Retrospective study of the efficacy and safety of docetaxel/carboplatin combination therapy as postoperative adjuvant chemotherapy for nonsquamous cell carcinoma of the cervix.

OBJECTIVE: Optimal adjuvant chemotherapy for nonsquamous cervical carcinoma has not yet been established. This study investigated the efficacy and safety of docetaxel/carboplatin (DC) for early-stage nonsquamous cell cervical carcinoma after radical hysterectomy (RH). METHODS: We evaluated 157 patients with stage IB-IIB nonsquamous cervical carcinoma with intermediate risk and high risk treated at our institution with DC after type II or III RH from 2007 to 2021. Patients received docetaxel (60-70 mg/m2) and carboplatin (area under the curve 5-6) every 3 weeks for six cycles. The primary endpoint was 2 year recurrence-free survival (RFS) and the secondary endpoint was adverse events (AEs). RESULTS: There were 106 intermediate-risk and 51 high-risk patients. The high-risk patients included 11 with positive parametrial involvement, 20 with pelvic lymph node metastases, and 20 with both parametrial involvement and pelvic lymph node metastases. The 2 year RFS rates for intermediate-risk, high-risk, and positive pelvic lymph nodes were 94.8% (95% confidence interval [CI], 87.9-97.8), 80.1% (95% CI, 64.1-89.5), and 74.5% (95% CI, 55.4-86.4), respectively. Sixteen patients had recurrence, including local recurrence (n = 6), distant metastasis (n = 9), and local and distant metastasis (n = 1). Hematologic toxicity was the most frequent AE, especially leukopenia and neutropenia. Nausea and constipation were the most frequent nonhematologic toxicities. CONCLUSION: DC therapy at our institution showed good 2 year RFS, and postoperative adjuvant therapy with DC therapy is suggested as a useful strategy for patients with nonsquamous cervical carcinoma.

Impact of the coverage of risk-reducing salpingo-oophorectomy by the national insurance system for women with BRCA pathogenic variants in Japan.

To determine the impact of the coverage of risk-reducing salpingo-oophorectomy (RRSO) and mastectomy (RRM) as well as genetic testing for BRCA pathogenic variants by the national insurance system in Japan. We compared the clinical background of women who underwent RRSO at our institution before and after its coverage by the national insurance system. Those who underwent RRSO between January 2017 and December 2019 and between April 2020 and March 2022 were classified as Period. A and B, respectively. Overall, 134 women underwent RRSO during the study period. In Period A and B, 45 and 89 women underwent RRSO for the study period was 36 and 24 months, respectively. Compared with Period A, the number of women who underwent RRSO per month increased by threefold in Period B (p < 0.01). In addition, the number of women who underwent surgery for breast cancer along with RRSO increased in Period B (p < 0.01). Although the number of women who underwent concurrent RRM with RRSO in Period B increased, the difference was not statistically significant. Compared with Period A, the number of women diagnosed with BRCA pathogenic variant increased by 3.9-fold, and the proportion of women who underwent concurrent hysterectomy at the time of RRSO decreased from 66 to 7.9% in Period B (p < 0.01). Owing to the introduction of the national insurance system, the number of women who underwent RRSO and concurrent surgery for breast cancer at the time of RRSO increased in Japan.

Detection of BRCA1 Pathogenic Variant in a 24-Year-Old Endometrial Cancer Patient: Risks of Several Hereditary Tumor Syndromes Assessed Using Germline Multigene Panel Testing.

A 24-year-old woman suspected of Lynch syndrome was found to carry a BRCA1 pathogenic variant, based on germline multigene panel testing (MGPT). The patient was diagnosed with endometrial carcinoma and underwent modified radical hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and omentectomy at the age of 23. Based on her father's history of colorectal cancer and her history of early onset endometrial cancer, mismatch repair protein immunohistochemistry analysis was performed. However, no loss of expression for mismatch repair proteins was found. Given her family history of ovarian and breast cancers, MGPT was recommended to identify the presence of any hereditary tumor syndromes. This testing revealed a BRCA1 pathogenic variant (exon13: c.1016delA, p.Lys339ArgfsX2) and diagnosed as hereditary breast and ovarian cancer syndrome (HBOC). Subsequently, the patient's mother also underwent single-site analysis for this variant, and the same pathogenic variant was detected. The patient and her mother are at high risk of developing BRCA1-associated HBOC-related cancers. Based on family history, clinical surveillance is currently underway for this patient and her mother. Currently, MGPT offers the potential for comprehensive genetic cancer risk assessment and may provide a more rational approach for the genetic assessment of those individuals whose personal and family cancer histories do not fit neatly into a single syndrome. This case suggests that if a patient is at high risk for hereditary tumor syndromes, MGPT should be considered to improve disease management strategies in clinical settings.

Impact on prognosis of unexpected uterine sarcoma with scalpel morcellation or enucleation.

Objective: It is well known that power morcellation of unexpected uterine sarcoma affects prognosis. There are few reports on the effects of scalpel morcellation or myomectomy of uterine sarcoma on prognosis, which is not well understood. This study investigated the effect on recurrence and prognosis when tumors of uterine sarcoma undergo scalpel morcellation or myomectomy. Methods: We performed a retrospective, observational study by collecting data from the medical records of patients who were histologically diagnosed with uterine sarcoma at our hospital between 2005 and 2017. All patients with unexpected uterine sarcoma were diagnosed after laparoscopic hysterectomy with scalpel morcellation or myomectomy (abdominal and laparoscopic) for presumed myoma. We evaluated recurrence rate, recurrence site, progression-free survival (PFS), and overall survival (OS). Results: A total of 15 patients were examined in this study. Twelve patients underwent myomectomy (7 patients with open surgery, 5 patients with laparoscopic surgery), and 3 patients underwent total laparoscopic hysterectomy with transvaginal scalpel morcellation. There were 11 cases of recurrence, and the recurrence rate was 78 %. The recurrence site was peritoneal dissemination in 10 cases (91 %) and lymph node metastasis in 1 case (9 %). The median PFS was 32 months [95 % confidence interval (CI) = 6.5-NA], and the median OS was 95.5 months [95 % CI = 55.8-NA]. Conclusion: Power morcellation, scalpel morcellation, and myomectomy may affect recurrence and prognosis. Further studies are needed in the future.

Indocyanine green-guided sentinel lymph node mapping during laparoscopic surgery with vaginal cuff closure but no uterine manipulator for cervical cancer.

BACKGROUND: Lymph node metastasis is a critical prognostic factor in cervical cancer. Considering the potential complications of lymphadenectomy and desirability of avoiding systemic lymphadenectomy, accurate intraoperative prediction of the existence of lymph node metastasis is important in patients undergoing surgery for cervical cancer. We evaluated the feasibility and value of indocyanine green (ICG) use for sentinel lymph node (SLN) mapping during laparoscopic surgery performed for cervical cancer. METHODS: This single-center cohort study included 77 patients undergoing a new laparoscopic radical surgery method with pelvic lymphadenectomy for early-stage cervical cancer. The surgery, performed without using a uterine manipulator, included creation of a vaginal cuff. Bilateral ICG-guided SLN mapping and rapid histopathological examination were performed, and results were analyzed in relation to final histopathologic diagnoses. RESULTS: The SLN pelvic side-specific detection rate was 93.5%, sensitivity (SLN-positive cases/SLN-detected pelvic lymph node-positive cases) was 100%, intraoperative negative predictive value (NPV) was 97.8%, and final pathological NPV was 100%. The detection rate was significantly lower for tumors ≥ 2 cm in diameter than for tumors < 2 cm in diameter. Micrometastases were missed by intraoperative examination in 3 cases. CONCLUSION: The high NPV suggests the feasibility and usefulness of ICG-based SLN mapping plus rapid intraoperative examination for identification of metastatic SLNs. Use of ICG-based mapping for intraoperative identification of SLNs in patients undergoing this new laparoscopic surgery method for early-stage cervical cancer was particularly effective for tumors < 2 cm in diameter. However, incorporating a search for micrometastases into rapid intraoperative histopathologic examination may be necessary.

Clinical Management of Atypical Endometrial Cells of Undetermined Significance Followed by Negative Cytology.

INTRODUCTION: In Japan, endometrial cytology is widely performed to evaluate the status of the endometrium in women with suspected endometrial cancer. A new classification system for endometrial cytology has recently been used: the Yokohama system, based on a descriptive reporting format. This study aimed to clarify the triage for patients with atypical endometrial cells of undetermined significance (ATEC-US) when followed by negative endometrial cytology. METHODS: We enrolled patients diagnosed with ATEC-US at the Cancer Institute Hospital between January 2016 and December 2017, based on the following inclusion criteria: (1) ATEC-US diagnosed by office endometrial cytology, with or without office endometrial biopsy; (2) follow-up endometrial cytology was performed 3-6 months after initial sampling, with a negative result for malignancy; and (3) no prior history of conservative treatment with progestin for endometrial cancer or atypical endometrial hyperplasia (ATEC-A). Among eligible patients, we analyzed those later diagnosed by endometrial biopsy with ATEC-A or carcinoma. RESULTS: Among 187 patients, 65 met the inclusion criteria. Forty-two patients (64.6%) were observed for more than 24 months. Two patients (3.1%) developed ATEC-A during a median observation time of 26.5 months; the times to diagnosis were 32 months and 22 months. DISCUSSION/CONCLUSION: No patient developed ATEC-A or worse within 1 year. For patients with ATEC-US, if negative cytology is obtained at the next examination, a close follow-up is not necessary.

Prognosis and adjuvant chemotherapy for patients with positive peritoneal cytology in stage IA endometrial cancer.

This study evaluated the influence of positive peritoneal cytology (PPC) on the prognosis of patients with stage IA endometrial cancer, and the usefulness of adjuvant chemotherapy in their treatment. We retrospectively analyzed the data of patients with stage IA endometrial cancer admitted in our hospital between 2005 and 2015. Among 989 patients who underwent peritoneal cytology, 135 (13.7%) had PPC. Multivariate analysis extracted several independent risk factors for recurrence in stage IA patients, including those with PPC. Adjuvant chemotherapy did not cause a significant difference in the 5-year relapse-free survival rate in patients with PPC (p = 0.78). Similarly, the 5-year recurrence-free survival rate with or without chemotherapy was not different among type II cancer patients (p = 0.11). However, the baseline risk of 5-year relapse-free survival without chemotherapy in patients with PPC and type II was very low (66.7%). While PPC was an independent risk factor for recurrence in stage IA endometrial cancer, adjuvant chemotherapy did not influence the survival rate in patients with PPC. While it is controversial whether adjuvant chemotherapy should be administered in stage IA uterine cancer with only PPC as a prognostic factor, it should be considered for early-stage patients who have multiple risk factors for recurrence.

Oncologic Outcomes of Laparoscopic Radical Hysterectomy Using the No-Look No-Touch Technique for Early Stage Cervical Cancer: A Propensity Score-Adjusted Analysis.

We evaluated oncologic outcomes of laparoscopic radical hysterectomy using the no-look no-touch technique (NLNT). We analyzed patients with early stage (IA2, IB1, and IIA1, FIGO2008) cervical cancer treated between December 2014 and December 2019. The primary endpoint was disease-free survival (DFS). We compared the outcomes of the abdominal radical hysterectomy (ARH) and NLNT groups using a Cox model with inverse probability of treatment weighting (IPTW), according to propensity scores. We also evaluated NLNT's non-inferiority to ARH using an evaluation of heterogeneity between the results of the Laparoscopic Approach to Cervical Cancer (LACC) trial and our study. ARH and NLNT were performed in 118 and 113 patients, respectively. The median follow-up duration was 3.2 years. After IPTW adjustment, the 3-year DFS rates (NLNT 92.4%; ARH 94.0%) and overall survival rates did not differ significantly between the groups. Furthermore, the 3-year DFS rates for patients with tumor sizes ≥ 2 cm in the NLNT (85.0%) and ARH (90.3%) groups did not differ significantly. No significant heterogeneity was observed between the LACC trial and our study (I2 = 60.5%, p = 0.111), although there was a trend toward a lower hazard ratio in our study. Laparoscopic radical hysterectomy using NLNT provides a favorable prognosis for early stage cervical cancer.

Feasibility and Outcomes of "No-Look No-Touch" Laparoscopic Radical Trachelectomy for Early-Stage Cervical Cancer.

Intraoperative tumor manipulation and dissemination may compromise the survival of women with early-stage cervical cancer who undergo laparoscopic surgery. This study aimed to examine survival and obstetrical outcomes related to laparoscopic radical trachelectomy (LRT) with a "no-look no-touch" technique in 40 women. This technique incorporates five measures to prevent tumor spillage and damage to the uterine artery perfusion. Five LRTs were aborted because of positive nodes or positive surgical margins. Compared with those of type III laparoscopic radical hysterectomy, the surgical outcomes of LRT in 35 patients were acceptable: operative time (380 min), estimated blood loss (140 mL), length of hospital stay (15 days), and lengths of excised parametrium and vagina. During follow-up (median, 41.3 months), the 5-year disease-free survival and overall survival were 95.0% (95% CI: 69.5-99.3%) and 100%, respectively. Of the nine patients (26%) who attempted pregnancy, seven conceived (nine pregnancies, 76%). Eight were delivered by term cesarean section, while one was miscarried in the first trimester. Our study suggests that the no-look no-touch technique may be effective in reducing the risk of recurrence and improving obstetrical outcomes during LRT for early-stage cervical cancer.

Positive surgical margin is an independent predictor of overall survival of patients with vulvar squamous cell carcinoma.

AIM: It is uncertain whether curative surgical treatment or a less radical surgery with adjuvant treatment should be provided to preserve function in patients with vulvar squamous cell carcinoma (SCC) that is adjacent to the urethra, anus, and vagina. The aim of this study was to investigate the surgical margin in patients with vulvar SCC with regard to local recurrence and overall survival. METHODS: Thirty-four patients were identified as having a diagnosis of vulvar SCC without distant metastasis. They had been treated surgically with curative intent at the Cancer Institute Hospital. Clinical data were analyzed retrospectively. RESULTS: Rates of 5-year local recurrence-free survival among patients with positive, <3-mm, <5-mm, <8-mm, and ≥8-mm surgical margins were 32%, 30.3%, 42.5%, 55.5%, and 73%, respectively. Rates of 5-year overall survival of patients with positive, <3-mm, <5-mm, <8-mm, and ≥8-mm surgical margins were 15.5%, 53.8%, 58.8%, 67.6%, and 83.3%, respectively. In the multivariable analysis, a tumor size of more than 2-cm (hazard ratio [HR] = 17.7, 95% confidence interval [CI] = 1.39-226) and a positive surgical margin (HR = 0.0092, 95% CI = 0.011-0.53) were risk factors for local recurrence, and a lymph node involvement (HR = 1.41, 95% CI = 0.31-6.43) and a positive surgical margin (HR = 0.0046, 95% CI = 0.011-0.53) were significant risk factors for overall mortality. CONCLUSIONS: To improve the prognosis, thorough resection with an adequate surgical margin is needed. But narrow surgical margin may be acceptable, particularly to preserve the function of adjacent organs.

Clinical and pathological outcomes of risk-reducing salpingo-oophorectomy for Japanese women with hereditary breast and ovarian cancer.

BACKGROUND: To clarify the clinical as well as pathological outcomes in Japanese women with germline pathogenic BRCA1/2 variants who underwent risk-reducing salpingo-oophorectomy (RRSO). METHODS: This prospective study examined the rate of occult cancer and primary peritoneal cancer after RRSO at our institution in the period from 2011 to 2020. Clinical records of genetically confirmed patients with germline pathogenic BRCA1/2 variants who desired to undergo RRSO were reviewed. Specimens obtained during RRSO were pathologically diagnosed as per SEE-FIM protocol. All the participants underwent magnetic resonance imaging (MRI) about 1 month preoperatively. RESULTS: One hundred and seventeen women underwent RRSO during this period. Of these, the numbers of women with germline pathogenic BRCA1 and BRCA2 variants were 72 and 45, respectively. The mean observational time after RRSO was 35.8 months. Despite negative preoperative screening results, three (2.6%) serous tubal intraepithelial carcinoma and three (2.6%) invasive carcinomas were identified. Of the three invasive carcinomas cases, two were International Federation of Gynecology and Obstetrics (FIGO) stage I primary fallopian tube cancer, and the third case was double cancer (ovarian cancer and fallopian tube cancer) with FIGO stage IC3. CONCLUSIONS: The rate of occult neoplasms was similar to those reported by studies performed in other countries. Although women with occult cancer were diagnosed with FIGO stage I, the MRI performed 1 month preoperatively did not show any such malignant findings. Thus, RRSO is the only promising method that can improve the prognosis in women with germline pathogenic BRCA1/2 variants.

Early oral feeding is safe and useful after rectosigmoid resection with anastomosis during cytoreductive surgery for primary ovarian cancer.

BACKGROUND: The aim of this study was to investigate the safety and clinical usefulness of early oral feeding (EOF) after rectosigmoid resection with anastomosis for the treatment of primary ovarian cancer. METHODS: We performed a retrospective review of all consecutive patients who had undergone rectosigmoid resection with anastomosis for primary ovarian, tubal, or peritoneal cancer between April 2012 and March 2019 in a single institution. Patient-related, disease-related, and surgery-related data including the incidence of anastomotic leakage and postoperative hospital stay were collected. EOF was introduced as a postoperative oral feeding protocol in September 2016. Before the introduction of EOF, conventional oral feeding (COF) had been used. RESULTS: Two hundred and one patients who underwent rectosigmoid resection with anastomosis, comprised of 95 patients in the COF group and 106 patients in the EOF group, were included in this study. The median number of postoperative days until the start of diet intake was 5 (range 2-8) in the COF group and 2 (range 2-8) in the EOF group (P < 0.001). Postoperative morbidity was equivalent between the groups. The incidence of anastomotic leakage was similar (1%) in both groups. The median length of the postoperative hospital stay was reduced by 6 days for the EOF group: 17 (range 9-67) days for the COF group versus 11 (8-49) days for the EOF group (P < 0.001). CONCLUSION: EOF provides a significant reduction in the length of the postoperative hospital stay without an increased complication risk after rectosigmoid resection with anastomosis as a part of cytoreductive surgery for primary ovarian cancer.

A retrospective study of internal small bowel herniation following pelvic lymphadenectomy for gynecologic carcinomas.

After pelvic lymphadenectomy (PLA), pelvic vessels, nerve, and ureter are skeletonized. Internal hernias beneath the skeletonized pelvic structure following pelvic lymphadenectomy (IBSPP) are a rare complication following PLA. To the best of our knowledge, only 12 IBSPP cases have been reported and clinical details on such hernias remain unknown. The aim of the study was to investigate the incident and etiology of IBSPP. 1313 patients who underwent open or laparoscopic pelvic lymphadenectomy were identified from our database. A retrospective review was performed. Mean follow-up period was 33.9 months. A total of 12 patients had IBSPP. Multivariate analysis of laparoscopic surgeries group as compared to open surgeries group, para-aortic lymphadenectomy rate, number of dissected lymph nodes by PLA, antiadhesive material use rate, and blood loss were lower in laparoscopic surgeries group: odd ratio (OR) = 0.13 [95% confidence interval (CI) 0.08-0.19], and OR = 0.70 [95% CI 0.50-0.99], OR = 0.17 [95% CI 0.10-0.28], OR = 0.93 [95% CI 0.92-0.94]. However, no significant difference was observed in the incidence of IBSPP between laparoscopic surgery (1.0%) and open surgery (0.8%). All IBSPP occurred in the right pelvic space. These findings may contribute to the development of prevention methods for this disease.

Laparoscopic pelvic exenteration and laterally extended endopelvic resection for postradiation recurrent cervical carcinoma: Technical feasibility and short-term oncologic outcome.

OBJECTIVE: Surgery is the only treatment for cervical cancer recurrence in a previously irradiated field. Pelvic exenteration (PE) and laterally extended endopelvic resection (LEER) are indicated for select patients; however, morbidity and mortality rates remain high, and new treatment modalities are required. Laparoscopy optimizes visualization and allows meticulous dissection while also reducing intraoperative blood loss and postoperative complications without worsening the outcomes. We aimed to clarify the feasibility and outcomes of laparoscopic PE and LEER for previously irradiated recurrent cervical cancer. METHODS: We prospectively investigated the outcomes of laparoscopic PE and LEER in 28 patients with recurrent cervical carcinoma after radiotherapy. RESULTS: Seventeen laparoscopic PEs for central recurrences and 11 laparoscopic LEERs for lateral recurrences were performed. The median operation time and blood loss were 454mins and 285 mL in the PE group, and 562mins and 325 mL in the LEER group, respectively, with no conversions to laparotomy. R0 resection was achieved in all patients in the PE group and 73% in the LEER group. The morbidity and mortality rates were 41% and 0% in PE group, and 55% and 0% in LEER group, respectively. The 2-year disease-free survival and overall survival were 68.9% and 76% in the PE group, and 27.3% and 29.6% in the LEER group, respectively. CONCLUSION: Laparoscopic PE is feasible for previously irradiated central recurrent cervical cancer and has acceptable outcomes. Laparoscopic LEER is also feasible for lateral recurrence, but oncologic outcome may be modest in this limited preliminary study. Further studies using a larger sample size with a longer follow-up period is warranted to determine the indications for laparoscopic LEER.

Continuous Administration of Bevacizumab After Disease Progression in Recurrent Ovarian Cancer: A Retrospective Observational Study.

BACKGROUND/AIM: Chemotherapy with additional bevacizumab is the standard treatment for primary and recurrent ovarian cancer. We aimed to investigate the clinical utility and safety of bevacizumab when used in combination with chemotherapy after disease progression. PATIENTS AND METHODS: This retrospective, observational study recruited patients treated for recurrent ovarian cancer from 2014 to 2016. We evaluated the effects of bevacizumab with chemotherapy in patients whose disease had progressed following treatment with bevacizumab. We assessed progression-free survival and adverse events. RESULTS: Thirty-three patients received post-progression treatment with bevacizumab. The median progression-free survival was 8.7 months (95% confidence interval=5.5-11). The progression-free survival was compared pre- and post-progression treatment, and was longer in platinum-resistant than platinum-sensitive cases after treatment (p=0.06). The most common non-hematological toxicity was proteinuria. The incidence of serious adverse events was low. CONCLUSION: Continuous administration of bevacizumab may be beneficial for ovarian cancer patients after disease progression.

A case of endometrial carcinoma progressed during pregnancy resulting in fetal death.

Most endometrial carcinomas (ECs) occurring during pregnancy are diagnosed in the first trimester. During the gestation period, progesterone level, which has a protective effect on the endometrium, is found to increase. In EC cases, administering high-dose progesterone is a therapeutic strategy because this hormone can considerably shrink tumors. Herein, the case of a woman in whom EC progressed during pregnancy is reported. Before pregnancy, she was diagnosed with atypical polypoid adenomyoma based on a blind office biopsy. She spontaneously conceived 2 months later, although she was suggested to undergo dilatation and curettage under general anesthesia to confirm the diagnosis. Subsequently, fetal death occurred at 26 weeks. A vaginal delivery was deemed impossible due to vaginal metastasis of EC; thus, cesarean section was performed. Computed tomography revealed multiple lung, pelvic, and inguinal lymph node metastases. Additional biopsy demonstrated poorly differentiated endometrioid carcinoma. She underwent systemic chemotherapy. However, eventually, the disease progressed, resulting in death 11 months after the cesarean section. In the present case, grade 3 EC may have existed before pregnancy, and this condition could have been diagnosed if hysteroscopic resection or total curettage under general anesthesia was performed. Grade 1 tumor may have been eliminated by the high progesterone level maintained during pregnancy, and thus, only grade 3 tumor progressed. Women who wish to preserve their fertility should undergo precise whole endometrial examination. If not, the fetus and mother may consequently experience an eventful clinical course.

Adjuvant treatment of endometrial cancer today.

Endometrial cancer frequently occurs in post-menopausal women, and the endometrium is a well-known site of cancer affecting women. Endometrial cancer is found with genital bleeding and often at an early stage. However, there are some risks of recurrence after hysterectomy. As a medical treatment after the diagnosis of endometrial cancer, appropriate adjuvant therapy is considered to lead to a decrease in the rate of recurrence and improvement of prognosis according to the determination of the cancer stage from the surgical and histopathological results. In this review, we describe post-operative adjuvant therapy administered for endometrial cancer and advanced disease, focusing on chemotherapy, radiation therapy and the combination of both. These treatments are divided according to the risk of recurrence as based primarily on the reported evidence.

Surgical outcomes of early-stage primary vaginal nonsquamous cell carcinoma.

OBJECTIVE: Definitive radiation therapy (RT), using external beam RT and/or brachytherapy, is a standard treatment option for primary vaginal carcinoma. However, this treatment has poor prognosis when applied to vaginal nonsquamous cell carcinoma (non-SCC). We aimed to clarify treatment outcome and surgical safety in early-stage primary vaginal non-SCC. METHODS: After receiving approval from the institutional review board, we retrospectively reviewed the clinical records and pathological samples of patients treated at our hospital between 1991 and 2018. Among 49 patients with primary vaginal carcinoma, 12 with histologically confirmed early-stage primary vaginal non-SCC were included in this study. RESULTS: In total, 40% of patients with primary vaginal carcinoma treated at our hospital had primary vaginal non-SCC. The average observation time was 34 months (median 53.3 months). Three patients had local recurrence: 2 in pelvic lymph nodes and 1 in the vagina. Furthermore, 2 patients died of their disease. Five-year local control rate of stage I and stage II non-SCC was 75% and 100%, respectively. Disease-specific survival rate of stage I and stage II non-SCC was 81.8% and 100%, respectively. No major morbidity was observed. Three patients required allogeneic blood transfusion, whereas 1 underwent autotransfusion. None of the 12 patients were discharged with self-catheterization. CONCLUSION: Five-year local control and disease-specific survival rates of patients surgically treated for vaginal non-SCC were favorable. Therefore, surgery could be a safe and reasonable option for early-stage primary vaginal non-SCC.

Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma.

Carcinosarcoma (CS) of the uterus or ovary is a rare, aggressive and biphasic neoplasm composed of carcinoma and sarcoma elements. Previous genomic studies have identified the driver genes and genomic properties associated with CS. However, there is still no molecular subtyping scheme with clinical relevance for this disease. Here, we sequence 109 CS samples, focusing on 596 genes. We identify four molecular subtypes that resemble those observed in endometrial carcinoma: POLE-mutated, microsatellite instability, copy number high, and copy number low subtypes. These molecular subtypes are linked with DNA repair deficiencies, potential therapeutic strategies, and multiple clinicopathological features, including patient outcomes. Multi-regional comparative sequencing reveals genomic alteration-independent CS cell differentiation. Transcriptome and DNA methylome analyses confirm epithelial-mesenchymal transition as a mechanism of sarcoma differentiation. The current study thus provides therapeutic possibilities for CS as well as clues to understanding the molecular histogenic mechanism of its development.

Tumor characteristics and outcome of uterine carcinosarcoma in women aged ≥80 years.

OBJECTIVE: To examine clinico-pathological characteristics and outcomes of uterine carcinosarcoma (UCS) in women aged ≥80 years. METHODS: This is a secondary analysis of a previous multicenter retrospective study examining 906 women with stage I-IV UCS who underwent primary hysterectomy. Patient demographics, treatment types, tumor characteristics, and survival were examined across aged ≥80 (n = 82 [9.1%]), aged 60-79, (n = 526 [58.1%]), and aged <60 (n = 298 [32.9%]). RESULTS: Women in the aged ≥80 group were more likely to be Caucasian, undergo simple hysterectomy without lymphadenectomy, and receive no postoperative therapy (all, P < 0.05). Tumors in the aged ≥80 group were more likely to have high-grade carcinoma, heterologous sarcoma, and sarcoma dominance but less likely to have lympho-vascular space invasion (all, P < 0.05). Lymphadenectomy did not improve survival in the aged ≥80 group (P > 0.05), whereas lymphadenectomy was protective for survival in the younger groups (both, P < 0.05). Postoperative chemotherapy was associated with improved progression-free survival (PFS) in the aged ≥80 group (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.22-0.89, P = 0.021). With chemotherapy treatment, women in the aged ≥80 group had PFS similar to those in the aged 60-79 group (HR 0.97, 95%CI 0.51-1.83, P = 0.92). In contrast, without chemotherapy treatment, women in the aged ≥80 group had significantly decreased PFS compared to the aged 60-79 group (HR 1.62, 95%CI 1.09-2.40, P = 0.016). Similar associations were observed for postoperative radiotherapy. CONCLUSION: Nearly 10% of women with UCS are aged ≥80 that are characterized by aggressive tumor factors. Postoperative therapy but not extensive surgery may improve survival in this age group.