Myong Cheol Lim

Sentinel lymph node biopsy in endometrial cancer: Meta-analysis of 26 studies

OBJECTIVE The validity of the sentinel lymph node (SLN) procedure for the assessment of nodal status in patients with endometrial cancer is unclear. We aimed to assess the diagnostic performance of this procedure. METHODS We searched the PubMed and Embase databases for studies published before June 1, 2011. Eligible studies had a sample size of at least 10 patients, and reported the detection rate and/or sensitivity of the SLN biopsy. RESULTS We identified 26 eligible studies, which included 1101 SLN procedures. The overall weighted-mean number of harvested SLNs was 2.6. The detection rate and the sensitivity were 78% (95% confidence interval [CI]=73%-84%) and 93% (95% CI=87%-100%), respectively. Significant between-study heterogeneity was observed in the analysis of the detection rate (I-squared statistic, 80%). The use of pericervical injection was correlated with the increase of the detection rate (P=0.031). The hysteroscopic injection technique was associated with the decrease of the detection rate (P=0.045) and the subserosal injection technique was associated with the decrease of the sensitivity (P=0.049), if they were not combined with other injection techniques. For the detection rate, significant small-study effects were noted (P<0.001). CONCLUSIONS Although SLN biopsy has shown good diagnostic performance in endometrial cancer, such performance should be interpreted with caution because of significant small study effects. Current evidence is not yet sufficient to establish the true performance of SLN biopsy in endometrial cancer.

Incidence of cervical, endometrial, and ovarian cancer in Korea, 1999-2010

Objective To investigate the recent incidence of and trends in cervical, endometrial, and ovarian cancer in Korean females. Methods Data from the Korea Central Cancer Registry between 1999 and 2010 were analyzed. Age-standardized rates (ASRs) and annual percent changes (APCs) were calculated. Results The absolute incidence rates of the three major gynecologic cancers increased: 6,394 in 1999 to 7,454 in 2010. The ASR for gynecologic cancer was 23.7 per 100,000 in 1999 and decreased to 21.0 in 2010 (APC, -1.1%; 95% confidence interval [CI], -1.53 to -0.70) due to a definitive decrease in the incidence of cervical cancer (APC, -4.3%). Endometrial cancer has been definitively increasing (APC, 6.9% during 1999-2010), especially in females <30 years old (APC, 11.2%) and in females ≥80 years old (APC, 9.5%). The incidence of ovarian cancer is increasing gradually (APC, 1.5%). Conclusion ASRs and APC for gynecologic cancers overall are decreasing due to the decrease in the incidence of cervical cancer. However, the incidence of endometrial and ovarian cancer has been increasing.

Laparoscopic and laparotomic staging in stage I epithelial ovarian cancer: a comparison of feasibility and safety.

The aim of this study was to compare laparoscopic and laparotomic surgical staging in patients with stage I epithelial ovarian cancer in terms of feasibility and safety. A retrospective chart review was undertaken of all patients with apparent stage I epithelial ovarian cancer who underwent laparoscopic (laparoscopy group) or laparotomic (laparotomy group) surgical staging at the Center for Uterine Cancer, National Cancer Center, Korea, between January 2001 and August 2006. During the study period, 19 patients underwent laparotomic surgical staging and 17 patients underwent laparoscopic surgical staging. No cases were converted from laparoscopy to laparotomy. The two groups were similar in terms of age, body mass index, procedures performed, number of lymph nodes retrieved, and operating time. The laparoscopy group had less estimated blood loss (P= 0.001), faster return of bowel movement (P< 0.001), and a shorter postoperative hospital stay (P= 0.002) compared to the laparotomy group. Transfusions were required only in two laparotomy patients, and postoperative complications occurred only in four laparotomy patients. However, two patients with stage IA grade 1 and 2 disease in laparoscopy group had recurrence with one patient dying of disease. The accuracy and adequacy of laparoscopic surgical staging were comparable to laparotomic approach, and the surgical outcomes were more favorable than laparotomic approach. However, the oncologic safety of laparoscopic staging was not certain. This is the first report on the possible hazards of laparoscopic staging in early-stage ovarian cancer. In the absence of a large prospective trial, this technique should be performed cautiously.

The clinical significance of hepatic parenchymal metastasis in patients with primary epithelial ovarian cancer

OBJECTIVE The objective of this study was to determine the clinical significance of hepatic parenchymal metastasis on survival in patients with advanced epithelial ovarian cancer. METHODS We conducted a retrospective review of ovarian cancer patients with stages IIIc and IV hepatic parenchymal metastasis who were treated at the National Cancer Center in Korea between January 2001 and January 2008. Hepatic metastases were divided into unresectable, hematogenous parenchymal metastasis and resectable, parenchymal metastasis from peritoneal seeding. RESULTS One hundred twenty patients were identified, 113 of whom were included in the study. The stage IIIc group included 97 patients, and the group with stage IV disease and hepatic parenchymal metastasis included 16 patients. Of the 16 patients with hepatic parenchymal metastasis, 2 patients had unresectable, hematogenous parenchymal metastasis with a poor prognosis compared to the patients with resectable, hepatic parenchymal metastasis from peritoneal seeding. Fourteen patients with hepatic parenchymal metastases from peritoneal seeding underwent complete resection without complications as follows: wedge resection (n=7), segmentectomy (n=5), and hemi-hepatectomy (n=2). Age, tumor grade, histology, serum CA-125 level, and the rate of optimal debulking were similar in patients with stage IIIc disease and patients with stage IV disease who had resectable, hepatic parenchymal metastasis from peritoneal seeding. The 5-year progression free survival rate and the 5-year overall survival rate for patients with stage IIIc disease and patients with stage IV disease and hepatic parenchymal metastasis from peritoneal seeding were 25 and 23% (p=0.8063), and 55 and 51% (p=0.5671), respectively. CONCLUSION Our findings suggest that complete hepatic resection should be attempted for patients with hepatic parenchymal metastasis from peritoneal seeding.

Association between the location of transposed ovary and ovarian function in patients with uterine cervical cancer treated with (postoperative or primary) pelvic radiotherapy

OBJECTIVE To evaluate the effectiveness of ovarian transposition procedures in preserving ovarian function in relation to the location of the transposed ovaries in patients who underwent surgery with or without pelvic radiotherapy. DESIGN Retrospective. SETTING Uterine cancer center. PATIENT(S) A total of 53 patients with cervical cancer who underwent ovarian transposition between November 2002 and November 2010. INTERVENTION(S) Ovarian transposition to the paracolic gutters with or without radical hysterectomy and lymph node dissection. MAIN OUTCOME MEASURE(S) Preservation of ovarian function, which was assessed by patients symptoms and serum FSH level. RESULT(S) Lateral ovarian transposition was performed in 53 patients. Based on receiver operator characteristic curve analysis, optimum cutoff value of location more than 1.5 cm above the iliac crest was significantly associated with preservation of ovarian function after treatment (area under receiver operator characteristic curve: 0.757, 95% confidence interval [CI]: 0.572-0.943). In univariate analysis, higher location of transposed ovary more than 1.5 cm from the iliac crest was the only independent factor for intact ovarian function (odds ratio 9.91, 95% CI: 1.75-56.3). Multivariate analysis confirmed that the location of transposed ovary (odds ratio 11.72, 95% CI 1.64-83.39) was the most important factor for intact ovarian function. CONCLUSION(S) Location of transposed ovary higher than 1.5 cm above the iliac crest is recommended to avoid ovarian failure after lateral ovarian transposition after primary or adjuvant pelvic radiotherapy in cervical cancer.

Programmed cell death 6 (PDCD6) inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of VEGFR-2.

Programmed cell death 6 (PDCD6) was originally found as a pro-apoptotic protein, but its molecular mechanism is not well understood. In this study, we have attempted to investigate the effects of PDCD6 on the inhibition of angiogenesis-mediated cell growth as a novel anti-angiogenic protein. Purified recombinant human PDCD6 inhibited cell migration in a concentration-time-dependent manner. We also found that overexpressed PDCD6 suppressed vascular endothelial growth factor (VEGF)-induced proliferation, invasion, and capillary-like structure tube formation in vitro. PDCD6 suppressed phosphorylation of signaling regulators downstream from PI3K, including Akt, mammalian target of rapamycin (mTOR), glycogen synthase kinase-3β(GSK-3β), ribosomal protein S6 kinase (p70S6K), and also decreased cyclin D1 expression. We found binding PDCD6 to VEGFR-2, a key player in the PI3K/mTOR/P70S6K signaling pathway. Taken together, these data suggest that PDCD6 plays a significant role in modulating cellular angiogenesis.

Residual Cancer Stem Cells after Interval Cytoreductive Surgery following Neoadjuvant Chemotherapy Could Result in Poor Treatment Outcomes for Ovarian Cancer

The objective of this review is to discuss the common surgical strategy of cytoreductive surgery after neoadjuvant chemotherapy, with an emphasis on incorporating extensive cytoreductive surgery to remove traces of regressed tumor. A review of the literature regarding cytoreductive surgery after neoadjuvant chemotherapy and cancer stem cells is given together with the authors’ own experience and comments. Most ovarian cancer cells consist of transformed cells that regress after neoadjuvant chemotherapy. Therefore, the extent of cytoreductive surgery usually tends to be limited because only visible tumors are removed. Scar tissue, which represents tumor after neoadjuvant chemotherapy, may contain cancer stem cells. This leads to chemotherapy-resistant cancer stem cells to persist in patients who have received neoadjuvant chemotherapy. If the extent of cytoreductive surgery is preserved based on initial images, and includes all scar tissue suggestive of previously existing ovarian cancer in patients who underwent interval debulking surgery after neoadjuvant chemotherapy, treatment outcome will be improved or be comparable to patients who underwent primary cytoreductive surgery with minimal morbidity. Further basic and clinical investigation is needed to serve as a standard surgical paradigm in the management of advanced ovarian cancer. Currently, the gynecologic oncologist should remove all traces of regressed tumor after neoadjuvant chemotherapy to eradicate potential cancer stem cells. Further investigation to clarify the role of cancer stem cell in the surgical management of ovarian cancer is warranted.

BRCA1 and BRCA2 germline mutations in Korean ovarian cancer patients

PurposeTo evaluate the proportion of Korean ovarian cancer patients with a strong family history and the genetic status in such patients.Methods and patientsPedigree analysis and genetic counseling were performed on 337 ovarian cancer patients in the National Cancer Center Korea between January 2005 and June 2008. Patients with a strong family history were defined as (1) patients with double primary ovarian and breast cancer and (2) ovarian cancer patients with one or more first-degree relatives with breast or ovarian cancer. Lymphocyte specimens from peripheral blood were processed for BRCA1 and BRCA2 by direct sequencing.ResultsSixteen percent (54/337) of patients had a strong family history. Of the 54 patients with a strong family history, 40 patients (74%) accepted the genetic test. Thirteen deleterious mutations (11 in BRCA1 and 2 in BRCA2) were identified (33%). Twenty-three of 283 patients (8%) without a strong family history underwent genetic testing and two deleterious mutations in BRCA1 were identified (9%). Eight of 15 mutations (53%) were novel, and c.1041delAGCinsT and c.2081insC in the BRCA1 gene were recurrent in two patients.ConclusionsThe proportion of Korean ovarian cancer patients with a strong family history was significant, and the prevalence of BRCA1 and BRCA2 mutations in such patients was high.

Prognostic factors of secondary cytoreductive surgery for patients with recurrent epithelial ovarian cancer.

OBJECTIVE The objective of this study was to identify the prognostic factors of secondary cytoreductive surgery on survival in patients with recurrent epithelial ovarian cancer. METHODS The medical records of all patients who underwent secondary cytoreductive surgery between May 2001 and October 2007 at the National Cancer Center, Korea were reviewed. Univariate and multivariate analyses were executed to evaluate the potential variables for overall survival. RESULTS In total, 54 patients met the inclusion criteria. Optimal cytoreduction to <0.5 cm residual disease was achieved in 87% of patients who had received secondary cytoreductive surgery. Univariate analysis revealed that site of recurrence (median survival, 53 months for the largest tumors in the pelvis vs. 24 months for the largest tumors except for the pelvis; p=0.007), progression free survival (PFS) (median survival, 43 months for PFS>/=12 months vs. 24 months for PFS<12 months; p=0.036), and number of recurrence sites (median survival, 49 months for single recurred tumor vs 29 months for multiple recurred tumors; p=0.036) were significantly associated with overall survival. On multivariate analysis, prognostic factors that correlated with improved survival were site of recurrence (p=0.013), and PFS (p=0.043). CONCLUSION In the authors analysis, a significant survival benefit was identified for the recurred largest tumors within the pelvis and PFS>/=12 months. Secondary cytoreductive surgery should be offered in selected patients and large prospective studies are needed to define the selection criteria for secondary cytoreductive surgery.

Efficacy and oncologic safety of nerve-sparing radical hysterectomy for cervical cancer: a randomized controlled trial

Objective A prospective, randomized controlled trial was conducted to evaluate the efficacy of nerve-sparing radical hysterectomy (NSRH) in preserving bladder function and its oncologic safety in the treatment of cervical cancer. Methods From March 2003 to November 2005, 92 patients with cervical cancer stage IA2 to IIA were randomly assigned for surgical treatment with conventional radical hysterectomy (CRH) or NSRH, and 86 patients finally included in the analysis. Adequacy of nerve sparing, radicality, bladder function, and oncologic safety were assessed by quantifying the nerve fibers in the paracervix, measuring the extent of paracervix and harvested lymph nodes (LNs), urodynamic study (UDS) with International Prostate Symptom Score (IPSS), and 10-year disease-free survival (DFS), respectively. Results There were no differences in clinicopathologic characteristics between two groups. The median number of nerve fiber was 12 (range, 6 to 21) and 30 (range, 17 to 45) in the NSRH and CRH, respectively (p<0.001). The extent of resected paracervix and number of LNs were not different between the two groups. Volume of residual urine and bladder compliance were significantly deteriorated at 12 months after CRH. On the contrary, all parameters of UDS were recovered no later than 3 months after NSRH. Evaluation of the IPSS showed that the frequency of long-term urinary symptom was higher in CRH than in the NSRH group. The median duration before the postvoid residual urine volume became less than 50 mL was 11 days (range, 7 to 26 days) in NSRH group and was 18 days (range, 10 to 85 days) in CRH group (p<0.001). No significant difference was observed in the 10-year DFS between two groups. Conclusion NSRH appears to be effective in preserving bladder function without sacrificing oncologic safety.