Successful management of pelvic recurrence of MSI-High endometrial cancer by total pelvic exenteration followed by administration of pembrolizumab:A case report

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

Scaffold-free bone-like 3D structure established through osteogenic differentiation from human gingiva-derived stem cells

Introduction & objectives: Stem cell therapy for regenerative medicine has been sincerely investigated, but not still popular although some clinical trials show hopeful results. This therapy is suggested to be a representative candidate such as bone defect due to the accident, iatrogenic resection oncological tumor, congenital disease, and severe periodontitis in oral region. Recently, the Bio-3D printer ''Regenova®'' has been introduced as an innovative three-dimensional culture system, equipped scaffold-free bio-assembling techniques without any biomaterials. Therefore, we expected a mount of bone defect could be repaired by the structure established from this Bio-3D printer using osteogenic potential stem cells. Material & methods: The gingival tissue (1x1 mm) was removed from the distal part of the lower wisdom tooth of the patients who agreed our study. Human Gingival Mesenchymal Stem Cells (hGMSCs) were isolated from this tissue and cultured, since we confirmed the characteristics such as facile isolation and accelerated proliferation, further, strong potential of osteogenic-differentiation. Spheroids were formed using hGMSC in 96-well plates designed for low cell adhesion. The size of the spheroids was measured, and fluorescent immunostaining was employed to verify the expression of stem cell and apoptosis marker, and extracellular matrix. Following four weeks of bone differentiation, μCT imaging was performed. Calcification was confirmed by alizarin red and von Kossa staining. Fluorescent immunostaining was utilized to assess the expression of markers indicative of advanced bone differentiation. Results: We have established and confirmed the spheroids (∼600 μm in diameter) constructed from human GMSCs (hGMSCs) still maintain stem cell potentials and osteogenic differentiation abilities from the results that CD73 and not CD34 were expressed as stem cell positive and negative marker, respectively. These spheroids were pilled up like cylindal shape to the “Kenzan” platform of Bio-3D printer and cultured for 7days. The cylindal structure originated from compound spheroids were tried to differentiate into bone four weeks with osteogenic induction medium. The calcification of bio-3D printed bone-like structures was confirmed by alizarin red and Von Kossa staining. In addition, μCT analysis revealed that the HU (Hounsfield Unit) of the calcified structures was almost identical to that of trabecular bone. Immunofluorescent staining detected osteocalcin expression, a late-stage bone differentiation marker. Conclusion: For the first time, we have achieved the construction of a scaffold-free, bone-like luminal structure through the assembly of spheroids comprised of this hGMSCs. This success is sure to be close to the induction of clinical application against regenerative medicine especially for bone defect disease

初回手術から1年後に肺転移で再発した卵巣粘液性境界悪性腫瘍の1例

卵巣粘液性境界悪性腫瘍（mucinous borderline ovarian tumor ; MBOT）は，再発することの少ない予後良好な疾患として知られている。まれに再発を経験することはあるが，腹腔内における再発がほとんどである。今回我々は，初回手術から1年後に肺転移で再発した，希少な経過を辿ったMBOTの症例を経験したので報告する。症例は60歳代の2経妊2経産の女性で，1ヶ月続く労作時呼吸苦を主訴に近医診療所を受診し，骨盤内腫瘍と胸水貯留を指摘され，さらなる精査のため福島県立医科大学附属病院産婦人科に紹介となった。画像検査で15cm大の多房性嚢胞性腫瘍が認められたことから卵巣がんが疑われ，腹式単純子宮全摘術，両側付属器切除術，大網部分切除術が行われた。組織診断はMBOTでpT1cN0M0，ステージICと診断した。術後補助化学療法は行わずに経過観察をしていたが，術後1年で撮影したCTで両下肺野に1箇所ずつ小結節影を認めた。胸腔鏡下両肺下葉切除術がおこなわれ，肺病変の組織像は卵巣腫瘍，すなわちMBOTとの形態学的類似性がみられていた。また，肺病変と卵巣腫瘍の免疫組織学的プロファイルが一致していたことや，原発性肺腺癌で高率に陽性となるTTF-1（Thyroid transcription factor-1）が陰性であったことから，MBOTの肺転移再発と診断した。MBOTの肺転移は非常にまれであるが，早期進行期での再発例や，初回手術後に長期間経過してからの再発例が報告されており，進行期の程度によらず肺も含めた長期間のサーベイランスが必要であることが示唆された。Mucinous borderline ovarian tumors (MBOT) are known to have a good prognosis with a low recurrence rate, and most recurrences occur in the abdominal cavity. We herein describe a case of MBOT which recurred with metastasis to the lung one year following initial surgery. A 60-year-old female gravida 2 para 2 presented to her local clinic complaining of exertional dyspnea lasting over one cytokeramonth. She was found to have a pelvic tumor and pleural effusions, and was referred to the department of obstetrics and gynecology of Fukushima Medical University Hospital for further examination. A multilocular cystic tumor measuring 15 cm in diameter was observed via imaging, leading to a suspicion of ovarian cancer, and abdominal, simple hysterectomy, bilateral adnexectomy, and partial omentectomy were performed. The tumor was histologically diagnosed as pT1cN0M0 stage IC MBOT. The patient was followed up without any adjuvant chemotherapy ; however, a CT taken 1 year following surgery revealed nodular shadows, with one each in both lower lung fields. A thoracoscopic bilateral lung lobectomy was conducted, and the resected lung lesion indicated morphological similarities to the ovarian tumor (MBOT). Furthermore, because the immunohistological profile of the lung lesion and the ovarian tumor matched, and thyroid transcription factor-1(TTF-1), which is usually positive in primary pulmonary adenocarcinomas, was negative. Based on these findings, we diagnosed the lung lesion as a metastatic recurrence of MBOT. Although lung metastatic recurrence of MBOT is very rare, there are reports on recurrence in the early stages or after a long interval following initial surgery, thus suggesting a need for long-term surveillance of tumor recurrence including the lungs metastasis, regardless of the disease stage

手術により診断し得た，卵巣腫大を伴わないライディッヒ細胞腫の一例

患者は71歳女性，4妊3産。不正性器出血と子宮内膜肥厚を認めた。子宮内膜細胞診で疑陽性であり，子宮体癌を疑われたため，当科紹介となった。経腟超音波検査では子宮内膜は11.5mmと肥厚を認めたが，両側付属器の腫大を認めなかった。続く子宮内膜全面掻爬による組織診では悪性所見を認めなかった。骨盤部MRIでは9mmの子宮内膜肥厚を認めたが，両側卵巣の腫大を認めなかった。血清エストラジオール（E2）は55pg/mLと高値であったが，CA125，CA19-9，CEAの上昇を認めなかった。ホルモン産生卵巣腫瘍を疑い，腹腔鏡下子宮全摘術，両側付属器切除術を施行した。卵巣に肉眼的に明らかな腫瘍性病変を認めなかったが，病理組織学的に右卵巣に1.5×1.5mm大のライディッヒ細胞腫を認めた。術後に血清E2の低下を認めた。閉経後の不正出血，子宮内膜肥厚では，画像検索で卵巣腫瘍を認めない場合にも臨床症状によりライディッヒ細胞腫を鑑別に置くことが肝要である。A 71-year-old woman, gravida 4 para 3, presented with abnormal genital bleeding. Transvaginal ultrasonography showed a thickened endometrium of 11.5 mm, but no bilateral adnexal enlargement. Cervical cytology was negative for intraepithelial lesion or malignancy, and endometrial curettage was performed, and no malignant findings were found histologically. Pelvic MRI showed only 9 mm endometrial thickening and no ovarian tumor. Serum estradiol was elevated (55 pg/mL), and CA125, CA19-9, and CEA were not elevated. A hormone-producing ovarian tumor was suspected, and total laparoscopic hysterectomy and bilateral salpingo-oophorectomy were performed. Although no tumor was found macroscopically in the bilateral ovaries, histopathology revealed a 1.5 × 1.5 mm Leydig cell tumor in the right ovary. Serum E2 decreased after surgery. Thus, in cases with postmenopausal irregular bleeding and endometrial thickening, it is essential to consider Leydig cell tumor, even in the absence of ovarian tumors on imaging