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1.
Fukushima J Med Sci ; 70(2): 65-73, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38494731

ABSTRACT

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.


Subject(s)
Adenocarcinoma, Clear Cell , Cystadenocarcinoma, Serous , Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Adenocarcinoma, Clear Cell/genetics , Adenocarcinoma, Clear Cell/pathology , Middle Aged , Cystadenocarcinoma, Serous/genetics , Cystadenocarcinoma, Serous/pathology , Aged , Diagnosis, Differential , Gene Expression Profiling , Adult , Biomarkers, Tumor/genetics
2.
In Vivo ; 38(2): 958-962, 2024.
Article in English | MEDLINE | ID: mdl-38418162

ABSTRACT

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.


Subject(s)
Cytoreduction Surgical Procedures , Indazoles , Ovarian Neoplasms , Phthalazines , Piperazines , Piperidines , Humans , Female , Aged , Poly(ADP-ribose) Polymerase Inhibitors/adverse effects , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/surgery , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Ovarian Neoplasms/pathology , Carcinoma, Ovarian Epithelial/drug therapy
3.
J Ovarian Res ; 16(1): 95, 2023 May 13.
Article in English | MEDLINE | ID: mdl-37179355

ABSTRACT

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.


Subject(s)
Cystadenocarcinoma, Serous , Fallopian Tube Neoplasms , Ovarian Neoplasms , Adult , Female , Humans , Ovarian Neoplasms/genetics , Prognosis , Cystadenocarcinoma, Serous/pathology , Fallopian Tube Neoplasms/pathology , Biomarkers , Biomarkers, Tumor/metabolism
4.
J Matern Fetal Neonatal Med ; 36(1): 2150392, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36443245

ABSTRACT

OBJECTIVE: Baroreflex is a regulatory mechanism that slows the fetal heart rate. This study aimed to investigate the effects of lipopolysaccharide (LPS)-induced endotoxemia on fetal baroreceptor sensitivity in preterm fetal sheep. METHODS: The changes in fetal baroreceptor sensitivity were measured in seven chronically instrumented preterm fetal sheep. Fetal baroreceptor sensitivity was measured in three phases: (A) control phase, defined as the 24 h before the first injection of LPS; (B) acute phase, defined as the 24 h between the first and second injections of LPS; and (C) fetal acidosis phase, defined as the time from the second LPS injection until intrauterine fetal death. Histological examinations of the fetal membrane and umbilical cord were also conducted. RESULTS: Each fetus developed metabolic acidosis after the second injection of LPS. The fetuses died 24.7 (SD = 6.1) hours after the second injection of LPS. Both the umbilical cord and fetal membranes showed histological evidence of severe inflammation. In total, 163 fetal baroreceptor measurements were performed in this experiment (A, n = 77 times; B, n = 60 times; C, n = 26 times). Fetal baroreceptor sensitivity showed significant differences in all three phases (A: 2.7 [SD = 0.2]; B: 2.5 [SD = 0.2]; and C: 1.5 [SD = 0.2]). Post hoc tests showed that baroreceptor sensitivity in the acidosis phase had decreased significantly compared to that in the control and acute phases (p<.001 and p=.002, respectively). CONCLUSIONS: Fetal baroreceptor sensitivity decreased during fetal acidosis induced by LPSs.


Subject(s)
Acidosis , Fetal Diseases , Pregnancy , Female , Humans , Sheep , Animals , Lipopolysaccharides , Pressoreceptors/metabolism , Pressoreceptors/pathology , Fetus/pathology , Inflammation/chemically induced , Inflammation/pathology , Heart Rate, Fetal
5.
Fukushima J Med Sci ; 68(3): 191-195, 2022 Dec 21.
Article in English | MEDLINE | ID: mdl-36351631

ABSTRACT

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.


Subject(s)
Endometrial Neoplasms , Pelvic Exenteration , Female , Humans , Neoplasm, Residual/surgery , Pelvis/pathology , Pelvis/surgery , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/pathology , Neoplasm Recurrence, Local/drug therapy
6.
Int J Clin Oncol ; 27(12): 1874-1880, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36214925

ABSTRACT

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.


Subject(s)
Fallopian Tube Neoplasms , Ovarian Neoplasms , Peritoneal Neoplasms , Humans , Female , Bevacizumab/adverse effects , Fallopian Tube Neoplasms/drug therapy , Fallopian Tube Neoplasms/pathology , Peritoneal Neoplasms/pathology , Fallopian Tubes/pathology , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Ovarian Neoplasms/pathology , Progression-Free Survival , Platinum/adverse effects , Neoplasm Recurrence, Local/pathology
7.
Int J Oncol ; 61(5)2022 Nov.
Article in English | MEDLINE | ID: mdl-36129146

ABSTRACT

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.


Subject(s)
Claudins , Endometrial Neoplasms , Biomarkers , Claudins/genetics , Claudins/metabolism , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Female , Formaldehyde , Humans , Prognosis , RNA, Messenger/metabolism
8.
Mol Clin Oncol ; 16(4): 90, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35251641

ABSTRACT

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.

9.
Int J Mol Sci ; 23(3)2022 Jan 29.
Article in English | MEDLINE | ID: mdl-35163487

ABSTRACT

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.


Subject(s)
Genital Neoplasms, Female/pathology , Neoplastic Syndromes, Hereditary/pathology , Female , Genetic Predisposition to Disease , Genital Neoplasms, Female/genetics , Humans , Molecular Biology , Neoplastic Syndromes, Hereditary/genetics
10.
J Ovarian Res ; 14(1): 129, 2021 Oct 06.
Article in English | MEDLINE | ID: mdl-34615547

ABSTRACT

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.


Subject(s)
Carcinoma, Ovarian Epithelial/physiopathology , High-Throughput Nucleotide Sequencing/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Mutation
11.
BMC Womens Health ; 21(1): 198, 2021 05 13.
Article in English | MEDLINE | ID: mdl-33985484

ABSTRACT

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.


Subject(s)
Laparoscopy , Ovarian Diseases , Salpingitis , Abscess/diagnostic imaging , Abscess/drug therapy , Abscess/surgery , Adolescent , Anti-Bacterial Agents/therapeutic use , Female , Humans , Ovarian Diseases/diagnostic imaging , Ovarian Diseases/surgery , Salpingitis/drug therapy , Staphylococcus aureus
12.
Int J Mol Sci ; 22(7)2021 Apr 06.
Article in English | MEDLINE | ID: mdl-33917356

ABSTRACT

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.


Subject(s)
Claudins/biosynthesis , Gene Expression Regulation, Neoplastic , Neoplasm Proteins/biosynthesis , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/mortality , Adult , Aged , Disease-Free Survival , Female , HEK293 Cells , Humans , Middle Aged , Predictive Value of Tests , Survival Rate , Uterine Cervical Neoplasms/pathology
13.
Transl Oncol ; 14(3): 101010, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33450701

ABSTRACT

PURPOSE: Endometrial carcinoma (EC) is a clinically heterogeneous disease characterized by a number of different histological subtypes, and its heterogeneity may be involved in the accumulation of multiple genetic alterations. The aim of this work was to investigate the comprehensive mutational profile of EC tumors, and examine the associations between somatic mutations and clinicopathological features or survival in EC patients. METHODS: A total of 100 surgical tumors were obtained from EC patients who had previously undergone surgery. Genomic DNA samples extracted from fresh-frozen tissues were analyzed using the Ion AmpliSeq Cancer Hotspot Panel v2 Kit, covering 50 tumor-related genes. RESULTS: Validated mutations were detected in 91 of the 100 tumors (91%) and identified in eight of the most frequently mutated genes, namely PTEN (57%), PIK3CA (51%), TP53 (30%), KRAS (23%), CTNNB1 (21%), FBFR2 (13%), FBXW7(10%) and RB1 (9%). PTEN mutations were found to associated with young age (< 60), early-stage, endometrioid histology, non-recurrence and better overall survival (OS). CTNNB1 mutations were associated with young age, endometrioid histology and better OS. On the other hands, TP53 mutations were associated with late-stage, non-endometrioid histology, high-grade, recurrence and worse OS. FBWX7 mutations were associated with late-stage, vascular invasion and lymph node metastasis. FGFR2 mutations correlated with deep (≥ 1/2) myometrial invasion. CONCLUSION: Our comprehensive mutational profile will be useful for understanding and evaluating the molecular characteristics of EC tumors, and may lead to the establishment of novel treatment strategies that improve the survival of patients with EC in the future.

14.
J Immunother Cancer ; 8(2)2020 10.
Article in English | MEDLINE | ID: mdl-33004543

ABSTRACT

BACKGROUND: Immune-related adverse events associated with immune checkpoint therapy cause autoimmune disease-like symptoms. People who carry specific genotypes or haplotypes of human leucocyte antigen (HLA) are known to be predisposed to develop autoimmune diseases including narcolepsy. Immunotherapy could be a trigger to develop narcolepsy in predisposing HLA positive patients. CASE PRESENTATION: A 66-year-old woman with stage IVB endometrial carcinosarcoma experienced daytime sleepiness and temporary muscle weakness 14 days after the administration of an immune checkpoint inhibitor, pembrolizumab. These were consistent with the main symptoms of narcolepsy with cataplexy. This patient carried a highly predisposing HLA haplotype for narcolepsy; HLA-DQB1*06:02, DRB1*15:01, DQA1*01:02 and DRB5*01:01:01. A hypocretin-1/orexin-A concentration in the patient's cerebrospinal fluid was low at 9.6 pg/mL in ELISA, and 155.5 pg/mL in radioimmunoassay that was below the normal level of 200 pg/mL. Therefore, she was diagnosed with narcolepsy tentatively according to the International Classification of Sleep Disorders, third edition diagnostic criteria for narcolepsy. The onset of narcolepsy in the 60s is very rare, and narcoleptic symptoms in our patient were likely to be caused by pembrolizumab. CONCLUSIONS: This case suggests that treatment with immune checkpoint inhibitors potentially causes narcolepsy in genetically predisposed patients.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Narcolepsy/chemically induced , Adolescent , Adult , Child , Female , Genetic Predisposition to Disease , Humans , Middle Aged , Young Adult
15.
Sci Rep ; 10(1): 18734, 2020 10 30.
Article in English | MEDLINE | ID: mdl-33127935

ABSTRACT

It is well known that tumour initiation and progression are primarily an accumulation of genetic mutations. The mutation status of a tumour may predict prognosis and enable better selection of targeted therapies. In the current study, we analysed a total of 55 surgical tumours from stage IB-IIB cervical cancer (CC) patients who had undergone radical hysterectomy including pelvic lymphadenectomy, using a cancer panel covering 50 highly mutated tumorigenesis-related genes. In 35 patients (63.6%), a total 52 mutations were detected (58.3% in squamous cell carcinoma, 73.7% in adenocarcinoma), mostly in PIK3CA (34.5%) and KRAS and TP53 (9.1%). Being mutation-positive was significantly correlated with pelvic lymph node (PLN) metastasis (P = 0.035) and tended to have a worse overall survival (P = 0.076). In particular, in the patients with squamous cell carcinoma, there was a significant association between being mutation-positive and relapse-free survival (P = 0.041). The patients with PLN metastasis had a significantly worse overall survival than those without (P = 0.006). These results indicate that somatic mutation status is a predictive biomarker for PLN metastasis in early-stage CC, and is consequently related to poor prognosis. Therefore, comprehensive genetic mutations, rather than a single genetic mutation, should be examined widely in order to identify novel genetic indicators with clinical usefulness.


Subject(s)
Hysterectomy/methods , Mutation/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Biomarkers/metabolism , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Class I Phosphatidylinositol 3-Kinases/genetics , Female , Humans , Lymph Nodes/metabolism , Prognosis , Proto-Oncogene Proteins p21(ras)/genetics , Tumor Suppressor Protein p53/genetics , Uterine Cervical Neoplasms/surgery
16.
Cancers (Basel) ; 12(10)2020 Sep 24.
Article in English | MEDLINE | ID: mdl-32987797

ABSTRACT

BACKGROUND: Among the claudin (CLDN) family, CLDN6 exhibits aberrant expression in various cancers, but its biological relevance has not yet been established. We generated a monoclonal antibody (mAb) against human CLDN6 and verified its specificity. By immunohistochemical staining and semi-quantification, we evaluated the relationship between CLDN6 expression and clinicopathological parameters in tissues from 173 cases of endometrial cancer. RESULTS: The established mAb selectively recognized CLDN6 protein. Ten of the 173 cases (5.8%) showed high CLDN6 expression (score 3+), whereas 19 (11.0%), 18 (10.4%) and 126 (72.4%) cases revealed low CLDN6 expression (score 2+, 1+ and 0, respectively). In addition, intratumor heterogeneity of CLDN6 expression was observed even in the cases with high CLDN6 expression. The 5-year survival rates in the high and low CLDN6 groups was approximately 30% and 90%, respectively. Among the clinicopathological factors, the high CLDN6 expression was significantly associated with surgical stage III/IV, histological grade 3, lymphovascular space involvement, lymph node metastasis and distant metastasis. Furthermore, the high CLDN6 expression was an independent prognostic marker for overall survival of endometrial cancer patients (hazard ratio 3.50, p = 0.014). CONCLUSIONS: It can be concluded that aberrant CLDN6 expression is useful to predict poor outcome for endometrial cancer and might be a promising therapeutic target.

17.
Anticancer Res ; 40(9): 5263-5270, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32878815

ABSTRACT

BACKGROUND: Treatment for platinum-resistant ovarian cancer is difficult and challenging because available chemotherapeutic agents only offer short survival improvements. The efficacy of re-treatment with platinum-based agents including nedaplatin for platinum-resistant patients has not been fully investigated. CASE REPORT: We describe herein three cases of heavily treated platinum-resistant ovarian cancer that were successfully treated with weekly nedaplatin followed by olaparib. After becoming platinum-resistant, the cases were treated with non-platinum chemotherapies. Following these regimens, weekly nedaplatin was introduced, followed by olaparib. At the time of writing, survival since the start of weekly nedaplatin was 30 months for case 1, 20 months for case 2, and 17 months for case 3, with all patients showing no evidence of disease. CONCLUSION: Weekly nedaplatin followed by olaparib might represent a good treatment option for platinum-resistant ovarian cancer and is a solid candidate for further evaluation.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Resistance, Neoplasm , Organoplatinum Compounds/administration & dosage , Ovarian Neoplasms/drug therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers, Tumor , Biopsy , Combined Modality Therapy , Drug Administration Schedule , Female , Humans , Middle Aged , Neoplasm Grading , Neoplasm Staging , Organoplatinum Compounds/therapeutic use , Ovarian Neoplasms/diagnosis , Phthalazines/administration & dosage , Piperazines/administration & dosage , Positron Emission Tomography Computed Tomography , Tomography, X-Ray Computed , Treatment Outcome
18.
J Obstet Gynaecol Res ; 46(11): 2450-2453, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32914517

ABSTRACT

Transcervical resection is widely used in the management of submucosal fibroids. However, uterine perforation and thermal bowel injuries are known complications associated with the procedure. This is a case report of a 44-year-old woman who presented with heavy menstrual bleeding and anemia. Magnetic resonance imaging and hysteroscopy revealed multiple fibroids, including a submucosal type 1 fibroid. She had previously undergone a total proctocolectomy with intestinal pouch-anal anastomosis for ulcerative colitis. Because there was a high risk of permanent colostomy in the event of a bowel injury, an electrode-free, operative hysteroscopy using the Intrauterine Bigatti Shaver (IBS), a hysteroscopic morcellator system, was employed to prevent thermal bowel injury. The fibroid was completely removed using the IBS system with no complications. Therefore, we recommend the electrode-free use of a hysteroscopic morcellator system in patients with a history of extensive pelvic surgery.


Subject(s)
Leiomyoma , Menorrhagia , Proctocolectomy, Restorative , Uterine Neoplasms , Adult , Female , Humans , Hysteroscopy , Leiomyoma/surgery , Pregnancy , Uterine Neoplasms/surgery
19.
Fukushima J Med Sci ; 66(1): 44-52, 2020 Apr 22.
Article in English | MEDLINE | ID: mdl-32161199

ABSTRACT

OBJECTIVE: Ovarian torsion is an acute gynecological condition. Torsion is more likely to occur with benign rather than malignant tumors. Mature cystic teratoma of the ovary (MCTO) is frequent in women of reproductive age; however, the incidence of malignant transformation is approximately 2%. We report a case of malignant transformation of MCTO presenting as ovarian tumor torsion. CASE REPORT: A 51-year-old premenopausal woman was diagnosed with mature cystic teratoma in the left ovary 7 years ago. The patient visited our hospital because she had been experiencing of pain in left lower abdomen for the past two days. She was diagnosed with ovarian tumor torsion and underwent emergency surgery. The left ovarian tumor was twisted, and left salpingo-oophorectomy was performed. Histopathological examination revealed squamous cell carcinoma arising from the MCTO. We carefully followed the patients without performing staging laparotomy. On postoperative day 112, multiple lymph node metastases in the pelvic and para-aortic areas were found by positron-emission tomography and computed tomography. After referral to a university hospital, total hysterectomy, right salpingo-oophorectomy, partial omentectomy, and pelvic and paraaortic lymphadenectomy were performed. Metastases of squamous cell carcinoma were confirmed in the pelvic and para-aortic lymph nodes. Six courses of adjuvant chemotherapy with paclitaxel and carboplatin were given following radical surgery to prevent the recurrence of malignant transformation of MCTO. No recurrence of the disease has been observed during 2 years of follow-up. CONCLUSION: When physicians diagnose large ovarian tumor torsion cases, preoperative examinations should be performed, with the possibility of malignancy in mind.


Subject(s)
Cell Transformation, Neoplastic , Ovarian Neoplasms/therapy , Ovarian Torsion/therapy , Teratoma/therapy , Combined Modality Therapy , Female , Humans , Middle Aged , Ovarian Neoplasms/pathology , Ovarian Torsion/pathology , Teratoma/pathology
20.
Anticancer Res ; 39(10): 5631-5637, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31570460

ABSTRACT

BACKGROUND/AIM: Pelvic exenteration is a radical procedure for certain advanced or recurrent gynaecological cancers, performed with curative or palliative intent. Its validity has evolved as operative mortality and morbidity have improved. This surgery was evaluated to determine the validity of these claims. PATIENTS AND METHODS: The details of surgery and outcomes of 13 patients who underwent pelvic exenteration (6 curative intent, 7 palliative intent) for advanced or recurrent gynaecological cancers in our Department were retrospectively evaluated. RESULTS: There were no significant differences in blood loss, surgical time, hospital stay, and complications between curative pelvic exenteration and palliative pelvic exenteration. The curative intent group had a good prognosis; the palliative-intent group showed a trend to a worse prognosis. All patients' symptoms were relieved, but in patients with short survival, symptom relief lasted for up to 3 months. CONCLUSION: Pelvic exenteration is an acceptable and valuable procedure for gynaecological cancers.


Subject(s)
Genital Neoplasms, Female/surgery , Neoplasm Recurrence, Local/surgery , Adult , Aged , Female , Genital Neoplasms, Female/mortality , Gynecology/methods , Humans , Middle Aged , Neoplasm Recurrence, Local/mortality , Operative Time , Pelvic Exenteration/methods , Postoperative Complications/surgery , Retrospective Studies , Young Adult
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