Hyperthermic intraperitoneal chemotherapy as consolidation treatment of advanced stage ovarian cancer

Objective@#To investigate the therapeutic efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) as consolidation treatment after completing first-line treatment in patients with advanced ovarian cancer. @*Methods@#A retrospective chart review was conducted on patients treated at the Comprehensive Gynecologic Cancer Center between January 2014 and 2019. Based on the inclusion criteria, 24 eligible patients who received HIPEC (paclitaxel 175 mg/m2, for 90 minutes, at 42°C) (HIPEC group) as consolidation treatment after terminating the adjuvant chemotherapy were identified. Another 24 patients who met the inclusion criteria and did not receive HIPEC were matched, representing the non-HIPEC group. Disease-free survival (DFS) and overall survival (OS) were examined between the two groups. @*Results@#The median DFS was 28.7 and 24.2 months in the HIPEC and non-HIPEC groups, respectively (P=0.688). The 3-year DFS rates in the HIPEC and non-HPEC groups were 39.5% and 32.6%, respectively. However, the median OS was not determined. The 5-year OS rates in the HIPEC and non-HIPEC groups were 86.2% and 81.3%, respectively (P=0.850). One patient developed grade 3 neutropenia. Other patients experienced mild adverse events after HIPEC. @*Conclusion@#This study suggests that consolidation HIPEC could not support the survival benefit after completing the first-line treatment for patients with advanced ovarian cancer, although no severe specific safety issues were found. Therefore, randomized trials evaluating consolidation HIPEC for the management of ovarian cancer are warranted.

Hyperthermic intraperitoneal chemotherapy as consolidation treatment of advanced stage ovarian cancer

Objective@#To investigate the therapeutic efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) as consolidation treatment after completing first-line treatment in patients with advanced ovarian cancer. @*Methods@#A retrospective chart review was conducted on patients treated at the Comprehensive Gynecologic Cancer Center between January 2014 and 2019. Based on the inclusion criteria, 24 eligible patients who received HIPEC (paclitaxel 175 mg/m2, for 90 minutes, at 42°C) (HIPEC group) as consolidation treatment after terminating the adjuvant chemotherapy were identified. Another 24 patients who met the inclusion criteria and did not receive HIPEC were matched, representing the non-HIPEC group. Disease-free survival (DFS) and overall survival (OS) were examined between the two groups. @*Results@#The median DFS was 28.7 and 24.2 months in the HIPEC and non-HIPEC groups, respectively (P=0.688). The 3-year DFS rates in the HIPEC and non-HPEC groups were 39.5% and 32.6%, respectively. However, the median OS was not determined. The 5-year OS rates in the HIPEC and non-HIPEC groups were 86.2% and 81.3%, respectively (P=0.850). One patient developed grade 3 neutropenia. Other patients experienced mild adverse events after HIPEC. @*Conclusion@#This study suggests that consolidation HIPEC could not support the survival benefit after completing the first-line treatment for patients with advanced ovarian cancer, although no severe specific safety issues were found. Therefore, randomized trials evaluating consolidation HIPEC for the management of ovarian cancer are warranted.

Real-World Experience with Pembrolizumab Treatment in Patients with Heavily Treated Recurrent Gynecologic Malignancies

Purpose@#We evaluated the efficacy and safety of pembrolizumab in patients with recurrent gynecologic cancers in real-world practice. @*Materials and Methods@#We conducted a retrospective, single-institution study of patients with recurrent gynecologic malignancies treated with pembrolizumab. The primary endpoints were the objective response rate (ORR) and safety. @*Results@#Thirty-one patients treated with pembrolizumab were included. The primary disease sites were the uterine cervix (n=18), ovaries (n=8), and uterine corpus (n=5). Fifteen of the 31 patients (48%) had an Eastern Cooperative Oncology Group performance status of ≥2. The median number of prior chemotherapy lines was 2 (range, 1–6), and 14 of 31 patients (45%) had received ≥ 3 prior lines of chemotherapy. The overall ORR was 22.6%: specifically, 22.3% (4 of 18 patients), 12.5% (1 of 8 patients), and 40% (2 of 5 patients) for cervical, ovarian, and endometrial cancers, respectively. During a median follow-up of 4.7 months (range, 0.2–35.3), the median time to response was 1.9 months (range, 1.4–5.7). The median duration of response was not reached (range, 8.8-not reached).The median progression-free survival was 2.5 months (95% confidence interval, 1.7-not reached). Adverse events occurred in 20 patients (64.5%), and only 3 (9.7%) were grade ≥3. There was one case of suspicious treatment-related mortality, apart from which most adverse events were manageable. @*Conclusion@#In real-world practice, pembrolizumab was feasible and effective in heavily treated recurrent gynecologic cancer patients with poor performance status who may not be eligible for enrollment in clinical trials.

Clinical Impact of Somatic Variants in Homologous RecombinationRepair-Related Genes in Ovarian High-Grade Serous Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#In this study, we investigated the frequencies of mutations in DNA damage repair genesincluding BRCA1, BRCA2, homologous recombination genes and TP53 gene in ovarian highgradeserous carcinoma, alongside those of germline and somatic BRCA mutations, withthe aim of improving the identification of patients suitable for treatment with poly(ADPribose)polymerase inhibitors. @*Materials and Methods@#Tissue samples from 77 Korean patients with ovarian high-grade serous carcinoma weresubjected to next-generation sequencing. Pathogenic alterations of 38 DNA damage repairgenes and TP53 gene and their relationships with patient survival were examined. Additionally,we analyzed BRCA germline variants in blood samples from 47 of the patients forcomparison. @*Results@#BRCA1, BRCA2, and TP53 mutations were detected in 28.6%, 5.2%, and 80.5% of the 77patients, respectively. Alterations in RAD50, ATR, MSH6, MSH2, and FANCA were also identified.At least one mutation in a DNA damage repair gene was detected in 40.3% of patients(31/77). Germline and somatic BRCA mutations were found in 20 of 47 patients (42.6%),and four patients had only somatic mutations without germline mutations (8.5%, 4/47).Patients with DNA damage repair gene alterations with or without TP53mutation, exhibitedbetter disease-free survival than those with TP53 mutation alone. @*Conclusion@#DNA damage repair genes were mutated in 40.3% of patients with high-grade serous carcinoma,with somatic BRCAmutations in the absence of germline mutation in 8.5%. Somaticvariant examination, along with germline testing of DNA damage repair genes, has potentialto detect additional candidates for PARP inhibitor treatment.

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.

Case Report of Menopausal Woman Diagnosed with Endometrial Cancer after Colon Cancer with Germline Mutation in MSH6 in Korea

We present a case of an endometrial cancer patient with germline mutation in MutS homolog 6 (MSH6), associated with Lynch syndrome. A 60-year-old Korean woman had a personal history of colon cancer 23 years ago. She also had a family history of endometrial cancer and colon cancer of her sisters and brothers. Immunohistochemistry was negative for MutL homolog 1 (MLH1) and positive for MutS homolog 2 (MSH2). Based on these findings, she underwent genetic counseling and testing that revealed a frameshift germline mutation at MSH6 (c. 3261dupC).

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.

Pregnancy and Natural Delivery Following Magnetic Resonance Imaging-Guided Focused Ultrasound Surgery of Uterine Myomas

This report discusses a pregnancy case following a series of two consecutive magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) procedures for the treatment of two different myomas in an individual patient. Both procedures were completed without adverse events, and the patient conceived naturally four months after treatment. At 39 weeks, she gave birth to a healthy baby girl, via a vaginal delivery. There were no complications in the pregnancy or during labor.

Magnetic resonance imaging-guided focused ultrasound surgery for uterine fibroids: Initial experience in Korea / 대한산부인과학회지

OBJECTIVE: The purpose of this report is to review the safety and short-term efficacy of non-invasive magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) on uterine myomas in Korean women. METHODS: A total of 29 outpatient Korean women, whose mean age was 39.1+/-5.8 years, were treated using the MRgFUS system for their symptomatic uterine myomas. Patients??symptoms were recorded using a validated symptom-specific questionnaire on treatment day, and at follow-up visits, 3 and 6 months post treatment. Data on adverse events was recorded on each follow up period. RESULTS: Symptom improvement was experienced by 83% of the patients at the three months follow-up, and 90% of the patients reported on improved quality of life by the six months follow-up. There were no serious adverse events during the treatments or the follow-up period. CONCLUSION: MRgFUS appears to be a safe and effective treatment for symptoms relief of uterine fibroids. Additional reports on longer follow up should verify long-term durability.

Comparison of postoperative radiotherapy versus postoperative paclitaxel and platinum chemotherapy in uterine endometrial carcinoma / 대한산부인과학회지

OBJECTIVE: This study was performed to compare postoperative adjuvant paclitaxel and platinum (TC) chemotherapy and radiation therapy in women with uterine endometrial carcinoma. METHODS: Total one hundred five patients were entered into this trial. Non-endometrioid histologic subtypes such as serous, clear cell and small cell types were excluded from the study because they have different biological potentials. Of 58 assessable patients, who were needed adjuvant treatment according to surgico-pathologic reports, after surgery, 34 were received TC chemotherapy and 24 were received radiation therapy. Chemotherapy consisted of paclitaxel 175 mg/m2 and carboplatin AUC 5 (or cisplatin 50 mg/m2) every 3 weeks for 3 or 6 cycles. Irradiation dosage was 4,500~5,040 cGy in 28 fractions. RESULTS: In 58 evaluated patients, median follow-up time was 40.3 months (range 7~64 months). The 5-year overall survival and 5-year disease-free survival were 91.3% and 91.0% in 34 patients treated with TC chemotherapy, and 91.4% and 82.8% in 24 cases who treated with radiation therapy, however, there were no significant difference (P=0.646, P=0.129). The most common adverse effect of TC chemotherapy was hematologic toxicity, which was manageable conservatively. The serious gastrointestinal complication of radiotherapy was noted in 5 patients (20.8%), three of these patients were received another bowel surgery, such as ileo-cecal bypass, however, symptoms were persisted after surgery. CONCLUSIONS: These data suggest that postoperative adjuvant TC chemotherapy is a promising treatment which could be substituted for radiation therapy, with major activity and a acceptable toxicity profile for the treatment of uterine endometrial carcinoma.

A case of huge uterine myoma associated with pulmonary thromboembolism / 대한산부인과학회지

Deep vein thrombosis (DVT) is a serious illness sometimes causing death due to acute pulmonary thromboembolism (PTE). Blood stasis of the pelvic vein is a major etiologic factor for DVT. Occasionally a huge uterine myoma can cause compression of the pelvic venous system leading to DVT. We experienced a very rare case of pulmonary thromboembolism in a 45-year-old woman with a huge uterine myoma and no other recognized risk factors for PTE and DVT. The patient was successfully treated with thrombolytic and anticoagulation therapy associated with total hysterectomy.

A Case of Sirenomelia In One Fetus of Twin Pregnancy / 대한산부인과학회잡지

Sirenomelia is a lethal congenital malformation characterized by single or fused lower limbs associated with other severe genitourinary and lower gastrointestinal tract anomalies. Associated anomalies include malformation of vertebrae and pelvis, oligohydroamnios, renal agenesis, imperforate anus, internal and external genital anomaly and single umbilical artery. Recently, sirenomelia is diagnosed by ultrasound at first trimester or early second trimester. Termination of pregnancy is recommended as soon as diagnosis is made. We report a case of sirenomelia in a monoamniotic twin gestation detected at IUP at 12 weeks which was maintained till IUP at 37 weeks and delivered by cesarean section. On autopsy, typical finding of sirenomelia was noted, whereas the contralateral twin showed no abnormalities.

Acute Leukemia and Myelodysplasitc Syndrome During Pregnancy A Single Institutional Experience of 4 Cases / 대한산부인과학회잡지

We have reviewed the medical records of 4 pregnant patients with concomitant acute leukemia at our institution in conjunction with determining the delivery process in order to reduce complications associated with the delivery. Of the 4 patients, three cases were diagnosed as acute leukemia and the other as myelodysplastic syndrome. One experienced an incomplete abortion at gestational age of 10 weeks, after remission induction chemotherapy. The remaining three patients made delivery at full term by Cesarean section. Our observation indicated that Cesarean delivery was advisable for these three patients. Most of the patients had thrombocytopenia or anemia. Before the Cesarean section or dilatation or evacuation, transfusion was undertaken to prevent hemorrhage or severe anemia. In the cases of refractoriness to blood transfusion, a greater amount was transfused. After Cesarean section, some complications were reported such as fever, delayed wound repair, and vaginal bleeding. Based on the our observations, we are of the opinion that pregnant women with acute leukemia or myelodysplastic syndrome can be managed even in those cases where the state of leukemia is not in complete remission or chemotherapy-induced cytopenia is. And the proper measures are timely undertaken to prevent complications associated with delivery.

A Case of False Positive Amniotic Fluid Acetylcholinestserase in One Fetus of Twin Pregnancy conceived by Intracytoplasmic Sperm Injection and Zygote Intrafallopian Tube Transfer / 대한주산의학회잡지

Maternal serum alpha-fetoprotein(MSAFP) has been a world wide screening test for open neural the tube defect. But elevation of MSAFP is related to not only neural tube defect, but also incorrect gestational age, congenital anomalies such as congenital nephrosis, esophageal and intestinal obstruction, low birth weight, oligohydroamnios, fetal death and chromosomal anomalies. If MSAFP is elevated, gestational age, congenital anomalies such as neural tube defect, multiple pregnancy and fetal death must be evaluated by ultrasound. When the ultrasound is nondiagnostic, amniotic fluid AFP(AFAFP) levels are measured and if AFAFP is elevated, presence or absence of aetylchoineststarase(AChE) is determined to rule out the false positive of amniotic AFP. Amniotic AChE test yielded detection rate of open spina bifida of 99%, 98% for anecephaly and a false-positive rate of 0.34%. We report a case with elevated AFAFP and positive amniotic AChE result in one fetus of the twin pregnancy conceived by ICSI and ZIFT, but in which targeted ultrasound findings were normal, maintained the pregnancy to term and normal twin was delivered by elective cesarean section.