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1.
J Surg Case Rep ; 2024(7): rjae452, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38993818

RESUMEN

Stage IVA cervical cancer is a tumor that invades the mucosa of the bladder or rectum without distant metastasis and is difficult to treat, and concurrent chemoradiotherapy is recommended. Although radical surgery following neoadjuvant chemotherapy is a treatment option for stage IVA cervical cancer, the evidence is limited. A 51-year-old woman with bulky cervical cancer and rectal invasion was referred to our hospital. Paclitaxel and cisplatin were administered as neoadjuvant chemotherapies. After two cycles of chemotherapy, the tumor size decreased markedly. Total pelvic exenteration was performed, and a complete resection was achieved. Four cycles of paclitaxel and cisplatin were administered postoperatively. Thirty-three months after the completion of adjuvant chemotherapy, the patient was alive and free of disease. Radical surgery after neoadjuvant chemotherapy may be a treatment option for stage IVA cervical cancer with bulky tumors.

2.
Immunotherapy ; : 1-10, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38889451

RESUMEN

Aim: Inherent variations in human leukocyte antigen (HLA) alleles have been revealed epidemiologically to influence the development of autoimmune diseases. HLA alleles may thus also be associated with the development of immune-related adverse events (irAEs), such as thyroid irAE. Materials & methods: In this case-control study, 71 cancer patients who received immune checkpoint inhibitors were enrolled and HLA-genotyped and the frequency of HLA alleles was compared. Results: A*26:01, DPA1*01:03 and DPB1*02:01 were significantly more frequent in patients with thyroid irAE than in patients without any irAEs (35.0 vs 3.2% [p = 0.004], 80.0 vs 45.2% [p = 0.020] and 55.0 vs 25.8% [p = 0.044], respectively). Conclusion: A*26:01, DPA1*01:03 and DPB1*02:01 appear to be associated with thyroid irAE.


Everyone has a unique combination of human leukocyte antigens (HLAs) in their body that help the immune system identify threats. HLAs were named from the fact that they were first identified on the surface of human leukocytes. Afterward, HLAs were also found on all human cells. HLAs present antigens to immune cells. These HLAs also influence how the immune system attacks cancer cells. Immune checkpoint inhibitors are drugs that can help the immune system fight cancer, but they sometimes cause severe adverse events. In this study, we investigated whether specific HLA genes are related to the development of an adverse event that affects the thyroid in cancer patients treated with immune checkpoint inhibitors. We found an association between three HLA genes (A*26:01, DPA1*01:03 and DPB1*02:01) and the development of the thyroid adverse event. However, larger studies are needed to confirm and generalize these initial exploratory findings.

3.
Mol Clin Oncol ; 21(1): 46, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38826696

RESUMEN

Clear cell carcinoma (CCC) of the diaphragm is rare, with an origin that is reported to be associated with malignant transformation of extraperitoneal endometriosis. Lynch syndrome (LS) is an autosomal dominant hereditary cancer syndrome caused by germline pathogenic variants in one of the DNA mismatch repair (MMR) genes, MLH1, MSH2, MSH6 and PMS2. Women with LS have a significantly increased lifetime risk of endometrial and ovarian cancer. CCC is a common histology of endometriosis- and LS-associated malignancy. The present study describes the case of a 51-year-old woman with an intra-abdominal mass found during a routine physical examination. The patient had undergone total hysterectomy and bilateral adnexectomy for atypical endometrial hyperplasia (AEH) and ovarian endometriosis, respectively, 3 years previously. Enhanced computed tomography showed a mass on the surface of the liver. Laparoscopic examination of the abdominal cavity revealed a tumor on the underside of the right diaphragm, which was then surgically excised. Pathological examination of the excised tumor, along with immunohistochemistry, led to a diagnosis of CCC. Since LS was suspected due to the genetic family history of the patient, microsatellite instability analysis was performed on the diaphragmatic tumor, and the results were positive. Immunohistochemistry was performed for MMR proteins in AEH and CCC cells, both of which revealed loss of MSH2 and MSH6 expression. Following detailed genetic counseling, genetic testing of MMR genes was performed, revealing a germline pathogenic variant in MSH2 (c.1000C>T, p.Gln344*), thus confirming the diagnosis of LS. To the best of our knowledge, this is the first case report of concurrent diaphragmatic CCC and LS. Patients with LS and endometriosis are at risk of developing ovarian cancer or intra-abdominal malignant tumors. In addition, immunohistochemistry screening for MMR proteins should be considered in patients with AEH and a family history of LS-related cancer, to enable early clinical intervention in cases of endometrial cancer.

4.
Fukushima J Med Sci ; 70(2): 65-73, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38494731

RESUMEN

AIM: Ovarian serous carcinoma (OSC) and ovarian clear cell carcinoma (OCCC) are two major histological types of epithelial ovarian carcinoma (EOC), each with different biological features and clinical behaviors. Although immunostaining is commonly used for differential diagnosis between OSC and OCCC, correct identification of EOC with mixed-type histology is sometimes a diagnostic challenge. The aim of the present study was to explore candidate genes as potential diagnostic biomarkers that distinguish OSC from OCCC. METHODS: A total of 57 surgical specimens were obtained from EOC patients who had previously undergone primary debulking surgery. Total RNAs were extracted from fresh-frozen tissues of EOC patients, and were used for comprehensive gene expression analysis using DNA microarray technology. RESULTS: Ten candidate genes, FXYD2, TMEM101, GABARAPL1, ARG2, GLRX, RBPMS, GDF15, PPP1R3B, TOB1, and GSTM3 were up-regulated in OCCC compared to OSC. All EOC patients were divided into two groups according to hierarchical clustering using a 10-gene signature. CONCLUSION: Our data suggest that the 10 candidate genes would be an excellent marker for distinguishing OSC from OCCC. Furthermore, the molecular signatures of the 10 genes may enlighten us on the differences in carcinogenesis, and provide a theoretical basis for OCCC's resistance to chemotherapy in the future.


Asunto(s)
Adenocarcinoma de Células Claras , Cistadenocarcinoma Seroso , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/patología , Persona de Mediana Edad , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patología , Anciano , Diagnóstico Diferencial , Perfilación de la Expresión Génica , Adulto , Biomarcadores de Tumor/genética
5.
In Vivo ; 38(2): 958-962, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38418162

RESUMEN

BACKGROUND: Polyadenosine 5'-diphosphoribose polymerase inhibitors (PARP-Is) are novel, effective agents for treating newly diagnosed epithelial ovarian cancer (EOC). However, the effect of PARP-I on the progression of recurrent EOC has not yet been determined. In particular, there is limited evidence regarding retreatment with PARP-I for recurrent EOC that has progressed on PARP-I in the short term. CASE REPORT: A 69-year-old woman with a BRCA1 mutated EOC relapsed five months after starting olaparib maintenance following neoadjuvant chemotherapy and interval debulking surgery. Although the platinum-free interval was within six months, secondary cytoreductive surgery was performed because the tumor was locoregional. Following two cycles of weekly nedaplatin, niraparib induced a complete response, and the patient maintained a progression-free status for 15 months. CONCLUSION: Even with short-term progression on PARP-I, local control combined with different platinum agents and PARP-I can be used to achieve good responses.


Asunto(s)
Procedimientos Quirúrgicos de Citorreducción , Indazoles , Neoplasias Ováricas , Ftalazinas , Piperazinas , Piperidinas , Humanos , Femenino , Anciano , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/cirugía , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patología , Carcinoma Epitelial de Ovario/tratamiento farmacológico
6.
J Obstet Gynaecol Res ; 49(11): 2629-2643, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37632362

RESUMEN

Traditionally, gynecological cancers have been classified based on histology. Since remarkable advancements in next-generation sequencing technology have enabled the exploration of somatic mutations in various cancer types, comprehensive sequencing efforts have revealed the genomic landscapes of some common forms of human cancer. The genomic features of various gynecological malignancies have been reported by several studies of large-scale genomic cohorts, including The Cancer Genome Atlas. Although recent comprehensive genomic profiling tests, which can detect hundreds of genetic mutations at a time from cancer tissues or blood samples, have been increasingly used as diagnostic clinical biomarkers and in therapeutic management decisions, germline pathogenic variants associated with hereditary cancers can also be detected using this test. Gynecological cancers are closely related to genetic factors, with approximately 5% of endometrial cancer cases and 20% of ovarian cancer cases being caused by germline pathogenic variants. Hereditary breast and ovarian cancer syndrome and Lynch syndrome are the two major cancer susceptibility syndromes among gynecological cancers. In addition, several other hereditary syndromes have been reported to be associated with gynecological cancers. In this review, we highlight the genes for somatic mutation and germline pathogenic variants commonly seen in gynecological cancers. We first describe the relationship between clinicopathological attributes and somatic mutated genes. Subsequently, we discuss the characteristics and clinical management of inherited cancer syndromes resulting from pathogenic germline variants in gynecological malignancies.


Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis , Neoplasias de los Genitales Femeninos , Femenino , Humanos , Neoplasias de los Genitales Femeninos/genética , Mutación , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Neoplasias Colorrectales Hereditarias sin Poliposis/genética
7.
J Ovarian Res ; 16(1): 95, 2023 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-37179355

RESUMEN

BACKGROUND: Ovarian cancer has the worst outcome among gynecological malignancies; therefore, biomarkers that could contribute to the early diagnosis and/or prognosis prediction are urgently required. In the present study, we focused on the secreted protein spondin-1 (SPON1) and clarified the prognostic relevance in ovarian cancer. METHODS: We developed a monoclonal antibody (mAb) that selectively recognizes SPON1. Using this specific mAb, we determined the expression of SPON1 protein in the normal ovary, serous tubal intraepithelial carcinoma (STIC), and ovarian cancer tissues, as well as in various normal adult tissues by immunohistochemistry, and verified its clinicopathological significance in ovarian cancer. RESULTS: The normal ovarian tissue was barely positive for SPON1, and no immunoreactive signals were detected in other healthy tissues examined, which was in good agreement with data obtained from gene expression databases. By contrast, upon semi-quantification, 22 of 242 ovarian cancer cases (9.1%) exhibited high SPON1 expression, whereas 64 (26.4%), 87 (36.0%), and 69 (28.5%) cases, which were designated as SPON1-low, possessed the moderate, weak, and negative SPON1 expression, respectively. The STIC tissues also possessed SPON1-positive signals. The 5-year recurrence-free survival (RFS) rate in the SPON1-high group (13.6%) was significantly lower than that in the SPON1-low group (51.2%). In addition, high SPON1 expression was significantly associated with several clinicopathological variables. Multivariable analysis revealed that high SPON1 was an independent prognostic factor for RFS of ovarian cancer. CONCLUSIONS: SPON1 represents a prognostic biomarker for ovarian cancer, and the anti-SPON1 mAb could be valuable as an outcome predictor.


Asunto(s)
Cistadenocarcinoma Seroso , Neoplasias de las Trompas Uterinas , Neoplasias Ováricas , Adulto , Femenino , Humanos , Neoplasias Ováricas/genética , Pronóstico , Cistadenocarcinoma Seroso/patología , Neoplasias de las Trompas Uterinas/patología , Biomarcadores , Biomarcadores de Tumor/metabolismo
8.
J Obstet Gynaecol Res ; 49(2): 769-774, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36305392

RESUMEN

Hydrosalpinx is rare in childhood, and its pathogenesis may differ from that in reproductive-aged women. Herein, we report a case of hydrosalpinx in a premenarcheal 14-year-old girl, which might be caused by thickening of the smooth muscle of the fallopian tube. The patient had recurrent right lower abdominal pain and was referred to our hospital with a suspected adnexal tumor. Laparoscopy revealed a hydrosalpinx with complete obstruction of the fimbria and scar-like stenosis of the proximal ampulla. Right salpingectomy was performed because of a severe hydrosalpinx. As the patient was a virgin and a vaginal culture showed normal flora, ascending infection to the fallopian tube was not considered to be the cause of the hydrosalpinx. Histopathological examination revealed that the resected fallopian tube had a markedly dilated lumen with no inflammatory cell infiltration. Immunohistochemically, estrogen- and progesterone-positive smooth muscle proliferation was found at the isthmus of the fallopian tube.


Asunto(s)
Enfermedades de las Trompas Uterinas , Laparoscopía , Salpingitis , Femenino , Humanos , Adulto , Adolescente , Enfermedades de las Trompas Uterinas/cirugía , Enfermedades de las Trompas Uterinas/diagnóstico , Anomalía Torsional/cirugía , Trompas Uterinas/patología , Salpingitis/cirugía , Miocitos del Músculo Liso , Laparoscopía/efectos adversos , Proliferación Celular
9.
Fukushima J Med Sci ; 68(3): 191-195, 2022 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-36351631

RESUMEN

Surgery can be curative treatment for pelvic locoregional recurrence of endometrial cancer; however, a cure is contingent on complete resection. Here, we report the case of a patient in whom recurrent endometrial tumor remained in the pelvis after resection; long-term control was achieved with postoperative administration of pembrolizumab.The patient had recurrent endometrial cancer of stage IA and was treated with chemotherapy and radiation, but tumor persisted in the pelvic cavity. We therefore attempted total pelvic exenteration, but the tumor was adherent to the pelvic wall and complete resection could not be achieved. However, postoperative administration of pembrolizumab controlled the residual tumor for more than two years without regrowth. We believe that since the resected tumor was MSI-High, the residual tumor responded well to pembrolizumab. It is not known whether cytoreductive surgery contributes to a long-term response to pembrolizumab, but at least in our patient, pembrolizumab appeared to be a very effective drug therapy for MSI-High endometrial cancer that was refractory to chemotherapy and radiotherapy.


Asunto(s)
Neoplasias Endometriales , Exenteración Pélvica , Femenino , Humanos , Neoplasia Residual/cirugía , Pelvis/patología , Pelvis/cirugía , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico
10.
Int J Clin Oncol ; 27(12): 1874-1880, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36214925

RESUMEN

BACKGROUND: Outcomes with and without bevacizumab as first-line chemotherapy in Japanese-only ovarian cancer patients have not been reported. In this study, we report a retrospective study conducted at the Tohoku Gynecologic Cancer Unit. PATIENTS AND METHODS: The study included 453 patients with stage III/IV ovarian, fallopian tube, and primary peritoneal cancer who received first-line platinum-based chemotherapy. The patients were divided into two groups: bevacizumab (168 patients) and without bevacizumab (285 patients). The primary endpoint was the rate of platinum-resistant recurrence and the secondary endpoints were the antitumor response, progression-free survival, overall survival, and adverse events. RESULTS: The objective response rates for patients with measurable diseases treated with and without bevacizumab were 84.5% and 73.0%, respectively (P = 0.0066). Platinum-resistant recurrence in the groups treated with and without bevacizumab was noted in 31 (18.4%) and 111 (38.6%) patients, respectively (P < 0.0001). The median progression-free survival for the bevacizumab and without bevacizumab groups was 23 and 15 months, respectively (P = 0.0002), and the median overall survival was not reached and 49 months, respectively (P = 0.0005). Hypertension of grade 3 or higher was observed in 21 patients (12.5%) in the bevacizumab group (P < 0.001), and proteinuria was observed in 18 patients (10.7%) and 1 patient (0.3%) in the bevacizumab and without bevacizumab groups, respectively (P < 0.001). Intestinal perforation was observed in only one patient (0.6%) in the bevacizumab group. CONCLUSION: Combination and maintenance with bevacizumab in primary chemotherapy for advanced ovarian, fallopian tube, and primary peritoneal cancer was effective in reducing platinum-resistant recurrence rates and prolonging progression-free and overall survival.


Asunto(s)
Neoplasias de las Trompas Uterinas , Neoplasias Ováricas , Neoplasias Peritoneales , Humanos , Femenino , Bevacizumab/efectos adversos , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Neoplasias de las Trompas Uterinas/patología , Neoplasias Peritoneales/patología , Trompas Uterinas/patología , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Ováricas/patología , Supervivencia sin Progresión , Platino (Metal)/efectos adversos , Recurrencia Local de Neoplasia/patología
11.
Int J Oncol ; 61(5)2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36129146

RESUMEN

The tight­junction protein claudin­9 (CLDN9) is barely distributed in normal adult tissues but is ectopically expressed in various cancer types. Although multiple databases indicated upregulation of CLDN9 in endometrial cancers at the mRNA level, its protein expression and biological roles remain obscure. In the present study, the prognostic significance of CLDN9 expression in endometrial cancer was evaluated by immunohistochemical staining and semi­quantification using formalin­fixed paraffin­embedded specimens obtained from 248 endometrial carcinoma cases. A total of 43 cases (17.3%) had high CLDN9 expression, whereas 205 cases (82.7%) exhibited low CLDN9 expression. The 5­year disease­specific survival rates in the high and low CLDN9 expression groups were 62.8 and 87.8% (P<0.001), respectively. In addition, multivariate analysis revealed that high CLDN9 expression was an independent prognostic factor (hazard ratio, 4.99; 95% CI, 1.96­12.70; P<0.001). Furthermore, CLDN9 expression was significantly correlated with the expression of CLDN6 (P<0.001), which is the closest CLDN member to CLDN9 and a poor prognostic factor for endometrial carcinoma. The 5­year disease­specific survival rate of cases with CLDN6­high/CLDN9­high, CLDN6­high/CLDN9­low and CLDN6­low/CLDN9­high status was 30.0, 37.5 and 72.7%, respectively, whereas that of CLDN6­low/CLDN9­low was 89.8% (P=0.004). In conclusion, aberrant CLDN9 expression is a predictor of poor prognosis for endometrial cancer and may be utilized in combination with CLDN6 to achieve higher sensitivity.


Asunto(s)
Claudinas , Neoplasias Endometriales , Biomarcadores , Claudinas/genética , Claudinas/metabolismo , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Femenino , Formaldehído , Humanos , Pronóstico , ARN Mensajero/metabolismo
12.
BMC Womens Health ; 22(1): 103, 2022 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-35382809

RESUMEN

BACKGROUND: Epithelial ovarian cancer is the most frequent gynecologic malignancy; it has a poor prognosis and often occurs bilaterally. Most cases of synchronous bilateral ovarian cancer (SBOC) are metastases from the other ovary, while bilateral primary ovarian cancer is rare. CASE PRESENTATION: The patient was a 47-year-old Japanese woman with a complaint of abdominal pain for 1 month. Imaging results revealed bilateral ovarian tumors with suspicion of malignancy. The patient underwent a laparotomy with total hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy, and resection of suspected dissemination in the peritoneum. Histopathological and immunohistochemical studies showed that the right ovarian tumor was an endometrioid carcinoma (G2) and had no association with endometriotic lesions. However, the left ovarian tumor was a high-grade serous carcinoma (HGSC). The final staging was stage 1 right endometrioid carcinoma and stage IIb left HGSC. Six courses of adjuvant chemotherapy with paclitaxel, docetaxel, and carboplatin were administered. The patient showed no signs of recurrence 24 months postoperatively. CONCLUSIONS: To the best of our knowledge, the combination of histological types in this case may be the first report of primary bilateral ovarian cancer. In SBOC, it is important to differentiate the subtypes of histology using immunostaining, in addition to morphopathology.


Asunto(s)
Carcinoma Endometrioide , Neoplasias Endometriales , Neoplasias Ováricas , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/secundario , Carcinoma Endometrioide/cirugía , Carcinoma Epitelial de Ovario , Neoplasias Endometriales/patología , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/patología
13.
Mol Clin Oncol ; 16(4): 90, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35251641

RESUMEN

NTRK gene fusion is rare in gynecological cancer. Entrectinib is a novel targeted drug, which is a potent inhibitor of TRK A, B and C. The present case report described a case of recurrent ovarian cancer with TPM3-NTRK1 rearrangement, which was detected by next-generation sequencing (NGS) and treated with entrectinib. A 56-year-old woman was diagnosed as having stage IV ovarian cancer with positive pleural fluid cytology. Neoadjuvant chemotherapy and interval debulking surgery, followed by chemotherapy, were performed. A total of 10 months after completion of chemotherapy, the disease recurred and the patient was treated with multimodal therapy for recurrence. DNA-based NGS detected TPM3-NTRK1 rearrangement and entrectinib therapy was initiated; however, the disease progressed despite 6 weeks of entrectinib administration, and 1 month after discontinuation of entrectinib, the patient died. After their death, immunohistochemistry with a pan-Trk monoclonal antibody was performed to determine the expression levels of TRK; however, immunohistochemistry was negative for TRK. In conclusion, the present case report described a rare case of recurrent ovarian cancer with TPM3-NTRK1 gene fusion, in which entrectinib was not effective. While NTRK gene fusion was detected by DNA-based NGS, immunohistochemistry was negative for TRK. These findings indicated that immunohistochemistry may be required for confirmation of TRK protein expression prior to entrectinib administration.

14.
Fukushima J Med Sci ; 68(1): 49-55, 2022 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-35314524

RESUMEN

Kallmann syndrome, a congenital disorder of idiopathic hypogonadotropic hypogonadism associated with anosmia, results in infertility because of anovulation. Assisted reproductive technology (ART) is considered when optimal ovulation induction therapy is difficult or when several cycles of ovulation induction therapy do not result in pregnancy. However, evidence is lacking regarding the optimal ART treatment for Kallmann syndrome. We report the case of a 33-year-old woman who successfully achieved pregnancy and delivery after ART treatment. At 29 years old, she was diagnosed with Kallmann syndrome due to hypothalamic amenorrhea and anosmia. At 33 years old, she revisited the hospital, desiring a child after one year of infertility. Due to anovulation, she was treated with gonadotropin therapy, but controlling follicular development was difficult, and thus ART treatment was initiated. The controlled ovarian stimulation (COS) protocol for ART treatment employed gonadotropins, recombinant follicular stimulating hormone/human menopausal gonadotropin plus human chorionic gonadotropin, to promote follicular growth. Four oocytes were retrieved, and two cleaved embryos were vitrified and cryopreserved. After vitrified-warmed embryo transfer of a morula stage embryo in a hormone replacement cycle, pregnancy was achieved but resulted in a miscarriage. A second oocyte retrieval was performed under the same COS; four oocytes were retrieved, and two cleaved embryos were vitrified and cryopreserved. Further, a pregnancy was achieved through the vitrified warmed embryo transfer. At 40 weeks and 6 days of gestation, a baby boy weighing 3,344 g with an Apgar score of 7/8 was delivered vaginally. The mother's postpartum course and neonate were free from adverse events. For women with Kallmann syndrome, ART treatment and selective embryo cryopreservation may be a reasonable and safe option.


Asunto(s)
Anovulación , Infertilidad , Síndrome de Kallmann , Anosmia , Transferencia de Embrión/métodos , Femenino , Hormonas , Humanos , Síndrome de Kallmann/terapia , Embarazo
15.
Int J Mol Sci ; 23(3)2022 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-35163487

RESUMEN

Hereditary cancer syndromes, which are characterized by onset at an early age and an increased risk of developing certain tumors, are caused by germline pathogenic variants in tumor suppressor genes and are mostly inherited in an autosomal dominant manner. Therefore, hereditary cancer syndromes have been used as powerful models to identify and characterize susceptibility genes associated with cancer. Furthermore, clarification of the association between genotypes and phenotypes in one disease has provided insights into the etiology of other seemingly different diseases. Molecular genetic discoveries from the study of hereditary cancer syndrome have not only changed the methods of diagnosis and management, but have also shed light on the molecular regulatory pathways that are important in the development and treatment of sporadic tumors. The main cancer susceptibility syndromes that involve gynecologic cancers include hereditary breast and ovarian cancer syndrome as well as Lynch syndrome. However, in addition to these two hereditary cancer syndromes, there are several other hereditary syndromes associated with gynecologic cancers. In the present review, we provide an overview of the clinical features, and discuss the molecular genetics, of four rare hereditary gynecological cancer syndromes; Cowden syndrome, Peutz-Jeghers syndrome, DICER1 syndrome and rhabdoid tumor predisposition syndrome 2.


Asunto(s)
Neoplasias de los Genitales Femeninos/patología , Síndromes Neoplásicos Hereditarios/patología , Femenino , Predisposición Genética a la Enfermedad , Neoplasias de los Genitales Femeninos/genética , Humanos , Biología Molecular , Síndromes Neoplásicos Hereditarios/genética
16.
J Ovarian Res ; 14(1): 129, 2021 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-34615547

RESUMEN

OBJECTIVE: Epithelial ovarian cancer (EOC) is a heterogeneous disease with diverse clinicopathological features and behaviors, and its heterogeneity may be concerned with the accumulation of multiple somatic oncogenic mutations. The major goals of this study are to systematically perform the comprehensive mutational profiling in EOC patients, and investigate the associations between somatic mutations and clinicopathological characteristics. METHODS: A total of 80 surgical specimens were obtained from EOC patients who had previously undergone primary debulking surgery, and genomic DNAs were extracted from fresh-frozen tissues. We investigated mutational status in hot spot regions of 50 cancer-related genes by targeted next-generation sequencing using an Ion AmpliSeq Cancer Hotspot Panel v2 Kit. RESULTS: Validated mutations were detected in 66 of the 80 tumors (82.5%). The five most frequently mutated genes were TP53 (43.8%), PIK3CA (27.5%), KRAS (23.8%), PTEN (10%) and CTNNB1 (10%). PTEN and CTNNB1 mutations were associated with younger age. PIK3CA1, KRAS and CTNNB1 mutations were observed in early-stage, whereas TP53 mutations were more common in advanced stage. Significant associations were observed between TP53 mutation and serous carcinoma, and between KRAS mutation and mucinous carcinoma. Both PIK3CA mutation and CTNNB1 mutation were also significantly associated with endometrioid and clear cell carcinoma. The patients with PIK3CA and KRAS mutations were significantly associated with favorable progression free survival (PFS). In particular, PIK3CA mutations had more significant associations with favorable PFS than PIK3CA wild-type in the endometrioid subtype (P = 0.012). Patients with mutations only in TP53 were significantly associated with worse PFS. CONCLUSION: EOCs were heterogeneous at the genomic level and harbored somatic oncogenic mutations. Our molecular profiling may have the potential for becoming a novel stratification within histological subtypes of EOC. Further studies are needed to define molecular classification for improved clinical outcomes and treatment of EOC patients in future.


Asunto(s)
Carcinoma Epitelial de Ovario/fisiopatología , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Mutación
17.
BMC Pregnancy Childbirth ; 21(1): 715, 2021 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-34702216

RESUMEN

BACKGROUND: Pregnancy in a rudimentary horn is an extremely rare type of ectopic pregnancy. A rudimentary uterine horn pregnancy is associated with a risk of spontaneous rupture and bleeding during surgery due to the increased uterine blood flow. Recent advances in imaging modalities have enabled laparoscopic surgery to be performed in cases without rupture in the early stages of pregnancy. However, there are few reports of successful pregnancies and deliveries after treatment of rudimentary horn pregnancies. We report the successful management of a case of non-communicating rudimentary horn pregnancy by local injection of methotrexate followed by complete laparoscopic excision along with a review of the literature. CASE PRESENTATION: The patient was a 29-year-old Japanese woman, gravida 2, nullipara. She was diagnosed with a left unicornuate uterus with a right non-communicating rudimentary horn on hysterosalpingography and magnetic resonance imaging. A gestational sac with a heartbeat was observed in the right rudimentary uterine horn at 6 weeks of gestation. A diagnosis of ectopic pregnancy in a non-communicating rudimentary horn was made. Color Doppler detected multiple blood flow signals around the gestational sac, which were clearly increased compared to the left unicornuate uterus. Her serum human chorionic gonadotropin level was 104,619 mIU/ml. A 100 mg methotrexate injection into the gestational sac was administered, and laparoscopic surgery was performed on day 48 after the methotrexate treatment. The right rudimentary horn and fallopian tube were successfully excised with minimal bleeding. A spontaneous normal pregnancy was established 6 months after the surgery. The pregnancy was uneventful, and a baby girl was born by elective cesarean section at 38w0d. CONCLUSION: Combined local methotrexate injection and laparoscopic surgery are safe treatment options for patients with a unicornuate uterus with a non-communicating rudimentary horn pregnancy.


Asunto(s)
Laparoscopía/métodos , Metotrexato/uso terapéutico , Embarazo Cornual/terapia , Adulto , Femenino , Humanos , Japón/epidemiología , Embarazo , Resultado del Embarazo , Nacimiento a Término , Anomalías Urogenitales/terapia , Útero/anomalías
18.
BMC Womens Health ; 21(1): 198, 2021 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-33985484

RESUMEN

BACKGROUND: Ovarian abscesses, which occur mostly in sexually active women via recurrent salpingitis, occur rarely in virginal adolescent girls. Here, we present a case of an ovarian abscess in a virginal adolescent girl who was diagnosed and treated by laparoscopy. CASE PRESENTATION: A 13-year-old healthy girl presented with fever lasting for a month without abdominal pain. Computed tomography scan and magnetic resonance imaging indicated a right ovarian abscess. Laparoscopic surgery revealed a right ovarian abscess with intact uterus and fallopian tubes. The abscess was caused by Staphylococcus aureus. The patient recovered completely after excision of the abscess, followed by antibiotic treatment. CONCLUSIONS: Ovarian abscess may occur in virginal adolescent girls; Staphylococcus aureus, an uncommon species causing ovarian abscess, may cause the infection.


Asunto(s)
Laparoscopía , Enfermedades del Ovario , Salpingitis , Absceso/diagnóstico por imagen , Absceso/tratamiento farmacológico , Absceso/cirugía , Adolescente , Antibacterianos/uso terapéutico , Femenino , Humanos , Enfermedades del Ovario/diagnóstico por imagen , Enfermedades del Ovario/cirugía , Salpingitis/tratamiento farmacológico , Staphylococcus aureus
19.
BMC Pregnancy Childbirth ; 21(1): 288, 2021 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-33838651

RESUMEN

BACKGROUND: Malignancy during pregnancy is increasing, and the most common type of malignancy is uterine cervical cancer. When planning the treatment of cervical cancer, it is important to look for signs of metastasis before surgery, especially metastasis to the lymph nodes. In this report, we assessed the diagnostic value of positron emission tomography/magnetic resonance imaging (PET/MRI) for evaluating cervical cancer propagation before surgery, with a focus on pregnant women. CASE PRESENTATION: 18F Fluorodeoxyglucose (FDG)-PET/MRI was performed in seven pregnant cervical cancer patients (28-34 years old) at 9-18 gestational weeks. In case #5, a second PET/MRI was performed at 24 gestational weeks. Of seven FDG-PET/MRI examination series in six cases (cases #1-6), FDG-PET/MR imaging could detect cervical tumors with abnormal FDG accumulation; these tumors were confirmed with a standardized uptake value max (SUV max) titer of 4.5-16. A second PET/MRI examination in case #5 revealed the same SUV max titer as the first examination. In these six imaging series (cases #1-5), there were no signs of cancer metastasis to the parametrium and lymph nodes. However, in case #6, abnormal FDG accumulation in the left parametrial lymph nodes was also detectable. Pathological examination showed lymph node metastasis in case #6. In case #7, PET/MRI could not detect any abnormal FDG accumulation in the cervix and other sites. Cone biopsy demonstrated only micro-invasive squamous cell carcinoma. After treatment for cervical cancer, all seven patients have had no recurrence of disease within the follow-up period (2.8-5.6 years), and their children have developed appropriately. CONCLUSION: PET/MRI is an effective imaging tool to evaluate cervical cancer progression in pregnancy.


Asunto(s)
Cuello del Útero/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Tomografía de Emisión de Positrones/métodos , Complicaciones Neoplásicas del Embarazo/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Progresión de la Enfermedad , Estudios de Factibilidad , Femenino , Fluorodesoxiglucosa F18/administración & dosificación , Humanos , Imagen Multimodal/métodos , Estadificación de Neoplasias , Prueba de Papanicolaou , Embarazo , Complicaciones Neoplásicas del Embarazo/patología , Complicaciones Neoplásicas del Embarazo/cirugía , Periodo Preoperatorio , Radiofármacos/administración & dosificación , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía , Frotis Vaginal
20.
Int J Mol Sci ; 22(7)2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33917356

RESUMEN

BACKGROUND: Within the claudin (CLDN) family, CLDN12 mRNA expression is altered in various types of cancer, but its clinicopathological relevance has yet to be established due to the absence of specific antibodies (Abs) with broad applications. METHODS: We generated a monoclonal Ab (mAb) against human/mouse CLDN12 and verified its specificity. By performing immunohistochemical staining and semiquantification, we evaluated the relationship between CLDN12 expression and clinicopathological parameters in tissues from 138 cases of cervical cancer. RESULTS: Western blot and immunohistochemical analyses revealed that the established mAb selectively recognized the CLDN12 protein. Twenty six of the 138 cases (18.8%) showed low CLDN12 expression, and the disease-specific survival (DSS) and recurrence-free survival rates were significantly decreased compared with those in the high CLDN12 expression group. We also demonstrated, via univariable and multivariable analyses, that the low CLDN12 expression represents a significant prognostic factor for the DSS of cervical cancer patients (HR 3.412, p = 0.002 and HR 2.615, p = 0.029, respectively). CONCLUSIONS: It can be concluded that a reduced CLDN12 expression predicts a poor outcome for cervical cancer. The novel anti-CLDN12 mAb could be a valuable tool to evaluate the biological relevance of the CLDN12 expression in diverse cancer types and other diseases.


Asunto(s)
Claudinas/biosíntesis , Regulación Neoplásica de la Expresión Génica , Proteínas de Neoplasias/biosíntesis , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/mortalidad , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Células HEK293 , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Tasa de Supervivencia , Neoplasias del Cuello Uterino/patología
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