Neoadjuvant chemotherapy followed by surgery （NCS） has not been fully evaluated clinically. Currently, the main regimen of neoadjuvant chemotherapy （NAC） used in NCS includes cisplatin. The antitumor effects of NA...Neoadjuvant chemotherapy followed by surgery （NCS） has not been fully evaluated clinically. Currently, the main regimen of neoadjuvant chemotherapy （NAC） used in NCS includes cisplatin. The antitumor effects of NAC reduce lymph node metastasis and the tumor diameter in patients prior to surgery, and this can reduce the number of high risk patients who require postoperative radiation therapy. Many randomized controlled trials （RCTs） have examined the long-term prognosis of NCS compared to primary surgery, but the utility of NCS remains uncertain. The advent of concurrent chemoradiotherapy （CCRT） has markedly improved the outcome of radiotherapy （RT）, and CCRT is now used as a standard method in many cases of advanced bulky cervical cancer. NCS gives a better treatment outcome than radiation therapy alone, but it is important to verify that NCS gives a similar or better outcome compared to CCRT.展开更多
Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by the development of hamartomatous polyposis in the gastrointestinal tract and melanin-pigmented macules on the skin mucosa. The responsibl...Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by the development of hamartomatous polyposis in the gastrointestinal tract and melanin-pigmented macules on the skin mucosa. The responsible gene is a tumor suppressor, STK11/LKB1, on chromosome 19p13.3. PJS complicates with benign and malignant tumors in various organs. In gynecology, there has been a particular focus on complications of PJS with sex cord tumor with annular tubules (SCTAT) and minimal deviation adenocarcinoma (MDA), which are rare diseases. Approximately 36% of patients with SCTAT are complicated with PJS and these patients are characterized by multifocal, bilateral, small and benign lesions that develop into tumors with mucinous to serous ratios of 8:1. In addition, 10% of cases of MDA are complicated with PJS and mutation of STK11, the gene responsible for PJS, has a major effect on onset and prognosis. The disease concept of lobular endocervical glandular hyper-plasia (LEGH) has recently been proposed and LEGH is thought to be a potential premalignant lesion of MDA, however, the relationship between PJS and LEGH remains unclear. Several case reports of PJS patients complicated with gynecological tumors have been published and further studies are needed to determine the underlying展开更多
Atypical polypoid adenomyoma (APAM) is a rare polypoid tumor that generally occurs in women of reproductive age who have abnormal genital bleeding. The tumor was reported as a new disease concept by Mazur in 1981. Pat...Atypical polypoid adenomyoma (APAM) is a rare polypoid tumor that generally occurs in women of reproductive age who have abnormal genital bleeding. The tumor was reported as a new disease concept by Mazur in 1981. Pathologically, APAM consist of irregularly proliferated endometrial gland cells and interlacing bundles of smooth muscle cells within the stroma, and have a similar form to adenocarcinoma, adenofibroma, adenosarcoma, and carcinosarcoma. Therefore, differential diagnosis is required in many cases. APAM is pathologically classified as a benign lesion and clinically has a comparatively favorable outcome. However, treatment and follow-up observation should be performed carefully because recurrence and residual lesions occur in many patients after conservative treatment. Concomitant development of endometrial adenocarcinoma also occurs in many cases and it is difficult to differentiate this disease from APAM. Thus, diagnosis of APAM should be made carefully, particularly since the number of cases of endometrial adenocarcinoma has increased in recent years. Furthermore, APAM tends to develop during a woman’s reproductive years, and fertility sparing treatment should be considered. Here, we review the clinicopathological characteristics of APAM, including the difficulty of diagnosis as a benign or malignant uterine tumor, and we examine the relationship between APAM and endometrial cancer.展开更多
Metformin is a widely used first-line drug for treatment of type 2 diabetes mellitus. In recent years, it has been reported that administration of metformin can reduce carcinogenic risk and inhibit proliferation of ca...Metformin is a widely used first-line drug for treatment of type 2 diabetes mellitus. In recent years, it has been reported that administration of metformin can reduce carcinogenic risk and inhibit proliferation of cancer cells including those from glioma and breast cancer. The underlying mechanism is thought to involve increased LKB-1 phosphorylation induced by metformin, followed by LKB-1 phosphorylation and activation of AMP-activated protein kinase (AMPK), which then inhibits the mammalian target of rapamycin (mTOR) pathway and results in inhibition of cell proliferation. In endometrial cancer, metformin causes cell cycle arrest in vitro, reduces hTERT mRNA, inhibits the mTOR pathway via AMPK, and is involved in inhibition of phosphorylation of S6 ribosomal protein (S6RP). Metformin promotes expression of progesterone receptor by an action opposite to that of insulin-like growth factor-2 (IGF-2) when used in combination with medroxyprogesterone acetate. This enhances the antitumor effect and this approach may be applicable in a clinical setting.展开更多
Objective: Cervical cystic lesions are often observed in gynecological clinical practice. Many are caused by benign diseases such as lobular endocervical glandular hyperplasia (LEGH), and it is important to differenti...Objective: Cervical cystic lesions are often observed in gynecological clinical practice. Many are caused by benign diseases such as lobular endocervical glandular hyperplasia (LEGH), and it is important to differentiate these lesions from those due to malignant diseases such as minimal deviation adenocarcinoma (MDA). In cases in which fertility preservation is not a concern, the final pathology is often confirmed by hysterectomy. To investigate the feasibility and safety of laparoscopic surgery for cervical cystic lesions, we retrospectively examined cases in which total laparoscopic hysterectomy (TLH) was performed for diagnosis and treatment. Methods: The subjects were 28 women who underwent TLH from April 2012 to March 2017 at Keio University Hospital. The pre- and post-operative courses of these patients were examined. Results: The average age was 49.4 (range 39 - 65) years and the mean body mass index was 21.7 (16.8 - 30.5) kg/m2. The average operation time was 159 (101 - 314) min and the average bleeding volume was 106.8 (0 - 600) g. There were no severe perioperative complications. The average hospital stay was 8.4 (7 - 14) days. In postoperative pathological diagnosis, 13 cases had benign diseases such as Nabot cysts, there were 14 cases of LEGH, and one patient was diagnosed with MDA. In the MDA case, additional bilateral salpingo-oophorectomy and pelvic lymph node dissection were performed at a later date. No metastasis was observed in these excised specimens. Conclusions: Our results suggest that TLH for cervical cystic lesions can be performed safely. However, it is important to consider the TLH indication before surgery based on the possibility of malignant disease.展开更多
Endometrial cancer is the seventh most common cancer worldwide among females and accounts for about 40% of cancers of the uterus in Japan. An increase in incidence and a reduction in onset age of this disease are also...Endometrial cancer is the seventh most common cancer worldwide among females and accounts for about 40% of cancers of the uterus in Japan. An increase in incidence and a reduction in onset age of this disease are also likely, which makes it important to define the pathogenesis and develop effective treatment. However, the mechanism of canceration in the endometrium is unclear and development of endometrial cancer cannot be explained only by mutations of cancer-related genes. In contrast, epigenetic analyses have shown the importance of aberrant DNA hypermethylation in the canceration mechanism. In development of type 1 endometrial cancer, breakdown of the DNA mismatch repair system plays a large role, with changes in the human mutL homologue 1 (hMLH1) gene being of most importance. Studies to detect aberrant DNA hypermethylation of cancer cells present in microscopic amounts in vivo and to apply these data to diagnosis of cancer have been started. Epigenetic changes have also been examined as a marker of sensitivity to anticancer drugs. Aberrant hypermethylation of checkpoint with forkhead-associated and ring finger (CHFR), a mitotic phase checkpoint gene, is correlated with sensitivity to treatment with microtubule inhibitors and may be a marker for the response of endometrial cancer to anticancer drugs. Epigenetic aberrant DNA methylation of other genes may also be useful as clinical biomarkers for diagnosis and treatment of endometrial cancer.展开更多
Long-term survival is the priority in treatment of patients with malignant tumors. In the field of gynecology, fertility preservation has also recently become an important objective due to improved treatment outcomes ...Long-term survival is the priority in treatment of patients with malignant tumors. In the field of gynecology, fertility preservation has also recently become an important objective due to improved treatment outcomes and different needs of patients. Methods for fertility preservation include cervical conization, ovarian protection against radiation or chemotherapy for ovarian cancer since the ovary is hypersensitive to cancer therapies, treatment of gynecological cancer during pregnancy, and cryopreservation of oocytes, embryos or ovarian tissue before treatment of malignant tumors. Radical trachelectomy for early cervical cancer and treatment with medroxy progesterone acetate for early endometrial carcinoma are also options for fertility preservation, but the efficacy and risk of recurrence have yet to be fully evaluated. The first childbirth following uterine transplantation was also achieved last year and this success has expanded the potential for pregnancy and delivery among cancer survivors.展开更多
Macromolecules are efficient as mechanical transducers for mechanically induced chemical bond cleavage reactions.Although various classes of polymers have been studied as effective mechanical-force transducers for mec...Macromolecules are efficient as mechanical transducers for mechanically induced chemical bond cleavage reactions.Although various classes of polymers have been studied as effective mechanical-force transducers for mechanophores,alternatives to polymer chains,that is,small molecules,have rarely been studied.In this paper,the role of hydrogen bonding as small-molecule mechanical-force transducers for the activation of mechano-responsive molecular units(mechanophores)in the bulk is investigated.The introduction of diarylurea linkage motifs,which are known as strong hydrogen bonding groups,enhances the mechanochemical activation of the fluorescent mechanophore tetraarylsuccinonitrile(TASN)as effectively as the attachment of a typical macromolecular transducer.Electron paramagnetic resonance measurements of mechanically activated TASN with diphenyl urea motifs demonstrate its higher carbon–carbon bond dissociation ratio compared to that of TASN without diphenyl urea motifs.This efficient supramolecular-forcetransducing system represents a new concept in the field of mechanochemistry,namely,the enhancement of mechanochemical bond scission by simply changing the substituents of a mechanophore,even in small molecules.展开更多
文摘Neoadjuvant chemotherapy followed by surgery （NCS） has not been fully evaluated clinically. Currently, the main regimen of neoadjuvant chemotherapy （NAC） used in NCS includes cisplatin. The antitumor effects of NAC reduce lymph node metastasis and the tumor diameter in patients prior to surgery, and this can reduce the number of high risk patients who require postoperative radiation therapy. Many randomized controlled trials （RCTs） have examined the long-term prognosis of NCS compared to primary surgery, but the utility of NCS remains uncertain. The advent of concurrent chemoradiotherapy （CCRT） has markedly improved the outcome of radiotherapy （RT）, and CCRT is now used as a standard method in many cases of advanced bulky cervical cancer. NCS gives a better treatment outcome than radiation therapy alone, but it is important to verify that NCS gives a similar or better outcome compared to CCRT.
文摘Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by the development of hamartomatous polyposis in the gastrointestinal tract and melanin-pigmented macules on the skin mucosa. The responsible gene is a tumor suppressor, STK11/LKB1, on chromosome 19p13.3. PJS complicates with benign and malignant tumors in various organs. In gynecology, there has been a particular focus on complications of PJS with sex cord tumor with annular tubules (SCTAT) and minimal deviation adenocarcinoma (MDA), which are rare diseases. Approximately 36% of patients with SCTAT are complicated with PJS and these patients are characterized by multifocal, bilateral, small and benign lesions that develop into tumors with mucinous to serous ratios of 8:1. In addition, 10% of cases of MDA are complicated with PJS and mutation of STK11, the gene responsible for PJS, has a major effect on onset and prognosis. The disease concept of lobular endocervical glandular hyper-plasia (LEGH) has recently been proposed and LEGH is thought to be a potential premalignant lesion of MDA, however, the relationship between PJS and LEGH remains unclear. Several case reports of PJS patients complicated with gynecological tumors have been published and further studies are needed to determine the underlying
文摘Atypical polypoid adenomyoma (APAM) is a rare polypoid tumor that generally occurs in women of reproductive age who have abnormal genital bleeding. The tumor was reported as a new disease concept by Mazur in 1981. Pathologically, APAM consist of irregularly proliferated endometrial gland cells and interlacing bundles of smooth muscle cells within the stroma, and have a similar form to adenocarcinoma, adenofibroma, adenosarcoma, and carcinosarcoma. Therefore, differential diagnosis is required in many cases. APAM is pathologically classified as a benign lesion and clinically has a comparatively favorable outcome. However, treatment and follow-up observation should be performed carefully because recurrence and residual lesions occur in many patients after conservative treatment. Concomitant development of endometrial adenocarcinoma also occurs in many cases and it is difficult to differentiate this disease from APAM. Thus, diagnosis of APAM should be made carefully, particularly since the number of cases of endometrial adenocarcinoma has increased in recent years. Furthermore, APAM tends to develop during a woman’s reproductive years, and fertility sparing treatment should be considered. Here, we review the clinicopathological characteristics of APAM, including the difficulty of diagnosis as a benign or malignant uterine tumor, and we examine the relationship between APAM and endometrial cancer.
文摘Metformin is a widely used first-line drug for treatment of type 2 diabetes mellitus. In recent years, it has been reported that administration of metformin can reduce carcinogenic risk and inhibit proliferation of cancer cells including those from glioma and breast cancer. The underlying mechanism is thought to involve increased LKB-1 phosphorylation induced by metformin, followed by LKB-1 phosphorylation and activation of AMP-activated protein kinase (AMPK), which then inhibits the mammalian target of rapamycin (mTOR) pathway and results in inhibition of cell proliferation. In endometrial cancer, metformin causes cell cycle arrest in vitro, reduces hTERT mRNA, inhibits the mTOR pathway via AMPK, and is involved in inhibition of phosphorylation of S6 ribosomal protein (S6RP). Metformin promotes expression of progesterone receptor by an action opposite to that of insulin-like growth factor-2 (IGF-2) when used in combination with medroxyprogesterone acetate. This enhances the antitumor effect and this approach may be applicable in a clinical setting.
文摘Objective: Cervical cystic lesions are often observed in gynecological clinical practice. Many are caused by benign diseases such as lobular endocervical glandular hyperplasia (LEGH), and it is important to differentiate these lesions from those due to malignant diseases such as minimal deviation adenocarcinoma (MDA). In cases in which fertility preservation is not a concern, the final pathology is often confirmed by hysterectomy. To investigate the feasibility and safety of laparoscopic surgery for cervical cystic lesions, we retrospectively examined cases in which total laparoscopic hysterectomy (TLH) was performed for diagnosis and treatment. Methods: The subjects were 28 women who underwent TLH from April 2012 to March 2017 at Keio University Hospital. The pre- and post-operative courses of these patients were examined. Results: The average age was 49.4 (range 39 - 65) years and the mean body mass index was 21.7 (16.8 - 30.5) kg/m2. The average operation time was 159 (101 - 314) min and the average bleeding volume was 106.8 (0 - 600) g. There were no severe perioperative complications. The average hospital stay was 8.4 (7 - 14) days. In postoperative pathological diagnosis, 13 cases had benign diseases such as Nabot cysts, there were 14 cases of LEGH, and one patient was diagnosed with MDA. In the MDA case, additional bilateral salpingo-oophorectomy and pelvic lymph node dissection were performed at a later date. No metastasis was observed in these excised specimens. Conclusions: Our results suggest that TLH for cervical cystic lesions can be performed safely. However, it is important to consider the TLH indication before surgery based on the possibility of malignant disease.
文摘Endometrial cancer is the seventh most common cancer worldwide among females and accounts for about 40% of cancers of the uterus in Japan. An increase in incidence and a reduction in onset age of this disease are also likely, which makes it important to define the pathogenesis and develop effective treatment. However, the mechanism of canceration in the endometrium is unclear and development of endometrial cancer cannot be explained only by mutations of cancer-related genes. In contrast, epigenetic analyses have shown the importance of aberrant DNA hypermethylation in the canceration mechanism. In development of type 1 endometrial cancer, breakdown of the DNA mismatch repair system plays a large role, with changes in the human mutL homologue 1 (hMLH1) gene being of most importance. Studies to detect aberrant DNA hypermethylation of cancer cells present in microscopic amounts in vivo and to apply these data to diagnosis of cancer have been started. Epigenetic changes have also been examined as a marker of sensitivity to anticancer drugs. Aberrant hypermethylation of checkpoint with forkhead-associated and ring finger (CHFR), a mitotic phase checkpoint gene, is correlated with sensitivity to treatment with microtubule inhibitors and may be a marker for the response of endometrial cancer to anticancer drugs. Epigenetic aberrant DNA methylation of other genes may also be useful as clinical biomarkers for diagnosis and treatment of endometrial cancer.
文摘Long-term survival is the priority in treatment of patients with malignant tumors. In the field of gynecology, fertility preservation has also recently become an important objective due to improved treatment outcomes and different needs of patients. Methods for fertility preservation include cervical conization, ovarian protection against radiation or chemotherapy for ovarian cancer since the ovary is hypersensitive to cancer therapies, treatment of gynecological cancer during pregnancy, and cryopreservation of oocytes, embryos or ovarian tissue before treatment of malignant tumors. Radical trachelectomy for early cervical cancer and treatment with medroxy progesterone acetate for early endometrial carcinoma are also options for fertility preservation, but the efficacy and risk of recurrence have yet to be fully evaluated. The first childbirth following uterine transplantation was also achieved last year and this success has expanded the potential for pregnancy and delivery among cancer survivors.
基金supported by KAKENHI grant 17H01205 (Hideyuki Otsuka)from the Japan Society for the Promotion of Science (JSPS)by JST CREST grant JPMJCR1991 (Japan)support from a JSPS Research Fellowship for Young Scientists (201914764).
文摘Macromolecules are efficient as mechanical transducers for mechanically induced chemical bond cleavage reactions.Although various classes of polymers have been studied as effective mechanical-force transducers for mechanophores,alternatives to polymer chains,that is,small molecules,have rarely been studied.In this paper,the role of hydrogen bonding as small-molecule mechanical-force transducers for the activation of mechano-responsive molecular units(mechanophores)in the bulk is investigated.The introduction of diarylurea linkage motifs,which are known as strong hydrogen bonding groups,enhances the mechanochemical activation of the fluorescent mechanophore tetraarylsuccinonitrile(TASN)as effectively as the attachment of a typical macromolecular transducer.Electron paramagnetic resonance measurements of mechanically activated TASN with diphenyl urea motifs demonstrate its higher carbon–carbon bond dissociation ratio compared to that of TASN without diphenyl urea motifs.This efficient supramolecular-forcetransducing system represents a new concept in the field of mechanochemistry,namely,the enhancement of mechanochemical bond scission by simply changing the substituents of a mechanophore,even in small molecules.
