Cervical Cancer Undergoing Radical Hysterectomy Research Articles

Prognostic value of lymph node ratio in patients with non-metastatic cervical cancer treated with radical hysterectomy: A population-based study

BackgroundThe lymph node ratio (LNR) is an emerging prognostic biomarker in multiple malignancies. This study aimed to explore the prognostic role of LNR in patients with non-metastatic cervical cancer undergoing radical hysterectomy. MethodsData were extracted from the SEER 17 registry. Univariate and multivariate Cox analyses were performed to identify the prognostic factors associated with cancer-specific survival (CSS). A nomogram was constructed to predict the 5-year and 10-year CSS. Survival analyses stratified by the status of LNR and different adjuvant treatments were performed using the Kaplan–Meier method. ResultsA total of 8128 female patients with non-metastatic cervical cancer who underwent radical hysterectomy and regional node examination (≥8) were enrolled. Of these, 1269 (15.6%) were confirmed as lymph node-positive. Cox regression analyses showed that age, race, tumor size, tumor grade, histology, and LNR were significant factors affecting CSS. A nomogram was developed for predicting the 5-year and 10-year CSS, which showed good discrimination and calibration. Patients without lymph node involvement had inferior CSS with adjuvant treatments compared to those who did not receive further treatment. In patients with LNR ≤10%, only those receiving adjuvant radiotherapy had a trend of better CSS. In patients with an LNR between 10% and 30% and more than 30%, concurrent radiochemotherapy (CCRT) proved to be the best treatment. ConclusionsLNR is an independent prognostic factor in patients with non-metastatic cervical cancer undergoing radical hysterectomy. For patients with negative lymph nodes, no further treatment is recommended. Patients with positive lymph nodes could benefit more from CCRT.

Role of Adjuvant Radiotherapy in Patients with Cervical Cancer Undergoing Radical Hysterectomy.

The benefit of adjuvant radiotherapy (RT) after radical hysterectomy in patients with cervical cancer remains controversial. The aim of this study was to determine adjuvant RT's impact on survival in accordance with Sedlis criteria. Patients with early-stage cervical cancer undergoing radical hysterectomy between 2005 and 2022 at a single tertiary care institution were included. A multivariate analysis was performed to determinate if RT was an independent prognostic factor for recurrence or death. We also analysed whether there was a statistically significant difference in overall survival (OS) between patients who met only one or two Sedlis criteria, depending on whether they received adjuvant RT or not. 121 patients were included in this retrospective study, of whom 48 (39.7%) received adjuvant RT due to the presence of unfavourable pathological findings. In multivariate analysis, RT was not found to be a statistically significant prognostic factor for OS (p = 0.584) or disease-free survival (DFS) (p = 0.559). When comparing patients who met one or two Sedlis criteria, there were no statistically significant differences in OS between RT and no adjuvant treatment in either group. Since the selection of patients with cervical cancer eligible for surgery is becoming more accurate, adjuvant RT might not be necessary for patients with intermediate risk factors.

CLPTM1L expression predicts recurrence of patients with intermediate‑ and high‑risk stage IB‑IIB cervical cancer undergoing radical hysterectomy followed by TP as adjuvant chemotherapy.

According to the National Comprehensive Cancer Network clinical practice guidelines of cervical cancer, concurrent chemoradiotherapy or radiotherapy is suggested for patients who receive radical hysterectomy and have intermediate- and high-risk cervical cancer. However, adjuvant chemotherapy has been increasingly chosen given the adverse events associated with chemoradiotherapy or radiotherapy and the increase in evidence regarding the efficacy of adjuvant chemotherapy. Given that adjuvant chemotherapy is not a standard treatment at present, if recurrence after adjuvant chemotherapy could be predicted, it would assist the decision of gynecological oncologists selecting which adjuvant therapy (chemotherapy or radiation therapy) to use. Cleft lip and palate transmembrane protein 1-like protein (CLPTM1L; also known as cisplatin resistance-related protein 9) is associated with apoptotic mechanisms and is related to the proliferation of the tumor cells and resistance against chemotherapy. In the present study, the association between CLPTM1L expression and recurrence of intermediate- and high-risk stage IB-IIB cervical cancer in patients undergoing radical hysterectomy followed by treatment with cisplatin and paclitaxel (TP) as adjuvant chemotherapy was determined. Patients were divided into two groups: Recurrence group and no-recurrence group. CLPTM1L expression was examined using immunohistochemistry in paraffin-embedded sections using weighted scores. Regarding the characteristics of the patients, a histology of non-squamous cell carcinoma, lymph node metastasis and parametrium invasion were more common in the recurrence group compared with the non-recurrence group. In the recurrence group, CLPTM1L expression was significantly higher than that in the no-recurrence group. Next, patients were divided into low and high-expression groups based on the weighted score with a cut-off value of 6. In the high expression group, patients exhibited a higher rate of recurrence (37.5 vs. 5.1%) and had worse overall survival. Multivariate analysis revealed that high CLPTM1L expression was independently related to recurrence. In in vitro analysis, small interfering RNA-mediated knockdown of CLPTM1L enhanced the sensitivity of cervical cancer cells to cisplatin. In conclusion, the present study revealed that CLPTM1L expression may be a predictive biomarker of recurrence of intermediate- and high-risk stage IB-IIB cervical cancer in patients undergoing radical hysterectomy followed by TP as adjuvant chemotherapy.

Survival associated with extent of radical hysterectomy in early-stage cervical cancer: a subanalysis of the Surveillance in Cervical CANcer (SCCAN) collaborative study

International guidelines recommend tailoring the radicality of hysterectomy according to the known preoperative tumor characteristics in patients with early-stage cervical cancer. This study aimed to assess whether increased radicality had an effect on 5-year disease-free survival in patients with early-stage cervical cancer undergoing radical hysterectomy. The secondary aims were 5-year overall survival and pattern of recurrence. This was an international, multicenter, retrospective study from the Surveillance in Cervical CANcer (SCCAN) collaborative cohort. Patients with the International Federation of Gynecology and Obstetrics 2009 stage IB1 and IIA1 who underwent open type B/C1/C2 radical hysterectomy according to Querleu-Morrow classification between January 2007 and December 2016, who did not undergo neoadjuvant chemotherapy and who had negative lymph nodes and free surgical margins at final histology, were included. Descriptive statistics and survival analyses were performed. Patients were stratified according to pathologic tumor diameter. Propensity score match analysis was performed to balance baseline characteristics in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy. A total of 1257 patients were included. Of note, 883 patients (70.2%) underwent nerve-sparing radical hysterectomy, and 374 patients (29.8%) underwent non-nerve-sparing radical hysterectomy. Baseline differences between the study groups were found for tumor stage and diameter (higher use of non-nerve-sparing radical hysterectomy for tumors >2 cm or with vaginal involvement; P<.0001). The use of adjuvant therapy in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy was 27.3% vs 28.6%, respectively (P=.63). Five-year disease-free survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 90.1% (95% confidence interval, 87.9-92.2) vs 93.8% (95% confidence interval, 91.1-96.5), respectively (P=.047). Non-nerve-sparing radical hysterectomy was independently associated with better disease-free survival at multivariable analysis performed on the entire cohort (hazard ratio, 0.50; 95% confidence interval, 0.31-0.81; P=.004). Furthermore, 5-year overall survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 95.7% (95% confidence interval, 94.1-97.2) vs non-nerve-sparing 96.5% (95% confidence interval, 94.3-98.7), respectively (P=.78). In patients with a tumor diameter ≤20 mm, 5-year disease-free survival was 94.7% in nerve-sparing radical hysterectomy vs 96.2% in non-nerve-sparing radical hysterectomy (P=.22). In patients with tumors between 21 and 40 mm, 5-year disease-free survival was 90.3% in non-nerve-sparing radical hysterectomy vs 83.1% in nerve-sparing radical hysterectomy (P=.016) (no significant difference in the rate of adjuvant treatment in this subgroup, P=.47). This was confirmed after propensity match score analysis (balancing the 2 study groups). The pattern of recurrence in the propensity-matched population did not demonstrate any difference (P=.70). For tumors ≤20 mm, no survival difference was found with more radical hysterectomy. For tumors between 21 and 40 mm, a more radical hysterectomy was associated with improved 5-year disease-free survival. No difference in the pattern of recurrence according to the extent of radicality was observed. Non-nerve-sparing radical hysterectomy was associated with better 5-year disease-free survival than nerve-sparing radical hysterectomy after propensity score match analysis.

Thirty-day Postoperative Adverse Events in Minimally Invasive versus Open Abdominal Radical Hysterectomy for Early-stage Cervical Cancer

To identify the incidence, type, and grade of postoperative adverse events in minimally invasive radical hysterectomy vs abdominal radical hysterectomy (ARH) for patients with early-stage cervical cancer and determine risk factors associated with these adverse events. The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) was queried to identify patients with early-stage cervical cancer undergoing radical hysterectomy. Multivariable logistic regression was used to assess risk factors associated with adverse postoperative outcomes among patients undergoing radical hysterectomy. ACS NSQIP participating institutions within the United States. Patients were collected from the ACS NSQIP databases (2014-2017) undergoing radical hysterectomy for early-stage cervical cancer. N/A MEASUREMENTS AND MAIN RESULTS: ARH had a significantly increased incidence of any 30-day postoperative adverse event compared with minimally invasive radical hysterectomy (31.2% vs 19.9%, p <.001). There was a higher incidence of surgical site infection, both deep and superficial, and blood transfusions in ARH. On multivariable logistic regression, the abdominal surgical approach was the only risk factor significantly associated with any postoperative adverse event (odds ratio, 1.4; confidence interval, 1.1-1.9; p=.018; 95% CIs). In this study, the abdominal surgical approach for radical hysterectomy in early-stage cervical cancer was associated with a higher incidence of postoperative adverse events than the minimally invasive approach.

Pattern of relapse in patients with stage IB1 cervical cancer after radical hysterectomy as primary treatment. Minimally invasive surgery vs. open approach. Systematic review and meta-analysis.

BackgroundAfter the LACC trial, the SUCCOR study, and other studies, we know that patients who have undergone minimally invasive surgery for cervical cancer have worse outcomes, but today, we do not know if the surgical approach can be a reason to change the pattern of relapses on these patients. We evaluated the relapse pattern in patients with stage IB1 cervical cancer (FIGO, 2009) who underwent radical hysterectomy with different surgical approaches. MethodsA systematic review of literature was performed in PubMed, Cochrane Library, Clinicaltrials.gov, and Web of science. Inclusion criteria were prospective or retrospective comparative studies of different surgical approaches that described patterns or locations of relapse in patients with stage IB1 cervical cancer. Heterogeneity was assessed by calculating I2. ResultsThe research resulted in 782 eligible citations from January 2010 to October 2020. After filtering, nine articles that met all inclusion criteria were analyzed, comprising data from 1663 patients who underwent radical hysterectomy for IB1 cervical cancer, and the incidence of relapse was 10.6%. When we compared the pattern of relapse (local, distant, and both) of each group (open surgery and minimally invasive surgery), we did not see statistically significant differences, (OR 0.963; 95% CI, 0.602–1.541; p = 0.898), (OR 0.788; 95% CI, 0.467–1.330; p = 0.542), and (OR 0.683; 95% CI, 0.331–1.407; p = 0.630), respectively. ConclusionThere are no differences in patterns of relapse across surgical approaches in patients with stage IB1 cervical cancer undergoing radical hysterectomy as primary treatment.

Increased incidence of neurogenic bladder after radical hysterectomy for cervical cancer: A nationwide population-based cohort study.

The effect of radical hysterectomy for patients with cervical cancer on voiding function remains controversial. The purpose of this study was to examine the association between radical hysterectomy for patients with cervical cancer and the odds of developing neurogenic bladder by using data from the National Health Insurance Research Database (NHIRD) in Taiwan. We identified 17 936 patients who underwent radical hysterectomy for cervical cancer between 2000 and 2013 among inpatients registered in the Longitudinal Health Insurance Database in Taiwan. Of the patients, those diagnosed as having cervical cancer without radical hysterectomy were selected and compared as a matched control group. Patients diagnosed as having cervical cancer before the index date, those with neurogenic bladder dysfunction before tracking, and those aged <20 years were excluded. The hazard ratios (HRs) of neurogenic bladder and other variants of interest were further calculated using a multivariate Cox regression analysis. The cutoff p value of <0.05 was regarded as statistically significant. The adjusted HR (aHR) of subsequent neurogenic bladder was higher in the hysterectomy group (aHR = 1.205; 95% CI, 1.086-1.440; p = 0.029) than in the control group during the follow-up period. As to the age subgroups, the patients aged 20 to 44 years (aHR = 3.321, p = 0.001) had a significantly increased risk of developing neurogenic bladder after radical hysterectomy as compared with those aged 45 to 64 years (aHR = 1.193, p = 0.012). Patients with cervical cancer undergoing radical hysterectomy have an increased risk of neurogenic bladder, which may result from nerve denervation caused by the operation. These patients should be informed of the potential risk of voiding dysfunction during discussion of the subsequent management for cervical cancer.

Impact of surgical waiting time on the outcomes of patients with early-stage cervical cancer undergoing radical hysterectomy

<h3>Objectives:</h3> Evaluate the impact of surgery wait-time on survival of patients with early stage cervical cancer undergoing radical hysterectomy. <h3>Methods:</h3> Patients with clinical stage I squamous, adenocarcinoma, adenosquamous carcinoma of the cervix, no history of another tumor or other cervical surgical procedure, who underwent primary radical hysterectomy with lymphadenectomy up to 12 weeks from initial diagnosis, with at least 1 month of follow-up were drawn from the National Cancer Database (2004-2015). Surgery wait-time was categorized into <4 weeks (group 1), 4-8 weeks (group 2) and 8-12 weeks (group 3). Impact of surgery wait-time on overall survival (OS) was assessed with the log-rank test. A Cox model was constructed to control for confounders. <h3>Results:</h3> A total of 4782 patients with clinical stage I cervical cancer who underwent primary radical hysterectomy were identified. Median time to surgery was 34 days (IQR:27); 1823 (38.1%) had surgery < 4 weeks from diagnosis, while 2207 (46.2%) and 752 (15.7%) had surgery 4-8 and 8-12 wks from diagnosis. Patients in group 3 (35.6%), group 2 (31.6%) were more likely to have government insurance compared to those in group 1 (24.6%), p<0.001. A higher rate of co-morbidities was observed among patients in group 3 (14.2%) compared to those in group 2 (11.6%) and group 1 (10.5%), p=0.029. Patients in group 3 were more likely to be Black (13.6%) compared to those in group 2 (9.9%) and group 1 (7.7%), p<0.001. Higher rate of positive lymph nodes was observed among patients in group 1 (18.4%) compared to those in group 2 (15.6%) and group 3 (14.7%). Median tumor size was 3 cm for patients in group 1, compared to 2.5 cm and 2.3 cm for those in group 2 and 3, p<0.001. Rate of unplanned re-admission was comparable between the groups (p=0.35). There was no difference in OS between the groups, p=0.12; 5-year OS rates for patients in group 1, 2, and 3 were 85.7%, 86.6% and 89.6% respectively. After controlling for tumor size, histology and extension, status of lymph nodes, receipt of radiotherapy, patient age, insurance, race and comorbidities, surgery waiting-time had no impact on survival. <h3>Conclusions:</h3> In a large cohort of patients with clinical stage I cervical cancer undergoing radical hysterectomy no detrimental effect of surgery wait-time on overall survival was found.

Older women with cervical cancer managed surgically have worse outcomes: a National Cancer database study

<h3>Objectives:</h3> Women with early stage cervical cancer are typically managed surgically; however, a subset of patients will have risk factors for recurrence (Sedlis and Peters criteria) and will be offered post-operative radiation or chemoradiation to improve outcomes. The purpose of this study is to evaluate if women ≥65 years old with early stage cervical cancer managed surgically are at an increased risk for requiring adjuvant chemoradiation. <h3>Methods:</h3> Data from 2004 to 2016 was abstracted from the National Cancer Database. All women with presumed early stage cervical cancer undergoing radical hysterectomy were included in the study. Adjuvant therapy (radiation or chemoradiation), margin status, regional lymph node involvement, lymphovascular space invasion (LVSI), length-of-stay (LOS), 30-day and 90-day morbidity and mortality, and overall survival were evaluated. Chi-squared, t-test, and Kaplan Meier methods were used for statistical analyses. <h3>Results:</h3> Of the 126,876 women, 16,718 women had a radical hysterectomy and were included in this study. 15,050 (90.0%) were < 65 years old (yo) while 1,668 (10.0%) were ≥65 yo. Women in the ≥65 group were more likely to be Black, have Medicare insurance, and a higher Charlson comorbidity score. Surgical margins and regional lymph nodes were more likely to be positive in women ≥65 yo compared to women < 65 yo (13.3% vs 5.7%; p<0.0001) and (19.3% vs 16.8%; p<0.01). Average tumor size was larger in women ≥65 yo compared to < 65 (3.6 cm vs. 2.5 cm; p<0.0001), and LVSI was more likely to be present (37.8% vs. 31.4%; p<0.001). Women ≥65 yo were more likely to receive adjuvant therapy as opposed to women < 65 yo (40.3% vs 29.3%; p<0.0001). LOS for women ≥65 yo was significantly longer than women < 65 yo (4.3 days vs. 3.4 days; p<0.0001), but 30-day readmission rates did not differ between groups (5.0% vs 6.2%; p=0.12). Women ≥65 yo had a worse prognosis with a mean survival of 51.4 months compared to 58.3 months in women < 65 yo (p<0.0001). Older women also had higher rates of mortality at 30 days (0.8% vs 0.1%; p<0.0001) and 90 days (2.1% vs 0.3%; p<0.0001). <h3>Conclusions:</h3> Women ≥65 yo with early stage cervical cancer were more likely to meet Sedlis and Peters criteria on surgical pathology and receive adjuvant therapy. While hospital readmission rates were similar between age groups, older women had longer LOS with worse overall survival and mortality rates. Women ≥65 years old diagnosed with early stage cervical cancer may benefit from primary chemoradiation.

Serum concentrations of S100-A11 and AIF-1 are elevated in cervical cancer patients with lymph node involvement.

The aim of this study was to compare the serum levels of TFF3, AIF-1, S100-A11 and DKK1 in surgically staged patients with cervical cancer, and in healthy female controls. In total 85 consecutive patients dia-gnosed at the Department of Obstetrics and Gynecology, University Hospital in Olomouc with cervical cancer undergoing radical hysterectomy or fertility sparing surgery with pelvic lymphadenectomy were included. Ninety patients who underwent elective total hysterectomy for nonmalignant disorder represented a control group. In all patients, preoperative serum samples were taken and separated; the sera were all stored at -80 °C until analysis for TFF3, AIF-1, S100-A11 and DKK1. According to the final histopathological examination, 32 (40.5%) out of 79 cervical cancer patients with microscopically examined lymph nodes were lymph node-positive. S100–A11 (P < 0.0001) and AIF-1 levels (P < 0.0001) were higher in cervical cancer patients than in controls. Furthermore, the serum levels of S100–A11 (P > 0.04) and AIF-1 (P > 0.01) were significantly higher in lymph node-positive patients as compared to lymph node-negative patients. The levels of TFF3 and DKK1 were higher (P < 0.0001) in controls than in cervical cancer patients and were not different in groups with or without nodal involvement.. S100-A11 and AIF-1 represent potential bio-markers in patients with cervical cancer. Moreover, the levels of S100-A11 and AIF-1 increase in patients with lymph node involvement.

Pathologic and clinical tumor size discordance in early-stage cervical cancer: Does it matter?

ObjectiveThe objective of this study was to assess the rate of discordance between clinical and pathologic tumor size for women with stage IB1 cervical cancer (FIGO 2009 criteria), assess risk factors for discordance, and determine the impact of discordance on oncologic outcomes. MethodsThis was a secondary analysis of a prior multi-institutional retrospective review of patients diagnosed with stage IB1 (FIGO 2009 staging) cervical cancer undergoing radical hysterectomy between 2010 and 2017. Demographic, clinicopathologic, and oncologic data were collected. Pathologic upstaging was defined as having a preoperative diagnosis of stage IB1 cervical cancer with pathology demonstrating a tumor size >4 cm. Demographic and clinicopathologic data was compared using chi-square, fisher exact or 2-sided t-test. Survival was estimated using the Kaplan-Meier method. ResultsOf the 630 patients, 77 (12%) were upstaged. Patients who were upstaged had lower rates of preoperative conization (p < .001) or preoperative tumor sizes ≤2 cm (p < .001). Upstaged patients had increased odds of deep stromal invasion, lymphovascular space invasion, positive margins and positive lymph nodes. Almost 88% of upstaged patients received adjuvant therapy compared to 29% of patients with tumors ≤4 cm (odds 18.49, 95% CI 8.99–37.94). Finally, pathologic upstaging was associated with an increased hazard of recurrence (hazard ratio [HR] 1.95, 95% CI 1.03–3.67) and all-cause death (HR 2.31, 95% CI 1.04–5.11). ConclusionsPathologic upstaging in stage IB1 cervical cancer is relatively common. Upstaging is associated with an 18-fold increased risk of receipt of adjuvant therapy. Patients undergoing preoperative conization and those with tumors <2 cm had lower risks of upstaging. Improvement in preoperative assessment of tumor size may better inform primary treatment decisions.

The upper limit of optimal tumor size in patients with FIGO 2018 stage IB2 cervical cancer undergoing radical hysterectomy

ObjectivePatients who undergo radical hysterectomy may require postoperative adjuvant radiotherapy, and all efforts should be made to reduce dual therapy in such patients. The aim of this study was to...

Association of MRI-derived radiomic biomarker with disease-free survival in patients with early-stage cervical cancer

Pre-treatment survival prediction plays a key role in many diseases. We aimed to determine the prognostic value of pre-treatment Magnetic Resonance Imaging (MRI) based radiomic score for disease-free survival (DFS) in patients with early-stage (IB-IIA) cervical cancer.Methods: A total of 248 patients with early-stage cervical cancer underwent radical hysterectomy were included from two institutions between January 1, 2011 and December 31, 2017, whose MR imaging data, clinicopathological data and DFS data were collected. Patients data were randomly divided into the training cohort (n = 166) and the validation cohort (n=82). Radiomic features were extracted from the pre-treatment T2-weighted (T2w) and contrast-enhanced T1-weighted (CET1w) MR imagings for each patient. Least absolute shrinkage and selection operator (LASSO) regression and Cox proportional hazard model were applied to construct radiomic score (Rad-score). According to the cutoff of Rad-score, patients were divided into low- and high- risk groups. Pearson's correlation and Kaplan-Meier analysis were used to evaluate the association of Rad-score with DFS. A combined model incorporating Rad-score, lymph node metastasis (LNM) and lymphovascular space invasion (LVI) by multivariate Cox proportional hazard model was constructed to estimate DFS individually.Results: Higher Rad-scores were significantly associated with worse DFS in the training and validation cohorts (P<0.001 and P=0.011, respectively). The Rad-score demonstrated better prognostic performance in estimating DFS (C-index, 0.753; 95% CI: 0.696-0.805) than the clinicopathological features (C-index, 0.632; 95% CI: 0.567-0.700). However, the combined model showed no significant improvement (C-index, 0.714; 95%CI: 0.642-0.784).Conclusion: The results demonstrated that MRI-derived Rad-score can be used as a prognostic biomarker for patients with early-stage (IB-IIA) cervical cancer, which can facilitate clinical decision-making.

Effect of different therapeutic methods on survival of stage I-IIA cervical cancer patients complicated with postoperative intermediate risk factors

Objective To compare the effect of different therapeutic methods upon the survival of stage Ⅰ-ⅡA cervical cancer patients with intermediate risk factors and explore the optimal treatment for patients with early-stage cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy. Methods Clinical data of 323 patients with the following intermediate risk factors of lymphovascular space invasion, depth of stromal invasion or tumor size>4 cm were retrospectively analyzed. The impact of observing (NT), chemotherapy (CT), radiotherapy (RT) and concurrent chemoradiotherapy (CCRT) on survival was statistically compared. The Kaplan-Meier method was used to survival analysis, and log-rank test difference, Cox model was used to prognostic factor analysis. Results The 5-year progression-free survival (PFS) and overall survival (OS) of all patients were 79.0% and 84.8%. Univariate and multivariate analyses demonstrated that TS> 4 cm and therapeutic method were the independent prognostic factors of PFS. The number of risk factors and therapeutic method were the independent prognostic factors of OS. In the whole group, both RT and CCRT could improve the prognosis of patients with no statistical significance (P>0.05). In the subgroup analysis, for patients with a single intermediate risk factor (low risk group), CT could significantly prolong the PFS (P=0.026) rather the 5-year OS (P=0.692). Compared with NT and CT, RT and CCRT could improve the PFS and OS, whereas no statistical significance was noted between the RT and CCRT (both P>0.05). For those with ≥2 risk factors (high risk group), CCRT could significantly prolong the PFS compared with CT (84.9% vs. 70%; P=0.006), but did not improve the OS (P=0.107). Compared with RT, CCRT could significantly improve the PFS and OS (both P<0.05). Conclusion For patients with only one risk factor, RT can enhance the clinical prognosis. CCRT can improve the clinical prognosis of stage Ⅰ-ⅡA cervical cancer patients with ≥2 risk factors. Key words: Cervical neoplasms/radiotherapy; Cervical neoplasms/chemotherapy; Cervical neoplasms/ concurrent chemoradiotherapy; Prognosis

Does the Robotic Platform Reduce Morbidity Associated With Combined Radical Surgery and Adjuvant Radiation for Early Cervical Cancers?

Open radical hysterectomy followed by adjuvant radiation for cervical cancer has been associated with significant rates of morbidity. Radical hysterectomy is now often performed robotically. We sought to examine if the robotic platform decreased the morbidity associated with radical hysterectomy followed by adjuvant radiation. A retrospective cohort of patients with cervical cancer undergoing radical hysterectomy from 1995 to 2013 was evaluated. Complications were assessed using electronic record review and graded. χ tests and Student t tests were used for analysis. Overall, 243 patients underwent radical hysterectomy for cervical cancer. Surgical approach was 43% open and 57% robotic. Eighty-three patients (34.2%) required adjuvant radiation. Overall, radical hysterectomy plus adjuvant radiation was associated with increased risk of complication (29%) compared to radical hysterectomy alone (7%) (P < 0.001). Complications included lymphedema (n = 18), bowel-associated complications (n = 10), and urinary complications (n = 7). There was no difference in time to initiation of radiation between open and robotic surgery (43 vs 47 days; P = 0.33). There was no difference in grade 2/3 complications in patients receiving adjuvant radiation between open and robotic surgery (27.5% vs 27.9%; P = 0.97). Patients undergoing open surgery followed by radiation experienced a trend toward increased adhesion-related complications, such as bowel obstruction and ureteral stricture (10% vs 2.3%; P = 0.19); whereas patients undergoing robotic surgery followed by radiation experienced a trend toward increased lymphedema (19% vs 8%; P = 0.20). We found no difference in long-term complications between patients who underwent robotic surgery compared to open radical hysterectomy with adjuvant radiation. There may be fewer adhesion-related complications with robotic surgery. However, as many radiation-related complications occur at later time points, continued follow-up to evaluate for potential differences between the 2 groups is necessary.

Intraoperative intravenous lidocaine exerts a protective effect on cell-mediated immunity in patients undergoing radical hysterectomy.

Surgical procedures cause a decrease in lymphocyte proliferation rate, an increase in apoptosis and shifts the balance of T‑helper (Th)1/Th2 cells towards anti‑cell‑mediated immunity (CMI) Th2 dominance, which is relevant to the immunosuppressive effects of CMI, postoperative septic complications and the formation of tumor metastasis. Previous studies have revealed that lidocaine exhibits antibacterial actions; regulating inflammatory responses, reducing postoperative pain and affecting the duration spent in hospital. Thus, the present study hypothesized that lidocaine may exert a protective effect on the CMI of patients undergoing surgery for the removal of a primary tumor. A total of 30 adult female patients diagnosed with cervical cancer were recruited to the present study and were randomized into two groups. The lidocaine group received an intravenous bolus dose of 1.5 mg/kg lidocaine, followed by continuous infusion at 1.5 mg/kg/h until discharge from the operating room. The control group received the same volume of normal saline. A 10 ml sample of venous blood was drawn, and the lymphocytes were isolated using Ficoll‑paque 1 day prior to surgery, at discharge from the operating room and 48 h post‑surgery. The proliferation rate of the lymphocytes was assessed using a Cell Counting Kit‑8 assay and was found to be higher in the lidocaine group. The early apoptosis of lymphocytes was attenuated following lidocaine treatment at 48 h post‑surgery, as detected using flow cytometry with Annexin V‑fluorescein isothiocyanate/propidium iodide staining. The level of interferon (IFN)‑γ in the serum at 48 h was significantly decreased following surgery in the control group, compared with the pre‑surgical values (3.782 ± 0.282, vs. 4.089 ± 0.339 pg/ml, respectively) and the ratio of IFN‑γ to interleukin‑4 was well preserved in the lidocaine group. In conclusion, the present study demonstrated that the intraoperative systemic administration of lidocaine exerted a protective effect on CMI in patients with cervical cancer undergoing radical hysterectomy. This may be beneficial in reducing the occurrence of postoperative septic complications and tumor metastasis formation.

Does use of uterine manipulator alter the rate of lymphovascular space invasion in patients with invasive cervical cancer undergoing radical hysterectomy?

Objectives: Lymphovascular space invasion (LVSI) is a prognostic factor in cervical cancer and an important determinant in selecting postoperative adjuvant therapy. The purpose of this study was to investigate whether the use of a uterine manipulator alters the rate of LVSI in patients undergoing radical hysterectomy (RH) for invasive cervical cancer.

Incidence and influencing factors of distal external iliac lymph node metastasis in early cervical cancer

The distal external iliac lymph nodes are located along the external iliac artery between the deep circumflex iliac vein and the inguinal canal. Our study aimed to investigate the incidence of metastasis in distal external iliac lymph nodes and its association with clinicopathological factors in patients with early stage cervical cancer, and to determine the role of distal external iliac lymph nodes dissection in the surgery. Five hundred and twenty-four patients with early stage cervical cancer underwent radical hysterectomy and bilateral pelvic lymphadenectomy in the Shandong Province Cancer Hospital between June 1995 and December 2011, and their clinicopathological features were analyzed retrospectively. Of the 524 patients, 124 (23.7%) had pelvic lymph node metastasis. The metastasis rates were 16.2% (85 of 524 patients) in the obturator lymph nodes, 12.2% (64 of 524 patients) in the internal and external iliac lymph nodes, 2.9% (15 of 524 patients) in the common iliac lymph nodes, 2.1% (11 of 524 patients) in the distal external iliac lymph nodes, and 1.7% (9 of 524 patients) in the para-aortic nodes. The incidence of isolated positive distal external iliac lymph nodes was 0.2%. Univariate analysis showed that lymphovascular space invasion, pelvic lymph node metastases (excluding distal external iliac lymph nodes) were significantly associated with distal external iliac lymph node metastasis (P < 0.05). Logistic regression analysis showed that pelvic lymph node metastasis (excluding distal external iliac lymph nodes) was the independent risk factor for metastasis to distal external iliac lymph nodes. In early stage cervical cancer, distal external iliac lymph node metastasis is rare, especially in cases with stage IA or without pelvic lymph node metastasis. Less extensive pelvic lymphadenectomy may be considered in these patients in order to reduce operative complications and improve patients' quality of life. The deep circumflex iliac vein may be an appropriate landmark for the caudal limit of external iliac lymphadenectomy. However, if pelvic lymph node metastasis (excluding distal external iliac lymph nodes) is found by intraoperative rapid pathological diagnosis, systematic pelvic lymphadenectomy including removal of the distal external iliac lymph nodes should be performed in order to reduce the risk of distant metastasis.

Ganglio centinela para estadios tempranos en cáncer de cuello uterino

Objetivo: Determinar la factibilidad y seguridad del ganglio centinela (GC) con el uso combinado del mapeo linfático con Tc 99 y la inyección de colorante azul (patent blue) en pacientes con cáncer de cérvix temprano sometidas a histerectomía radical con linfadenectomía pélvica bilateral. Diseño: Estudio prospectivo. Institución: Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú. Participantes: Pacientes con cáncer temprano de cuello uterino. Intervenciones: Entre diciembre de 2003 y diciembre de 2006, 66 pacientes con cáncer temprano de cuello estadios IA2 (n=2), IB1 (n=63) y IIA (n=1) fueron sometidas a detección del ganglio linfático centinela con linfoscintigrafía el día previo a la operación y mapeo linfático intraoperatorio con colorante azul y sonda detectora de radiación gama. El tratamiento quirúrgico se completó con la realización de la histerectomía radical y linfadenectomía pélvica bilateral, por laparotomía. Principales medidas de resultados: Detección de ganglios centinelas. Resultados: En las 66 pacientes estudiadas se detectó 136 ganglios centinelas, con un promedio de 2,06 por paciente. Se utilizó el método combinado (Tc 99 y patent blue). La localización más frecuente fue la región obturatriz con un 69,9% (n=95). Se halló metástasis en los ganglios pélvicos en 11 pacientes, que fueron correctamente localizadas en el ganglio centinela con una sensibilidad de 100%. Cuando el ganglio centinela fue negativo, no se encontró metástasis en los ganglios no centinela (VPN 100%). Conclusiones: La identificación del ganglio centinela con tecnecio-99 combinado con la inyección de colorante azul es factible y mostró un valor predictivo negativo de 100%.

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.