Soon-Beom Kang

Suppressor of Cytokine Signaling (SOCS) Genes Are Silenced by DNA Hypermethylation and Histone Deacetylation and Regulate Response to Radiotherapy in Cervical Cancer Cells

Suppressor of cytokine signaling (SOCS) family is an important negative regulator of cytokine signaling and deregulation of SOCS has been involved in many types of cancer. All cervical cancer cell lines tested showed lower expression of SOCS1, SOCS3, and SOCS5 than normal tissue or cell lines. The immunohistochemistry result for SOCS proteins in human cervical tissue also confirmed that normal tissue expressed higher level of SOCS proteins than neighboring tumor. Similar to the regulation of SOCS in other types of cancer, DNA methylation contributed to SOCS1 downregulation in CaSki, ME-180, and HeLa cells. However, the expression of SOCS3 or SOCS5 was not recovered by the inhibition of DNA methylation. Histone deacetylation may be another regulatory mechanism involved in SOCS1 and SOCS3 expression, however, SOCS5 expression was neither affected by DNA methylation nor histone deacetylation. Ectopic expression of SOCS1 or SOCS3 conferred radioresistance to HeLa cells, which implied SOCS signaling regulates the response to radiation in cervical cancer. In this study, we have shown that SOCS expression repressed by, in part, epigenetically and altered SOCS1 and SOCS3 expression could contribute to the radiosensitive phenotype in cervical cancer.

L1 cell adhesion molecule expression is associated with pelvic lymph node metastasis and advanced stage in diabetic patients with endometrial cancer: a matched case control study.

Background: Diabetic patients with endometrial cancer had more lymph node metastasis than non-diabetic patients with endometrial cancer. L1 cell adhesion molecule (L1CAM) could be possibly associated with lymph node metastasis in diabetic patients with endometrial cancer via epithelial-mesenchymal transition. We aimed to investigate the association between L1CAM expression and lymph node metastasis in diabetic patients with endometrial cancer. Methods: We conducted a matched case control study of 68 endometrial cancer patients who comprise each 34 diabetic and non-diabetic patients. L1CAM expression was evaluated by immunohistochemistry using fresh formalin-fixed paraffin-embedded tissue block of the patients. The association between L1CAM expression and pelvic lymph node metastasis was assessed according to the presence of diabetes. Results: Of the 68 patients, 13 (19.1%) were positive for L1CAM immunostaining. Positive rate of L1CAM expression in diabetic endometrial cancer patients was similar to that in non-diabetic endometrial cancer patients (14.7% vs. 23.5%, P = 0.355). Tumor recurred more frequently in patients with positive L1CAM expression than those with negative L1CAM expression (33.3% vs. 1.6%, P = 0.019). However, we failed to find any significant association between L1CAM expression and lymph node metastasis. Only for the diabetic patients (n = 34), patients with pelvic lymph node metastasis had more L1CAM expression than those without lymph node metastasis (50.0% vs. 3.6%, P = 0.035). Advanced stage was the only risk factor for recurrence that showed a significant association with L1CAM expression for the diabetic endometrial cancer patients (P = 0.006), as well as all the enrolled patients (P = 0.014). Conclusion: L1CAM expression is associated with pelvic lymph node metastasis and advanced stage in diabetic patients with endometrial cancer.

Prediction model for para-aortic lymph node metastasis in patients with locally advanced cervical cancer.

OBJECTIVE Concurrent chemoradiotherapy is usually administered to patients with locally advanced cervical cancer (LACC). Extended-field chemoradiotherapy is required if para-aortic lymph node (PALN) metastasis is detected. This study aimed to construct a prediction model for PALN metastasis in patients with LACC before definitive treatment. METHODS Between 2009 and 2016, all consecutive patients with LACC who underwent para-aortic lymphadenectomy at two tertiary centers were retrospectively analyzed. A multivariate logistic model was constructed, from which a prediction model for PALN metastasis was developed and internally validated. Before analysis, risk grouping was predefined based on the likelihood ratio. RESULTS In total, 245 patients satisfied the eligibility criteria. Thirty-four patients (13.9%) had pathologically proven PALN metastases. Additionally, 16/222 (7.2%) patients with negative PALNs on positron emission tomography/computed tomography (PET/CT) had PALN metastasis. Moreover, 11/105 (10.5%) patients with both negative PALNs and positive pelvic lymph nodes on PET/CT had PALN metastasis. Tumor size on magnetic resonance imaging and PALN status on PET/CT were independent predictors of PALN metastasis. The model incorporating these two predictors displayed good discrimination and calibration (bootstrap-corrected concordance index=0.886; 95% confidence interval=0.825-0.947). The model categorized 169 (69%), 52 (22%), and 23 (9%) patients into low-, intermediate-, and high-risk groups, respectively. The predicted probabilities of PALN metastasis for these groups were 2.9, 20.8, and 76.2%, respectively. CONCLUSION We constructed a robust model predicting PALN metastasis in patients with LACC that may improve clinical trial design and help clinicians determine whether nodal-staging surgery should be performed.

Prediction model for 30-day morbidity after gynecological malignancy surgery

Objective The potential risk of postoperative morbidity is important for gynecologic cancer patients because it leads to delays in adjunctive therapy and additional costs. We aimed to develop a preoperative nomogram to predict 30-day morbidity after gynecological cancer surgery. Methods Between 2005 and 2015, 533 consecutive patients with elective gynecological cancer surgery in our center were reviewed. Of those patients, 373 and 160 patients were assigned to the model development or validation cohort, respectively. To investigate independent predictors of 30-day morbidity, a multivariate Cox regression model with backward stepwise elimination was utilized. A nomogram based on this Cox model was developed and externally validated. Its performance was assessed using the concordance index and a calibration curve. Results Ninety-seven (18.2%) patients had at least one postoperative complication within 30 days after surgery. After bootstrap resampling, the final model indicated age, operating time, and serum albumin level as statistically significant predictors of postoperative morbidity. The bootstrap-corrected concordance index of the nomogram incorporating these three predictors was 0.656 (95% CI, 0.608–0.723). In the validation cohort, the nomogram showed fair discrimination [concordance index: 0.674 (95% CI = 0.619–0.732] and good calibration (P = 0.614; Hosmer-Lemeshow test). Conclusion The 30-day morbidity after gynecologic cancer surgery could be predicted according to age, operation time, and serum albumin level. After further validation using an independent dataset, the constructed nomogram could be valuable for predicting operative risk in individual patients.

Port site infiltration of local anesthetic after laparoendoscopic single site surgery for benign adnexal disease

Objective To determine whether local bupivacaine injection into the incision site after gynecologic laparoendoscopic single site surgery (LESS) improves postoperative pain. Methods This prospective cohort study included consecutive 158 patients who had LESS for benign adnexal disease from March 2013 to December 2015. Chronologically, 82 patients (March 2013 to August 2014) received no bupivacaine (group 1) and 76 (August 2014 to December 2015) received a bupivacaine block (group 2). For group 2, 10 mL 0.25% bupivacaine was injected into the 20 mm-incision site through all preperitoneal layers after LESS completion. Primary outcome is postoperative pain score using the visual analog scale (VAS). Results There was no difference in clinicopathological characteristics between the groups. Operating time (expressed as median [range], 92 [55–222] vs. 100 [50–185] minutes, P=0.137) and estimated blood loss (50 [30–1,500] vs. 125 [30–1,000] mL, P=0.482) were similar between the groups. Post-surgical VAS pain scores after 3 hours (3.5 [2–6] vs. 3.5 [2–5], P=0.478), 6 to 8 hours (3.5 [2–6] vs. 3 [1–8], P=0.478), and 16 to 24 hours (3 [2–4] vs. 3 [1–7], P=0.664) did not differ between groups. Conclusion Bupivacaine injection into the trocar site did not improve postoperative pain after LESS. Randomized trials are needed to evaluate the benefits of local bupivacaine anesthetic for postoperative pain reduction.

Phase III study of cisplatin with or without S-1 in patients with stage IVB, recurrent, or persistent cervical cancer

BackgroundThis open-label phase III trial evaluated efficacy and safety of S-1 plus cisplatin vs. cisplatin alone as first-line chemotherapy in patients with stage IVB, recurrent, or persistent cervical cancer.MethodsPatients were randomised (1:1) to S-1 plus cisplatin (study group) or cisplatin alone (control group). In each cycle, cisplatin 50 mg/m2 was administered on Day 1 in both groups. S-1 was administered orally at 80–120 mg daily on Days 1–14 of a 21-day cycle in the study group. The primary endpoint was overall survival (OS).ResultsA total of 375 patients were enrolled, of whom 364 (188, study group; 176, control group) received treatment. Median OS was 21.9 and 19.5 months in the study and control groups, respectively (log-rank P = 0.125; hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.67–1.05). Median progression-free survival (PFS) was 7.3 and 4.9 months in the study and control groups, respectively (HR 0.62, 95% CI 0.48–0.80, P < 0.001). The adverse event (AE) rate increased in the study group despite the absence of any unexpected AEs.ConclusionsS-1 plus cisplatin did not show superiority over cisplatin alone in OS but significantly increased PFS in patients with stage IVB, recurrent, or persistent cervical cancer. Since the standard therapy has changed in the course of this study, further studies are warranted to confirm the clinical positioning of S-1 combined with cisplatin for this population.

The impact of positive peritoneal cytology on prognosis in patients with cervical cancer: a meta-analysis

Background:The impact of positive peritoneal cytology on the prognosis of cervical cancer is controversial. Thus, we performed a meta-analysis to determine its impact on recurrence, and to investigate correlations between abnormal cytology and/or lymph node metastasis in cervical cancer.Methods:A systematic literature review was conducted through July 2014. Odds ratios (ORs) and their 95% confidence intervals (95% CIs) were calculated by standard meta-analysis techniques with the fixed-effects models, if there was no significant statistical heterogeneity across studies by using I2.Results:Of 303 studies retrieved, 6 were included in the meta-analysis. These six case–control observational studies included 1360 cervical cancer patients who showed negative peritoneal cytology and 64 who showed positive peritoneal cytology. Over the combined study period, 20 of 45 in the positive peritoneal cytology group experienced recurrence, whereas 88 of 539 controls did. The meta-analysis based on the fixed-effects model indicated a significant increase in the risk of recurrence in the positive peritoneal cytology group relative to the control group (OR: 4.47; 95% CI: 2.33–8.58, P<0.001, I2=0.0%). Moreover, the results of our meta-analysis suggested that the positive peritoneal cytology group displayed more lymph node metastasis than the negative peritoneal cytology group (OR: 3.73; 95% CI: 2.13–6.53, P<0.001, I2=0.0%).Conclusions:Although based mainly on retrospective observational studies, our meta-analysis indicates that abnormal peritoneal cytology may be strongly associated with poor prognosis in patients with cervical cancer. Future research should verify this relationship through prospective observational studies over a longer term.

Polymorphisms of interleukin (IL)-1β and the risk of epithelial ovarian cancer

5036 Background: The aim of this investigation was to analyze the association between a single nucleotide polymorphism (SNP) in the interleukin (IL)-1β-511 and ovarian cancer risk. Methods: The blo...