Effect of delayed palliative chemotherapy on survival of patients with recurrent ovarian cancer.

For patients with recurrent ovarian cancer, the goals of chemotherapy include palliation of disease-related symptoms with minimum treatment-related side effects. However, there is currently a paucity of data regarding the initiation of palliative chemotherapy. This study aimed to compare the differences in survival rates and toxicities between patients with recurrent ovarian cancer who started palliative chemotherapy immediately versus those who received delayed chemotherapy. Through a retrospective chart review, patients who received more than three lines of chemotherapy were included. Based on the timing of third-line chemotherapy initiation, the patients were divided into two groups: delayed (DTG) and immediate (ITG) treatment groups. The chi-square test or Fisher's exact tests, and t-test or Mann-Whitney U test were used for comparing variables, as appropriate. The Kaplan-Meier method was used for survival analysis. P-value of <0.05 was considered significant. Although there was no statistically significant difference, the total number of regimens and cycles was lower in the DTG than in the ITG. No differences in toxicities and survival rates were observed between the two groups. Overall, survival and toxicity did not differ significantly between the two groups. In a palliative care setting, our findings suggest that delaying the treatment had no adverse effect on survival. Despite the lack of evidence of a survival benefit with aggressive treatment, patients chose to continue chemotherapy. Because recurrent ovarian cancer is a complex condition, patients require sufficient explanation and time to fully understand the costs and benefits related to aggressive chemotherapy.

Can simple trachelectomy or conization show comparable survival rate compared with radical trachelectomy in IA1 cervical cancer patients with lymphovascular space invasion who wish to save fertility? A systematic review and guideline recommendation.

OBJECTIVE: This study aims to analyze the published literatures on the effect of less radical fertility-preserving procedures, such as conization or simple trachelectomy, on oncological outcomes in IA1 cervical cancer patients with lymphovascular space invasion (LVSI) through a systematic-review. METHODS: The EMBASE and MEDLINE databases and Cochrane Library were searched for published studies reporting the oncological outcomes of conization/simple trachelectomy in these patients, through April 2017. The endpoints were recurrence and mortality rates. Data were presented as per the Meta-analysis Of Observational Studies in Epidemiology checklist. Practice guidelines were generated via the Grading of Recommendation, Assessment, Development and Evaluation system. RESULTS: From 6,755 records, 94 full-texts articles were reviewed for eligibility, and five studies were included in this systematic review. All included studies were nonrandomized studies: two case-control studies comparing conization (n = 14) with hysterectomy (n = 24), and the other three were interrupted time series including conization (n = 20) and simple vaginal trachelectomy (n = 59). During the median follow-up duration of 43 months, no recurrence was reported in both conization and simple trachelectomy groups in IA1 patients with LVSI. From three studies reporting the fertility outcomes, the rates of pregnancy, live birth, preterm delivery, and second-trimester miscarriage were 73% (35/48), 64% (32/50), 10% (5/48), and 6% (3/48), respectively. CONCLUSION: Results suggest that simple trachelectomy or conization could be performed for IA1 cervical cancer patients with LVSI who want to preserve fertility, although these results are only based on a small number of nonrandomized studies (recommendation grade 2 = weak; evidence level D = very low). Further randomized trials with long-term study period are needed to address this issue.

Practice guidelines for management of cervical cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement.

Clinical practice guidelines for gynecologic cancers have been developed by academic society from several countries. Each guideline reflected their own insurance system and unique medical environment, based on the published evidence. The Korean Society of Gynecologic Oncology (KSGO) published the first edition of practice guidelines for gynecologic cancer treatment in late 2006; the second edition was released in July 2010 as an evidence-based recommendation. The Guidelines Revision Committee was established in 2015 and decided to develop the third edition of the guidelines in an advanced format based on evidence-based medicine, embracing up-to-date clinical trials and qualified Korean data. These guidelines cover strategies for diagnosis and treatment of primary and recurrent cervical cancer. The committee members and many gynecologic oncologists derived key questions through discussions, and a number of relevant scientific literature were reviewed in advance. Recommendations for each specific question were developed by the consensus conference, and they are summarized here, along with the details. The objective of these practice guidelines is to establish standard policies on issues in clinical practice related to the management in cervical cancer based on the results in published papers to date and the consensus of experts as a KSGO Consensus Statement.

Syndrome of inappropriate antidiuretic hormone secretion following irinotecan-cisplatin administration as a treatment for recurrent ovarian clear cell carcinoma.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) has various causes including central nervous system disorders, pulmonary and endocrine diseases, paraneoplastic syndromes, and use of certain drugs. SIADH induced by chemotherapy with irinotecan-cisplatin is not a common complication. Here, we review a case of SIADH after treatment with irinotecan-cisplatin. A 45-year-old woman received adjuvant chemotherapy (paclitaxel-carboplatin) for ovarian clear cell carcinoma, but the cancer recurred within 9 months of chemotherapy. Subsequently, a second line of combination chemotherapy containing irinotecan-cisplatin was initiated. However, 5 days after chemotherapy administration, her general condition began to deteriorate; her hematological tests revealed hyponatremia. Therefore, it is imperative to consider the possibility of SIADH in patients being treated with irinotecan-cisplatin-based chemotherapy. Proper monitoring of serum sodium levels and assessment of clinical symptoms should be performed in such patients for early diagnosis and prompt management.

Right ventricular metastatic tumor from a primary carcinoma of uterine cervix: A cause of pulmonary embolism.

The presence of intracavitary cardiac metastasis from squamous cell carcinoma of the uterine cervix is extremely rare. The diagnosis is made almost exclusively postmortem. Apart from causing intracardiac obstruction, it can present as pulmonary emboli and the prognosis is extremely poor. It is important to suspect this diagnosis in patient with recurrent pulmonary emboli. Due to the rarity of this condition it is very difficult to standardize care for these patients. However, it is possible that aggressive therapy may lengthen patients' survival and quality of life. We present a case of isolated intracavitary cardiac metastasis arising from a squamous cell carcinoma of the cervix, 44-year-old woman, diagnosed as stage complaint of fatigue and dyspnea on mild exertion. The echocardiogram showed a mass in the right ventricle and suspicious pulmonary embolism. We took an aggressive therapeutic approach. The pathological examination of the resected tissue revealed metastatic squamous cell carcinoma.

Tissue injuries after single-port and multiport laparoscopic gynecologic surgeries: A prospective multicenter study.

The present study focused on the degree of tissue injury following single-port laparoscopic surgery (SPLS) and multiport laparoscopic surgery (MPLS) for the treatment of various benign gynecologic diseases. A total of 228 patients were prospectively enrolled at seven academic centers in South Korea between April 2011 and September 2012. Of these, 122 patients underwent SPLS and 106 patients underwent MPLS. The serum levels of C-reactive protein, creatine phosphokinase, lactic dehydrogenase and cancer antigen 125 were measured preoperatively and on postoperative day 4 by immunonephelometry. Cosmetic satisfaction and postoperative pain scores (visual analogue scale) were analyzed. Postoperative changes in the levels of the serum markers were found to be similar between the SPLS and MPLS groups. However, the postoperative pain scores at 48 h were significantly lower in the SPLS group when compared with those in the MPLS (P=0.001). In addition, patient-controlled analgesia was used more frequently by patients in the MPLS group (P=0.003). The present study is the first prospective investigation of tissue injury resulting from SPLS and MPLS in gynecology. In conclusion, the current study demonstrated that serum marker levels during SPLS were similar to those during MPLS in the treatment of benign gynecologic diseases. However, SPLS is a reasonable alternative to MPLS and is associated with comparable tissue injury, improved cosmesis and reduced postoperative pain.

Abnormally high level of CA-19-9 in a benign ovarian cyst.

CA-19-9 antigen is mainly elevated in cases of gastrointestinal tract malignancy, including of the pancreas, colorectum, and biliary tract. CA 19-9 antigen can also be elevated in ovarian mucinous neoplasms, however, as well as in many benign conditions. Markedly raised levels of more than 10,000 U/mL were almost observed in advanced stage of malignancy. We report herein the case of a 37-year-old woman who presented with an abnormally high level of CA 19-9 antigen associated with benign mucinous cystadenoma.

Comparison of diagnostic accuracy between endometrial curettage and pipelle aspiration biopsy in patients treated with progestin for endometrial hyperplasia: a Korean Gynecologic Oncology Group Study (KGOG 2019).

A prospective multicenter trial has been started in Korea to evaluate the diagnostic accuracy of endometrial aspiration biopsy compared with dilatation and curettage in patients treated with progestin for endometrial hyperplasia. For conservative treatment of endometrial hyperplasia, orally administered progestins are most commonly used method with various treatment regimens and more recently, the levonorgestrel-releasing intrauterine system also has been used successfully to treat endometrial hyperplasia. However, there is no report about the accuracy of endometrial sampling during hormonal treatment for follow-up evaluation of endometrial hyperplasia. Patients with histologically confirmed endometrial hyperplasia are offered hormonal treatment with any one of the following three options: oral medroxyprogesterone acetate 10 mg/day for 14 days per cycle, continuous oral medroxyprogesterone acetate 10 mg/day or insertion of levonorgestrel-releasing intrauterine system. Histological surveillance is performed at 3 months or 6 months following initial treatment. Endometrial tissues are obtained via endometrial aspiration biopsy using a pipelle and dilatation and curettage. In the case of levonorgestrel-releasing intrauterine system, endometrial aspiration biopsy will be done with levonorgestrel-releasing intrauterine system in uterus and then, after the removal of levonorgestrel-releasing intrauterine system, dilatation and curettage will be done. The biopsy findings will be compared. The primary endpoint is to compare the pathological outcome of endometrial aspiration with dilatation and curettage. The secondary endpoint is the response rate with three types of progestin treatment at 6 months.

Cytotoxic and targeted systemic therapy in advanced and recurrent cervical cancer: experience from clinical trials.

Cervical cancer is the third most common malignant disease of women worldwide. Despite advances in screening and treatment strategies, a significant number of patients have advanced and recurrent disease. These patients are not amenable to curative treatments, such as surgery and radiation, and have poor prognosis. Therefore, palliative treatment remains the standard of care for these patients. Several phase II/III trials have demonstrated that cisplatin is the most active single agent, and the combination of cisplatin and paclitaxel is considered a standard regimen for clinical practice and trials in these patients with improved response rates and progression-free intervals. Although other cisplatin doublet chemotherapy regimens were not superior to cisplatin plus paclitaxel, substituting topotecan or gemcitabine for paclitaxel might be helpful for some patients considering different toxicity profiles. Because the response to palliative chemotherapy is poor, several targeted agents including bevacizumab, erlotinib, pazopanib, lapatinib, sunitinib and cetuximab, each of which inhibits cell proliferation and angiogenesis, were evaluated in these patients. Of them, bevacizumab, targeting vascular endothelial growth factor, showed favorable results. Recent phase III trial showed that bevacizumab combined with chemotherapy was shown to significantly improve the response rate, progression-free interval, and overall survival compared to chemotherapy alone. These results suggest that targeted agents could significantly improve survival and affect practice guidelines in these patients showing poor prognosis. Thus, future trials using newly developed targeted agents are warranted to improve treatment strategies in these patients.

Epidemiologic characteristics of cervical cancer in Korean women.

Cervical cancer is the most common female genital tract malignancy in Korean women. Although age-standardized cancer incidence rate of cervical cancer has decreased from 18.6 per 100,000 women in 1999 to 12.3 per 100,000 women in 2010 in Korea with widespread routine screening, several epidemiologic characteristics are still present. Incidence of cervical cancer still varies according to geographic area, and a significant portion of cases are detected at a locoregionally advanced stage, without significant improvement of five-year survival rate.2014-01-15 Cervical screening techniques such as the Pap smear should be the gold standard strategy to decrease incidence and to improve the survival outcomes of patients with cervical cancer. In addition, screening programs for cervical cancer should be designed, organized and directed within the context of a nationwide program for cancer control.

Genetic polymorphism of PRKCDBP is associated with an increased risk of endometrial cancer.

PRKCDBP is a putative tumor suppressor located at 11p15.4, where frequent genomic loss has been observed in human cancers. We explored the possible association between an intra-exonic single nucleotide polymorphism (SNP), rs1051992, that results in a Leu to Pro substitution, and risk for endometrial carcinogenesis. We assessed the genotype of rs1051992 in endometrial cancer tissues from 147 patients and normal endometrial tissue from 191 healthy individuals by restriction endonuclease PvuII-based genotyping. Allele frequencies in the cancer specimens were compared with those in the healthy controls. We also evaluated the association between polymorphisms at this locus and histopathological features of endometrial cancer.

Correlation between FDG uptake by PET/CT and the expressions of glucose transporter type 1 and hexokinase II in cervical cancer.

BACKGROUND: The aim of this study was to explore the association between 2-deoxy-2-F18-fluoro-D-glucose uptake and the expressions of glucose transporter type 1 (GLUT-1) and hexokinase II (HK-II) in the lymph nodes of patients with cervical cancer. METHODS: This prospective study included 20 women with International Federation of Gynecology and Obstetrics stage IB to stage IIA cervical cancer who underwent positron emission tomography (PET)-computed tomography (CT) (PET/CT) before surgical treatment. In 333 dissected lymph nodes (LNs) obtained, we examined the size, tumor involvement, and expressions of GLUT-1 and HK-II. These characteristics were compared with PET/CT and pathological findings. RESULTS: Pathological analysis found that 21% (70) of the 333 surgically dissected LNs were metastatic. Positron emission tomography/CT detected metastasis with 22.8% sensitivity and 98.5% specificity. The levels of GLUT-1 and HK-II expression in false-positive LNs were higher than those in pathologically confirmed negative nodes (P = 0.015 and P = 0.001, respectively). In metastatic LNs, PET/CT-positive nodes were significantly different from PET/CT-negative nodes in mean size (P = 0.043), tumor involvement (P = 0.008), and proportion of GLUT-1-positive tumor cells (P = 0.042). CONCLUSIONS: Our results indicate that overexpression of GLUT-1 and HK-II may be related to 2-deoxy-2-F18-fluoro-D-glucose uptake in false-positive tissues on PET/CT. In metastatic lymph nodes, the ability of PET/CT to detect cancer may depend on tumor involvement, lymph node size, and GLUT-1 expression.

Ganglioneuroma of the uterine cervix--a case report.

Ganglioneuroma is a rare, benign tumor usually found in the mediastinum, retroperitoneum, or adrenal glands. We present a case of ganglioneuroma arising in the uterine cervix. A 65-year-old woman (gravida 3, para 3, abortus 0) showed vaginal spotting. The clinician observed a mild erosive lesion of her cervix and performed a biopsy and then conization. Histopathology revealed ganglioneuroma arising in the cervix. To our knowledge, this is the first report of a ganglioneuroma in the uterine cervix. Although ganglioneuroma is normally benign, a few malignant changes have been reported. Regular follow-up is necessary.

Frequent inactivation of hSRBC in ovarian cancers by promoter CpG island hypermethylation.

OBJECTIVE: To explore the implication of human SRBC gene [serum deprivation response factor-related gene product that binds to the c-kinase (hSRBC)] abnormality in ovarian tumorigenesis. DESIGN: Retrospective study. SETTING: Medical center. SAMPLE: Twenty-two epithelial ovarian cancer and six normal ovary tissues. MEASURES: Mutation and altered expression of hSRBC gene. METHODS: hSRBC expression was characterized by polymerase chain reaction (PCR) analysis. Promoter CG dinucleotide (CpG) site methylation was determined using methylation specific PCR and bisulfite sequencing. RESULTS: Expression of hSRBC transcript was easily detectable in all normal tissues we examined, but 50% (two of four) of cancer cell lines and 41% (nine of 22) of primary carcinomas exhibited undetectable or substantially decreased expression. While genomic deletion or somatic mutations of the gene was not identified, its expression was reactivated in tumor cells by 5-aza-2'-deoxycytidine treatment, suggesting epigenetic inactivation of the gene in tumors. Promoter methylation was detected in all nine tumors with low expression but in only one of 13 (7.7%) tumors with normal expression. Bisulfite DNA sequencing analysis of 23 CpG sites within the promoter region revealed that the CpG sites are highly methylated in low-expressing tumors. In addition, promoter CpG sites methylation status showed a tight association with gene expression level. CONCLUSION: Our data demonstrate that epigenetic inactivation of hSRBC due to aberrant promoter hypermethylation is a common event and might be implicated in human ovarian tumorigenesis.

Pulmonary toxicity after a quick course of combinatorial vincristine, bleomycin, and cisplatin neoadjuvant chemotherapy in cervical cancer.

Pulmonary toxicity is one of the most serious adverse effects associated with a quick course of vincristine, bleomycin, and cisplatin neoadjuvant chemotherapy (NAC-VBP). The aim of this study was to evaluate pulmonary toxicity related to a quick course NAC-VBP. A total of consecutive 61 patients, who underwent at most 3 cycles of NAC-VBP every 10 days in the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIB cervical cancer from 1995 to 2007, were retrospectively analyzed. Of the 61 study subjects, 7 (11.5%) were identified to have pulmonary toxicity and 2 (3.3%) died of pulmonary fibrosis progression despite aggressive treatment and the use of a multidisciplinary approach. No factor predisposing pulmonary toxicity was identified. Initial symptoms were non-specific, but bronchiolitis obliterans organizing pneumonia and interstitial pneumonitis were characteristic findings by high-resolution computed tomography of the chest. The benefit of steroid therapy was uncertain and was associated with steroid-induced diabetes mellitus requiring insulin therapy in two patients. Fatal pulmonary toxicity is a major concern of a quick course NAC-VBP. In conclusion, these patients require special monitoring for bleomycin-induced pulmonary toxicity.

Giant superficial angiomyxoma of the vulva: a case report and review of the literature.

Superficial angiomyxomas (SAMs) are rare, benign cutaneous tumors frequently involving the subcutis. Only 15 cases of SAM involving the vulva have been reported, ranging from 0.9 to 4 cm in diameter. A 26-year-old woman presented with a 7-year history of a large, pedunculated cutaneous mass on the left labium major, measuring 12.5 x 11 x 10.5 cm and mimicking a soft tissue sarcoma. The mass was relatively well-circumscribed, but unencapsulated and multilobulated. Microscopically, the mass showed a conglomerate of moderately-to-sparsely cellular angiomyxoid lobules. Each lobule consisted of scattered spindle-shaped or stellate tumor cells set in an abundant myxoid stroma. Thin-walled, small-to-medium-sized blood vessels were distributed diffusely throughout the stroma. Scattered stromal neutrophils were also observed. No large vessels or plexiform capillaries were apparent. There was no perivascular accentuation of stromal cells or smooth muscle bundles. The tumor cells constantly expressed vimentin, CD34, CD44 and S-100, but none expressed estrogen receptors (ERs) and progesterone receptors (PRs), desmin or cytokeratin. Together, these findings were diagnostic of a SAM. Giant SAMs of the vulva can mimic aggressive angiomyxomas (AAMs) and angiomyofibroblastomas (AMB), as well as soft tissue sarcomas. Giant SAMs should be included in the differential diagnosis of vulvar soft tissue tumors.

Increased fetal nuchal translucency as a sole clue in the prenatal diagnosis of a fetus with trisomy 13.

Trisomy 13 is a fatal chromosomal abnormality. A body of literature supports the assessment of fetal nuchal translucency as an adjunct in the prenatal diagnosis of trisomy 13. Over 90% of affected fetuses are readily diagnosed by ultrasound, as they present typical sonographic features; however, there is no consensus regarding trisomy 13 showing normal second trimester sonographic findings. We report an interesting case of trisomy 13, demonstrating increased nuchal translucency as an apparently isolated prenatal sonographic finding.

Expression and mutational analysis of TGF-beta/Smads signaling in human cervical cancers.

OBJECTIVE: To define the molecular basis of TGF-beta1 function in cervical carcinogenesis, we explored the expression and mutational status of TGF-beta1, TGF-beta1 receptors, and Smads, the regulators of the TGF-beta1 signaling pathway, in human cervical cancers. METHODS: Expression of TGF-beta1, TGF-beta1 receptors, and Smads transcripts were determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR), and sequence alteration was analyzed using RT-PCR-single-strand conformation polymorphism (SSCP) analysis. Genomic levels of TGF-beta1, TGF-beta1 receptors and Smads was also measured by quantitative genomic PCR. RESULTS: Abnormal overexpression of TGF-beta1 and abnormal reduction of type II TGF-beta1 receptor were identified in 36% (18 of 50) and 20% (10 of 50) of cervical cancer tissues, respectively. 22% (11 of 50) in Smad2 and 14% (7 of 50) in Smad4 revealed tumor specific mRNA reduction less than a half of normal means. In addition, no evidence for sequence alterations of the gene was found by RT-PCR-SSCP analysis. CONCLUSION: Our study demonstrates that disruption of TGF-beta/Smad signaling pathway exist in human cervical cancer, suggesting that abnormal expressions of the member of TGF-beta/Smad signaling pathway might contribute to the malignant progression of human cervical tumors via suppressing the tumor suppression function of TGF-beta1 1's tumor suppression function.

The risk of lymph node metastasis based on myometrial invasion and tumor grade in endometrioid uterine cancers: a multicenter, retrospective Korean study.

BACKGROUND: Knowledge of the risk factors for lymph node metastasis (LNM) is necessary to treat patients with endometrioid uterine cancer to optimize and further individualize treatment. This study was designed to determine the risk of LNM based on myometrial invasion and tumor grade in endometrioid uterine cancer. METHODS: The authors retrospectively reviewed the medical records and pathological findings of 834 patients who underwent surgical staging, including pelvic lymphadenectomy with or without para-aortic lymphadenectomy, for endometrioid uterine cancer from 2002 to 2008 in Korea. RESULTS: Of the 834 patients with endometrioid uterine cancer, 107 (12.8%) patients had LNM. Sixty-one (57%) patients had only pelvic LNM, 39 (36.4%) had pelvic and para-aortic LNM, and 7 (6.6%) had isolated para-aortic LNM. Tumor grade, myometrial invasion, tumor diameter, cervical extension, lymphovascular space invasion, and adnexal involvement were found to be significant predictors of LNM. Of 215 patients with no myometrial invasion and tumor grade I/II, only 1 (0.47%) had LNM. However, in other patients, the risk of LNM was significant and at least > 3.5%. Furthermore, the risk of LNM was found to be well correlated with increases in myometrial invasion and tumor grade based on subgroup analyses, when patients with no myometrial invasion and tumor grade I/II were used as a reference group (p < 0.0001). CONCLUSIONS: Patients with endometrioid uterine cancers with no myometrial invasion and tumor grade I/II might have minimal risk of LNM, whereas others might require complete pelvic and para-aortic lymphadenectomy for surgical staging.

Video-assisted thoracoscopic surgery for recurrent ovarian cancer with a metastatic mediastinal mass.

BACKGROUND: Although primary cytoreductive surgery is well accepted as a cornerstone of the management for epithelial ovarian cancer, the benefits of secondary cytoreduction in recurrent ovarian cancer remain unclear. Furthermore, no consensus has been reached regarding treatment strategies for extraperitoneal metastasis. CASE REPORT: A 29-year-old woman was admitted to our hospital due to suspected recurrent ovarian cancer. Four years previously, she had undergone primary debulking surgery which was followed by adjuvant chemotherapy consisting of paclitaxel (175 mg/m(2)) and carboplatin (area under the curve = 5) for 6 cycles due to an ovarian papillary serous adenocarcinoma stage IIIc. Preoperative evaluation revealed a palpable inguinal mass and multiple enlarged pelvic lymph nodes with a well-defined mediastinal mass on abdomino-pelvic and chest computed tomography. Secondary debulking combined with video-assisted thoracoscopic surgery (VATS) was performed. The patient had no discernable evidence of disease at her 18-month follow-up. CONCLUSION: VATS may be a reasonable option for secondary debulking in selected patients with isolated mediastinal metastasis.