Endometrial Cancer Diagnosed at an Early Stage during Lynch Syndrome Surveillance: A Case Report.

Lynch syndrome is an autosomal dominant inherited disorder caused by a germline pathogenic variant in DNA mismatch repair genes, resulting in multi-organ cancer. Annual transvaginal ultrasonography and endometrial biopsy are recommended for endometrial cancer surveillance in patients with Lynch syndrome in several guidelines; however, evidence is limited. Here, we present the case of a 51-year-old woman with endometrial cancer who underwent robot-assisted laparoscopic simple hysterectomy at an early stage detected by Lynch syndrome surveillance. The patient was a 51-year-old gravida zero woman without any medical history or symptoms. Her sister suffered from bladder, breast, rectal, and endometrial cancer and was diagnosed with Lynch syndrome using a hereditary cancer panel test (VistaSeq®). During gynecologic surveillance, the patient's endometrial cytology was classified as Papanicolaou class III. Therefore, she underwent endometrial curettage with hysteroscopy and was diagnosed with atypical endometrial hyperplasia. Robot-assisted hysterectomy was performed with a final pathological diagnosis of endometrial cancer (endometrioid carcinoma, Grade 1), stage 1A. She has remained disease-free for more than 12 months. Owing to advances in genetic medicine, prophylactic and therapeutic surgeries for hereditary cancers are increasing. To achieve an early diagnosis and treatment of Lynch syndrome-associated cancers, the importance of Lynch syndrome surveillance should be more widely recognized.

[Is Surgery Really Useful for Breast Cancer Management in Elderly Patients?]

PURPOSE: The Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer 2018 indicated that operation is the standard treatment for breast cancer in elderly patients. This study aimed to assess the safety and efficacy of surgery for elderly patients with breast cancer. METHODS: Between April 2009 and November 2019, 545 patients underwent surgery in our hospital. The medical records of the elderly group(≥80 years, n=62)and the control(55-65 years, n=128)groups were compared and analyzed retrospectively. RESULTS: The elderly group had more comorbidities(p<0.001)than those of the control group. Although no significant difference in the pathological stage was noted between the 2 groups, dermal infiltrations were more common(p=0.003)in the elderly group than those of the other, and 27% of them did not undergo any surgery to the axilla. This group experienced more post-surgery complications than those of the other; however, such complications did not extend beyond the duration of hospital stays. No difference in the recurrence rate between the groups was noted. In the elderly group, 64% died of comorbidities. The 3-year survival rate was 88.3% and 95.4% in the elderly and control groups, respectively(p=0.18). CONCLUSIONS: Our study revealed that surgery was safe for the management of breast cancer in elderly patients. However, their prognosis was poor owing to their comorbidities. Hence, careful therapy for their comorbidity is also important.

Risk Factors for Septic Shock After Irinotecan-Containing Chemotherapy: An Exploratory Case-Control Study.

BACKGROUND AND OBJECTIVES: Irinotecan sometimes causes lethal septic shock but the risk factors remain unclear. This retrospective case-control study explored the potential risk factors for septic shock following irinotecan treatment. METHODS: All women who received irinotecan-containing chemotherapy for gynecologic malignancies at Shizuoka General Hospital from October 2014 to September 2020 were investigated. The clinical backgrounds and blood test results of those who developed septic shock after irinotecan-containing chemotherapy were compared with those who did not. Odds ratios (ORs) for developing septic shock after receiving irinotecan were calculated with 95% confidence intervals (CIs), using univariable logistic regression analysis. RESULTS: During the study period, 147 women received irinotecan-containing chemotherapy. Three women developed septic shock due to neutropenic enterocolitis after irinotecan treatment, and 144 did not. The three patients with septic shock had recurrent cervical cancer, heterozygous variants in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene (two patients had *1/*6, one had *1/*28 variants), a history of concurrent chemoradiation therapy, 50-60 Gy of pelvic irradiation, and platinum-combined chemotherapy. A history of pelvic irradiation was identified as a possible risk factor for developing septic shock after irinotecan-containing chemotherapy (OR 63.0, 95% CI 5.71-8635; p < 0.001). The OR of UGT1A1 polymorphism for septic shock was 9.09 (95% CI 0.86-1233; p = 0.070) in the complete case analysis. CONCLUSION: Medical personnel involved in cancer therapy should consider the possible risk of septic shock developing due to neutropenic enterocolitis when administering irinotecan-containing chemotherapy in patients with a history of pelvic irradiation.

Validity of Weekly Administration of Carboplatin after Carboplatin-Induced SIADH: Two Case Reports and Literature Review.

Chemotherapy-induced severe hyponatremia is a life-threatening condition. Platinum-based agents play a key role in ovarian cancer treatment but are more likely to cause hyponatremia than other anticancer agents. The optimal strategy for treating ovarian cancer in cases of severe platinum agent-induced hyponatremia remains unclear. We encountered 2 patients with ovarian cancer who developed syndrome of inappropriate antidiuretic hormone secretion (SIADH) after chemotherapy with involved carboplatin. Case 1 was a recurrent ovarian clear-cell carcinoma with peritoneal dissemination, and the patient developed severe hyponatremia due to SIADH on day 5 after receiving triweekly docetaxel and carboplatin (DC) therapy. The chemotherapy regimen was changed to weekly DC therapy, and she completed six cycles of regimen without electrolyte disturbance or tumor recurrence. Case 2 was a newly diagnosed advanced high-grade serous ovarian carcinoma, stage IIIC, with a BRCA1 mutation. She developed SIADH on day 8 after receiving triweekly paclitaxel and carboplatin (TC) therapy as adjuvant therapy after primary debulking surgery. The regimen was changed to weekly TC therapy, and she completed the schedule of chemotherapy without electrolyte disturbance and transitioned to maintenance therapy with a PARP inhibitor. In conclusion, weekly carboplatin administration might be a promising alternative to triweekly carboplatin administration after the development of carboplatin-induced SIADH.

Olaparib-induced cutaneous side effects in a patient with recurrent ovarian cancer.

Over the past decade, the treatment of ovarian cancer has been revolutionised by poly(ADP-ribose polymerase (PARP)) inhibitors. Based on the results from clinical trials, olaparib, a PARP inhibitor, is indicated for use in the first-line treatment for patients with BRCA gene mutations, and as a maintenance treatment in platinum-sensitive relapsed ovarian cancer after a complete or partial response to platinum-based chemotherapy. Although PARP inhibitors have been shown to be well tolerated, adverse side effects can affect the quality of life of patients and lead to the discontinuation of therapy. Here, we report a case of dermatosis of the left dorsal hand as a rare adverse side effect of olaparib. Dermatological adverse side effects may become the crux of a clinical problem that requires the cooperation of professionals in many fields.

Feasibility of Laparoscopic Para-Aortic Lymphadenectomy for Locally Advanced Cervical Cancer.

Background: Radiological evaluation of para-aortic lymph node metastasis in patients with locally advanced cervical cancer (LACC) possess the risk of missing microscopic metastasis. We commenced laparoscopic para-aortic lymphadenectomy (Lap-PAN) on patients with LACC for surgical staging in 2016. We assessed the feasibility of Lap-PAN in patients with LACC. Methods: We retrospectively reviewed the records of 31 patients with LACC who were staged at International Federation of Gynecology and Obstetrics (FIGO) 2009 IIB to IVA without enlargement of the para-aortic lymph nodes who underwent radiation therapy in our hospital between January 1, 2011 and December 31, 2018. The postoperative outcomes of Lap-PAN were analyzed, and distinct parameters for each patient, including sites of recurrence and disease-free survival, were compared between the Lap-PAN (n = 12) and no surgery (n = 19) groups. Results: The average operation time for Lap-PAN was 167 min, and the estimated blood loss was less than 50 ml in all patients. There were no perioperative complications. The average number of excised lymph nodes was 25, and no pathological metastases were observed. There was no difference in disease-free survival rates between the Lap-PAN and no surgery groups (p = 0.42). During the follow-up period, there were two cases of recurrence in the cervix in the Lap-PAN group, and three and four cases of lung and para-aortic lymph node recurrence, respectively in the no-surgery group. Conclusions: Lap-PAN was safely performed as a pretherapeutic staging method for LACC without worsening patient prognosis. Although Lap-PAN requires a high level of skill, it may be a method to avoid excessive radiation for LACC.

Immunosuppressive tumor microenvironment in uterine serous carcinoma via CCL7 signal with myeloid-derived suppressor cells.

Serous carcinoma of the uterus (USC) is a pathological subtype of high-grade endometrial cancers, with no effective treatment for advanced cases. Since such refractory tumors frequently harbor antitumor immune tolerance, many immunotherapies have been investigated for various malignant tumors using immuno-competent animal models mimicking their local immunities. In this study, we established an orthotopic mouse model of high-grade endometrial cancer and evaluated the local tumor immunity to explore the efficacy of immunotherapies against USC. A multivariate analysis of 62 human USC cases revealed that the tumor-infiltrating cell status, few CD8+ cells and abundant myeloid-derived suppressor cells (MDSCs), was an independent prognostic factor (P < 0.005). A murine endometrial cancer cell (mECC) was obtained from C57BL/6 mice via endometrium-specific deletion of Pten and Tp53, and another high-grade cell (HPmECC) was established by further overexpressing Myc in mECCs. HPmECCs exhibited higher capacities of migration and anchorage-independent proliferation than mECCs (P < 0.01, P < 0.0001), and when both types of cells were inoculated into the uterus of C57BL/6 mice, the prognosis of mice bearing HPmECC-derived tumors was significantly poorer (P < 0.001). Histopathological analysis of HPmECC orthotopic tumors showed serous carcinoma-like features with prominent tumor infiltration of MDSCs (P < 0.05), and anti-Gr-1 antibody treatment significantly prolonged the prognosis of HPmECC-derived tumor-bearing mice (P < 0.05). High CCL7 expression was observed in human USC and HPmECC, and MDSCs migration was promoted in a CCL7 concentration-dependent manner. These results indicate that antitumor immunity is suppressed in USC due to increased number of tumor-infiltrating MDSCs via CCL signal.

B7-H3 Suppresses Antitumor Immunity via the CCL2-CCR2-M2 Macrophage Axis and Contributes to Ovarian Cancer Progression.

New approaches beyond PD-1/PD-L1 inhibition are required to target the immunologically diverse tumor microenvironment (TME) in high-grade serous ovarian cancer (HGSOC). In this study, we explored the immunosuppressive effect of B7-H3 (CD276) via the CCL2-CCR2-M2 macrophage axis and its potential as a therapeutic target. Transcriptome analysis revealed that B7-H3 is highly expressed in PD-L1-low, nonimmunoreactive HGSOC tumors, and its expression negatively correlated with an IFNγ signature, which reflects the tumor immune reactivity. In syngeneic mouse models, B7-H3 (Cd276) knockout (KO) in tumor cells, but not in stromal cells, suppressed tumor progression, with a reduced number of M2 macrophages and an increased number of IFNγ+CD8+ T cells. CCL2 expression was downregulated in the B7-H3 KO tumor cell lines. Inhibition of the CCL2-CCR2 axis partly negated the effects of B7-H3 suppression on M2 macrophage migration and differentiation, and tumor progression. In patients with HGSOC, B7-H3 expression positively correlated with CCL2 expression and M2 macrophage abundance, and patients with B7-H3-high tumors had fewer tumoral IFNγ+CD8+ T cells and poorer prognosis than patients with B7-H3-low tumors. Thus, B7-H3 expression in tumor cells contributes to CCL2-CCR2-M2 macrophage axis-mediated immunosuppression and tumor progression. These findings provide new insights into the immunologic TME and could aid the development of new therapeutic approaches against the unfavorable HGSOC phenotype.

A Case of Torsion in an Otherwise-Normal Ovary with a Giant Hematosalpinx Larger than Enlarged Ovary: Utilization of Diagnostic Laparoscopy for the Accurate Diagnosis.

We report a case of torsion in an otherwise-normal ovary with a giant hematosalpinx. A 23-year-old woman presented with complaints of abdominal pain and nausea. At initial visit, there was few abnormal findings of imaging tests, and we made a diagnosis of ovarian hemorrhage. Three days later, she came back with increased symptoms, and we detected the mass of a complex solid cystic structure with a unilocular cyst much larger than solid component. A diagnostic laparoscopy was performed immediately, and we could make a diagnosis of torsion in an otherwise-normal ovary with a giant hematosalpinx. We performed a salpingectomy and could preserve her ovary. This is the first case of torsion in an otherwise-normal ovary with a giant hematosalpinx which enlarged to a greater extent than the ovary.

A 36 kg Giant Ovarian Fibroma with Meigs Syndrome: A Case Report and Literature Review of Extremely Giant Ovarian Tumor.

Ovarian tumors can get extremely giant to occupy the whole abdominal cavity. We report a case of 36 kg solid ovarian tumor, which was the largest ovarian solid tumor that have been ever reported. A 54-year-old woman presented to our hospital with a chief complaint of markedly distended abdominal wall. Preoperative imaging examinations revealed that most of the tumor was uniform and its density was like that of subcutaneous fat. Pleural effusion was detected in the right thoracic region. We organized a multidisciplinary team and successfully resected the right adnexa. The patient had an uneventful postoperative course, and she was discharged on the 7th postoperative day and diagnosed with a fibroma of the ovary with Meigs syndrome. A comprehensive literature search revealed 48 cases of extremely giant ovarian tumor in these 20 years. Six out of 48 cases are solid. Twelve out of 48 cases are malignant or borderline malignant, and patients' age and tumor size/weight were not related to the frequency of malignancy/borderline malignancy. As many as 4 out of 48 patients died before their first hospital visit or early after surgery. Clinicians should consider a considerable high mortality and frequency of severe surgical complications when planning the treatment strategy for extremely giant ovarian tumors.

[A Case of Stage â £ Cholangiocarcinoma with an Improved Quality of Life after Resection of a Symptomatic Giant Ovarian Teratoma].

An 82‒year‒old female presented to our hospital with abdominal fullness and loss of appetite. Abdominal computed tomography revealed a cholangiocarcinoma(Stage Ⅳ)with liver metastases and multiple lymph node metastases. In addition, we found a left ovarian teratoma(approximately 33 cm in diameter)occupying most of the abdominal cavity. She did not want an aggressive treatment for cholangiocarcinoma, but hoped to receive the best supportive care. She was treated with a fentanyl patch, although there was no symptomatic improvement. We explained that resection of the giant ovarian tumor may improve the symptoms. As a result, she accepted the surgery. The laparotomy was performed, and a left ovarian tumor(approximately 10,600 g in weight)was resected. Operation time was 2 hours and 35 minutes, and the amount of blood loss was small. No postoperative complications were observed. She started oral intake at POD 2. The abdominal symptom was relieved by the surgery, and she was discharged to her own home on POD 12. She was readmitted on POD 46 for general malaise, and died of advanced cholangiocarcinoma on POD 66. It was suggested that the QOL may be improved by resecting symptomatic benign tumors even in terminal cancer patients.

Management of an obstructed recurrent inguinal hernia using a hybrid method: a case report.

BACKGROUND: For recurrent incarcerated and strangulated hernias, the optimal treatment strategy for each case is needed. CASE PRESENTATION: The study patient was a 70-year-old man. TAPP repair was performed for a left inguinal hernia (JHS Classification II-1) 7 years earlier. The patient experienced transient pain and swelling of the left inguinal region for 5 months and visited our emergency department for abdominal pain and vomiting. A CT scan showed a recurrent left inguinal hernia and small bowel incarceration, and emergency surgery was performed. Laparoscopic observation of the abdominal cavity revealed recurrent left inguinal hernia (Rec II-1) with small bowel incarceration. The small bowel was reduced after pneumoperitoneum, and no findings suggested intestinal tract necrosis. Adhesions around the herniated sac were dissected using an extraperitoneal approach and then shifted to mesh plug repair. No perioperative complications or hernia recurrence were observed in the 10 months after the surgery. CONCLUSIONS: This report describes a novel, successful surgical treatment for a recurrent incarcerated hernia. In our patient, we could easily perform dissection and understand the positional relationship by hybrid surgery using the TEP method. Additionally, in patients with incarcerated hernias, we believe that performing hybrid surgery by combining the TEP method would be useful because bowel dilation caused by intestinal obstruction would not disturb the operative field.

Prognosis of Immune-related Adverse Events in Patients With Advanced Gastric Cancer Treated With Nivolumab or Pembrolizumab: A Multicenter Retrospective Analysis.

BACKGROUND: Immune-checkpoint inhibitors (ICI), including nivolumab and pembrolizumab, are among the standard treatments for previously treated advanced gastric cancer (AGC). This study aimed to evaluate the frequency of immune-related adverse events (irAEs) and the correlation between irAEs and their efficacy in AGC cases. PATIENTS AND METHODS: Patients were divided into two groups according to irAE occurrence. The frequency of irAEs and the treatment outcome (response rate [RR], progression-free survival [PFS], and overall survival [OS]) were evaluated. The survival rates were evaluated by landmark analysis considering lead-time bias. RESULTS: Among 108 patients who received nivolumab or pembrolizumab, 17 (15.7%) had irAEs. In a 4-week landmark analysis, the RR, median PFS, and median OS were 28.5%, 3.9 months (95% CI=2.8-9.3), and 12.2 months (95% CI=3.8-NA) in patients with irAEs, while 3.0% (2/65), 1.8 months (95% CI=1.4-2.1), and 3.5 months (95% CI, 2.9-5.1) in patients without irAEs, respectively. In multivariate analysis, irAEs were associated with better PFS (HR=2.08, 95% CI=1.34-3.21). CONCLUSION: The occurrence of irAEs was associated with a better clinical outcome of ICIs in patients with AGC.

Three cases of seromucinous carcinoma of the ovary arising in endometriotic cysts.

Ovarian seromucinous carcinoma (SMC) is an uncommon neoplasia and is composed predominantly of serous and endocervical-type mucinous epithelium. Due to its low frequency and difficult diagnosis, the natural history, characteristic imaging findings, and pathological features of SMC have not been adequately described in the literature thus far. We herein report three cases of ovarian SMC along with magnetic resonance imaging (MRI) findings. The diagnosis of SMC was made after staging laparotomy in all cases, and systemic chemotherapy was performed in two cases. No recurrence was observed in any of the cases. The MRI findings in SMC were so varied that characteristic imaging features useful for diagnosis were not found. In two cases, MRI suggested endometriotic cysts, and endometriosis and seromucinous borderline tumors (SMBTs) were detected concurrently in all cases by histological examination. Thus, it was suggested that SMC develops in multiple stages via endometriosis and SMBT. The cooccurrence of endometriosis and SMBT could also make the diagnosis of SMC more convincing.

A Novel Direct Approach to the Deep Uterine Vein in Laparoscopic Radical Hysterectomy.

STUDY OBJECTIVE: To describe a direct approach to the deep uterine vein in laparoscopic radical hysterectomy. DESIGN: Demonstration of the laparoscopic technique with narrated video footage. SETTING: Securing sufficient radicality is extremely important when performing a radical hysterectomy for cervical cancer, either by laparotomy or by minimally invasive surgery. The nerve-sparing Okabayashi radical hysterectomy (NS-RH) was originally aimed at achieving both radical resection and function preservation [1-3]. A key procedure when performing NS-RH is intraoperative identification of the relationship between the deep uterine vein and pelvic splanchnic nerve fibers [4]. With this in mind, a safe and easy method for identifying the crossing point of the deep uterine vein and pelvic splanchnic nerve in the initial phase of the surgery may greatly improve the safety and efficacy of functional preservation in NS-RH. Herein, we describe a minimally invasive "direct approach" to the deep uterine vein. INTERVENTIONS: Before undergoing the pelvic lymphadenectomy, all steps of laparoscopic radical hysterectomy were performed. First, we identified the ureter on the posterior peritoneum, and the peritoneum was dissected just above the ureter. By continuously exploring the pelvic cavity along the ureter, especially through the opening of the space below the ureter in a cranial to caudal direction, we could easily identify the deep uterine vein. This procedure also exposed the fibers of the hypogastric nerve, clarifying the relationship of these structures. CONCLUSION: Because the relationship between the deep uterine vein and nerve fibers is the most important guidepost of this surgery, their identification in the early phase of the surgery enables us to perform the subsequent procedure precisely and securely. This direct approach to the deep uterine vein can be easily and safely performed.

Anti-VEGF therapy resistance in ovarian cancer is caused by GM-CSF-induced myeloid-derived suppressor cell recruitment.

BACKGROUND: The mechanism of resistance development to anti-VEGF therapy in ovarian cancer is unclear. We focused on the changes in tumour immunity post anti-VEGF therapy. METHODS: The frequencies of immune cell populations and hypoxic conditions in the resistant murine tumours and clinical samples were examined. The expression profiles of both the proteins and genes in the resistant tumours were analysed. The impact of granulocyte-monocyte colony-stimulating factor (GM-CSF) expression on myeloid-derived suppressor cell (MDSC) function in the resistant tumours was evaluated. RESULTS: We found a marked increase and reduction in the number of Gr-1 + MDSCs and CD8 + lymphocytes in the resistant tumour, and the MDSCs preferentially infiltrated the hypoxic region. Protein array analysis showed upregulation of GM-CSF post anti-VEGF therapy. GM-CSF promoted migration and differentiation of MDSCs, which inhibited the CD8 + lymphocyte proliferation. Anti-GM-CSF therapy improved the anti-VEGF therapy efficacy, which reduced the infiltrating MDSCs and increased CD8 + lymphocytes. In immunohistochemical analysis of clinical samples, GM-CSF expression and MDSC infiltration was enhanced in the bevacizumab-resistant case. CONCLUSIONS: The anti-VEGF therapy induces tumour hypoxia and GM-CSF expression, which recruits MDSCs and inhibits tumour immunity. Targeting the GM-CSF could help overcome the anti-VEGF therapy resistance in ovarian cancers.

Real-World Effectiveness of Ramelteon and Suvorexant for Delirium Prevention in 948 Patients With Delirium Risk Factors.

OBJECTIVE: The aim of this study was to examine the effectiveness of ramelteon and suvorexant for delirium prevention in real-world practice. It explored whether ramelteon and/or suvorexant would affect delirium prevention among both patients at risk for but without delirium (patients at risk) and those with delirium the night before a consultation. METHODS: This multicenter, prospective, observational study was conducted by trained psychiatrists at consultation-liaison psychiatric services from October 1, 2017, to October 7, 2018. Patients who were aged 65 years or older and hospitalized because of acute diseases or elective surgery, had risk factors for delirium, and had insomnia or delirium on the night before the consultation were prescribed ramelteon and/or suvorexant. The decision to take medication was left to the discretion of each patient. The primary outcome was incidence of delirium based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, during the first 7 days. RESULTS: Among 526 patients at risk, those taking ramelteon and/or suvorexant developed delirium significantly less frequently than those who did not, after control for the effects of risk factors on the estimate of an independent association between the effects of ramelteon and/or suvorexant and the outcome of developing delirium (15.7% vs 24.0%; odds ratio [OR] = 0.48;, 95% CI, 0.29-0.80; P = .005). Similar results were found among 422 patients with delirium (39.9% vs 66.3%; OR = 0.36; 95% CI, 0.22-0.59; P < .0001). CONCLUSIONS: Ramelteon and suvorexant appear to be effective for delirium prevention in real-world practice.

Magnetic resonance relaxometry improves the accuracy of conventional MRI in the diagnosis of endometriosis-associated ovarian cancer: A case report.

Endometriosis is a precancerous condition for endometriosis-associated ovarian cancer (EAOC). In the present study, conventional magnetic resonance imaging (MRI) and MR relaxometry were used to examine a case of clear cell carcinoma that arose in a pre-existing right-sided benign ovarian endometrioma (OE). The 42-year-old nulliparous woman suspected of EOAC, as assessed by conventional MRI, requested fertility-sparing surgery such as laparoscopic endometrioma cystectomy. Furthermore, the MR transverse relaxation rate (R2) was determined using a single-voxel, multi-echo MR sequence using a 3 Tesla-MR system. An R2 value <12.1 s-1 was indicative of malignancy, as described in previous studies. In the present study, MR relaxometry identified an R2 value of 7.98 s-1 in the right cyst, which suggested the malignant transformation of benign OE. Based on these findings, fertility-sparing surgery was contraindicated. In conclusion, MR relaxometry may represent a new clinical approach as an adjunctive modality for the diagnosis of EAOC. When patients exhibiting a pelvic mass suspected of EAOC desire fertility-sparing treatment options, MR relaxometry can facilitate the selection of conservative management.

Phosphorylation of STAT1 serine 727 enhances platinum resistance in uterine serous carcinoma.

Uterine serous carcinoma (USC) is a highly aggressive histological subtype of endometrial cancers harboring highly metastatic and chemoresistant features. Our previous study showed that STAT1 is highly expressed in USC and acts as a key molecule that is positively correlated with tumor progression, but it remains unclear whether STAT1 is relevant to the malicious chemorefractory nature of USC. In the present study, we investigated the regulatory role of STAT1 toward platinum-cytotoxicity in USC. STAT1 suppression sensitized USC cells to increase cisplatin-mediated apoptosis (p < 0.001). Furthermore, phosphorylation of STAT1 was prominently observed on serine-727 (pSTAT1-Ser727), but not on tyrosine-701, in the nucleus of USC cells treated with cisplatin. Mechanistically, the inhibition of pSTAT1-Ser727 by dominant-negative plasmid elevated cisplatin-mediated apoptosis by increasing intracellular accumulation of cisplatin through upregulation of CTR1 expression. TBB has an inhibitory effect on casein kinase 2 (CK2), which phosphorylate STAT1 at serine residues. Sequential treatment with TBB and cisplatin on USC cells greatly reduced nuclear pSTAT1-Ser727, enhanced intracellular accumulation of cisplatin, and subsequently increased apoptosis. Tumor load was significantly reduced by combination therapy of TBB and cisplatin in in vivo xenograft models (p < 0.001). Our results collectively suggest that pSTAT1-Ser727 may play a key role in platinum resistance as well as tumor progression in USC. Thus, targeting the STAT1 pathway via CK2 inhibitor can be a novel method for attenuating the chemorefractory nature of USC.