Minimal deviation adenocarcinoma (adenoma malignum) of the uterine cervix: clinicopathological analysis of 17 cases

OBJECTIVE: The aim of this study was to evaluate the clinicopathological features of minimal deviation adenocarcinoma (MDA) and to analyze its prognostic factors. METHODS: We retrospectively analyzed the medical records of 17 patients who were diagnosed with MDA at a single institution between January 2005 and December 2015. RESULTS: The median age of the patients was 47.7 years (33–75 years). MDA was diagnosed in 7 patients (41.2%) before performing definitive surgery. Stage IB disease was diagnosed in 12 patients (70.6%) and advanced stage disease (stage II: 3, stage III: 2) in 5. MDA was incidentally diagnosed following hysterectomy for benign conditions in 6 patients. Adjuvant therapy was administered to 13 patients (76.5%). During median follow-up over 33.6 months (7–99 months), 11 patients (64.7%) showed no evidence of disease, 6 (35.3%) showed persistent or recurrent disease and 5 died of the disease. Peutz-Jeghers syndrome was not suspected in any patient, and no mutation was detected in the 3 patients who underwent genetic testing. Univariate analysis showed that advanced stage disease (P=0.016) and lymphovascular space invasion (P=0.002) demonstrated a statistically significant association with poor overall survival (OS) rates. Advanced stage disease continued to show a significant association with poor OS rates (hazard ratio, 2.92; 95% confidence interval, 1.097–7.746; P=0.032) even after multivariate analysis. CONCLUSION: Early diagnosis is important to manage MDA. Clinicians should consider MDA among the differential diagnoses in patients with a suspicious clinical presentation even with negative cervical screening tests.

Erratum: Prevalence of germline BRCA mutations among women with carcinoma of the peritoneum or fallopian tube / 부인종양

The original article contained errors.

Prevalence of germline BRCA mutations among women with carcinoma of the peritoneum or fallopian tube / 부인종양

OBJECTIVE: The aim of the present study was to assess the frequency of germline mutations in patients with peritoneal carcinoma (PC) or the fallopian tube carcinoma (FTC), using a multi-gene panel. METHODS: Twenty-six patients diagnosed with either PC or FTC between January 2013 and December 2016 were recruited consecutively. Germline DNA was sequenced using a 6-gene next generation sequencing (NGS) panel following genetic counseling. Surgico-medical information was obtained from hospital records. Genetic variations were detected using the panel and were cross-validated by Sanger direct sequencing. RESULTS: Germline BRCA1/2 mutations were identified in 6 patients (23.1%). Four were detected in patients with PC and 2 were in FTC patients. No mutations were detected in TP53, PTEN, CDH1, or PALB2. We identified 11 variant of uncertain significance (VUS) in 9 patients; 2 in BRCA1, 3 in BRCA2, 2 in TP53, and 4 in CDH1. We also detected a CDH1 c.2164+16->A VUS in 3 patients. CONCLUSION: The prevalence of germline BRCA1/2 mutations in patients with PC or FTC is comparable to that of BRCA1/2 mutations in epithelial ovarian cancer patients.

Oncologic and obstetric outcomes of conservative surgery for borderline ovarian tumors in women of reproductive age

OBJECTIVE: To compare the oncologic and obstetric outcomes in reproductive-age females with borderline ovarian tumors (BOTs) treated with cyst enucleation (CE) or unilateral salpingo-oophorectomy (USO). METHODS: The medical records of patients with BOTs treated between 1998 and 2014 were retrospectively reviewed. The recurrence rates in the USO and CE groups were compared, and the postoperative obstetric outcomes were assessed via telephone survey. RESULTS: Eighty-nine patients with BOTs underwent USO, and 19 underwent CE. Of these, six patients had recurrent BOTs. The recurrence rate was significantly lower in the USO group (3/89, 3.4%) than in the CE group (3/19, 15.8%) (P=0.032). All patients with recurrent disease were successfully treated with further surgery. Of the 76 patients interviewed by telephone, 71 (93.4%) resumed regular menstruation after surgery. Twenty-six of the 32 patients (81.3%) who attempted to conceive had successful pregnancies. USO (19/24, 79.2%), like CE (7/8, 87.5%), resulted in favorable pregnancy rates for patients with BOTs. CONCLUSION: USO is a suitable fertility-preserving surgery for women with BOTs. CE is also an acceptable option for select patients.

Metastatic Skin Lesions on Lower Extremities in a Patient with Recurrent Serous Papillary Ovarian Carcinoma: A Case Report and Literature Review / Journal of the Korean Cancer Association, 대한암학회지

Clinical observation of skin metastasis in ovarian cancer cases is relatively uncommon. And distant metastatic skin lesions including the extremities are much rarer still as most metastatic skin lesions are located in the skin in the abdominal wall adjacent to where the primary ovarian tumors exist. We report the case of a 60-year-old woman who presented skin lesions on both lower extremities as a consequence of the metastasis of serous papillary adenocarcinoma of the ovary. She presented with erythematous and painful cutaneous nodules on both upper legs and in the inguinal area 42 months after initial diagnosis of ovarian cancer. Skin biopsy revealed metastasis of adenocarcinoma in the dermis. She was treated with surgical excision and systemic chemotherapy. Literature review has suggested that a combined modality approach including surgical excision and chemotherapy may be useful in the management of skin metastases due to ovarian cancer.

Comparative study of laparoscopy and laparotomy for the pregnant women with non-malignant ovarian tumors / 대한산부인과내시경학회지

OBJECTIVE: The purpose of our study is to investigate the feasibility of the laparoscopy and compare perioperative outcomes between laparoscopy and laparotomy in pregnant women with non-malignant ovarian tumor. METHODS: Retrospective comparative analysis of 56 pregnant women who underwent laparoscopy or laparotomy due to non-malignant ovarian tumors at Samsung Medical Center, Seoul, Korea, between October 1994 and December 2010 were performed. RESULTS: Among 56 patients, 22 and 34 pregnant women underwent laparotomy and laparoscopy, respectively. There were no statistically significant differences between the two groups about general characteristics including age, gestational age, torsion, surgeon type, pain at diagnosis and clinical outcomes including tocolytics use, operation type, operation time, the ratio of normal full-term vaginal delivery, Apgar score. However, pathological longest tumor size was larger in laparotomy group than laparoscopy group (9.0 cm vs. 5.8 cm; p=0.001) and laparoscopy was related with significantly less estimated blood loss (200 vs. 50 mL; p=0.001) and short hospital days (7 vs. 4 days; p<0.001). CONCLUSION: Laparoscopy for the treatment of non-malignant ovarian tumors in pregnant women is feasible and has benefits such as less estimated blood loss during the surgery and hospital stays when compared with laparotomy. However, laparoscopic adnexal surgery for large tumor size may be still challenging in pregnant women.

AGR2, a mucinous ovarian cancer marker, promotes cell proliferation and migration

Ovarian cancer is a leading cause of death in women. Early detection of ovarian cancer is essential to decrease mortality. However, the early diagnosis of ovarian cancer is difficult due to a lack of clinical symptoms and suitable molecular diagnostic markers. Thus, identification of meaningful tumor biomarkers with potential clinical application is clearly needed. To search for a biomarker for the early detection of ovarian cancer, we identified human anterior gradient 2 (AGR2) from our systematic analysis of paired normal and ovarian tumor tissue cDNA microarray. We noted a marked overexpression of AGR2 mRNA and protein in early stage mucinous ovarian tumors compared to normal ovarian tissues and serous type ovarian tumors by Western blot analysis and immunohistochemistry. To further elucidate the role of AGR2 in ovarian tumorigenesis, stable 2774 human ovarian cancer cell lines overexpressing AGR2 were established. Forced expression of AGR2 in 2774 cells enhanced the growth and migration of ovarian cancer cells. AGR2 protein was detected in the serum of mucinous ovarian cancer patients by Western blot and ELISA analysis. Thus, AGR2 is a potential biomarker for the diagnosis of mucinous ovarian cancer and an ELISA assay may facilitate the early detection of mucinous ovarian cancer using patient serum.

Benign Metastasizing Leiomyoma with Multiple Lymph Node Metastasis: A Case Report / Journal of the Korean Cancer Association, 대한암학회지

This is a case report about benign metastasizing leiomyoma with multiple lymph node metastasis. A 34-year-old woman received an abdominal myomectomy for a suspicious leiomyoma. On the pathology report, atypical leiomyoma was suspected. Due to the suspicion of multiple lymph node metastasis on pelvis computed tomography (CT) 1 year after the operation, she was transferred to the Samsung Medical Center on October, 2009 for further work up. According to original slide review, it was determined to be a benign leiomyoma with a mitotic count <5/10 high-power fields, little cytological atypia and no tumor cell necrosis. Additional immunostaining was done. Multiple lymph node metastasis and a small lung nodule were identified on positron emission tomogarphy-CT and chest CT. Extensive debulking surgery and diagnostic video-assisted thoracoscopic surgery (VATS) wedge resection were subsequently done. Metastatic lesions were reported to have a histology similar to that of the original mass. VATS right upper lobectomy with mediastinal lymph node dissection was performed because of the pathology result of VATS (adenocarcinoma). She started taking an aromatase inhibitor (Letrozole(R)) and there was no evidence of recurrence of disease on an imaging study and no post-operative complications until recently.

Adhesion formation after applying adhesion barrier in laparoscopic gynecologic surgery: Experience of 7 patients / 대한산부인과내시경학회지

OBJECTIVE: Adhesion barrier has been commonly used in gynecologic surgery. The objective of this study is to evaluate the outcome of applying adhesion barrier in preventing adhesion formation after laparoscopic surgery. METHODS: Between March 2000 and March 2010, we retrospectively reviewed the medical records of patients who performed laparoscopic surgery twice at Samsung Medical Center. The patients to whom adhesion barrier was applied at the end of the first laparoscopic surgery and had imaging files of pelvic cavity at second laparoscopic surgery were included. The patients with recurrent endometriosis and pelvic inflammatory disease which can make postoperative adhesion by itself due to the nature of the disease were excluded. RESULTS: Ten patients were eligible to be analyzed. Only 3 among 10 showed adhesion free and we could find de novo adhesion formation in 7 patients at second laparoscopic surgery. Eight patients used Intercede(R) (oxidized regenerated cellulose mesh; Johnson & Johnson, New Brunswick, NJ, USA) and two patients used Guardix(R) (sodium hyaluronic acid solution and carboxymethylcellulose: Hanmi, Seoul, Korea). In six patients, adhesion formation was found at the operation site and one patient showed postoperative adhesion distant from operation site between omentum and anterior peritoneum of pelvic wall. CONCLUSION: We observed adhesion formation despite of prior use of adhesion barrier after laparoscopic gynecological surgery. These results suggest that the use of adhesion barrier alone after gynecologic laparoscopic surgery may not guarantee adhesion prevention.

A case of robotic laparoscopic radical trachelectomy / 대한산부인과학회지

To present a case of successful robotic assisted radical trachelectomy. A nulliparous woman with early cervical cancer underwent a laparoscopic radical trachelectomy and pelvic lymphadenectomy with the da Vinci robot (Intuitive Surgical Inc., Sunnyvale, CA). After the pelvic lymph nodes were found negative on frozen section, the parametria, paracolpia and uterosacral ligaments were dissected transabdominally sparing the ascending branches of the uterine arteries. Cervical transection and vaginal closure were performed transvaginally. Surgical time was 450 min. No perioperative complications were noted. Robotic laparoscopic radical trachelectomy may bridge the gap between laparotomy and laparoscopy for radical trachelectomy.

Impacted supernumerary tooth in coronoid process: a case report / 대한구강악안면방사선학회지

Impaction of tooth is a situation in which an unerupted tooth is wedged against another tooth or teeth or otherwise located so that it cannot erupt normally. The supernumerary tooth is also called as hyperdontia and defined as the condition of having additional tooth to the regular number of teeth. The most common supernumerary tooth is a mesiodens, which is a mal-formed, peg-like tooth that occurs between the maxillary incisors. The supernumerary tooth is commonly impacted but they are frequently impacted on maxilla. Ectopic impaction of supernumerary tooth on mandibular condyle, coronoid process, ascending ramus, and pterygomandibular space is very rare condition. In this case, we report a case of impacted supernumerary tooth on mandibular sigmoid notch without definite pathologic change.

Phase II Study of Combination Chemotherapy with Etoposide and Ifosfamide in Patients with Heavily Pretreated Recurrent or Persistent Epithelial Ovarian Cancer

The aim of this trial was to investigate the efficacy and toxicity of combination chemotherapy with etoposide and ifosfamide (ETI) in the management of heavily pretreated recurrent or persistent epithelial ovarian cancer (EOC). Patients with recurrent or persistent EOC who had measurable disease and at least two prior chemotherapy participating in this phase II trial were to receive etoposide at a dose of 100 mg/m2/day intravenously (IV) on days 1 to 3 in combination with ifosfamide 1 g/m2/day IV on days 1 to 5, every 21 days. Thirty-seven patients were treated; about 78% had previously received more than two separate regimens. The response rate (RR) was 18.9% and median duration of response was 7 months (range, 1-15). Treatment free interval prior to ETI (TFI) has significant correlation with RR rate (P=0.034). Patients (n=6) with TFI > or =6 months had 50% of RR, while patients (n=31) with TFI or =6 months.

Correlation between tumor volume response to radiotherapy and expression of biological markers in patients with cervical squamous cell carcinoma / 부인종양

OBJECTIVE: To determine the factors associated with tumor volume response to radiotherapy (RT) in cervical cancer patients, and the relationship between the tumor volume response and alteration of the expression of biological markers during RT. METHODS: Twenty consecutive patients with cervical squamous cell carcinoma who received definitive RT were enrolled. Tumor volumes were calculated by MRI examinations performed at the start of RT (pre-RT), at the fourth week of RT (mid-RT), and 1 month after RT completion (post-RT). Two serial punch biopsies were performed at pre- and mid-RT, and immunohistochemical staining was performed for cyclooxygenase (COX)-2 and epidermal growth factor receptor (EGFR). RESULTS: For the pre-RT evaluation, fourteen (70%) and eleven (55%) patients showed positive immunoreactivity for COX-2 and EGFR, respectively. Among the seven patients whose median percentage residual tumor at mid-RT (V2R) was greater than 0.5, seven (100%, p=0.0515) and five (71.4%, p=0.3742) patients showed positive immunoreactivity for COX-2 and EGFR, respectively. The logistic regression analysis showed that positive immunoreactivity for both COX-2 and EGFR at pre-RT were associated with V2R (p=0.0782). For the mid-RT evaluation, eight cases showed an interval increase in the distribution of immunoreactivity for COX-2, and six out of the eight patients had a V2R greater than 0.5 (p=0.2222). CONCLUSION: The poor mid-RT tumor response was associated with the coexpression of COX-2 and EGFR.

Isoflavone-deprived soy peptide suppresses mammary tumorigenesis by inducing apoptosis

During carcinogenesis, NF-kappaB mediates processes associated with deregulation of the normal control of proliferation, angiogenesis, and metastasis. Thus, suppression of NF-kappaB has been linked with chemoprevention of cancer. Accumulating findings reveal that heat shock protein 90 (HSP90) is a molecular chaperone and a component of the IkappaB kinase (IKK) complex that plays a central role in NF-kappaB activation. HSP90 also stabilizes key proteins involved in cell cycle control and apoptosis signaling. We have determined whether the exogenous administration of isoflavone-deprived soy peptide prevents 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced rat mammary tumorigenesis and investigated the mechanism of action. Dietary administration of soy peptide (3.3 g/rat/day) significantly reduced the incidence of ductal carcinomas (50%), the number of tumors per multiple tumor-bearing rats (49%; P < 0.05), and extended the latency period of tumor development (8.07 +/- 0.92 weeks) compared to control diet animals (10.80 +/- 1.30; P < 0.05). Our results have further demonstrated that soy peptide (1) dramatically inhibits the expression of HSP90, thereby suppressing signaling pathway leading to NF-kappaB activation; (2) induces expression of p21, p53, and caspase-3 proteins; and (3) inhibits expression of VEGF. In agreement with our in vivo data, soy peptide treatment inhibited the growth of human breast MCF-7 tumor cells in a dose-dependent manner and induced apoptosis. Taken together, our in vivo and in vitro results suggest chemopreventive and tumor suppressive functions of isoflavone-deprived soy peptide by inducing growth arrest and apoptosis.

A case of metachronous multiple primary malignant neoplasm of the gastric cancer and ovarian cancer and breast cancer / 대한산부인과학회지

Multiple primary cancer means that more than two cancers are independently developed in one individual. The incidence of multiple primary malignancy is extremely rare although the prevalence rate is increasing recently. Gynecologic malignancies are especially prone to be associated with primary neoplasms elsewhere. Most of multiple primary cancer is double primary, however triple primary cancer is rare. We experienced a case of metachronous triple primary cancer involving stomach, breast and ovary. So, we report the case with a brief review of literatures.

Expression of TLR-4 in epithelial serous ovarian cancer / 부인종양

OBJECTIVE: This study was to determine the expression of Toll-like receptor 4 (TLR-4) in ovarian serous adenocarcinoma tissues. METHODS: TLR-4 expression was evaluated at the RNA level by real-time quantitative RT-PCR, in 24 fresh frozen ovarian serous adenocarcinoma tissues and 9 normal ovarian tissues. TLR-4 expression was also evaluated by immunohistochemistry (IHC) in each three ovarian carcinoma tissues and normal ovarian tissues. RESULTS: Positive immunoreactivity for TLR-4 was observed in the normal ovarian tissues but not in the ovarian carcinoma tissues. The staining was localized in the cytoplasm as well as on the cell surface. Real-time quantitative RT-PCR revealed that TLR-4 expression was significantly lower in tumors than in normal ovarian tissues (p=0.0003). There were no significant correlations between clinical parameters and the expression level of TLR-4 mRNA in ovarian serous adenocarcinomas. However, tumors without LN metastasis (p=0.068) and lower grade (p=0.075) showed trends of higher TLR-4 mRNA expression. CONCLUSION: TLR-4 expression was significantly lower in ovarian serous adenocarcinoma tissues than in normal ovarian tissues, and further studies on TLR-4 signaling pathway in ovarian carcinoma are needed.

Promoter hypermethylation and loss of heterozygosity of FHIT genes in squamous cell carcinoma of uterine cervix / 부인종양

OBJECTIVE: This study was to investigate the status of hypermethylation and loss of heterozygosity (LOH) in chromosome 3p tumor-suppressor gene for cervical carcinoma. METHODS: We examined the promoter methylation status of the chromosome 3p gene, fragile histidine triad (FHIT), in 37 samples of cervical squamous cell carcinoma and corresponding noncancerous tissues using a methylation-specific polymerase chain reaction. We also analyzed the 37 paired samples for LOH at two loci on chromosome 3p. RESULTS: Promoter hypermethylation in FHIT was detected in 24% of tumors, whereas no hypermethylation was detected in the corresponding noncancerous tissues. LOH in the regions of FHIT was observed in 10% of informative cases. There were no correlations between LOH and promoter hypermethylation for the gene. FHIT hypermethylation was associated with small tumors and, when adjusted for tumor size, correlated significantly with more frequent lymph node metastasis. CONCLUSION: Promoter hypermethylation and LOH of FHIT gene may play a role in cervical carcinogenesis. In addition, hypermethylation of FHIT may be associated with the status (aggressiveness) of cervical carcinoma.

MR Imaging in Endometrial Carcinoma as a Diagnostic Tool for the Prediction of Myometrial Invasion and Lymph Node Metastasis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate the factors that are associated with the accuracy of magnetic resonance (MR) imaging for predicting myometrial invasion and lymph node metastasis in women with endometrial carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the medical records and preoperative MR imaging reports of 128 women who had pathologically proven endometrial carcinoma. We compared the MR imaging and the histopathology findings. RESULTS: The sensitivity, specificity and accuracy for identifing any myometrial invasion (superficial or deep) were 0.81, 0.61 and 0.74, respectively; these values for deep myometrial invasion were 0.60, 0.94 and 0.86, respectively. The sensitivity, specificity and accuracy of MR imaging for detecting lymph node metastasis were 50.0%, 96.6% and 93.0%, respectively. The patients who were older, had more deliveries and a larger tumor size more frequently had incorrect prediction of deep myometrial invasion (p=0.034, p=0.044, p=0.061, respectively). A higher tumor grade, a histology other than the endometrioid type, myometrial invasion on MR findings and a larger tumor size were associated with a more frequent false-negative prediction of lymph node metastasis (p=0.018, p=0.017, p=0.002, p=0.047, respectively). A larger tumor size was also associated with more frequent false-positive results (p=0.009). CONCLUSIONS: There are several factors that make accurate assessment of myometrial invasion or lymph node metastasis difficult with using MRI; therefore, the patients with these factors should have their MR findings cautiously interpreted.

Neoadjuvant chemotherapy with mitomycin-C, vincristine and cisplatin (MVC) for patients with loco-regionally advanced cervical carcinoma / 부인종양

OBJECTIVE: The efficacy and toxicity of neoadjuvant chemotherapy (NAC) with mitomycin-C, vincristine and cisplatin (MVC) were assessed in bulky cervical carcinoma patients. METHODS: Forty-six patients with stage Ib2 to IIb bulky cervical cancer were treated with intravenous combination of mitomycin-C 10 mg/m2, vincristine 1 mg/m2 and cisplatin 75 mg/m2 every three weeks. After three cycles of NAC, the patients either underwent surgery or radiation therapy, depending on their suitability for radical hysterectomy. RESULTS: All 46 patients enrolled in this study underwent surgery after NAC. Toxic nonhematologic reactions consisted primarily of grade 1-2 nausea and vomiting (86.8%) and the most common hematologic toxicity was anemia (59.6%). Clinical responses occurred in 82.6% (38/46) of patients, including 23.9% (11/46) with a complete response (CR) and 13.0% (6/46) with a pathologically determined complete response. For a median follow up period of 28 months, the 3-year disease-free and overall survival rates were 74.0% and 80.0%, respectively. Pathologically confirmed lymph node metastasis or parametrial involvement or an initial tumor size > or = 16 cm2 were associated with shorter disease-free survival (p=0.040, p=0.000, p=0.001, respectively). Adjuvant postoperative RT did not show a survival benefit in patients who had no indications for adjuvant therapy after surgery (p=0.970). Therefore, 26 patients (56.5%) could have been managed without RT; these patients traditionally require RT without the NAC protocol. CONCLUSION: Intravenous administration of MVC as a NAC seems to be well tolerated and beneficial in patients with loco-regionally advanced cervical cancer.

Increased expression of pAKT is associated with radiation resistance in cervical cancer / 부인종양

OBJECTIVE: The aim of this study was to investigate the association of phosphorylated AKT (pAKT) expression and radiation resistance in cervical cancer. METHODS: A retrospective review was made of the records of 25 women who received primary radiation therapy due to locally advanced cervical cancer (LACC) with FIGO stage IIB-IVA. Nine patients regarded as radiation resistant developed local recurrences with a median progression free interval of 10 months. Sixteen patients did not show local recurrences, and were regarded as a radiation sensitive group. Using pretreatment paraffin-embedded tissues, we evaluated pAKT expression by immunohistochemistry. RESULTS: A significant association was found between the level of pAKT expression and local recurrence. Immunohistochemical staining for pAKT was significantly more frequent in the radiation resistant than in the radiation sensitive group (p=0.007). The mean progression free survival (PFS) was 84 months for patients with pAKT negative staining (17 cases) and 44 months for patients with pAKT positive expression (8 cases)(p=0.015). CONCLUSION: These results suggest that signaling from PI3K/pAKT can lead to radiation resistance in LACC.