Objective: Vaccine efficacy among previously exposed, but currently uninfected women, i.e., those who have serological evidence of a prior human papillomavirus (HPV) infection without corresponding detectable HPV DNA, remains incompletely defined. This meta-analysis assessed the serotype-specific efficacy of prophylactic HPV vaccination against HPV16/18 persistent infection (PI) and cervical intraepithelial neoplasia (CIN) among seropositive, DNA negative (SPDN) women enrolled to randomized controlled trials (RCTs) of HPV L1-based vaccines.
Methods: Searches were conducted on 08/16/20 on MEDLINE, Embase, Scopus and CENTRAL. RCTs of L1-based prophylactic bivalent or quadrivalent HPV vaccines, reporting serotype-specific clinical efficacy endpoints in the HPV16/18 seropositive, DNA-negative populations were included. Relative risks (RRs) of 6-month PI (6mPI), 12-month PI (12mPI), CIN1+ and CIN2+ were pooled using a random-effects model.
Results: A total of 1,727 citations were reviewed. 8 studies, with a total of 9,569 SPDN participants, met all eligibility criteria. The RR of 6mPI (RR=0.22; 95% confidence interval [CI]=0.08-0.61; p=0.018), 12mPI (RR=0.20; 95% CI=0.05-0.80; p=0.035), CIN1+ (RR=0.13; 95% CI=0.05-0.30; p=0.003) and CIN2+ (RR=0.15; 95% CI=0.04-0.59; p=0.022) was significantly reduced in the vaccinated compared to the unvaccinated group.
Conclusion: Our findings suggest high serotype-specific efficacy for HPV vaccination among cohorts of women with evidence of prior HPV16/18 infections, including 87% efficacy (95% CI=70%-95%; p=0.003) against HPV16/18 cervical dysplasia. HPV vaccination is highly effective among uninfected women, regardless of prior exposure history.

Up to 1% of women with endometriosis develop endometriosis-associated neoplasms [1]. Most endometriosis-associated malignant tumors develop from the ovarian endometriomas, whereas those developing from extragonadal lesions are extremely rare, estimated at 0.2% [2]. Because they are uncommon, a treatment protocol for the malignant transformation of extragonadal endometriosis lesions has not been clearly defined. When the lesion is confined to the site of origin and R0 resection is achieved, the 5-year survival rate is between 82% and 100%; therefore, complete resection should be performed [3]. The patient in this video had previously undergone hysterectomy, bilateral salpingo-oophorectomy, left nephrectomy, and low-anterior resection of the rectum due to severe endometriosis. Ten years after the surgery, the patient had a 6 cm endometrioid adenocarcinoma developing from the residual endometriosis lesion at the left uterosacral ligament that involved the bladder, left ureter, and rectum. In this case, the tumor was attached to the pelvis due to infiltration of the left sacrospinous ligament. To completely remove the tumor, we used laterally extended endopelvic resection with abdominoperineal resection of the rectum. We used the laparoscopic-perineal-laparoscopic approach (pincer approach) because improved visualization of the left sacrospinous ligament increases the probability of achieving complete resection [4]. Pathological R0 resection was achieved without intraoperative or postoperative complications. Thus, for tumors that are firmly attached to the pelvic floor, the pincer approach can be useful for achieving R0 resection. The informed consent for use of this video was taken from the patient.

Objective: The molecular classification system of endometrial carcinoma (EC) in 'The Cancer Genome Atlas' is widely acknowledged for its prognostic utility. Subsequently, more simplified classification system that incorporate DNA polymerase epsilon (POLE) exonuclease domain mutations, mismatch repair deficiencies (MMRd), and abnormal p53 (P53abn) has also demonstrated its clinical utility. These classifications helped identifying a 'POLE ultramutated' (POLEmut) category of patients, most of whom show excellent prognoses despite having high-grade ECs. We aimed to investigate the clinicopathological and molecular characteristics of high-grade ECs with POLEmut.
Methods: We investigated 414 patients with high-grade ECs (including endometrioid carcinomas grade 3, serous carcinomas, clear cell carcinomas, mixed carcinomas, undifferentiated and dedifferentiated carcinomas, and carcinosarcomas) by sequencing and immunohistochemical staining.
Results: Forty-three tumors (10.4%) were classified as POLEmut, including 2 with new, possibly pathogenic POLE mutations at P286C and L424V. These patients had very good prognoses except for 1 with stage IV disease and residual tumor. Eleven patients in this group also had P53abn and 4 had MMRd; molecular analysis revealed that patients with synchronous POLE pathogenic mutation and other mutations had a POLEmut or MMRd phenotype; survival analysis found no difference in prognosis between these patient categories. The prognoses of patients in the POLEmut EC group were not significantly influenced by treatment or risk category.
Conclusions: Patients with high-grade EC exhibiting POLEmut have very good clinical outcomes, and should be identified urgently in daily work owing to their conflicting morphology. Our findings also provide guidance on subclassifying ECs with poor histological appearance.

The use of PARP inhibitors (PARPi) in patients with epithelial ovarian cancer is expanding, with the transition from use in recurrent disease to the first-line setting. This is accompanied with an increasing population of patients who develop acquired PARPi resistance. Coupled with those patients with primary PARPi resistance, there is an urgent need to better understand mechanisms of resistance and identify means to overcome this resistance. Combination therapy offers the potential to overcome innate and acquired resistance, by either working synergistically with PARPi or by restoring homologous recombination deficiency, targeting the homologous recombination repair pathway through an alternate strategy. We discuss mechanisms of PARPi resistance and data on novel combinations which may restore PARPi sensitivity.

Objective: To investigate the clinical characteristics, treatments, and prognostic factors among patients with gestational trophoblastic neoplasia (GTN) exhibiting brain metastases who underwent craniotomy.
Methods: Thirty-five patients with GTN who had brain metastases and subsequently underwent craniotomies between January 1990 and December 2018 at Peking Union Medical College Hospital were identified using the GTN database. Their clinical manifestations, treatments, outcomes, and prognostic factors were retrospectively analyzed.
Results: All 35 patients underwent decompressive craniotomy, hematoma removal, and metastatic tumor resection combined with multiagent chemotherapy. Eighty percent (28/35) achieved complete remission, 11.4% (4/35) achieved partial remission, and 8.6% (3/35) had progressive disease. Not counting 2 patients who were lost to follow-up, 81.8% of the patients (27/33) were alive after a median follow-up of 72 months. The 5-year overall survival rate was 80.4%. Univariate analysis revealed that a history of chemotherapy failure (p=0.020) and a >1-week interval between craniotomy and chemotherapy commencement (p=0.027) were adverse risk factors for survival. Multivariate analysis showed that previous chemotherapy failure remained an independent risk factor for poor survival (odds ratio=11.50; 95% confidence interval=1.55-85.15; p=0.017).
Conclusion: Decompressive craniotomy is a life-saving option if metastatic hemorrhage and intracranial hypertension produce a risk of cerebral hernia in patients with GTN who have brain metastases. Higher survival rates and improved prognoses can be achieved through perioperative multidisciplinary cooperation and timely standard postoperative chemotherapy.

Objective: This study aimed to evaluate the oncologic outcomes according to disease burden in uterine cervical cancer patients with metachronous distant metastases.
Methods: Between 2005 and 2015, 163 patients with metachronous distant metastases from uterine cervical cancer after receiving a definitive therapy were evaluated at seven institutions in Korea. Low metastatic burden was defined as less than 5 metastatic sites, whereas high metastatic burden was others. Each metastasis site was divided based on the lymph node (LN) and organs affected. The overall survival (OS) and progression-free survival (PFS) were assessed. Cox proportional hazards models, including other clinical variables, were used to evaluate the survival outcomes.
Results: The median follow-up duration was 22.2 months (range: 0.3-174.8 months). Para-aortic LNs (56.4%), lungs (26.4%), supraclavicular LNs (18.4%), and peritoneum (13.5%) were found to be the common metastasis sites. Among 37 patients with a single metastasis, 17 (45.9%) had LN metastases and 20 (54.1%) had organ metastases. The 1- and 2-year OS rates were 73.9% and 55.0%, respectively, whereas the PFS rates were 67.2% and 42.9%, respectively. SCC Ag after recurrence and high metastatic burden were significant factors affecting the OS (p=0.004 and p<0.001, respectively). Distant organ recurrence, short disease-free interval (≤2 years), and high metastatic burden were unfavorable factors for PFS (p=0.003, p=0.011, and p=0.002, respectively).
Conclusion: A favorable oncologic outcome can be expected by performing salvage treatments in selected patients with a long disease-free interval, low metastatic burden, and/ or lymphatic-only metastasis.

Objective: Splenectomy with or without distal pancreatectomy is occasionally performed during cytoreductive surgery for advanced ovarian cancer. We investigated pre-, intra-, postoperative risk factors and predictors of clinically relevant postoperative pancreatic fistula (CR-POPF) in patients who underwent cytoreductive surgery for advanced ovarian cancer.
Methods: We investigated 165 consecutive patients with ovarian, fallopian tube, and peritoneal carcinoma categorized as stage III/IV disease, who underwent splenectomy with or without distal pancreatectomy as a component of cytoreductive surgery performed as initial treatment at Chiba University Hospital. Patient characteristics, clinical factors, and surgical outcomes were compared between those with and without CR-POPF.
Results: CR-POPF occurred in 20 patients (12%). There were no significant intergroup differences in the characteristics between patients with CR-POPF and patients without CR-POPF except for operative time, intraoperative blood loss, amylase (AMY) levels in drain fluid on postoperative day (POD)1 and POD3, and pancreatic stump thickness. Multivariate analysis showed that the POD3 drain fluid AMY level was the only significant risk factor and predictor of CR-POPF in patients who underwent cytoreductive surgery for advanced ovarian cancer. The receiver operating characteristic curve of the POD3 drain fluid AMY level, which predicted development of CR-POPF showed an area under the curve of 0.77, and the optimal cut-off value of AMY was 808 U/L. A pancreatic fistula did not occur in patients with POD3 drain fluid AMY levels <130 U/L.
Conclusion: The POD3 drain fluid AMY level can be early diagnostic predictor CR-POPF after splenectomy with or without distal pancreatectomy for advanced ovarian cancer.