Yong Jung Song

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.

Extended cytoreduction of tumor at the porta hepatis by an interdisciplinary team approach in patients with epithelial ovarian cancer

OBJECTIVE The objective of this study was to describe the development and experience in resection of tumor at the porta hepatis in patients with ovarian cancer by an interdisciplinary team approach. METHODS From August 2007 to June 2009, 11 women (2 primary and 9 recurrent ovarian cancers) underwent extended cytoreductive surgery including resection of tumor at the porta hepatis by hepatobiliary surgeons. RESULTS Tumor resection at the porta hepatis was required in 7.1% of the patients (11/155) during the study period. The median tumor size of the porta hepatis was 2.0cm (range, 0.7-4cm). All visible tumors at the porta hepatis were completely resected with co-operation of hepatobiliary surgeons. Optimal cytoreduction was achieved in all patients. There was no significant morbidity related to tumor resection of the porta hepatis and mortality associated with surgery. Five of 11 patients had recurrent disease at median 8months (range, 1-13) after the surgery with a median follow-up of 8months (range, 3-21months). CONCLUSION Tumor resection at the porta hepatis is feasible with acceptable morbidities in patients with ovarian cancer by an interdisciplinary team approach with hepatobiliary surgeons. Long term follow up is needed to know the impact on survival.

Learning curve analysis of laparoscopic radical hysterectomy and lymph node dissection in early cervical cancer.

OBJECTIVE We aimed to evaluate the learning curve for laparoscopic radical hysterectomy and lymph node dissection (LRHND) in uterine cervical cancer and to compare the surgicopathologic outcomes of cases treated in the first half of the curve with those treated in the second half of the curve. STUDY DESIGN The medical records of LRHND patients between August 2004 and April 2011 were reviewed retrospectively. The patients were divided into two groups of the first 35 cases (phase I) and the second 35 cases (phase II). All operations were performed by the same surgeon. Demographic data and surgicopathologic parameters were analyzed. The learning curve was evaluated using the cumulative summation (CUSUM) technique. RESULTS No difference was found in demographics and histologic type between the two groups. The mean operating time (307.7±85.8 min) of phase I was significantly longer than phase II (266.3±58.8 min) (P=0.021). The number of complications in phase I patients (N=9) was significantly higher than that (N=1) of phase II patients (P=0.013). There were no significant differences between the two groups with respect to lymph node yield and likelihood of identifying positive lymph nodes, resection margins, parametrium, stromal invasion, and lymphovascular space invasion. Disease-free survival did not differ between the two groups (P=0.142). The learning period for LRHND to reach a turning point was calculated to be 40 cases. CONCLUSIONS An extended learning period can be required for LRHND, during which survival and pathologic outcome of LRHND may not be adversely affected.

Total colectomy as part of primary cytoreductive surgery in advanced Müllerian cancer

OBJECTIVE To investigate morbidities and surgical outcomes of total colectomy conducted during primary cytoreductive surgery in advanced Müllerian cancer. METHODS The authors reviewed the medical records of 22 patients with stage IIIC or IV advanced Müllerian cancer that underwent total colectomy at the National Cancer Center Korea between January 2003 and December 2007. RESULTS Total colectomy was performed in 22 patients, of whom 2 (9.1%) underwent prophylactic ileostomy and 1 (4.5%) permanent ileostomy. Optimal cytoreduction (residual tumor <1 cm) was possible in 20 patients (90.9%). Median times at passage of flatus and initiation of tolerable diet were days 4 (2-10) and 6 (4-18) postoperatively, respectively. Nine postoperative morbidities, not directly related to ileo-rectal anatomosis, occurred in 7 patients (31.8%) and were successfully managed conservatively. No fistula developed during a mean follow-up of 16 months (range, 2-56). There was no surgery-related mortality. Diarrhea after total colectomy was well managed by medical treatment in most patients. Median time to recovery to previous bowel habits was 12 months (range, 6-20) in the 11 patients evaluable. Five-year progression free survival and overall survival rates were 38.6% and 74.4%, respectively. CONCLUSIONS Total colectomy is a feasible and safe procedure in terms of minimizing residual tumor in most patients with advanced Müllerian cancer with acceptable morbidities.

Transabdominal cardiophrenic lymph node dissection (CPLND) via incised diaphragm replace conventional video-assisted thoracic surgery for cytoreductive surgery in advanced ovarian cancer

OBJECTIVE The objective of this study is to describe the feasibility of the new approach, transabdominal CPLND, via incised diaphragm in patients with ovarian cancer by gynecologic oncologists instead of the conventional video-assisted thoracic surgery. METHODS From November 2008 to December 2011, 11 women (10 primary and 1 recurrent ovarian cancers) underwent CPLND for the extensive cytoreductive surgeries via incised muscle of the right diaphragm by gynecologic oncologists. All ≥5 mm tumors in CPLN, which were the criterion for suspicious malignancy on preoperative axial computed tomogram, were completely resected by gynecologic oncologists. RESULTS The median tumor size of the CPLN was 10mm (range, 7-17 mm) and metastasis was identified in 45% (5/11) of ≥5 mm CPLN on preoperative computed tomogram. The median number of harvested CPLND was 3 (range 1-12) and metastatic node was 1 (range, 0-10). There was no significant morbidity related to CPLND and mortality associated with surgery. Ten patients achieved the no gross residual disease and one patient accomplished gross residual-1, indicating residual disease measuring ≤1 cm in maximal diameter. CONCLUSION Transabdominal CPLND via incised diaphragm is feasible as a part of the cytoreductive surgery without significant morbidities by gynecologic oncologist. This procedure could substitute the conventional video-assisted thoracic surgery.

Persistent human papillomavirus DNA is associated with local recurrence after radiotherapy of uterine cervical cancer.

Human papillomavirus (HPV) DNA is considered as a hallmark of cervical cancer. We investigated whether persistent HPV DNA at the cervix is associated with local recurrence after radiotherapy in patients with locally advanced cervical cancer. A total of 156 patients with HPV‐positive cervical cancer (International Federation of Gynecology and Obstetrics stage IB–IVB) treated with radiotherapy between July 2003 and December 2006 were analyzed. HPV DNA was measured prior to radiotherapy and after completion of radiotherapy. The results of HPV DNA test at postradiotherapy 1, 3, 6 and 12 months were analyzed individually for association with local recurrence‐free survival (LRFS). In addition, the result of any last follow‐up HPV test within 24 months postradiotherapy was defined as the overall status of HPV at 24 months and was also analyzed for association with LRFS. HPV DNA was cleared in 127 patients (81.4%) and persistent in 29 patients (18.6%) by 24 months. In 18 patients with local recurrences, 14 patients (78%) showed positive HPV tests at 1–3 months. Among the various time points analyzed, a positive HPV test at 3 months was the most accurate predictor of local recurrence. Multivariate analysis indicated that overall status of HPV at 24 months, low HPV viral load and histologic grade as being significantly related to poor LRFS. In HPV‐positive cervical carcinoma treated primarily with radiotherapy, persistent HPV DNA within 24 months after treatment indicates a high risk of local recurrence. Diagnostic accuracy of HPV test was highest at 3 months.

Feasibility and Safety of Extensive Upper Abdominal Surgery in Elderly Patients with Advanced Epithelial Ovarian Cancer

We performed a retrospective study to evaluate the feasibility and safety of extensive upper abdominal surgery (EUAS) in elderly (≥65 yr) patients with advanced ovarian cancer. Records of patients with advanced epithelial ovarian cancer who received surgery at our institution between January 2001 and June 2005 were reviewed. A total of 137 patients including 32 (20.9%) elderly patients were identified. Co-morbidities were present in 37.5% of the elderly patients. Optimal cytoreduction was feasible in 87.5% of the elderly while 95.2% of young patients were optimally debulked (P=0.237). Among 77 patients who received one or more EUAS procedures, 16 (20.8%) were elderly. Within the cohort, the complication profile was not significantly different between the young and the elderly, except for pleural effusion and pneumothorax (P=0.028). Elderly patients who received 2 or more EUAS procedures, when compared to those 1 or less EUAS procedure, had significantly longer operation times (P=0.009), greater blood loss (P=0.002) and more intraoperative transfusions (P=0.030). EUAS procedures are feasible in elderly patients with good general condition. However, cautious peri-operative care should be given to this group because of their vulnerability to pulmonary complications and multiple EUAS procedures.

Position statements on genetic test for peritoneal, ovarian, and fallopian tubal cancers: Korean Society of Gynecologic Oncology (KSGO)

This statement sets out the position of the Korean Society of Gynecologic Oncology regarding the assessment of genetic tests on women with peritoneal, ovarian, and fallopian tubal (POFT) cancers and their families.

Preventive vaccination against cervical cancer: Korean Society of Gynecologic Oncology Guideline

After human papillomavirus (HPV) vaccine guidelines published by Korean Society of Gynecologic Oncology (KSGO) in 2011, new studies have been published, leading to additional data regarding efficacy, safety, number of vaccination rounds, and ideal age of vaccine administration. We searched and reviewed the literatures focused on the efficacy of 2-dose schedule vaccination, the efficacy of 3-dose schedule vaccination in middle-aged women, the ideal age of 3-dose schedule vaccination, the safety of HPV preventive vaccine, and the ability of cross-protection of each HPV preventive vaccine. The KSGO has revised the previous guideline based on the results of the above studies.