed with Stage IA–IIB cervical squamous cell carcinoma who received extensive/sub-extensive hysterectomy with pelvic lymphadenectomy/pelvic LN sampling at Peking University People's Hospital from November 2004 to July 2013. Ten clinicopathological variables were evaluated as risk factors for pelvic LNM: Age at diagnosis, gravidity, clinical stage, histological grade, tumor diameter, lymph-vascular space involvement (LVSI), depth of cervical stromal invasion, uterine invasion, parametrial invasion, and neoadjuvant chemotherapy.Results:The incidence of pelvic LNM was 20.27% (60/296 cases). Pelvic LNM (P = 0.00) was significantly correlated with recurrence. Pelvic LNM (P = 0.00), the number of positive pelvic LNs (P = 0.04) and a single group versus multiple groups of pelvic LNM (P = 0.03) had a significant influence on survival. Multivariate analysis revealed that LVSI (P = 0.00), depth of cervical stromal invasion (P = 0.00) and parametrial invasion (P = 0.03) were independently associated with pelvic LNM.Conclusions:Patients with pelvic LNM had a higher recurrence rate and poor survival outcomes. Furthermore, more than 2 positive pelvic LNs and multiple groups of pelvic LNM appeared to identify patients with worse survival outcomes in node-positive IA-IIB cervical squamous cell carcinoma. LVSI, parametrial invasion, and depth of cervical stromal invasion were identified as independent clinicopathological risk factors for pelvic LNM.

DNA polymerase ζ as a potential biomarker of chemoradiation resistance and poor prognosis for cervical cancer

DNA Polymerase ζ (Polζ), an error-prone DNA polymerase involved in translesion DNA synthesis, plays a significant role in the cytotoxicity, mutagenicity, and chemoresistance of several cancers. To evaluate the association of Polζ with chemoradiation resistance and prognosis in cervical cancer, we enrolled 123 patients with squamous cell carcinoma of cervical cancer, who had adjuvant concurrent chemoradiation therapy after radical surgery treated at Fudan University Shanghai Cancer Center between 2008 and 2009, and tested their in vitro tumor inhibition rates using the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide method and Polζ protein expression in paraffin-embedded tissues using immunohistochemistry. We found that the Polζ-positive expression was detected in 22 % of the cases. The median in vitro inhibition rate of tumor cell growth by cisplatin, carboplatin, nedaplatin, and oxaliplatin was 80, 37, 78, and 51 %, respectively. Among the tumor-related variables, FIGO stage, tumor grade, and Polζ protein expression (adjusted HR 6.7, 4.2 and 6.7; 95 % CI 1.7-26.3, 1.0-17.3 and 1.8-25.4; P = 0.007, 0.046 and 0.005, respectively) were found to be significant predictors for recurrence. Kaplan-Meier survival estimates showed that the patients with more advanced stage (IIB) or Polζ-positive expression had a significantly shorter progression-free survival. Polζ-positive expression was significantly associated with depth of cervical stromal invasion (P = 0.012). However, the association between Polζ expression and in vitro tumor inhibition rates was not significant. Taken together, Polζ expression can be used as the predictor for poor prognosis, which might be caused by the potential chemoradiation resistance of the cervical cancer patients. The mechanism deserves further exploration.

Clinical and Pathological Factors Related to the Prognosis of Chinese Patients with Stage Ⅰb To Ⅱb Cervical Cancer

The aim of this retrospective study is to analyze the clinical and pathological factors related to the prognosis of Chinese patients with stage Ib to IIb cervical cancer. 13 clinical pathological factors in 255 patients with stage Ib to IIb cervical cancer undergoing radical hysterectomy and systematic lymphadenectomy were analyzed to screen for factors related to prognosis. The cumulative 5-year survival of the 255 patients was 75.7%. The result of the univariate analysis suggested that clinical stage, cell differentiation, depth of cervical stromal invasion, parametrial tissue involvement, and lymph node metastasis were prognostic factors for patients with stage Ib to IIb cervical cancer (P<0.05). Compared with cases with involvement of iliac nodes, obturator nodes, or inguinal lymph nodes, cases with metastasis to the common iliac lymph nodes had a poorer prognosis (P<0.05). Cases with involvement of four or more lymph nodes had a poorer prognosis than those with involvement of three or fewer lymph nodes (P<0.05). Using multivariate Cox proportional hazards model regression analysis, non-squamous histological type, poor differentiation, parametrial tissue involvement, and outer 1/3 stromal invasion were found to be independently related to patients poor prognosis (P<0.05). Non-squamous histological type, poor cell differentiation, parametrial tissue involvement, and outer 1/3 stromal invasion are the independent poor prognostic factors for patients with stage Ib to IIb cervical cancer.

Genomic instability induced by the HPV E7 Oncogene

Chyong-Huey Lai Departments of Obstetrics and Gynecology Chang Gung Memorial Hospital and Chang Gung University, Taiwan W fi rst established our methodology using SPF1/GP6+ PCR followed by hybridization with a genechip (Easychip® HPV Blot, King Car, Taiwan) for paraffi n-embedded tissue. Consecutive patients treated for cervical carcinoma of International Federation of Gynecology and Obstetrics stage I–IV between 1993 and 2000 were included. A total of 2,118 patients were eligible for analysis. HPV DNA sequences were detected in 96•6% of the specimens, among which 82% harbored single-type and 18% contained multiple-type HPV sequences. Th e leading 5 were: HPV16 (50•0%), HPV18 (17•8%), HPV58 (16•3%), HPV33 (8•7%), and HPV52 (6•8%). Th e relation of HPV genotype to prognosis of invasive cervical cancer has been controversial. Our study off ered a conclusion on (n=1067) this issue. By multivariate analysis, FIGO stage, lymph node metastasis, depth of cervical stromal invasion, grade of diff erentiation, and HPV 18-positivity were signifi cantly related to cancer relapse. FIGO stage II, deep stromal invasion, parametrial extension, HPV 18-positivity, and age older than 45 were signifi cant predictors for death. Using the seven selected variables from either recurrence-free or overall survival analysis, death and relapse predicting models classifying three risk groups (low-risk, intermediate-risk, and high-risk) were constructed and endorsed by internal validation. Th e prognostic models could be useful in counseling patients and stratifying subjects in future clinical trials. Among the 992 patients treated with primary radiotherapy, the high-risk group consisted of the patients without HPV infection or the ones infected with the alpha-7 species only in addition to stage, lymph node metastasis, histologic type and squamous cell carcinoma antigen.

Cervical Stromal Invasion Predicting Survival in Endometrial Cancer

To estimate the extent to which cervical stromal invasion would predict survival. Cases of stage II endometrioid endometrial adenocarcinoma from three academic institutions were reviewed. A gynecologic pathologist reevaluated archived slides and measured the depth of cervical stromal invasion. Clinical data were abstracted and statistical analysis performed. Of 116 cases, 31 (27%) had gland involvement and 85 (73%) cervical stromal invasion. Cervical stromal invasion was categorized as the inner two thirds (n=59 [69%]) compared with the outer third (n=26 [31%]). Women with outer third cervical stromal invasion compared with those with inner two-thirds cervical stromal invasion were more likely to be aged at least 65 years (69% compared with 46%, P=.038), have at least 50% myometrial invasion (77% compared with 44%, P=.004), lymphvascular space invasion (46% compared with 20%, P=.016), and to have died (50% compared with 19%, P=.004). Overall survival for patients with no invasion and inner two-thirds cervical stromal invasion did not differ (106 compared with 146 months, P=.89). Survival for outer third cervical stromal invasion was 91 months (P=.021). Multivariable analysis found deep myometrial invasion (hazard ratio 3.1; confidence interval [CI], 1.2-8.2), lymphvascular space invasion (hazard ratio 3.2; CI 1.2-8.4), and outer third cervical stromal invasion (hazard ratio 2.8; CI 1.1-7.2) were independent predictors of death. Deep (outer third) cervical stromal invasion is an independent predictor of death in stage II endometrial cancers and these patients should receive radiation therapy. Superficial cervical stromal invasion did not increase risk of death and adjuvant radiation for this patient group may not be necessary. III.

Prospective Phase I-II Trial of Helical Tomotherapy With or Without Chemotherapy for Postoperative Cervical Cancer Patients

To investigate, in a prospective trial, the acute and chronic toxicity of patients with cervical cancer treated with surgery and postoperative intensity-modulated radiotherapy (RT) delivered using helical tomotherapy, with or without the administration of concurrent chemotherapy. A total of 24 evaluable patients entered the study between March 2006 and August 2009. The indications for postoperative RT were tumor size, lymphovascular space invasion, and the depth of cervical stromal invasion in 15 patients; 9 patients underwent postoperative RT because of surgically positive lymph nodes. All patients underwent pelvic RT delivered with helical tomotherapy and intracavitary high-dose-rate brachytherapy. Treatment consisted of concurrent weekly platinum in 17, sequential carboplatin/Taxol in 1, and RT alone in 6. The patients were monitored for acute and chronic toxicity using the Common Toxicity Criteria, version 3.0. The median follow-up was 24 months (range, 4-49). At the last follow-up visit, 23 patients were alive and disease free. Of the 24 patients, 12 (50%) experienced acute Grade 3 gastrointestinal toxicity (anorexia in 5, diarrhea in 4, and nausea in 3). One patient developed acute Grade 4 genitourinary toxicity (vesicovaginal fistula). For patients treated with concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 71% and 24%, respectively. For patients treated without concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 29% and 14%, respectively. Two long-term toxicities occurred (vesicovaginal fistula at 25 months and small bowel obstruction at 30 months). The overall and progression-free survival rate at 3 years for all patients was 100% and 89%, respectively. The results of our study have shown that postoperative external RT for cervical cancer delivered with helical tomotherapy and high-dose-rate brachytherapy and with or without chemotherapy is feasible, with acceptable acute and chronic toxicity.

Surgical and radiologic staging of cervical cancer

The roles of radiologic and surgical staging in cervical carcinoma have been controversial. This review updates publications in this area. Conventional computed tomography or MRI has been suboptimal in detecting depth of cervical stromal invasion and nodal metastasis.18-Fluorodeoxyglucose PET or integrated PET/computed tomography (thereafter as PET collectively) is valuable for assessing prognosis, treatment response after the completion of concurrent chemoradiation, documented recurrent cervical cancer, and posttreatment unexplained tumor marker elevation. Results of MRI using nanoparticle contrast media, higher Tesla machines, or diffusion-weighted imaging without contrast may be promising. Although surgical staging is feasible, level 1 evidence is still lacking for survival benefit before definitive radiotherapy/chemoradiation in locally advanced cervical cancer. A randomized controlled trial of additional PET in MRI-defined pelvic node-positive patients prior to chemoradiation did not show significant survival benefit. Nonsurgical staging is still the gold standard for advanced cervical cancer treatment planning unless well designed phase III study could show a significant survival benefit of surgical staging. The roles of molecular imaging (new MRI technology or PET with fluorodeoxyglucose or other radiotracers) as an early predictor of response to treatment need more researches.