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Aim: 5‐Fluorouracil/folinic acid and oxaliplatin plus bevacizumab (FOLFOX + BV) is a standard chemotherapy regimen for metastatic colorectal cancer (mCRC). This study was aimed at evaluating the preventive effects of shakuyakukanzoto against oxaliplatin‐induced neurotoxicity associated with FOLFOX + BV administration. Methods: In this single‐arm, open‐label, phase II clinical trial, we enrolled patients with previously untreated, histologically confirmed mCRC from six hospitals in Japan who were aged 20 years and older and had an Eastern Cooperative Oncology Group performance status of 0–1. The patients received shakuyakukanzoto 2.5 g thrice daily, orally, until disease progression and/or unacceptable toxicity was noted. The primary endpoint was the incidence of neurotoxicity following oxaliplatin administration at a dose of 500 mg/m2. Neurotoxicity was evaluated according to the Neurotoxicity Criteria of Debiopharm (DEB‐NTC). The trial was registered in the UMIN Clinical Trials Registry of Japan (UMIN000001853). Results: Forty‐one non‐pretreated mCRC patients were included between April 2009 and September 2013. At an oxaliplatin dose of 500 mg/m2, neurotoxicity of DEB‐NTC grade 1–2 developed in 25.0% of patients; no patient had DEB‐NTC grade 3 neurotoxicity. The most common grade 3/4 adverse events were neutropenia (34.1%), hypertension (24.4%), and fatigue (9.8%). The response rate of the 38 patients with measurable lesions was 55.2%. The median progression‐free and overall survival was 14.9 and 35.2 months respectively. Conclusion: Shakuyakukanzoto substantially reduced oxaliplatin‐induced neurotoxicity without negatively affecting tumor response or survival in FOLFOX + BV‐treated patients with CRC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: Approximately one‐third of patients with major depressive disorder develop treatment‐resistant depression. One‐third of patients with treatment‐resistant depression demonstrate resistance to ketamine, which is a novel antidepressant effective for this disorder. The objective of this study was to examine the utility of resting‐state functional magnetic resonance imaging for the prediction of treatment response to ketamine in treatment‐resistant depression. Methods: An exploratory seed‐based resting‐state functional magnetic resonance imaging analysis was performed to examine baseline resting‐state functional connectivity differences between ketamine responders and nonresponders before treatment with multiple intravenous ketamine infusions. Results: Fifteen patients with treatment‐resistant depression received multiple intravenous subanesthetic (0.5 mg/kg/40 minutes) ketamine infusions, and nine were identified as responders. The exploratory resting‐state functional magnetic resonance imaging analysis identified a cluster of significant baseline resting‐state functional connectivity differences associating ketamine response between the amygdala and subgenual anterior cingulate gyrus in the right hemisphere. Using anatomical region of interest analysis of the resting‐state functional connectivity, ketamine response was predicted with 88.9% sensitivity and 100% specificity. The resting‐state functional connectivity of significant group differences between responders and nonresponders retained throughout the treatment were considered a trait‐like feature of heterogeneity in treatment‐resistant depression. Conclusion: This study suggests the possible clinical utility of resting‐state functional magnetic resonance imaging for predicting the antidepressant effects of ketamine in treatment‐resistant depression patients and implicated resting‐state functional connectivity alterations to determine the trait‐like pathophysiology underlying treatment response heterogeneity in treatment‐resistant depression. [ABSTRACT FROM AUTHOR]

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. What's new? The molecular mechanisms underlying chemoresistance in uterine serous carcinoma (USC), a rare but highly aggressive subtype of endometrial cancer, remain unclear. This study shows that the prognostic outcome for USC patients with high STAT1 expression is poor and STAT1 is involved in platinum resistance. Mechanistically, cisplatin‐induced STAT1 Ser727 phosphorylation alters cellular platinum accumulation to promote resistance and CK2 inhibitors can suppress STAT1 Ser727 phosphorylation. The results suggest that STAT1 could serve as a biomarker to predict tumor chemoresponse, and premedication with a CK2 inhibitor may represent a potent strategy to increase the efficacy of platinum‐based chemotherapeutics in STAT1‐high USC patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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Background: It has been reported that morphologic response to preoperative chemotherapy is an independent prognostic factor in patients who undergo hepatic resection of colorectal liver metastases (CLM). The aim of this study was to evaluate the predictive value of morphologic response to first-line chemotherapy in patients with CLM. Methods: We assessed 41 patients with CLM who received fluorouracil-based chemotherapy with or without bevacizumab as the first-line chemotherapy between April 2006 and June 2012. Three blinded radiologists evaluated computed tomography images and classified them as optimal, incomplete or no response according to the morphologic criteria. Response to systemic chemotherapy was also evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). Predictive factors associated with progression-free survival (PFS) were identified in multivariate analysis. Results: Twenty-three patients (56%) received chemotherapy with bevacizumab, while 18 patients (44%) received chemotherapy without bevacizumab. Optimal morphologic response was observed in 11 patients (48%) treated with bevacizumab and in 5 patients (28%) treated without bevacizumab (p = 0.19). Eight patients (20%) underwent hepatic resection after chemotherapy. The median follow-up period was 31.3 months. The median PFS was 13.3 months for patients with optical morphologic response and 8.7 months in those with incomplete/no morphologic response (p = 0.0026). On multivariate analysis, performance status and morphologic response were significant independent predictors of PFS. Conclusion: Optimal morphologic response was significantly associated with PFS in patients with CLM who were treated with fluorouracil-based chemotherapy as the first-line chemotherapy. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The human skin is weak-acidic in a healthy condition, so that it is important keeping a slightly acidic skin to suppress the breeding of ill-function microorganisms on skin. In this study, we have applied newly developed weak- acidic PET fabrics for sportswear in order to examine the effect on the pH at skin surface and its consequent condition. Two types of weak-acidic PETs were prepared by chemical modification and subsequent processing, and the skin condition was compared by human subjects wearing the sportswear made of untreated and two weak-acidic PET fabrics. The weak-acidic PET fabrics were found effective to maintain the pH value lower at skin surface. Here the pH value was even lower after exercise than before exercise. The pH value at skin surface did not change before and after exercise in the case of untreated PET fabric. The results indicate that the pH of sweat is buffered by weak-acidic PET and the breeding of ill-function microorganism is suppressed. In fact the generation of foul smell due to the fermentation of sweat components is less detected. [ABSTRACT FROM AUTHOR]

Increased release of thromboxane A2 (TXA2) has been shown to be involved in inflammatory bowel diseases. In the present study, we have investigated the effect of a stable TXA2 analogue (STA2) on the electrical parameters in isolated human colonic mucosa. In the human mucosa set between Ussing chambers, STA2 stimulated Cl− secretion in a concentration-dependent manner with an EC50 of 0.06μm. The STA2-induced Cl− secretion was significantly inhibited by ONO-3708 (10μm), a specific TXA2 receptor antagonist. The effect of STA2 (0.3μm) was independent of the colonic segment from which the tissue was obtained, from caecum to rectum. Chromanol 293B, an inhibitor of the cAMP-dependent KvLQT1 channel, attenuated the STA2-induced Cl− secretion in the human colonic mucosa (IC50 value 1.18μm). We found that KvLQT1 mRNA and protein were expressed in all the tested segments of the human colon. The STA2-induced Cl− secretion was significantly inhibited by 8-bromo-2′-monobutyryladenosine-3′,5′-cyclic monophosphorothioate (50μm), a membrane-permeant cAMP antagonist. STA2 (0.3μm) significantly increased the intracellular cAMP levels and the short-circuit current via TXA2 receptor in a human colonic cell line. These results suggest that the TXA2-induced Cl− secretion in the colon is mediated via the cAMP pathway in addition to the Ca2+–calmodulin pathway which was previously reported. [ABSTRACT FROM AUTHOR]

It has been controversial whether the ClC-2 chloride channel is involved in hydrochloric acid secretion of gastric parietal cells. Here, we investigated whether ClC-2 is the apical Cl- channel associated with gastric acid secretion. Two anti-ClC-2 antibodies used in this study reacted with cloned ClC-2 protein expressed in HEK293 cells. In isolated rabbit gastric glands, significant expression of ClC-2 mRNA was observed, but the presence of ClC-2 protein was not clear. Furthermore, no expression of ClC-2 protein was observed in isolated rat and human gastric mucosa. Immunohistochemistry on the rat gastric mucosa showed no significant expression of ClC-2 protein in the parietal cells which showed abundant expression of H+,K+-ATPase. These results indicate that ClC-2 may not be a Cl--transporting protein for gastric acid secretion in parietal cells. [Copyright &y& Elsevier]

We investigated expression levels of Na+,K+-ATPase α-isoforms and their ATPase activities in human colorectal cancer tissue and the accompanying normal mucosa. A decrease in expression of the α1-isoform protein was observed in all sampled cancer tissues compared with the normal mucosae. The level of ouabain (5 μM)-sensitive Na+,K+-ATPase activity in carcinomas was 81±5% that of in the normal mucosae. The mRNA expression of α2- and α4-isoforms was decreased in almost all the carcinoma samples. Interestingly, the expression level of the α3-isoform protein in the cancer tissue was higher than that of the normal mucosa. These results indicate that a decrease in the α1-isoform expression and an increase in the α3-isoform expression may be associated with colorectal cancer. [Copyright &y& Elsevier]

Objective: Adenomyosis-related infertility is increasingly being diagnosed, and surgical intervention has been suggested to improve fertility. Elastography, a noninvasive ultrasound technique, is promising for diagnosing and guiding the resection of adenomyosis. This report presents the first case of successful delivery after twin pregnancies achieved with IVF following intraoperative elastography-guided laparoscopic adenomyomectomy., Case Report: A 35-year-old Japanese woman with uterine adenomyosis received a gonadotropin analog before surgery. Preoperative MRI revealed a 5.0 × 7.0 cm adenomyoma, leading to scheduled laparoscopic adenomyomectomy with intraoperative elastography. During surgery, elastography ensured the complete resection of the adenomyotic tissue while preserving the endometrium. Postoperative MRI confirmed the absence of residual adenomyosis. The patient underwent in vitro fertilization and embryo transfer, leading to a successful twin pregnancy after double blastocyst transfer. Despite a stable perinatal course, she required hospitalization to prevent preterm labor. At 32 weeks, an elective cesarean section delivered healthy twins. The intra- and post-operation was uncomplicated, and the patient and infants had an optimal health., Conclusion: This is the first reported case of a twin pregnancy resulting from vitrified-warmed embryo transfer after elastography-guided laparoscopic adenomyomectomy, culminating in a successful delivery via cesarean section. This technique allows precise resection and mitigates the risks of uterine rupture and placenta accreta spectrum disorders. Although promising, further studies are required to validate the safety and efficacy of this innovative surgical approach., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ota, Ota, Takahashi, Horikawa, Kuroda, Okamoto, Tanaka, Kusumoto, Oda, Matsuyama, Miyake, Honda and Shimoya.)

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.

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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2022 by SLS, Society of Laparoscopic & Robotic Surgeons.)

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., (©2021 The Authors; Published by the American Association for Cancer Research.)

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.

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., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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., (© Copyright 2019 Physicians Postgraduate Press, Inc.)

A 61-year-old woman presented to our hospital with abdominal distension. Abdominal CT showed massive ascites and disseminated peritoneal nodules. The patient was diagnosed with primary peritoneal cancer based on ascites and disseminated peritoneal nodules following laparoscopic surgery(initial operation). After receiving neoadjuvant chemotherapy, she underwent hysterectomy, bilateral salpingo-oophorectomy, and omentectomy(2nd operation). During chemotherapy, she experienced small bowel obstruction owing to disseminated peritoneal recurrence and splenic metastasis. Therefore, she underwent a laparoscopic partial small bowel resection(3rd operation)and laparoscopic splenectomy(4th operation). Treatment of primary peritoneal carcinoma consists of debulking surgery and chemotherapy. Laparoscopic debulking surgery may be useful for preventing adhesions and facilitating early postoperative recovery.

Snail is a major transcriptional factor that induces epithelial-mesenchymal transition (EMT). In this study, we explore the effect of Snail on tumor immunity. Snail knockdown in mouse ovarian cancer cells suppresses tumor growth in immunocompetent mice, associated with an increase of CD8 + tumor-infiltrating lymphocytes and a decrease of myeloid-derived suppressor cells (MDSCs). Snail knockdown reduces the expression of CXCR2 ligands (CXCL1 and CXCL2), chemokines that attract MDSCs to the tumor via CXCR2. Snail upregulates CXCR ligands through NF-kB pathway, and most likely, through direct binding to the promoters. A CXCR2 antagonist suppresses MDSC infiltration and delays tumor growth in Snail-expressing mouse tumors. Ovarian cancer patients show elevated serum CXCL1/2, which correlates with Snail expression, MDSC infiltration, and short overall survival. Thus, Snail induces cancer progression via upregulation of CXCR2 ligands and recruitment of MDSCs. Blocking CXCR2 represents an immunological therapeutic approach to inhibit progression of Snail-high tumors undergoing EMT.

Purpose: High VEGF expression in ovarian cancer is an unfavorable prognostic factor. However, the role of VEGF in tumor immunity remains unclear. Here, we examined the impact of VEGF on local immunity, including induction of myeloid-derived suppressor cells (MDSC), in ovarian cancer., Experimental Design: High-grade serous ovarian cancer (HGSOC) cases were analyzed by gene expression microarray and IHC for VEGF, CD8, and CD33. VEGF receptor (VEGFR) 1 and VEGFR2 expression levels on MDSCs were analyzed in a mouse model, and the direct effects of VEGF-A on MDSC expansion were investigated. Gr1 + MDSCs and lymphocyte frequencies were analyzed in control tumors and tumors derived from cells harboring short hairpin RNA targeting Vegf-a. In addition, the therapeutic effects of anti-Gr-1 antibodies were examined., Results: Microarray analysis revealed the upregulation of several myeloid cell chemoattractants and the downregulation of lymphocyte-related pathways in cases with high VEGF expression. In immunohistochemical analysis, VEGF expression in peritoneal dissemination correlated with MDSC infiltration. Cases with high MDSC infiltration, which was inversely correlated with intratumoral CD8 + T-cell infiltration, exhibited shorter overall survival. In a mouse model, intratumoral MDSCs expressed both VEGFR1 and VEGFR2. MDSC migration and differentiation were augmented by VEGF signaling. Vegf-a knockdown in tumor cells resulted in decreased MDSC infiltration and increased CD8 + T-cell infiltration. Moreover, treatment with anti-Gr-1 antibodies delayed the growth of control tumors, whereas Vegf-a-knockdown tumors were unaffected by anti-Gr-1 antibody treatment., Conclusions: VEGF expression in ovarian cancer induced MDSCs, inhibited local immunity, and contributed to poor prognosis. Clin Cancer Res; 23(2); 587-99. ©2016 AACR., (©2016 American Association for Cancer Research.)

Emerging evidence has highlighted the host immune system in modulating the patient response to chemotherapy, but the mechanism of this modulation remains unclear. The aim of this study was to analyze the effect of chemotherapy on antitumor immunity in the tumor microenvironment of ovarian cancer. Treatment of ovarian cancer cell lines with various chemotherapeutic agents resulted in upregulated expression of MHC class I and programmed cell death 1 ligand 1 (PD-L1) in a NF-κB-dependent manner and suppression of antigen-specific T-cell function in vitro. In a mouse model of ovarian cancer, treatment with paclitaxel increased CD8(+) T-cell infiltration into the tumor site, upregulated PD-L1 expression, and activated NF-κB signaling. In particular, tumor-bearing mice treated with a combination of paclitaxel and a PD-L1/PD-1 signal blockade survived longer than mice treated with paclitaxel alone. In summary, we found that chemotherapy induces local immune suppression in ovarian cancer through NF-κB-mediated PD-L1 upregulation. Thus, a combination of chemotherapy and immunotherapy targeting the PD-L1/PD-1 signaling axis may improve the antitumor response and offers a promising new treatment modality against ovarian cancer., (©2015 American Association for Cancer Research.)