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1.
Artigo em Inglês | MEDLINE | ID: mdl-32007268

RESUMO

Neuroendocrine carcinoma of small cell type (SCNEC) is a rare pathological subtype in cervical cancer, which has a worse prognosis than other histological cell types. Due to its low incidence and the lack of experimental platforms, the molecular characteristics of SCNEC in the cervix remain largely unknown. Using the cancer tissue-originated spheroid (CTOS) method-an ex vivo 3D culture system that preserves the differentiation status of the original tumors-we established a panel of CTOS lines of SCNEC. We demonstrated that xenograft tumors and CTOSs, respectively, exhibited substantial intra-tumor and intra-CTOS variation in the expression levels of chromogranin A (CHGA), a neuroendocrine tumor marker. Since hypoxia affects differentiation in various tumors and in stem cells, we also investigated how hypoxia affected neuroendocrine differentiation of SCNEC of the uterine cervix. In the CTOS line cerv21, hypoxia suppressed expression of the neuroendocrine markers CHGA and synaptophysin (SYP). Flow cytometry analysis using CD99 (a membrane protein marker of SCNEC) revealed decreased CD99 expression in a subset of cells under hypoxic conditions. These expression changes were attenuated by HIF-1α knockdown, and by a Notch inhibitor, suggesting that these molecules played a role in the regulation of neuroendocrine differentiation. The examined SCNEC markers were suppressed under hypoxia in multiple CTOS lines. Overall, our present results indicated that neuroendocrine differentiation in SCNEC of the uterus is a variable phenotype, and that hypoxia may be one of the factors regulating the differentiation status.

2.
Int Immunol ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32009163

RESUMO

Persistent exposure to tumor antigens results in exhausted tumor-infiltrating T cells (TILs) that express the immune checkpoint molecules, PD-1 and Tim3, and lack anti-tumor immunity. To examine the exhausted status of TILs in ovarian cancer, the potential for cytokine production, proliferation, and cytotoxicity by purified PD-1+ Tim3+ CD8 TILs was assessed. The production of IFN-γ and TNF-α by PD-1+ Tim3+ CD8 TILs remained the same in an intracellular cytokine staining assay and was higher in a cytokine catch assay than that by PD-1- Tim3- and PD-1+ Tim3- CD8 TILs. %Ki67+ was higher in PD-1+ Tim3+ CD8 TILs than in PD-1- Tim3- CD8 TILs. However, patients with high PD-1+ Tim3+ CD8 TILs had a poor prognosis. The potential for cytotoxicity was then examined. %Perforin+ and %granzyme B+ were lower in PD-1+ Tim3+ CD8 TILs than in PD-1- Tim3- and PD-1+ Tim3- CD8 TILs. To observe the potential for direct cytotoxicity by T cells, a target cell line expressing membrane-bound anti-CD3scFv was newly established and a cytotoxic assay targeting these cells was performed. The cytotoxicity of PD-1+ Tim3+ CD8 TILs was significantly lower than that of PD-1- Tim3- and PD-1+ Tim3- CD8 TILs. Even though PD-1+ Tim3+ CD8 TILs in ovarian cancer showed a sustained potential for cytokine production and proliferation, cytotoxicity was markedly impaired, which may contribute to the poor prognosis of patients with ovarian cancer. Among the impaired functions of exhausted TILs, cytotoxicity may be an essential target for cancer immunotherapy.

3.
Gynecol Oncol ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31983515

RESUMO

OBJECTIVE: Uterine leiomyosarcoma (uLMS) is a rare gynecologic malignancy for which the currently available treatments do not consistently provide long-term disease control. This study aimed to reveal the current clinical status of uLMS to support future clinical trials. METHODS: This study enrolled patients with uLMS treated at 53 Japanese institutions from 2000 to 2012. Central pathological review (CPR) was performed. All cases were confirmed by CPR, and epidemiological features, treatment, and prognosis were analyzed statistically. RESULTS: A total of 307 patients were enrolled. A diagnosis of uLMS was confirmed in 266 patients (86.6%) of patients after CPR, of whom data for 259 were analyzed. Of these, 186 (71.8%) patients underwent complete gross resection as primary therapy. Ninety-eight patients received no additional adjuvant therapy, while docetaxel and gemcitabine was the most frequent regimen among 155 patients treated with adjuvant chemotherapy. In all cases, the median overall survival (OS) was 44.2 months. Multivariate analyses of prognostic factors in all cases identified stage III and IV disease, high serum lactate dehydrogenase level, and menopausal status as poor prognostic factors. However, in stage I cases, high serum lactate dehydrogenase level and no adjuvant treatment were identified as poor prognostic factors. The 5-year OS of patients with stage I uLMS treated with adjuvant chemotherapy was significantly better than that of those without adjuvant treatment (67.8% vs 46.7%, P = 0.0461). CONCLUSIONS: Despite complete removal of the primary lesion, the clinical course of patients with uLMS was poor due to recurrence of distant metastasis. The application of a suitable biomarker and effective adjuvant chemotherapy are required to improve the prognosis of patients with uLMS.

4.
Hum Vaccin Immunother ; : 1-6, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31944155

RESUMO

In Japan, the governmental recommendation for HPV vaccination was suspended in June 2013 because of media reports of so-called adverse vaccine events. The HPV vaccination rate in Japan prior to this suspension was almost 70%, but fell afterward to almost zero. To explore ways to bolster HPV vaccination, between 2014 and 2019 we conducted three serial surveys of the opinions of obstetricians and gynecologists about HPV vaccination. This study aimed to discuss the changing attitudes found in this 5-year follow-up survey. In August 2014, January 2017, and June 2019, we posted questionnaires to about 570 obstetricians and gynecologists practicing in Osaka, Japan. All three surveys used the same structured and closed-ended questionnaire, including questions about their personal opinions regarding HPV vaccination. We compared our new results to those of the previous two surveys. The response rate for the latest survey was 51.1% (293/573), which was equivalent to the previous two surveys. Among the responders, 83.3% (244/293) now thought that the Japanese government should restart its HPV vaccine recommendation, and 84.6% (248/293) were already recommending HPV vaccines for teenagers in their daily care. Eleven of 30 doctors (36.7%) had their own teenage daughters vaccinated against HPV after the suspension of recommendation. The rate has maintained an increasing trend from the previous two surveys. This study indicated that the attitude of obstetricians and gynecologists in Japan toward HPV vaccination has changed positively over 5 years. The results should serve as an encouragement to resume the governmental recommendation of HPV vaccines.

5.
Am J Obstet Gynecol ; 222(1): 64.e1-64.e16, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31351063

RESUMO

BACKGROUND: Multidrug resistance is a major concern in uterine leiomyosarcoma treatment. Development of effective chemotherapies and management of drug resistance in patients is necessary. The copper efflux transporter adenosine triphosphatase copper transporting beta is a member of the P-type adenosine triphosphatase family and is also known as a strong platinum efflux transporter. Various reports have shown the association between adenosine triphosphatase copper transporting beta and platinum resistance; however, suitable inhibitors or methods for inhibiting platinum efflux via adenosine triphosphatase copper transporting beta are not developed. OBJECTIVE: Our study focused on platinum resistance in uterine leiomyosarcoma. The role of adenosine triphosphatase copper transporting beta in uterine leiomyosarcoma resistance to platinum drugs was investigated both in vitro and in vivo. STUDY DESIGN: Adenosine triphosphatase copper transporting beta expression was investigated by Western blotting and the efficacy of copper sulfate pretreatment and cisplatin administration in adenosine triphosphatase copper transporting beta-expressing cells was investigated both in vitro and in vivo. RESULTS: Western blot analysis of SK-LMS-1 cells (uterine leiomyosarcoma cell line) revealed strong adenosine triphosphatase copper transporting beta expression. A permanent SK-LMS-ATPase copper transporting beta-suppressed cell line (SK-LMS-7B cells) was generated, and cisplatin exhibited a significant antitumor effect in SK-LMS-7B cells, both in vitro (SK-LMS-1 cells, half-maximal inhibitory concentration, 17.2 µM; SK-LMS-7B cells, half-maximal inhibitory concentration, 4.2 µM, P < .01) and in xenografts compared with that in SK-LMS-1 cells (5.8% vs 62.8%, P < .01). Copper sulfate was identified as a preferential inhibitor of platinum efflux via adenosine triphosphatase copper transporting beta. In SK-LMS-1 cells pretreated with 15 µM copper sulfate for 3 hours, the cisplatin half-maximal inhibitory concentration decreased significantly compared with that in untreated cells and resulted in significantly increased intracellular platinum accumulation (1.9 pg/cell vs 8.6 pg/cell, P < .01). The combination of copper sulfate pretreatment with cisplatin administration was also effective in vivo and caused cisplatin to exhibit significantly increased antitumor effects in mice with SK-LMS-1 xenografts (3.1% vs 62.7%, P < .01). CONCLUSION: Our study demonstrates that adenosine triphosphatase copper transporting beta is overexpressed in uterine leiomyosarcoma cells and that copper sulfate, which acts as an inhibitor of platinum efflux via adenosine triphosphatase copper transporting beta, may be a therapeutic agent in the treatment of uterine leiomyosarcoma.

6.
Nature ; 577(7789): 260-265, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31853061

RESUMO

Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer1-3. However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGR and HNRNPF genes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals. Mutational profiles vary substantially between colitis-associated cancer and non-dysplastic tissues in ulcerative colitis, which indicates that there are distinct mechanisms of positive selection in both tissues. In particular, mutations in NFKBIZ are highly prevalent in the epithelium of patients with ulcerative colitis but rarely found in both sporadic and colitis-associated cancer, indicating that NFKBIZ-mutant cells are selected against during colorectal carcinogenesis. In further support of this negative selection, we found that tumour formation was significantly attenuated in Nfkbiz-mutant mice and cell competition was compromised by disruption of NFKBIZ in human colorectal cancer cells. Our results highlight common and discrete mechanisms of clonal selection in inflammatory tissues, which reveal unexpected cancer vulnerabilities that could potentially be exploited for therapeutics in colorectal cancer.

7.
Eur J Hum Genet ; 28(1): 95-107, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31488892

RESUMO

We performed genome-wide association studies of five gynecologic diseases using data of 46,837 subjects (5236 uterine fibroid, 645 endometriosis, 647 ovarian cancer (OC), 909 uterine endometrial cancer (UEC), and 538 uterine cervical cancer (UCC) cases allowing overlaps, and 39,556 shared female controls) from Biobank Japan Project. We used the population-specific imputation reference panel (n = 3541), yielding 7,645,193 imputed variants. Analyses performed under logistic model, linear mixed model, and model incorporating correlations identified nine significant associations with three gynecologic diseases including four novel findings (rs79219469:C > T, LINC02183, P = 3.3 × 10-8 and rs567534295:C > T, BRCA1, P = 3.1 × 10-8 with OC, rs150806792:C > T, INS-IGF2, P = 4.9 × 10-8 and rs140991990:A > G, SOX9, P = 3.3 × 10-8 with UCC). Random-effect meta-analysis of the five GWASs correcting for the overlapping subjects suggested one novel shared risk locus (rs937380553:A > G, LOC730100, P = 2.0 × 10-8). Reverse regression analysis identified three additional novel associations (rs73494486:C > T, GABBR2, P = 4.8 × 10-8, rs145152209:A > G, SH3GL3/BNC1, P = 3.3 × 10-8, and rs147427629:G > A, LOC107985484, P = 3.8 × 10-8). Estimated heritability ranged from 0.026 for OC to 0.220 for endometriosis. Genetic correlations were relatively strong between OC and UEC, endometriosis and OC, and uterine fibroid and OC (rg > 0.79) compared with relatively weak correlations between UCC and the other four (rg = -0.08 ~ 0.25). We successfully identified genetic associations with gynecologic diseases in the Japanese population. Shared genetic effects among multiple related diseases may help understanding the pathophysiology.

8.
J Clin Med ; 8(12)2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31817169

RESUMO

: We aimed to identify a magnetic resonance imaging (MRI) feature that can predict posterior extrauterine adhesion (posterior adhesion) antenatally, in patients with placenta previa. We retrospectively reviewed patients with placenta previa who underwent a preoperative MRI examination of placenta accreta spectrum. We categorized the patients into two groups based on whether the cervix was anterior or posterior to a line perpendicular to the anatomical conjugate on the MRI. We projected the perpendicular line toward a straight line through the broad of the back on T2-weighted sagittal MRI images and measured the angle between this line and the line passing through the cervical canal. We analyzed the correlation of the cervical canal angle with the presence of posterior adhesions. Of the 96 patients analyzed, 71 patients had an anteverted cervix and 25 patients had a retroverted cervix. There were 21 posterior adhesions. The adhesion rate was significantly higher in patients with a retroverted cervix than those with an anteverted cervix (8.5% vs. 60%; p = 0.00). The cervical canal angle was ≤10° in 25 patients; of these 17 had adhesions (sensitivity, 81.0%; specificity, 89.3%; area under the curve, 0.887; 95% confidence interval, 0.792-0.981). This finding, labeled "positive horizontal cervix sign," may be a promising indicator of posterior adhesions in patients with placenta previa.

9.
BMC Pregnancy Childbirth ; 19(1): 425, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747899

RESUMO

BACKGROUND: Endometrial carcinoma (EC) is rarely diagnosed during pregnancy. Therefore, the histopathological findings, clinical course, and gross appearance of the resected uterus during pregnancy are not well known. We present a case of EC diagnosed during pregnancy. In addition, we reviewed the literature dating from January 1995 to March 2019 for cases of EC diagnosed during pregnancy and within 15 months after pregnancy, and we discussed this topic to improve the understanding of this rare condition. CASE PRESENTATION: A 35-year-old woman underwent an urgent cesarean delivery in gestational week 35 due to antepartum bleeding caused by placenta previa. Hysterectomy was performed with the diagnosis of placenta accreta spectrum (PAS). Remarkably, the postoperative gross and histopathological examinations revealed an endometrioid adenocarcinoma (grade 1). The histopathological findings revealed a pattern similar to that of EC not related with pregnancy. Immunohistochemistry revealed an overexpression of the estrogen and progesterone receptors; however, the p53 expression was negative. We performed laparoscopic bilateral salpingo-oophorectomy and pelvic lymphadenectomy 102 days after the cesarean hysterectomy, and confirmed surgical stage IA without metastases. Our patient has had no recurrence in 4 years after the cesarean delivery. An electronic search of the literature revealed 25 cases of EC (including our case) diagnosed during or after pregnancy. Sixteen of the 25 patients were diagnosed after abortions in the first trimester, 9 were diagnosed within 14 months of childbirth, and our case was the first with diagnosis from a surgical specimen of peripartum hysterectomy due to the PAS. In 23 of the 25 cases endometrioid adenocarcinoma grade 1 to 2 was found, and it seemed to have a good prognosis. CONCLUSION: The present findings suggest that careful examination of a resected uterus is essential, even when surgery is performed for an obstetric indication. Our case is an extremely rare case of EC during pregnancy; the histopathological pattern was similar to that of typical EC, and no recurrence was noted. The high levels of estrogen and progesterone during pregnancy did not seem to promote tumor progression in our case.

10.
World J Surg Oncol ; 17(1): 166, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590673

RESUMO

BACKGROUND: The coexistence of hematological malignancy with endometrial cancer is a rare phenomenon. We report a case of coexistence of endometrial cancer with follicular lymphoma which we suspected preoperatively and diagnosed during surgery by a multidisciplinary intraoperative assessment. CASE PRESENTATION: A 67-year-old woman was referred to our hospital due to a suspicion of an endometrial cancer. Endometrial biopsy revealed grade 1 endometrioid adenocarcinoma. MRI showed invasion of the tumor into the outer half of the myometrium, and abdominal CT showed para-aortic and atypical mesentery lymphadenopathy which was suspected to be metastasis of endometrial cancer or malignant lymphoma. Abdominal hysterectomy with bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, partial omentectomy, and mesentery lymph node biopsy for endometrial cancer were performed. The mesentery and para-aortic lymph nodes that were sent for frozen section analysis showed no metastasis of the endometrial cancer. We simultaneously conducted an unusual intraoperative emergent four-color flow cytometry and intraoperatively diagnosed a B cell lymphoma in the mesenteric lymph nodes. Because this multidisciplinary assessment, we were able to avoid an unnecessary intestinal resection. The final pathological diagnosis was an endometrioid carcinoma (G1, FIGO stage IA), with a synchronous follicular lymphoma. CONCLUSION: Although a rare event in endometrial cancer surgery, it is necessary to be alert to the possibility of a synchronous lymphoma in cases of unusual site adenopathy.

11.
Phys Rev Lett ; 123(8): 086601, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31491218

RESUMO

We investigate the magnetic phase diagram of a solid solution BaFe_{2}(S_{1-x}Se_{x})_{3}, which is categorized into a new family of Fe-based superconductors hosting a quasi-one-dimensional ladder lattice. We show that the antiferromagnetic order is largely suppressed due to bicritical fluctuations in the vicinity of the magnetic transition at x=0.23 from the stripe-type to block-type ordering. Moreover, we observed large magnon contributions in the thermal conductance in a wide x range. These results indicate the quasi-one-dimensional nature of spin systems and give a solid foundation for modeling the material toward unraveling the microscopic mechanism of superconductivity.

12.
J Asthma ; : 1-10, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31433689

RESUMO

Objective: Pulmonary function and airway inflammation were investigated in stable pre- to late-adolescent asthmatics without long-term control medications and compared with those in currently medicated asthmatics. Methods: Subjects comprised 34 well-controlled asthmatic children (aged 8.1-18.0 years; group without medication). Flow volume curves before and after inhaling a ß2 agonist, a bronchodilator (BD), were compared and fractional exhaled nitric oxide (FENO) concentrations were measured. All patients were attack-free for at least 12 months prior to testing without the use of asthma medications for at least three months. Fifty-one age-matched stable asthmatics with medications at the time of the present study (group with current medication) underwent the same examinations. Results: The rate of children whose respiratory function after BD improved by 20% or more in both the central and peripheral airways (High responder at total airways subtype: HTA) was significantly higher in the group without medication than in that with current medication (17.6 and 2.0%, respectively; p < 0.01). Furthermore, FEV1.0% pred after BD was significantly lower for HTA than for the low responder subtype in the same group (94.8 ± 3.5 and 104.1 ± 1.5% respectively, p < 0.05). FENO concentrations in the group without medication were high, but not significantly different from those in the group with current medication. Conclusions: Stable asthmatic children without medication include a certain percentage of those with irreversible airflow limitation possibly due to airway remodeling. The control of daily asthma symptoms with long-term control medications may effectively prevent airway remodeling.

13.
Int J Gynaecol Obstet ; 147(2): 252-257, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31420876

RESUMO

OBJECTIVE: To retrospectively review the efficacy and safety of novel direct oral anticoagulants (DOACs) and compare the results with those of vitamin K antagonists (VKA) when used in clinical practice to treat venous thromboembolism (VTE) because there is insufficient evidence regarding its use in patients with gynecological cancers. METHODS: A study was conducted of patients diagnosed with gynecological cancers at Osaka University Hospital between January 2010 and December 2017. The medical records of those who suffered from deep venous thrombosis (DVT) and/or pulmonary embolism (PE) were retrospectively reviewed. RESULTS: Among the 1698 cases of gynecological cancers, 107 (6.3%) cases were diagnosed as having VTE. A total of 34 (31.8%) patients presented DVT plus PE and 73 (68.2%) patients had DVT alone. Fifty-four cases were treated with DOACs and 53 with VKA. Although 3 of the 53 patients (5.7%) in the VKA group developed recurrent VTE, only 1 (1.9%) patient in the DOAC group showed clinically relevant bleeding from a tumor penetrating the rectum. DOACs were non-inferior to VKA with respect to the composite outcome, including recurrent venous thrombosis and relevant bleeding (hazard ratio 0.31, 95% confidence interval 0.03-3.12, P=0.363). CONCLUSION: DOACs can be effectively and safely used in VTE patients with gynecological cancers.


Assuntos
Anticoagulantes/administração & dosagem , Heparina/administração & dosagem , Tromboembolia Venosa/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Administração Oral , Idoso , Feminino , Neoplasias dos Genitais Femininos/epidemiologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Tromboembolia Venosa/epidemiologia
14.
Gynecol Oncol ; 155(1): 39-50, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31427143

RESUMO

OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.


Assuntos
Carcinoma Endometrioide/epidemiologia , Carcinoma Endometrioide/terapia , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/terapia , Segunda Neoplasia Primária/epidemiologia , Tratamentos com Preservação do Órgão/estatística & dados numéricos , Ovário/fisiologia , Adulto , Estudos de Coortes , Intervalo Livre de Doença , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia/métodos , Histerectomia/estatística & dados numéricos , Japão/epidemiologia , Gradação de Tumores , Estudos Retrospectivos , Estados Unidos/epidemiologia
15.
Vaccine ; 37(32): 4424-4426, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31272873

RESUMO

BACKGROUND: The incidence of cervical cancer has been increasing, especially in younger generation, in Japan. The females born between 1994 and 1999, who achieved rates of HPV vaccination approaching 70%, have become the target of cervical cancer screening programs. Here, we have analyzed the cervical cancer screening rates among the vaccinated and unvaccinated women. METHODS: The survey data for cervical cancer screening at age 20 in FY 2015 was derived from two cities, Toyonaka and Iwaki. RESULTS: Among 2,727 females, in Toyonaka and Iwaki, who were born in FY 1995 and targeted in FY 2015 at age 20 for cervical cancer screening, their HPV vaccination rate was 64.2% (1,753/2,727). The screening rate was 6.4% (112/1,753) in the vaccinated and 3.9% (38/974) in the unvaccinated. This difference was statistically significant (p < 0.01). CONCLUSIONS: We have demonstrated that HPV-vaccinated females tended to be effectively protected from future cervical cancer than the unvaccinated.

16.
Surg Oncol ; 29: 25-32, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31196490

RESUMO

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.


Assuntos
Carcinossarcoma/patologia , Quimioterapia Adjuvante/mortalidade , Histerectomia/mortalidade , Excisão de Linfonodo/mortalidade , Radioterapia Adjuvante/mortalidade , Neoplasias Uterinas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinossarcoma/mortalidade , Carcinossarcoma/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/terapia
17.
Chest ; 156(2): 357-366, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31072612

RESUMO

BACKGROUND: Human epidermal growth factor 2 (HER2) is a potential driver oncogene. Although HER2-targeted precision therapy has been tested in non-small cell lung cancer (NSCLC), the demographic characteristics of HER2-positive NSCLC have not been systematically defined. METHODS: Patients with pathologically confirmed stage IIIB/IV or recurrent NSCLC, Eastern Cooperative Oncology Group performance status 0 to 2, were prospectively registered. HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays were performed to screen patients. HER2 mutations were identified by using direct gene sequencing. The aim of this study was to clarify the frequency, characteristics, and outcome of HER2-positive NSCLC. HER2 was defined as positive if the tumor harbored IHC3+, IHC2+/FISH+, or exon 20 insertion mutations. RESULTS: Of the 1,126 tumors screened, 34 (3.0%) were IHC3+, and 34 (3.0%) were IHC2+/FISH+. Among the 724 epidermal growth factor receptor wild-type tumors, 21 (2.9%) were HER2-mutant tumors, including A775-G776insYVMA (n = 15). Interestingly, the IHC3+ tumors and mutant tumors were entirely exclusive. Female patients had HER2-mutant tumors more frequently, whereas both IHC3+ and IHC2+/FISH+ tumors were detected more often in male subjects and smokers. Patients with an HER2-aberrant tumor had a significantly worse prognosis than those with epidermal growth factor receptor-positive and anaplastic lymphoma kinase-positive tumors, possibly due to the low proportion that received HER2-targeted therapies (n = 15 [26%]) and low response rates of 0% and 14% in patients with HER2-overexpressing and HER2-mutant tumors, respectively. CONCLUSIONS: This prospective large-scale cohort study is the first to show comprehensively the frequency and clinical demographic characteristics of those with HER2-positive advanced lung tumors in detail, providing critical historical data for future drug development against HER2-positive NSCLC. Future treatment strategies would be developed stratified according to the types of HER2 aberrations. TRIAL REGISTRY: UMIN Registration No. 000017003; URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019691.

18.
Am J Obstet Gynecol ; 221(3): 241.e1-241.e6, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075244

RESUMO

BACKGROUND: Smartphones recently have been applied in the medical setting. However, the literature evaluating the utility of smartphones in gynecologic oncology is limited. OBJECTIVE: To evaluate the utility of a smartphone in the detection of uterine cervical lesions in patients with abnormal cervical cytology. STUDY DESIGN: Seventy-five women with abnormal cervical cytology were enrolled. Two doctors independently inspected the uterine cervix by using smartphone or colposcopy. Images were captured using acetic acid, and biopsies were taken as standard-of-care procedures. The diagnostic performance of the smartphone for cervical intraepithelial neoplasm 1 or worse and cervical intraepithelial neoplasm 2 or worse were evaluated, and the kappa value was calculated to determine the chance corrected agreement of the histologic diagnoses based on the smartphone and colposcopic findings. RESULTS: There was a substantial agreement between histologic diagnoses based on the smartphone and colposcopic findings, with a kappa value of 0.67 (95% confidence interval, 0.43-0.90). The sensitivity, specificity, positive predictive value, and negative predictive value of the smartphone in the diagnosis of cervical intraepithelial neoplasm 1 or worse were 0.89 (95% confidence interval, 0.79-0.96), 0.33 (95% confidence interval, 0.08-0.70), 0.91 (95% confidence interval, 0.81-0.97), and 0.30 (95% confidence interval, 0.07-0.65), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value in the diagnosis of cervical intraepithelial neoplasm 2 or worse were 0.92 (95% confidence interval, 0.81-0.98), 0.24 (95% confidence interval, 0.09-0.45), 0.71 (95% confidence interval, 0.58-0.81), and 0.60 (95% confidence interval, 0.26-0.88), respectively. CONCLUSION: We found that there was a substantial agreement between the histologic diagnoses based on the smartphone and colposcopic findings. The smartphone seems to be useful and may be an alternative to colposcopy.

19.
Int J Clin Oncol ; 24(9): 1137-1142, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31025128

RESUMO

OBJECTIVE: The incidence and long-term survival analysis for vulvar cancer, due to its rarity, has not been fully described in Asian population. The objective of the study is to determine the trends in incidence and long-term survival for vulvar cancer in a Japanese population, using a population-based cancer registry data in Osaka, Japan. METHODS: The age-standardized incidence rate of 389 cases of vulvar squamous cell carcinoma (SCC) diagnosed between 1976 and 2010 was calculated, using the 1985 model population of Japan. The annual percentage change (APC) of the age-standardized incidence was estimated by the joinpoint regression models. The 5- and 10-year relative survival of 290 cases with vulvar SCC diagnosed between 1976 and 2008 were analyzed, using a cohort or period approach. Using the 10-year relative survival, the conditional 5-year survival for patients who lived for some years after diagnosis was also calculated. RESULTS: We have found that the age-standardized incidence rate for vulvar cancer trended downward during the period of 1979-1992 (APC - 6.3%; 95% confidence interval (CI) [- 11.3% to - 1.0%]), whereas it trended upward from 1993 to 2010 (APC 1.9%; 95% CI [- 0.7% to 4.6%]). There was no statistically significant difference for the 5- and 10-year relative survival between the two periods of 1976-2000 and 2001-2008. A statistically significant increase in the conditional 5-year survival at 2 years after diagnosis was observed (48.4%; 95% CI [41.1-55.3] versus 75.6%; 95% CI [64.0-83.9]). CONCLUSION: Despite an increasing trend in vulvar cancer incidence among Japanese population, the relative survival rate for vulvar cancer did not change over the 35 years of this study. We found that the conditional 5-year survival for vulvar cancer, as patients survived additional years, approached within reach of 100%. These data can provide valuable information for both patients and clinicians.


Assuntos
Neoplasias Vulvares/epidemiologia , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Japão/epidemiologia , Pessoa de Meia-Idade , Neoplasias Vulvares/mortalidade , Neoplasias Vulvares/patologia
20.
Vaccine ; 37(22): 2889-2891, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31027925

RESUMO

In 2013, following the Ministry of Health, Labor and Welfare (MHLW)'s announced suspension of its vaccine recommendation due to media reports of "adverse events", HPV vaccination dropped to almost 0%. Here, we analyzed, by birth year, the cumulative vaccinations for girls up to age 16 (maximum age for public subsidies) and the results of cervical cancer screening in Matsuyama City. The incidence of CIN3 or worse was 0.09% (7/7872) for these unvaccinated generation born between 1991 and 1993, and 0.00% (0/7389) for the vaccination generation born between 1994 and 1996. This study is the first to show the significant reduction in incidence of CIN3+depending on birth year in Japan. We must keep in mind that the unacceptable high risk for cervical cancer has already begun for an entire new generation of unvaccinated girls born in or after 2000. This data encourages a resumption of MHLW's recommendation for HPV vaccination.

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