Search

Background: We previously demonstrated the applicability of the concept of "platinum sensitivity" in recurrent endometrial cancer. Although immune checkpoint inhibitors have been widely incorporated into endometrial cancer treatment, the debate continues regarding treatment options in patients with recurrent endometrial cancer who have previously received platinum-based chemotherapy. In this study, we assessed the duration of response to secondary platinum-based treatment using pooled data from the SGSG-012/GOTIC-004/Intergroup study. Methods: Among the 279 participants in the SGSG-012/GOTIC-004/Intergroup study wherein platinum-based chemotherapy was re-administered for managing recurrent endometrial cancer between January 2005 and December 2009, 130 (47%) responded to chemotherapy. We compared the relationship between platinum-free interval and duration of secondary platinum-based treatment using pooled data. Results: In 40 patients (31%), the duration of response to secondary platinum-based treatment exceeded the platinum-free interval. The duration of response to secondary platinum-based treatment exceeded 12 months in 51 patients (39%) [platinum-free interval: < 12 months, 14/48 (29%); 12–23 months, 18/43 (42%); 24–35 months, 8/19 (42%); ≥ 36 months, 11/20 (55%)]. In particular, in eight patients (6%), the duration of response to secondary platinum-based treatment exceeded 36 months [platinum-free interval: < 12 months, 3/48 (6%); 12–23 months, 0/19 (0%); 24–35 months, 2/19 (11%); ≥ 36 months, 3/20 (15%)]. Conclusions: Re-administration of platinum-based chemotherapy for recurrent endometrial cancer may result in a long-term response exceeding the platinum-free interval in some patients. Even in the current situation, where immune checkpoint inhibitors have been introduced, re-administration of platinum-based chemotherapy is worth considering. [ABSTRACT FROM AUTHOR]

Background: In the phase 3 EMPOWER‐Cervical 1/GOG‐3016/ENGOT‐cx9 study, cemiplimab significantly improved overall survival (OS) versus chemotherapy for patients with recurrent or metastatic cervical cancer who progressed after first‐line platinum‐based chemotherapy. We present a post hoc subgroup analysis of patients enrolled in Japan. Methods: Patients were enrolled regardless of programmed cell death‐ligand 1 status and randomized 1:1 to cemiplimab 350 mg intravenously every 3 weeks or investigator's choice single‐agent chemotherapy for up to 96 weeks. Primary endpoint was OS. Key secondary endpoints were progression‐free survival (PFS) and objective response rate (ORR). Results: Overall, 608 patients were randomized, of whom 56 (9.2%) were in Japan (cemiplimab, n = 29; chemotherapy, n = 27). The median (range) duration of follow‐up was 13.6 (6.0–25.3) versus 18.2 (6.0–38.2) months for patients in Japan and for the overall population, respectively. Median OS (95% confidence interval [CI]) was 8.4 (7.0‐not evaluable) and 9.4 (5.4–14.9) months for cemiplimab versus chemotherapy (hazard ratio [HR]: 0.86; 95% CI: 0.43–1.68). Median PFS (95% CI) was 4.0 (1.4–8.2) versus 3.7 (1.8–4.2) months with cemiplimab and chemotherapy (HR: 0.90; 95% CI: 0.50–1.61), respectively. ORR was 17.2% for cemiplimab and 7.4% for chemotherapy (odds ratio, 2.47; 95% CI, 0.44–13.99). Incidence of treatment‐emergent adverse events at any grade was 79.3% for cemiplimab and 100% for chemotherapy. Grade ≥3 adverse events were 37.9% versus 66.7% with cemiplimab and chemotherapy, respectively. Discussion: While acknowledging limitations inherent to a small subgroup analysis, the HR of 0.86 observed in Japanese patients suggests an emerging survival benefit despite a 4.6‐month shorter median duration of follow‐up versus the overall study population. [ABSTRACT FROM AUTHOR]

Purpose: TAS-117 is a highly potent and selective, oral, allosteric pan-AKT inhibitor under development for advanced/metastatic solid tumors. The safety, clinical pharmacology, pharmacogenomics and efficacy were investigated. Methods: This phase I, open-label, non-randomized, dose-escalating, first-in-human study enrolled patients with advanced/metastatic solid tumors and comprised three phases (dose escalation phase [DEP], regimen modification phase [RMP], and safety assessment phase [SAP]). The SAP dose and regimen were determined in the DEP and RMP. Once-daily and intermittent dosing (4 days on/3 days off, 21-day cycles) were investigated. The primary endpoints were dose-limiting toxicities (DLTs) in Cycle 1 of the DEP and RMP and incidences of adverse events (AEs) and adverse drug reactions (ADRs) in the SAP. Secondary endpoints included pharmacokinetics, pharmacodynamics, pharmacogenomics, and antitumor activity. Results: Of 66 enrolled patients, 65 received TAS-117 (DEP, n = 12; RMP, n = 10; SAP, n = 43). No DLTs were reported with 24-mg/day intermittent dosing, which was selected as a recommended dose in SAP. In the SAP, 98.5% of patients experienced both AEs and ADRs (grade ≥ 3, 67.7% and 60.0%, respectively). In the dose range tested (8 to 32 mg/day), TAS-117 pharmacokinetics were dose proportional, and pharmacodynamic analysis showed a reduction of phosphorylated PRAS40, a direct substrate of AKT. Four patients in the SAP had confirmed partial response. Conclusion: Oral doses of TAS-117 once daily up to 16 mg/day and intermittent dosing of 24 mg/day were well tolerated. TAS-117 pharmacokinetics were dose proportional at the doses evaluated. Antitumor activity may occur through AKT inhibition. Trial registration: jRCT2080222728 (January 29, 2015). [ABSTRACT FROM AUTHOR]

The first prophylactic vaccine against human papillomavirus (HPV) 16 and HPV18 was licensed in Japan in 2009. HPV vaccine effectiveness against high‐grade cervical lesions has been demonstrated among young Japanese women, but evidence of its effects on invasive cervical cancer (ICC) is lacking. Using data from two different cancer registries, we compared recent trends of new ICC cases by age group using Poisson regression analysis. We also analyzed time trends in HPV16/18 prevalence among 1414 Japanese women aged <40 years newly diagnosed with ICC in the past decade. Based on the population‐based cancer registry, the incidence of ICC among young women aged 20–29 years showed a significant decline from 3.6 to 2.8 per 100 000 women‐years during 2016–2019, but no similar decline was observed for older age groups (p < 0.01). Similarly, using data from the gynecological cancer registry of the Japan Society of Obstetrics and Gynecology, the annual number of ICCs among women aged 20–29 years also decreased from 256 cases to 135 cases during 2011–2020 (p < 0.0001). Furthermore, a declining trend in HPV16/18 prevalence in ICC was observed only among women aged 20–29 years during 2017–2022 (90.5%–64.7%, p = 0.05; Cochran–Armitage trend test). This is the first report to suggest population‐level effects of HPV vaccination on ICC in Japan. Although the declining trend in HPV16/18 prevalence among young women with ICC supports a causal linkage between vaccination and results from cancer registries, further studies are warranted to confirm that our findings are attributable to vaccination. [ABSTRACT FROM AUTHOR]

Simple Summary: Cervical adenocarcinomas have been divided into human papilloma virus-associated (HPVa) and -independent (HPVi) tumors in the updated pathological classification issued by the World Health Organization in 2020. However, few studies have investigated the impact of this new classification on the treatment outcomes and prognosis of locally advanced cervical adenocarcinoma. We investigated the treatment outcomes of 103 and 48 patients with locally advanced (stages IB3–IIIC1) HPVa and HPVi cervical adenocarcinomas, respectively. Most patients underwent radical hysterectomy with or without adjuvant therapy for both tumor types. The overall survival time and survival to progression or death were significantly shorter in the HPVi group than in the HPVa group. In particular, patients with parametrial invasion had highly significant differences in survival. Only five patients with HPVi carcinomas received definitive radiotherapy, and all demonstrated a treatment response. HPVi tumors showed poor outcomes with the current treatment strategy. The revised World Health Organization classification of cervical cancer divides adenocarcinomas into human papillomavirus-associated (HPVa) and -independent (HPVi) types; the HPVi type is represented by the gastric type. The treatment outcomes of locally advanced adenocarcinoma (LaAC), based on this classification, are understudied. We investigated the outcomes of patients with HPVa and HPVi LaACs. Data for all consecutive patients with stage IB3 to IIIC1 adenocarcinoma who received treatment at 12 institutions throughout Japan between 2004 and 2009 were retrieved to analyze progression-free and overall survival. Central pathological review classified 103 and 48 patients as having HPVa and HPVi tumors, respectively. Usual- (84%) and gastric- (90%) type adenocarcinomas were the most frequent subtypes. Surgery was the primary treatment strategy for most patients. Progression-free and overall survival of patients with HPVi were worse than those of patients with HPVa (p = 0.009 and 0.032, respectively). Subgroup analysis by stage showed that progression-free survival was significantly different for stage IIB. The current surgical treatment strategy for LaACs is less effective for HPVi tumors than for HPVa tumors, especially those in stage IIB. [ABSTRACT FROM AUTHOR]

Background: We evaluated the feasibility of neoadjuvant chemotherapy, followed by debulking surgery, for clinically diagnosed FIGO stage IVb endometrial cancer (protocol number: JGOG2046). Methods: The experimental treatment consisted of 3 cycles of paclitaxel (180 mg/m2) plus carboplatin (AUC5) followed by debulking surgery, including total abdominal hysterectomy, bilateral salpingo-oophorectomy, and 3 cycles of adjuvant chemotherapy. Patients were considered as eligible if they were pathologically diagnosed as primary endometrial cancer, and had both endometrial tumor and distant metastasis confirmed by imaging examinations. The primary endpoint was the incidence of patients who completed debulking surgery after the neoadjuvant chemotherapy. Results: While 51 patients were enrolled from 23 hospitals, the final study cohort consisted of 49 patients with a mean age of 59.0 years. Although the response ratio of the neoadjuvant chemotherapy was 65.3% (95% CI 50.4–78.3%), 67.3% (95% confidence interval (CI) 52.5–80.1%) underwent debulking surgery after the neoadjuvant chemotherapy and 59.2% (95% CI 45.2–71.8%) completed the protocol treatment including 3 courses of adjuvant chemotherapy. The median disease-free survival time was 9.1 months (95% CI 6.5–11.9), while the median overall survival time was 23.2 months (95% CI 11.9–27.8). A patient with sigmoid colon cancer and another with cervical cancer were included in this study. Conclusions: Neoadjuvant chemotherapy followed by debulking surgery was a feasible and acceptable treatment for metastatic endometrial cancer. (225 words). [ABSTRACT FROM AUTHOR]

Cowden syndrome is characterized by several clinical features related to tumorous lesions primarily consisting of systemic hamartomas. The mutation of a tumor suppressor gene, the PTEN gene, is etiologically involved. As gastrointestinal lesions, polyps of all digestive tracts involving the esophagus to rectum develop. In patients with Cowden syndrome, the risk of colorectal cancer may increase. However, the characteristics of colorectal cancer in these patients remain to be clarified and sufficient findings regarding chemotherapy have not been obtained. A 39-year-old man was treated with a colonic stent for colitis obstructive due to circumferential transverse colon carcinoma. After decompression, elective extended laparoscopic right hemicolectomy was performed. Preoperative systemic detailed examination revealed characteristic dermal/mucosal findings, polyposis of the upper digestive tract, and a thyroid tumor. On PTEN gene sequencing, a mutation was detected at codon 130 of exon 5, leading to a diagnosis of Cowden syndrome. Postoperative adjuvant chemotherapy was performed for 6 months, but recurrent peritoneal dissemination was observed 1 month after its completion. FOLFOXIRI + bevacizumab therapy was started. Transiently, a partial response was achieved in peritoneally disseminated nodes according to the RECIST. There was no increase in the volume of cancerous ascites. However, an increase in the volume of ascites and local relapse were noted at the completion of the tenth course. The regimen was switched to FOLFIRI + panitumumab, but peritoneal dissemination exacerbated and the patient died 18 months after surgery. [ABSTRACT FROM AUTHOR]

Purpose: Post-operative paralytic ileus (POI) occurs after surgery because of gastrointestinal dysfunction caused by surgical invasion. We therefore investigated the frequency of POI after laparoscopic colorectal surgery in patients with colorectal cancer using a strictly defined POI diagnosis and identified associated risk factors. Methods: Patients who underwent initial laparoscopic surgery for colorectal cancer between January 2014 and December 2018 were included. The primary end point was the incidence of POI. A multivariate logistic regression analysis revealed the contributing risk factors for POI. Results: Of the 436 patients, 94 (21.6%) had POI. Compared with the non-POI group, the POI group had significantly higher frequencies of infectious complications (p < 0.001), pneumonia (p < 0.001), intra-abdominal abscess (p = 0.012), anastomotic leakage (p = 0.016), and post-operative bleeding (p = 0.001). In the multivariate analysis, the right colon (odds ratio [OR] 2.180, p = 0.005), pre-operative chemotherapy (OR 2.530, p = 0.047), pre-operative antithrombotic drug (OR 2.210, p = 0.032), and post-operative complications of CD grade ≥ 3 (OR 12.90, p < 0.001) were independent risk factors for POI. Conclusion: Post-operative management considering the risk of post-operative bowel palsy may be necessary for patients with right colon, pre-operative chemotherapy, pre-operative antithrombotic drug or severe post-operative complications. [ABSTRACT FROM AUTHOR]

Study 309/KEYNOTE‐775 is a phase 3 open‐label, randomized trial of lenvatinib plus pembrolizumab versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer with progression after platinum‐based therapy. Primary endpoints of superiority for lenvatinib plus pembrolizumab were met for progression‐free survival (PFS) and overall survival (OS) in all‐comers (ie, regardless of mismatch repair [MMR] status) and patients with MMR proficiency (pMMR). We present results for the Japanese subset. Patients were randomized to oral lenvatinib 20 mg/day plus intravenous pembrolizumab 200 mg every 3 weeks (Q3W; up to 35 cycles of pembrolizumab) or TPC (intravenous doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 QW [3 weeks on/1 week off]). Primary endpoints were PFS by blinded independent central review per RECIST version 1.1 and OS. One hundred four patients were randomized in Japan (data cutoff, October 26, 2020; median follow‐up, 11.8 [range, 1.1–26.9] months). Hazard ratios (HRs) for PFS with lenvatinib plus pembrolizumab versus TPC were 1.04 (95% CI, 0.63–1.73) in patients with pMMR and 0.81 (0.50–1.31) in all‐comers. Hazard ratios for OS were 0.74 (0.41–1.34) with pMMR and 0.59 (0.33–1.04) for all‐comers. Adverse events were manageable and led to discontinuation of one/both study drugs in 36.5% of patients in the lenvatinib plus pembrolizumab group versus 7.8% in the TPC group. Similar to the global Study 309/KEYNOTE‐775 results, this analysis suggested favorable efficacy and manageable safety with lenvatinib plus pembrolizumab after platinum‐based chemotherapy in Japanese patients with advanced endometrial cancer and supports this combination as a new standard of care in this population. [ABSTRACT FROM AUTHOR]

New treatments, particularly second‐line options, are needed to improve outcomes for patients with recurrent/metastatic cervical cancer (r/mCC). Tisotumab vedotin (TV) is an antibody–drug conjugate directed to tissue factor, a transmembrane protein commonly expressed in cancer cells, to deliver cytotoxic monomethyl auristatin E. This single‐arm, open‐label phase 1/2 trial evaluated the consistency of safety and efficacy outcomes of TV in Japanese patients with r/mCC to bridge the current findings with those reported in previous trials in non‐Japanese patients in the United States and Europe. In part 1 (dose escalation; N = 6), patients with advanced solid tumors received TV 1.5 or 2.0 mg/kg once every 3 weeks to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Part 2 (dose expansion; N = 17) evaluated the RP2D in r/mCC patients with 1–2 prior lines of therapy. In part 1, no dose‐limiting toxicities were observed, the MTD was not reached, and TV 2.0 mg/kg was established as the RP2D. In part 2, the most common treatment‐emergent adverse events were anemia (58.8%), nausea (58.8%), alopecia (47.1%), epistaxis (47.1%), and diarrhea (35.3%); adverse events of special interest were bleeding (76.5%), ocular events (35.3%), and peripheral neuropathy (17.6%), and were mostly grade 1/2. In part 2, confirmed objective response rate was 29.4%, median duration of response was 7.1 months, and median time to response was 1.2 months. In Japanese patients with r/mCC, TV demonstrated a manageable and tolerable safety, pharmacokinetics, and efficacy profile consistent with that observed in non‐Japanese patients. [ABSTRACT FROM AUTHOR]

In Japan, the National Immunization Program against human papillomavirus (HPV) targets girls aged 12‐16 years, and catch‐up vaccination is recommended for young women up to age 26 years. Because HPV infection rates increase soon after sexual debut, we evaluated HPV vaccine effectiveness by age at first vaccination. Along with vaccination history, HPV genotyping results from 5795 women younger than 40 years diagnosed with cervical intraepithelial neoplasia grade 2‐3 (CIN2‐3), adenocarcinoma in situ (AIS), or invasive cervical cancer were analyzed. The attribution of vaccine‐targeted types HPV16 or HPV18 to CIN2‐3/AIS was 47.0% for unvaccinated women (n = 4297), but 0.0%, 13.0%, 35.7%, and 39.6% for women vaccinated at ages 12‐15 years (n = 36), 16‐18 years (n = 23), 19–22 years (n = 14), and older than 22 years (n = 91), respectively, indicating the greater effectiveness of HPV vaccination among those initiating vaccination at age 18 years or younger (P <.001). This finding was supported by age at first sexual intercourse; among women with CIN2‐3/AIS, only 9.2% were sexually active by age 14 years, but the percentage quickly increased to 47.2% by age 16 and 77.1% by age 18. Additionally, the HPV16/18 prevalence in CIN2‐3/AIS was 0.0%, 12.5%, and 40.0% for women vaccinated before (n = 16), within 3 years (n = 8), and more than 3 years after (n = 15) first intercourse, respectively (P =.004). In conclusion, our data appear to support routine HPV vaccination for girls aged 12‐14 years and catch‐up vaccination for adolescents aged 18 years and younger in Japan. [ABSTRACT FROM AUTHOR]

Intestinal endometriosis is a benign disease characterized by ectopic growth of the endometrium and causes extensive fibrosis and adhesions in response to repeated episodes of bleeding and inflammation with the menstrual cycle. We encountered a rare case of intestinal endometriosis that caused complete rectal obstruction in a 34-year-old woman undergoing infertility treatment. Colonoscopy showed rectal stenosis and obstruction but no evidence of a tumor. Bowel obstruction due to endometriosis was diagnosed based on the history and imaging findings. Transanal decompression was performed. Subsequent laparoscopic surgery revealed severe inflammation around both ovaries and a tumor-like rectal stenosis. Similar findings were obtained in the transverse colon and terminal ileum. We performed laparoscopic low anterior resection, partial transverse colon resection, ileocecal resection, bilateral cystectomy, and left salpingectomy. Infertility treatment was restarted and resulted in a successful term pregnancy. The patient remains well. Laparoscopic surgery, which has the advantage of being minimally invasive, allows for early postoperative recovery and discharge in patients with endometriosis; furthermore, the uterus and adnexa can be preserved due to the magnifying effect of the laparoscope. In this case, it was possible to resume infertility treatment. Intestinal endometriosis is a rare cause of bowel obstruction, but should be kept in mind if intestinal obstruction occurs during infertility treatment. Laparoscopic surgery may be useful for multiple endometriotic lesions and serve as a bridge to infertility treatment. [ABSTRACT FROM AUTHOR]

Background: Advanced relapsed ovarian cancer has a poor prognosis, and treatment options are limited. Methods: This phase I trial investigated the dosage, safety, pharmacokinetics and efficacy of trabectedin plus pegylated liposomal doxorubicin (PLD) in Japanese patients with advanced relapsed ovarian, fallopian tube, or primary peritoneal cancer. Patients received trabectedin 0.9 or 1.1 mg/m2 immediately after PLD 30 mg/m2; both drugs were given by intravenous infusion. Treatment was repeated every 21 days until disease progression or unacceptable toxicity. The maximum tolerated dose (MTD) was determined in an initial dose escalation phase, and this was used in a subsequent safety assessment phase. Safety and tumor response were monitored throughout the trial, and drug concentrations for pharmacokinetic analysis were measured during cycle 1. Results: Eighteen patients were included. The MTD of trabectedin was determined as 1.1 mg/m2. Gastrointestinal adverse events were experienced by all patients, but were mostly grade 1 or 2 in intensity. Most patients had grade ≥ 3 elevations in transaminase levels or grade ≥ 3 reductions in neutrophil count, but these events were generally manageable through dose reduction and/or supportive therapies, as appropriate. There were no deaths during the trial. Trabectedin exposure increased in a dose-dependent manner. The overall response rate was 27.8%. Conclusions: Trabectedin, in combination with PLD, may have clinical benefits in Japanese patients with relapsed advanced ovarian cancer. The recommended dosage of trabectedin for further study in this population is 1.1 mg/m2 once every 21 days. Clinical trial registration number: JapicCTI-163164 [ABSTRACT FROM AUTHOR]

Background: This phase II study evaluated the efficacy and safety of docetaxel/carboplatin chemotherapy for treating patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix. Methods: A total of 50 patients with International Federation of Gynecology and Obstetrics stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix were enrolled and administered docetaxel at a dose of 60 mg/m2, followed by carboplatin at a dose based on the area under the receiver operating characteristic curve of 6. The treatments were repeated every 21 days until disease progression or unacceptable adverse events. Except for two patients, 48 were eligible for evaluation. Another patient withdrew consent before treatment; adverse events were evaluated in 47. Results: The response rate was 47.9% with 5 patients achieving complete response, 18 partial response, 14 stable disease, and 6 progressive disease. The disease control rate was 77.1%. With a median follow-up duration of 368 days, the median progression-free survival and overall survival were 6.1 months (95% CI 5.5–8.6) and 15.8 months (95% CI 18.2–28.3), respectively. The most frequent grade 3 and grade 4 hematological toxicity was neutropenia, with 38 patients (81%) having grade 4 and 4 (9%) having grade 3 neutropenia. The non-hematological toxicities were mainly grade 1 or 2 in severity. Conclusion: Docetaxel/carboplatin chemotherapy was effective, with a higher disease control rate and well-tolerated chemotherapeutic regimen for patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix. [ABSTRACT FROM AUTHOR]

Uterine carcinosarcoma (UCS) is an uncommon and highly aggressive tumor. There is no HER2 testing protocol for UCS despite the development of HER2 antibody conjugates. We aimed to elucidate histopathological HER2 expression details in UCS, to compare HER2 scores between ASCO/CAP criteria for gastric and breast cancer, and to propose requirements for HER2 testing for UCS. Eighty-nine specimens from 84 patients with metastatic/recurrent UCS were prospectively collected from May 2018 to July 2020. We performed HER2 immunohistochemistry (IHC) for 89 specimens and FISH for 44 specimens. HER2 expression details and HER2 score were evaluated according to the latest ASCO/CAP criteria for gastric (2016) and breast cancer (2018). HER2 IHC scores according to the gastric cancer criteria were 0 in 31 cases (35%), 1+ in 26 (29%), 2+ in 22 (25%), and 3+ in 10 cases (11%) of the 89 specimens. A lateral/basolateral membranous staining pattern was observed in 28/32 (88%) specimens with HER2 scores of 2+/3+. HER2 intratumoral heterogeneity was identified in 28/32 (88%) of the specimens with HER2 scores of 2+/3+. The overall concordance rate of HER2 score was 70% between the gastric and breast criteria. FISH revealed HER2 gene amplification in 10/44 (23%) specimens containing only lateral/basolateral membranous staining pattern. Based on the histopathological features of HER2 expression in UCS, a scoring system that accepts lateral/basolateral staining patterns should be applied. Furthermore, we proposed specific requirements for UCS testing, including specimen selection, scoring system, and calculating the proportion of HER2-positive cells. [ABSTRACT FROM AUTHOR]

Background: We proposed a novel treatment strategy, consisting of triweekly cisplatin plus dose-dense weekly paclitaxel before and after radical hysterectomy without adjuvant radiation therapy to treat locally advanced cervical cancer. However, cisplatin-related severe non-hematologic toxicities were frequent during this strategy. This study aimed to assess the applicability of replacing cisplatin with carboplatin in our proposed strategy. Methods: Women with International Federation of Gynecology and Obstetrics (FIGO) 2008 stage IB2, IIA2, or IIB cervical cancer received three cycles of carboplatin (based on an area under the curve of six), each 21 days apart, starting on day 1, and 80 mg/m2 of paclitaxel on days 1, 8, and 15 of each 21-day cycle before undergoing radical hysterectomy. Patients with one or more high-risk factors, including lymph vascular invasion, parametrial invasion, lymph-node metastasis, or positive margins, received three additional cycles of chemotherapy after hysterectomy. Concurrent chemoradiation therapy was only applied to those patients who failed to respond to neoadjuvant chemotherapy. Results: Between September 2014 and July 2016, 50 women (13 women with FIGO stage IB2, 5 with stage IIA2, and 32 with stage IIB) were enrolled in this study. The overall response rate to chemotherapy was 92%, including 22% with pathological complete response. Forty-nine women (98%) completed the planned radical hysterectomy, and 11 (22%) women with one or more high-risk factors received three additional cycles of chemotherapy. Only four women (8%) received concurrent chemoradiation therapy after surgery. The 2- and 3-year progression-free survival rates were 88.0% and 83.8%, respectively, and the 2- and 3-year overall survival rates were 98.0% and 95.4%, respectively. Only two patients reported grade 3 or higher non-hematologic toxicities including grade 3 nausea in one patient and grade 3 liver dysfunction in one patient. Conclusions: Replacement the platinum agent resulted in equivalent efficacy, with reduced toxicity, in women with locally advanced cervical cancer. This strategy could considerably diminish the application of radiation therapy without reduced survival. A study to identify those patients who will benefit from this new multidisciplinary strategy is warranted. [ABSTRACT FROM AUTHOR]

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012‐2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2‐3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type‐specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type‐specific RCs between CIN1 and CIN2‐3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type‐specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2‐3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2‐3/AIS, and 23.7% in ICC (P <.0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01‐4.98), followed by HPV31 (2.51, 1.54‐5.24), HPV18 (2.43, 1.59‐4.32), HPV35 (1.56, 0.43‐8.36), HPV33 (1.01, 0.49‐3.31), HPV52 (0.99, 0.76‐1.33), and HPV58 (0.97, 0.75‐1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71‐2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14‐0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9‐valent vaccine contributed to 89.7% (95% CI, 88.7‐90.7) of CIN2‐3/AIS and 93.8% (95% CI, 92.4‐95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9‐valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women. [ABSTRACT FROM AUTHOR]

Interim results from the two‐cohort, phase 2 KEYNOTE‐100 study (NCT02674061) of 376 patients with previously treated advanced recurrent ovarian cancer (ROC) showed that pembrolizumab monotherapy was associated with an objective response rate (ORR) of 8.0% (95% CI, 5.4‐11.2). We present outcomes for the Japanese patients (n = 21) enrolled in KEYNOTE‐100. Patients with epithelial ROC had received either 1‐3 prior chemotherapy lines and had platinum‐free interval or treatment‐free interval (PFI; TFI) of 3‐12 months (cohort A) or 4‐6 prior chemotherapy lines and had PFI/TFI of ≥3 months (cohort B). All patients received pembrolizumab 200 mg every 3 weeks as monotherapy for 2 years or until progression, death, unacceptable toxicity or consent withdrawal. Primary objectives were ORR per RECIST v1.1 for each cohort and higher programmed death ligand‐1 (PD‐L1) tumor expression. The relationship between PD‐L1 expression (measured as combined positive score [CPS]) and ORR was assessed. Twenty‐one Japanese patients (cohort A, n = 19; cohort B, n = 2) were treated. The median (range) age was 57 (37‐78) years; 19 (90.5%) patients had ECOG status of 0 and 16 (76.2%) patients had stage III‐IV disease. ORR was 19.0% (95% CI, 5.4‐41.9) and seemed to increase with increasing PD‐L1 expression. A total of 13 (61.9%) patients had treatment‐related adverse events (TRAE), and 5 (23.8%) had grade 3‐4 TRAE. There were no treatment‐related deaths in this subpopulation. Pembrolizumab monotherapy was associated with antitumor activity in Japanese patients with ROC, with no new safety signals identified in this subpopulation. The data suggested a trend toward higher PD‐L1 expression among some patients with higher ORR. [ABSTRACT FROM AUTHOR]

The aim of the present study was to explore the feasibility of using deep learning, such as artificial intelligence (AI), to classify cervical squamous epithelial lesions (SILs) from colposcopy images combined with human papilloma virus (HPV) types. Among 330 patients who underwent colposcopy and biopsy performed by gynecological oncologists, a total of 253 patients with confirmed HPV typing tests were enrolled in the present study. Of these patients, 210 were diagnosed with high-grade SIL (HSIL) and 43 were diagnosed with low-grade SIL (LSIL). An original AI classifier with a convolutional neural network catenating with an HPV tensor was developed and trained. The accuracy of the AI classifier and gynecological oncologists was 0.941 and 0.843, respectively. The AI classifier performed better compared with the oncologists, although not significantly. The sensitivity, specificity, positive predictive value, negative predictive value, Youden's J index and the area under the receiver-operating characteristic curve ± standard error for AI colposcopy combined with HPV types and pathological results were 0.956 (43/45), 0.833 (5/6), 0.977 (43/44), 0.714 (5/7), 0.789 and 0.963±0.026, respectively. Although further study is required, the clinical use of AI for the classification of HSIL/LSIL by both colposcopy and HPV type may be feasible. [ABSTRACT FROM AUTHOR]

The Japanese government began a human papillomavirus (HPV) vaccination program for girls aged 12‐16 years in 2010 but withdrew its recommendation in 2013 because of potential adverse effects, leading to drastically reduced vaccination uptake. To evaluate population‐level effects of HPV vaccination, women younger than 40 years of age newly diagnosed with cervical intraepithelial neoplasia grade 1‐3 (CIN1‐3), adenocarcinoma in situ (AIS), or invasive cervical cancer (ICC) have been registered at 21 participating institutes each year since 2012. A total of 7709 women were registered during 2012‐2017, of which 5045 were HPV genotyped. Declining trends in prevalence of vaccine types HPV16 and HPV18 during a 6‐year period were observed in CIN1 (50.0% to 0.0%, Ptrend < .0001) and CIN2‐3/AIS (83.3% to 45.0%, Ptrend = .07) only among women younger than 25 years of age. Overall, HPV vaccination reduced the proportion of HPV16/18‐attributable CIN2‐3/AIS from 47.7% to 33.0% (P = .003): from 43.5% to 12.5% as routine vaccination (P = .08) and from 47.8% to 36.7% as catch‐up vaccination (P = .04). The HPV16/18 prevalence in CIN2‐3/AIS cases was significantly reduced among female individuals who received their first vaccination at age 20 years or younger (P = .02). We could not evaluate vaccination effects on ICC owing to low incidence of ICC among women aged less than 25 years. We found HPV vaccination to be effective in protecting against HPV16/18‐positive CIN/AIS in Japan; however, our data did not support catch‐up vaccination for women older than 20 years. Older adolescents who skipped routine vaccination due to the government's suspension of its vaccine recommendation could benefit from receiving catch‐up vaccination before age 20 years. [ABSTRACT FROM AUTHOR]

The aim of the present study was to explore the feasibility of using deep learning as artificial intelligence (AI) to classify cervical squamous epithelial lesions (SIL) from colposcopy images. A total of 330 patients who underwent colposcopy and biopsy by gynecologic oncologists were enrolled in the current study. A total of 97 patients received a pathological diagnosis of low-grade SIL (LSIL) and 213 of high-grade SIL (HSIL). An original AI-classifier with 11 layers of the convolutional neural network was developed and trained. The accuracy, sensitivity, specificity and Youden's J index of the AI-classifier and oncologists for diagnosing HSIL were 0.823 and 0.797, 0.800 and 0.831, 0.882 and 0.773, and 0.682 and 0.604, respectively. The area under the receiver-operating characteristic curve was 0.826±0.052 (mean ± standard error), and the 95% confidence interval 0.721–0.928. The optimal cut-off point was 0.692. Cohen's Kappa coefficient for AI and colposcopy was 0.437 (P<0.0005). The AI-classifier performed better than oncologists, although not significantly. Although further study is required, the clinical use of AI for the classification of HSIL/LSIL from by colposcopy may be feasible. [ABSTRACT FROM AUTHOR]

Background: Taxane/platinum (TP)-based combination chemotherapy is standard for the treatment of metastatic or recurrent cervical cancer. The aim of this study was to investigate the efficacy of postoperative TP therapy in early stage cervical cancer.Methods: A retrospective review of patients with FIGO IB-IIB stage cervical cancer who were treated with radical hysterectomy and displayed surgical-pathological risk factors was performed. 122 patients were identified between 2003 and 2012. Survival was analyzed by Kaplan-Meier method and compared by the log-rank test. The Cox proportional hazards model was used to investigate predictors of survival.Results: The median follow-up period was 82.4 months. The postoperative adjuvant therapy was TP in 82 (67.2%) patients, other chemotherapies in 10 (8.2%), radiotherapy (RT) in 25 (20.5%), and no further therapy (NFT) in 5 (4.1%). Survival was analyzed using 4 subgroups according to the postoperative adjuvant therapy. The estimated 5-year overall survival was 95.1% in the TP group, 90.0% in the other chemotherapy group, 78.9% in the RT group, and 100% in the NFT group. No significant difference of survival was observed in the subgroups. However, when analyzing only patients who displayed high-risk factors, non-TP adjuvant therapy (including RT and other chemotherapies) was independently associated with shorter survival on multivariate analysis. In the TP group, multivariate analysis revealed that a positive surgical margin was a significant predictor of shorter survival.Conclusions: Postoperative TP is effective in patients with surgically treated early stage cervical cancer. In these populations, a positive surgical margin could be associated with poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Lynch syndrome is an autosomal dominant inherited disease caused by germline mutations in mismatch repair genes. Analysis for microsatellite instability (MSI) and immunohistochemistry (IHC) of protein expressions of disease-associated genes is used to screen for Lynch syndrome in endometrial cancer patients. When losses of both MLH1 and PMS2 proteins are observed by IHC, MLH1 promoter methylation analysis is conducted to distinguish Lynch syndrome-associated endometrial cancer from sporadic cancer.Case Presentation: Here we report a woman who developed endometrial cancer at the age of 49 years. She had a family history of colorectal cancer (first-degree relative aged 52 years) and stomach cancer (second-degree relative with the age of onset unknown). No other family history was present, and she failed to meet the Amsterdam II criteria for the diagnosis of Lynch syndrome. Losses of MLH1 and PMS2, but not MSH2 and MSH6, proteins were observed by IHC in endometrial cancer tissues. Because MLH1 promoter hypermethylation was detected in endometrial cancer tissue samples, the epigenetic silencing of MLH1 was suspected as the cause of the protein loss. However, because of the early onset of endometrial cancer and the positive family history, a diagnosis of Lynch syndrome was also suspected. Therefore, we provided her with genetic counseling. After obtaining her consent, MLH1 promoter methylation testing and genetic testing of peripheral blood were performed. MLH1 promoter methylation was not observed in peripheral blood. However, genetic testing revealed a large deletion of exon 5 in MLH1; thus, we diagnosed the presence of Lynch syndrome.Conclusions: Both MLH1 germline mutation and MLH1 promoter hypermethylation may be observed in endometrial cancer. Therefore, even if MLH1 promoter hypermethylation is detected, a diagnosis of Lynch syndrome cannot be excluded. [ABSTRACT FROM AUTHOR]

Objective Perifosine exhibits anti-tumor activity by inhibiting AKT phosphorylation. The purpose of this phase II basket trial was to evaluate the efficacy and safety of perifosine monotherapy for ovarian, endometrial, and cervical cancers. Methods Recurrent or persistent ovarian, endometrial, or cervical cancer patients were assigned to PIK3CA wild-type or mutant groups. Each patient received 600 mg oral perifosine on day 1 followed by a maintenance dose of 100 mg daily. The primary endpoint was disease control rate; secondary endpoints included response rate, progression-free survival, overall survival, and safety. Immunohistochemical staining and targeted sequencing were used to explore new biomarkers in such patients. Results Sixteen and 5 ovarian, 17 and 7 endometrial, and 18 and 8 cervical cancer patients with PIK3CA wild-type and mutant, respectively, were enrolled. Disease control rates (wild-type/mutant) were 12.5/40.0%, 47.1/14.3%, and 11.1/25.0% in ovarian, endometrial, and cervical cancer, respectively. The most common grade 3/4 toxicities were anemia (22.5%) and anorexia (11.3%). Immunohistochemical staining revealed that the disease control rate in patients with negative phosphatase and tensin homolog (PTEN) expression was 50.0%, and the odds ratio of positive to negative patients was 0.24 in all patients. Conclusions Perifosine monotherapy showed good tolerability but expected efficacy was not achieved. Modest efficacy was demonstrated in ovarian cancer patients with PIK3CA mutations and endometrial cancer patients with PIK3CA wild-type; no difference was observed between PIK3CA wild-type and mutant in cervical cancer. Absence of PTEN expression may be predictive of clinical efficacy with perifosine monotherapy. [ABSTRACT FROM AUTHOR]

Background: Ovarian clear cell carcinoma (OCCC) is mostly resistant to standard chemotherapy that results in poor patient survival. To understand the genetic background of these tumours, we performed whole-genome sequencing of OCCC tumours.Methods: Tumour tissue samples and matched blood samples were obtained from 55 Japanese women diagnosed with OCCC. Whole-genome sequencing was performed using the Illumina HiSeq platform according to standard protocols.Results: Alterations to the switch/sucrose non-fermentable (SWI/SNF) subunit, the phosphatidylinositol-3-kinase (PI3K)/Akt signalling pathway, and the receptor tyrosine kinase (RTK)/Ras signalling pathway were found in 51%, 42%, and 29% of OCCC tumours, respectively. The 3-year overall survival (OS) rate for patients with an activated PI3K/Akt signalling pathway was significantly higher than that for those with inactive pathway (91 vs 40%, hazard ratio 0.24 (95% confidence interval (CI) 0.10-0.56), P=0.0010). Similarly, the OS was significantly higher in patients with the activated RTK/Ras signalling pathway than in those with the inactive pathway (91 vs 53%, hazard ratio 0.35 (95% CI 0.13-0.94), P=0.0373). Multivariable analysis revealed that activation of the PI3K/Akt and RTK/Ras signalling pathways was an independent prognostic factor for patients with OCCC.Conclusions: The PI3K/Akt and RTK/Ras signalling pathways may be potential prognostic biomarkers for OCCC patients. Furthermore, our whole-genome sequencing data highlight important pathways for molecular and biological characterisations and potential therapeutic targeting in OCCC. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the outcome and safety of the multidisciplinary strategy using cisplatin plus dose-dense paclitaxel (dose-dense TP) before and after radical hysterectomy (RH) for stage IB2, IIA2, or IIB patients with cervical cancer. In the dose-finding phase, 12 patients received 3 cycles of cisplatin (75 mg/m2, day 1) with paclitaxel (70 or 80 mg/m2, days 1, 8, and 15) every 21 days as neoadjuvant chemotherapy (NAC). In the phase II study, 51 patients received 3 cycles of dose-dense TP at the recommended dose as NAC, and another 2 cycles of the same regimen after RH. The primary endpoint was 2-year progression-free survival (PFS). The secondary endpoints were 2-year overall survival (OS), adverse events (AEs), response rate (RR), and pathological complete response (pCR) rates. The recommended dose of paclitaxel at dose-finding phase was 80 mg/m2. In the phase II study, 34 patients (66.7%) had FIGO stage IIB disease. The RR and pCR rates were 94 and 28%. With a median follow-up duration of 58 months, each of the 2- and 5-year PFS rates was 88.2%, the 2- and 5-year OS rates were 94.1 and 88.2%, respectively. The incidence of grade 3/4 AEs was neutropenia (34%), nausea (12%), appetite loss (10%), fatigue (6%), and anemia (6%). Febrile neutropenia was uncommon (2%). Dose-dense TP before and after RH achieved a good long-term survival and was feasible for patients with locally advanced cervical cancer. [ABSTRACT FROM AUTHOR]

Background: It is not known whether radiotherapy or surgery is better as initial treatment for locally advanced mucinous adenocarcinoma of the uterine cervix. Methods: We reviewed the medical records and pathological materials of 32 patients with International Federation of Gynecology and Obstetrics stage IB2-IIB mucinous adenocarcinoma, who had undergone radiotherapy or radical hysterectomy as primary treatment between 2001 and 2010. p16 immunohistochemistry was performed as a marker for human papillomavirus-related adenocarcinoma. Results: Thirteen patients received radiotherapy and 19 patients underwent radical hysterectomy. The cumulative 3-year locoregional control rates in the radical hysterectomy and radiotherapy groups were 79.0 and 46.2 % ( P = 0.03), and 5-year overall survival rates were 70.7 and 38.5 % ( P = 0.09), respectively. Of patients with p16-positive tumors ( n = 19), the cumulative 3-year locoregional control rates in the radical hysterectomy and radiotherapy groups were 100 and 60.0 % ( P = 0.01), and 5-year overall survival rates were 88.9 and 40.0 % ( P = 0.04), respectively. Conversely, the cumulative 3-year locoregional control rates in the human papillomavirus-negative radical hysterectomy group and radiotherapy group were 20.0 and 37.5 % ( P = 0.66), and 5-year overall survival rates were 20.0 and 37.5 % ( P = 0.60), respectively. Conclusions: Radical hysterectomy may significantly improve locoregional control and overall survival compared with radiotherapy for stage IB2-IIB mucinous adenocarcinoma patients, especially those with p16-positive mucinous adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Uterine carcinosarcomas (UCSs) are rare and aggressive tumors. The prognostic factors are not sufficiently known. Methods: We performed a multi-institutional, retrospective study of women with stage I-IV UCS, diagnosed between 2007 and 2012. Data obtained from medical records included demographic, clinicopathological, treatment, and outcome information. Results: A total of 486 patients (median age 65 years) were identified-224 (46 %) were stage I, 32 (7 %) were stage II, 139 (28 %) were stage III, and 91 (19 %) were stage IV. Among them, 277 (57 %) had disease recurrence. Median disease-free survival (DFS) was 16.4 months [95 % confidence interval (CI) 15.7-27.2], and median overall survival (OS) was 72.0 months (95 % CI 43.0-not reached). In total, 454 (94 %) patients received adjuvant treatment, and 440 (91 %) received adjuvant chemotherapy. In multivariate analysis, stage III-IV disease, CA-125 level, and lymphovascular space invasion (LVSI) were significantly associated with shorter median DFS. Stage III-IV disease, performance status 2-4, ≥50 % myometrial invasion depth, and postsurgical residual tumor size >1 cm were significantly associated with shorter median OS. Conversely, pelvic lymph node lymphadenectomy was associated with improved DFS and OS. Conclusions: Stage, performance status, CA-125 level, LVSI, and myometrial invasion were associated with poor prognoses. Pelvic lymphadenectomy was associated with improved survival, and may be necessary for the surgical management of UCS. [ABSTRACT FROM AUTHOR]

Background: The present study investigates the usefulness of 18F-FDG-PET/CT (PET/CT) in distinguishing between benign and malignant ovarian teratomas. Methods: This study includes 4 mature teratomas (MTs) with malignant transformation, 8 immature teratomas (ITs), and 16 MTs that were diagnosed after surgical resection. Preoperative tumor marker values, MRI findings, PET/CT SUVmax values, and other clinical parameters were retrospectively compared with those of 14 patients who had MTs. Results: The median CA125 was significantly higher for ITs than for MTs ( P = 0.04). The median AFP was significantly higher for ITs than for MTs ( P = 0.0034). The median SUVmax values for MTs with malignant transformation, ITs, and MTs were 18.3 (5.3-23.3), 6.0 (3.6-22.6), and 1.1 (1.0-15.5), respectively. SUVmax was significantly higher in MTs with malignant transformation and ITs than in MTs ( P = 0.004, P = 0.0007). With a cut-off SUVmax of 3.6 to distinguish between benign and malignant MTs, sensitivity was 100 %, specificity was 81 %, positive predictive value was 80 %, negative predictive value was 100 %, and diagnostic accuracy was 89 % (AUC 0.94). However, one patient with an MT had a high SUVmax corresponding to values in the central nervous system (CNS). Conclusions: 18F-FDG-PET/CT has a high diagnostic accuracy in distinguishing between benign and malignant ovarian teratomas. Thus, PET/CT may be useful in cases where the diagnosis is unclear on MRI and other clinical findings. However, some MTs with abundant CNS tissue may have a high SUVmax. Therefore, the diagnosis of a benign or malignant lesion should be made carefully in conjunction with other clinical findings. [ABSTRACT FROM AUTHOR]

Background: This survey sought to determine Japanese gynecologists' attitudes concerning administering hormone replacement therapy (HRT) for patients after surgery for endometrial cancer (EC). Methods: Eight hundred and eighty-eight members of the Japanese Gynecologic Oncology Group (JGOG) were asked to respond to an anonymous questionnaire on the JGOG website. The survey asked whether or not HRT was to be administered when surgery was performed (including a hysterectomy and bilateral oophorectomy) to treat EC before or after menopause. If HRT was not to be administered, respondents were asked the reason why. Respondents were presented with the same hypothetical patients that were featured in a previous survey in Germany, and differences in the mindsets of Japanese and German physicians were compared. Results: Responses from 363 individuals (response rate 40.9 %) were analyzed. Seventy-eight percent of physicians considered HRT for patients undergoing surgery before menopause. The most prevalent reason of refusal to prescribe HRT was the risk of EC recurrence. Forty-eight percent of physicians considered HRT for patients undergoing surgery after menopause. The most prevalent reasons of refusal of HRT were its limited benefit and the availability of alternative therapies. Sixty-five percent of Japanese physicians responded that they would administer HRT to patients with low risk of recurrence vs. 46 % of physicians in Germany ( P < 0.0002). Forty-nine percent of Japanese physicians approved of prescribing HRT for patients with high risk of recurrence vs. 25 % of physicians in Germany ( P < 0.0001). Conclusion: Many Japanese gynecologists have a favorable attitude toward prescribing HRT after treatment of EC. [ABSTRACT FROM AUTHOR]

Background and Aim Colorectal endoscopic submucosal dissection ( ESD) is a useful treatment method; however, no index has been established for time for patient to start food ingestion or be discharged after ESD. We investigated the potential of a clinical pathway in which patients started food ingestion on day 2 after ESD and were discharged on day 3. Methods A total of 382 patients underwent colorectal ESD between 2006 and 2012. A flow chart of a clinical pathway was prepared based on the data obtained, with the aim of shortening hospital stay after ESD. Results Mean duration of postoperative hospital stay in the 382 patients was 5.3 ± 1.8 days. The most common cause of extended hospital stay was abnormal blood test finding, as detected in 50 patients in group C ( n = 131; 38.2%), followed by careful course observations, as noted in 48 patients in group C ( n = 131; 36.6%). Regarding procedural accidents as a result of ESD, intraoperative perforation occurred in 15 patients (3.9%) and post- ESD bleeding in seven patients (1.8%), which extended the hospital stay. Food ingestion was started on day 2 when no abnormality was noted during ESD or in physical and imaging findings or blood tests on day 1. In the 86 patients who underwent the prepared clinical pathway as a validation study, 68 (79.0%) were discharged on day 3. Duration of postoperative hospital stay was 3.4 ± 1.2 days. Conclusion Discharge may be possible 3 days after ESD when no abnormalities are noted during ESD or on post- ESD day 1. [ABSTRACT FROM AUTHOR]

Background: The therapeutic value of systematic lymphadenectomy for early-stage epithelial ovarian cancer (EOC) is controversial. This study evaluates the survival impact and adverse events of systematic pelvic and para-aortic lymphadenectomy in patients with pT1 and pT2 EOC. Methods: A retrospective investigation was performed using data from patients with pT1 and pT2 EOC at multi-institutions belonging to the Sankai Gynecologic Study Group (SGSG). We selected patients who had undergone systematic pelvic and para-aortic lymphadenectomy (Group LA) ( n = 284) and patients who had not undergone lymph node resection (Group no-LA) ( n = 138). Outcomes for patients and peri-operative adverse events were compared between the two groups. Results: The median operation time was significantly longer in Group LA (288 min) than in Group no-LA (128 min) ( P < 0.0001). Total blood loss was significantly higher in Group LA, 43.7 % of patients receiving blood transfusions. There were no significant differences between the treatment groups for progression-free survival (PFS) or overall survival (OS). However, for patients with pT2, PFS was significantly longer in Group LA than in Group no-LA ( P = 0.0150). Lymph node metastases were detected in 23 cases (8.1 %) and these patients had significantly shorter PFS than those without metastasis ( P = 0.0409). The outcome for patients who underwent chemotherapy after surgery was significantly improved in the Group no-LA, but no improvement was observed in Group LA. Conclusions: Systematic lymphadenectomy may improve outcomes only in pT2 EOC patients with acceptable peri-operative events. Furthermore, accurate surgical staging may avoid unnecessary adjuvant chemotherapy in selected early-stage cases. [ABSTRACT FROM AUTHOR]

Since the human papillomavirus (HPV) vaccination program for Japanese girls aged 12–16 years began in 2010, vaccination uptake has been low in women born before 1993 but high (approximately 70%) in those born during 1994–1999. We previously compared the prevalence of vaccine types HPV16 and HPV18 in cervical intraepithelial neoplasia grade 1–3 (CIN1–3) or adenocarcinoma in situ (AIS) between vaccinated and unvaccinated cohorts and found direct protection effects among vaccinated women in Japan. In this study, we focused on changes in HPV16/18 prevalence among "unvaccinated" cohorts with CIN/AIS. We analyzed HPV16/18 prevalence among 5051 unvaccinated women aged <40 years, newly diagnosed with CIN/AIS during 2012–2021 for time trends. Declining trends in HPV16/18 prevalence over 9 years were observed in CIN1 (36.0–10.0%, Ptrend = 0.03) and CIN2–3/AIS (62.5–36.4%, Ptrend = 0.07) among women aged <25 years. HPV16/18 prevalence in CIN1 and CIN2–3/AIS diagnosed at age 20–24 years was lower in 1994–1999 birth cohorts compared with 1988–1993 birth cohorts (4.5% vs. 25.7% for CIN1 and 40.0% vs. 58.1% for CIN2–3/AIS, both p = 0.04). Significant reduction in HPV16/18 prevalence among young unvaccinated women with CIN1 and CIN2–3/AIS suggests herd effects of HPV vaccination in Japan. [ABSTRACT FROM AUTHOR]

Since superior mesenteric vein thrombosis (SMVT) is a relatively rare disease and shows no specific symptom, its diagnosis tends to be delayed. In this report, we present a patient in whom acute appendicitis was complicated by SMVT and portal vein thrombosis (PVT). A definitive diagnosis could be made by abdominal contrast-enhanced CT, and acute appendicitis was surgically treated. Anticoagulant therapy was continued for about half a year after surgery. Abdominal contrast-enhanced CT after discharge showed no recurrence of SMVT or PVT. We consider that acute appendicitis induced SMVT or PVT caused by the effect of inflammation. There is the possibility that these conditions lead to intestinal congestion or necrosis and liver dysfunction; appropriate diagnosis and treatment are necessary. [ABSTRACT FROM AUTHOR]

Ferritin-binding proteins circulating in mammalian blood are thought to be involved in the clearance of ferritin. The present study characterizes canine serum autoantibodies (IgM and IgA) that react with ferritin. Canine IgM and IgA bound to bovine spleen ferritin as well as canine liver ferritin. To examine the specificity of canine IgM and IgA to ferritin H and L subunits, we used canine heart ferritin and canine liver ferritin with H/L subunit ratios of 3.69 and 0.43, respectively. Canine IgM and IgA recognized both of the H- and L-subunit-rich isoferritins, showing that their binding activities to ferritin depend on the H-subunit content. Recombinant bovine H-chain ferritin homopolymer expressed in a baculovirus expression system bound more with IgM and IgA than the recombinant L-chain homopolymer expressed under the same conditions. These results suggest that canine IgM and IgA recognize H-subunit-rich isoferritins, and that H-subunit-rich isoferritins are cleared from the circulation more rapidly than L-subunit-rich isoferritins. [ABSTRACT FROM AUTHOR]

Background: To examine trends in the clinicopathological characteristics of vulvar cancer in Japan. Methods: This is a nationwide retrospective study examining consecutive women with vulvar cancer between 2001 and 2010 in Japan (n = 1061). Temporal trends in demographics, tumor characteristics, and survival were assessed by cohort-level analysis. The National Cancer Institute's Surveillance, Epidemiology, and End Result Program was used for external validation (n = 10,154). Results: The number of oldest-old women aged ≥80 years significantly increased (from 18.0% in 2001 to 30.6% in 2010; 70.5% relative increase) in the study period. A stage shift was observed, with stage I disease decreasing from 43.0% to 34.0% (21.0% relative decrease), and tumors with distant metastases increasing from 23.2% to 35.6% (53.3% relative increase, p < 0.05). The number of women who underwent surgical treatment decreased from 84.0% to 69.7% (17.0% relative decrease), whereas utilization of radiotherapy increased from 34.4% to 43.2% (25.7% relative increase) over time (p < 0.05). In the cohort-level analysis, the five-year survival rates significantly decreased from 2001 to 2010 (p < 0.05), specifically, 66.9% to 51.0% for progression-free survival (23.7% relative decrease), 79.5% to 67.9% for cause-specific survival (14.6% relative decrease), and 74.9% to 62.3% for overall survival (16.9% relative decrease). In the patient-level analysis, oldest-old women were less likely to undergo surgical treatment and were independently associated with decreased survival (p < 0.05). In the US cohort, the number of oldest-old women (25.2% to 27.8%) and the five-year cause-specific survival rate (81.8% to 79.9%) remained unchanged during the study period (p > 0.05). Conclusion: Demographics and outcomes of vulvar cancer in Japan significantly changed during the study period. An increasing oldest-old population and a stage shift to more metastatic disease resulted in a cohort-level decrease in survival rates. [ABSTRACT FROM AUTHOR]

A letter to the editor on acantholytic squamous cell carcinoma of the uterine cervix is presented.