Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer.

BACKGROUND: Mirvetuximab soravtansine-gynx (MIRV), a first-in-class antibody-drug conjugate targeting folate receptor α (FRα), is approved for the treatment of platinum-resistant ovarian cancer in the United States. METHODS: We conducted a phase 3, global, confirmatory, open-label, randomized, controlled trial to compare the efficacy and safety of MIRV with the investigator's choice of chemotherapy in the treatment of platinum-resistant, high-grade serous ovarian cancer. Participants who had previously received one to three lines of therapy and had high FRα tumor expression (≥75% of cells with ≥2+ staining intensity) were randomly assigned in a 1:1 ratio to receive MIRV (6 mg per kilogram of adjusted ideal body weight every 3 weeks) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary end point was investigator-assessed progression-free survival; key secondary analytic end points included objective response, overall survival, and participant-reported outcomes. RESULTS: A total of 453 participants underwent randomization; 227 were assigned to the MIRV group and 226 to the chemotherapy group. The median progression-free survival was 5.62 months (95% confidence interval [CI], 4.34 to 5.95) with MIRV and 3.98 months (95% CI, 2.86 to 4.47) with chemotherapy (P<0.001). An objective response occurred in 42.3% of the participants in the MIRV group and in 15.9% of those in the chemotherapy group (odds ratio, 3.81; 95% CI, 2.44 to 5.94; P<0.001). Overall survival was significantly longer with MIRV than with chemotherapy (median, 16.46 months vs. 12.75 months; hazard ratio for death, 0.67; 95% CI, 0.50 to 0.89; P = 0.005). During the treatment period, fewer adverse events of grade 3 or higher occurred with MIRV than with chemotherapy (41.7% vs. 54.1%), as did serious adverse events of any grade (23.9% vs. 32.9%) and events leading to discontinuation (9.2% vs. 15.9%). CONCLUSIONS: Among participants with platinum-resistant, FRα-positive ovarian cancer, treatment with MIRV showed a significant benefit over chemotherapy with respect to progression-free and overall survival and objective response. (Funded by ImmunoGen; MIRASOL ClinicalTrials.gov number, NCT04209855.).

The anti-tumor effects of AZD4547 on ovarian cancer cells: differential responses based on c-Met and FGF19/FGFR4 expression.

BACKGROUND: The FGF/FGFR signaling pathway plays a critical role in human cancers. We analyzed the anti-tumor effect of AZD4547, an inhibitor targeting the FGF/FGFR pathway, in epithelial ovarian cancer (EOC) and strategies on overcoming AZD4547 resistance. METHODS: The effect of AZD4547 on cell viability/migration was evaluated and in vivo experiments in intraperitoneal xenografts using EOC cells and a patient-derived xenograft (PDX) model were performed. The effect of the combination of AZD4547 with SU11274, a c-Met-specific inhibitor, FGF19-specific siRNA, or an FGFR4 inhibitor was evaluated by MTT assay. RESULTS: AZD4547 significantly decreased cell survival and migration in drug-sensitive EOC cells but not drug-resistant cells. AZD4547 significantly decreased tumor weight in xenograft models of drug-sensitive A2780 and SKOV3ip1 cells and in a PDX with drug sensitivity but not in models with drug-resistant A2780-CP20 and SKOV3-TR cells. Furthermore, c-Met expression was high in SKOV3-TR and HeyA8-MDR cells, and co-administration of SU11274 and AZD4547 synergistically induced cell death. In addition, expressions of FGF19 and FGFR4 were high in A2780-CP20 cells. Combining AZD4547 with FGF19 siRNA or with a selective FGFR4 inhibitor led to significantly reduced cell proliferation in A2780-CP20 cells. CONCLUSIONS: This study showed that AZD4547 has significant anti-cancer effects in drug-sensitive cells and PDX models but not in drug-resistant EOC cells. In drug-resistant cells, the expression level of c-Met or FGF19/FGFR4 may be a predictive biomarker for AZD4547 treatment response, and a combination strategy of drugs targeting c-Met or FGF19/FGFR4 together with AZD4547 may be an effective therapeutic strategy for EOC.

Active Surface Area-Dependent Water Harvesting of Desert Beetle-Inspired Hybrid Wetting Surfaces.

The increasing frequency of water scarcity is an acute worldwide problem. Nature-inspired water harvesting from fog is an important method to obtain freshwater in arid areas. Existing literature reports varied and diversified results in water harvesting capacity by employing a biphilic surface with control over hydrophilic and hydrophobic patterns. In this study, we first demonstrate a facile and scalable method to fabricate a biphilic surface using a simple electroless etching and desilanization technique. Considering the nucleation, growth, and transport of condensate, biphilic surfaces with controlled active surface area of hydrophilic spots were given special attention. We studied the water collection performance of pattern shape with its associated active surface area and further evaluated the critical surface area beyond which the water collection efficiency decreases. A high water collection capacity of 2050 mg cm-2 h-1 was achieved, and the hydrophilic active area-engineered surface retained its efficiency even after 50 test cycles. We further demonstrate high collection efficiency with a square pattern compared to a triangular path-like-patterned surface. The observations and surface engineering strategies reported in this study can provide insights into efficient and sustainable water harvesting devices.

Anti-cancer effects of benzimidazole derivative BNZ-111 on paclitaxel-resistant ovarian cancer.

OBJECTIVE: Ovarian cancer, a leading cause of cancer-related deaths in women, remains a formidable challenge, especially in the context of platinum-resistant disease. This study investigated the potential of the benzimidazole derivative BNZ-111 as a novel treatment strategy for platinum-resistant ovarian cancer. METHODS: The human EOC cell lines A2780, HeyA8, SKOV3ip1, A2780-CP20, HeyA8-MDR, and SKOV3-TR were treated with BNZ-111, and cell proliferation, apoptosis, and cell cycle were assessed. RESULTS: It demonstrated strong cytotoxicity in both chemo-sensitive and chemo-resistant epithelial ovarian cancer cell lines, inducing apoptosis and G2/M cell cycle arrest. In vivo experiments using orthotopic and patient-derived xenograft models showed significant tumor growth inhibition without apparent toxicity to vital organs. Unlike paclitaxel, BNZ-111 proved effective in paclitaxel-resistant cells, potentially by bypassing interaction with MDR1 and modulating ß-3 tubulin expression to suppress microtubule dynamics. CONCLUSION: BNZ-111, with favorable drug-like properties, holds promise as a therapeutic option for platinum-resistant ovarian cancer, addressing a critical clinical need in gynecologic oncology.

Risk Factors Affecting Clinical Outcomes of Low-risk Early-stage Human Papillomavirus-Associated Endocervical Adenocarcinoma Treated by Surgery Alone: Application of Silva Pattern.

This study aimed to report the clinical outcomes and risk factors for survival of patients with low-risk early-stage human papillomavirus-associated (HPVA) endocervical adenocarcinoma (EAC) treated with surgery alone. This retrospective study obtained the clinicopathological data of patients with early-stage HPVA EAC who underwent surgery between 2012 and 2018. The Silva pattern of invasion was determined by reviewing pathology slides. Locoregional recurrence-free survival (RFS), RFS, and overall survival were calculated, and the risk factors for survival were analyzed. One hundred seventeen patients with a median follow-up of 5.2 years (0.5-9.7 yr) were included. The most common histologic type was usual (94/117, 80.3%). The Silva pattern was A in 79 patients (67.5%), B in 30 (25.6%), and C in 8 (6.8%). The 5-year locoregional RFS, RFS, and overall survival rates were 92.4%, 87.8%, and 97.2%, respectively. The presence of intermediate-risk factors and Silva pattern C were significantly associated with worse survival. Based on these findings, patients were categorized into 2 groups: Group 1 (Silva pattern A or Silva pattern B without intermediate-risk factors) and Group 2 (Silva pattern B with intermediate-risk factors or Silva pattern C). Group 2 showed significantly worse outcomes than Group 1, including the 5-year locoregional RFS (98.6% vs 68.0%), RFS (96.4% vs 54.6%), and overall survival (100.0% vs 86.5%). In conclusion, surgery alone for early-stage HPVA EAC resulted in favorable outcomes. Consideration of the Silva pattern, in addition to well-known risk factors, could help in precise risk group stratification of low-risk, early-stage HPVA EAC.

Prognostic Impact of Visceral Adipose Tissue Imaging Parameters in Patients with Cholangiocarcinoma after Surgical Resection.

Visceral adiposity is known to be related to poor prognosis in patients with cholangiocarcinoma; however, the prognostic significance of the qualitative features of adipose tissue in cholangiocarcinoma has yet to be well defined. This study investigated the prognostic impact of adipose tissue imaging parameters reflecting the quantity and qualitative characteristics of subcutaneous (SAT) and visceral (VAT) adipose tissue on recurrence-free survival (RFS) and overall survival (OS) in 94 patients undergoing resection of cholangiocarcinoma. The area, mean computed tomography (CT) attenuation, and mean 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake of SAT and VAT on positron emission tomography (PET)/CT for staging work-up were measured, and the relationship of these adipose tissue imaging parameters with clinicopathological factors and survival was assessed. TNM stage, histologic grade, lymphovascular invasion, and the size of cholangiocarcinoma showed positive correlations with adipose tissue imaging parameters. Multivariate survival analysis demonstrated that the visceral-to-subcutaneous adipose tissue area ratio (VSR) (p = 0.024; hazard ratio, 1.718) and mean FDG uptake of VAT (p = 0.033; hazard ratio, 9.781) were significant predictors for RFS, but all of the adipose tissue imaging parameters failed to show statistical significance for predicting OS. In addition to visceral adiposity, FDG uptake of VAT might be a promising prognostic parameter for predicting RFS in patients with cholangiocarcinoma.

Comparison of Minimally Invasive and Open Surgery for the Treatment of Endometrial Cancer with a High Risk of Recurrence: A Propensity Score Matching Study in Korea and Taiwan.

BACKGROUND: This study compared oncologic outcomes between minimally invasive surgery (MIS) and open surgery for the treatment of endometrial cancer with a high risk of recurrence. METHODS: This study included patients with endometrial cancer who underwent primary surgery at two tertiary centers in Korea and Taiwan. Low-grade advanced-stage endometrial cancer (endometrioid grade 1 or 2) or endometrial cancer with aggressive histology (endometrioid grade 3 or non-endometrioid) at any stage was considered to have a high risk of recurrence. We conducted 1:1 propensity score matching between the MIS and open surgery groups to adjust for the baseline characteristics. RESULTS: Of the total of 582 patients, 284 patients were included in analysis after matching. Compared with open surgery, MIS did not show a difference in disease-free survival [hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.67-1.77, P = 0.717] or overall survival (HR 0.67; 95% CI 0.36-1.24, P = 0.198). In the multivariate analysis, non-endometrioid histology, tumor size, tumor cytology, depth of invasion, and lymphovascular space invasion were risk factors for recurrence. There was no association between the surgical approach and either recurrence or mortality in the subgroup analysis according to stage and histology. CONCLUSIONS: MIS did not compromise survival outcomes for patients with endometrial cancer with a high risk of recurrence when compared with open surgery.

Effects of sarpogrelate on blood viscosity.

The objective of the present study was to evaluate the effects and safety of sarpogrelate hydrochloride (sarpogrelate) in patients with elevated blood viscosity (BV), after 12 and 24 weeks of twice (BID) or thrice (TID) daily administrations of sarpogrelate (100 mg). The participants received oral sarpogrelate administration for 24 weeks and visited the hospital every 12 ± 2 week for blood viscosity measurements at shear rates of 5 and 300 s-1. The BV measured at shear rate of 5 s-1 in male patients decreased significantly from 18.91 cP at the baseline to 16.3 cP after 24 weeks of sarpogrelate administration (13.6 % drop, p < 0.001). The BV measured at 5 s-1 in female decreased more significantly from 17.5 cP at the baseline to 13.4 cP after 24 weeks of sarpogrelate administration (23.0 % drop, p < 0.001). In summary, sarpogrelate may be considered as a possible therapeutic option for improving BV in patients with elevated blood viscosity. In particular, the reduction of the low-shear BV with the help of a viscosity-reducing drug such as sarpogrelate may be considered as a potentially new pharmacological tool for microvascular disease.

Arteriovenous Malformation Associated with Intravenous Leiomyomatosis of the Uterus: Characteristic CT Findings and Treatment by Embolization and Surgery.

Seven consecutive female patients with pathologically confirmed arteriovenous malformation (AVM) with intravenous leiomyomatosis (IVL) of the uterus (age range, 32-61 years; mean age, 43 years) treated between 2005 and 2021 from a single institution were reviewed. Computed tomography (CT) findings of congenital pelvic AVM of 10 female patients were compared with those of AVM with IVL. Characteristic CT findings of AVM with IVL revealed a focal soft tissue mass inside a dilated venous structure of the AVM. Multiple sessions of transvenous coil embolization of the AVM with or without the injection of ethanol were performed. After complete (6/7, 86%) or partial (1/7, 14%) embolization of the AVM, complete surgical resection of the IVL and embolized AVM mass was performed in 4 patients. Patients with lung metastasis or residual embolized AVM masses are under follow-up with antiestrogen hormonal therapy.

Role of salvage radiotherapy for recurrent ovarian cancer.

OBJECTIVE: This study aimed to report clinical outcomes of salvage radiotherapy for recurrent ovarian cancer and identify predictors of clinical outcomes. METHODS: We retrospectively reviewed data of patients who received salvage radiotherapy for recurrent ovarian cancer between January 2011 and June 2021. Stereotactic body radiotherapy, involved-field radiotherapy with conventional fractionation, and non-involved-field radiotherapy with conventional fractionation were included in this study. Local failure-free survival, progression-free survival, chemotherapy-free survival, and overall survival were assessed. Additionally, potential prognostic factors for survival were analyzed. RESULTS: A total of 79 patients were included with 114 recurrent lesions. The median follow-up was 18.3 months (range 1.7-83). The 2-year local failure-free survival, progression-free survival, chemotherapy-free survival, and overall survival rates were 80.7%, 10.6%, 21.2%, and 74.7%, respectively. Pre-radiotherapy platinum resistance (hazard ratio (HR) 3.326, p<0.001) and short pre-radiotherapy CA-125 doubling time (HR 3.664, p<0.001) were associated with poor chemotherapy-free survival. The 1-year chemotherapy-free survival rates of patients with both risk factors, a single risk factor, and no risk factor were 0%, 20.4%, and 53.5%, respectively. The difference between risk groups was statistically significant: low risk versus intermediate risk (p<0.001) and intermediate risk versus high risk (p<0.001). CONCLUSIONS: Salvage radiotherapy for recurrent ovarian cancer resulted in local control with improved chemotherapy-free survival in carefully selected patients. Our results suggest that the consideration of pre-radiotherapy platinum resistance and pre-radiotherapy CA-125 doubling time could help with patient selection.

The Effect of Intrathecal Morphine on Postoperative Opioid Consumption in Patients Undergoing Abdominal Surgery for Gynecologic Malignancy: A Randomized Sham-Controlled Trial.

BACKGROUND: Surgery for gynecologic malignancy via midline-laparotomy leads to severe postoperative pain. Adequate pain control while sparing opioid consumption does offer benefits in postoperative complications and recovery. Intrathecal morphine (ITM) provides simple and effective analgesia. In this randomized trial, we compared postoperative opioid consumption in patients who received either ITM or a sham procedure. METHODS: We enrolled 68 adult patients undergoing open gynecologic oncology surgery from June 2021 to November 2021. They were randomly allocated to the ITM group (ITM; 200 µg injection) or sham group (sham procedure) to achieve a final 1:1 ratio between groups. We compared opioid consumption and pain severity during 72 hours after surgery. The variables regarding postoperative recovery and patient-centered outcomes were collected. The primary outcome is cumulative intravenous (IV) opioid consumption 24 hours after surgery. RESULTS: The median (interquartile range) cumulative IV opioid consumption during 24 hours after surgery was 18 mg (12-29) in the ITM group and 36 mg (27-42) in the sham group (median difference, 13; 95% confidence interval, 7.2-20.7; P < .001). Patient satisfaction regarding pain control was statistically significantly higher in the ITM group than in the sham group at postoperative 24 and 48 hours ( P < .001 and P = .005, respectively). There were no significant differences in the variables associated with postoperative recovery and frequency of complications requiring treatment. CONCLUSIONS: ITM is a safe and effective analgesic method after curative intent laparotomy for gynecologic malignancy. ITM provides better pain relief, reduces opioid consumption, and improves patient satisfaction without additional evident adverse events.

Somatic genomic landscape of East Asian epithelial ovarian carcinoma and its clinical implications from prospective clinical sequencing: A Korean Gynecologic Oncology Group study (KGOG 3047).

Through the wide adaptation of next-generation sequencing (NGS) technology within clinical practice, molecular profiling of the tumor has been the principal component of personalized treatment. In our study, we have generated a large collection of cancer genomes on East Asian epithelial ovarian carcinoma (EOC) patients and demonstrate the feasibility and utility of NGS platforms to explore the dynamic interrelations of major cancer driver alterations and their impacts on clinical prognosis and management. A total of 652 EOC patients have undergone clinical NGS panels to determine the prevalence of germline and somatic mutations. Notably, TP53 was the most frequently altered event (73%), followed by both BRCA1 and BRCA2 (22% each) and MYC (19%) through pan-EOC analysis. When analyzed based on individual histopathological levels, TP53 mutation was highly dominant in high-grade serous and mucinous histology, whereas mutations in PIK3CA and ARID1A were mostly observed in clear cell carcinoma, and KRAS, BRAF, and CDKN2A mutations were enriched in endometrioid, low-grade serous, and mucinous tumors, respectively. The network-based probabilistic model showed significant co-occurrences of TP53 with BRCA1 and ALK with BRCA2, NOTCH1, and ROS1, whereas mutual exclusivity of TP53 with KRAS and PIK3CA was evident. Furthermore, we utilized machine-learning algorithms to identify molecular correlates that conferred increased sensitivity to platinum and olaparib treatments including somatic mutations in BRCA1, ATM, and MYC. Conversely, patients with ALK mutation were considerably resistant to both treatment modalities. Collectively, our results demonstrate the clinical feasibility of prospective genetic sequencing to facilitate personalized treatment opportunities for patients with EOC.

Real-world experience of pembrolizumab and lenvatinib in recurrent endometrial cancer: A multicenter study in Korea.

OBJECTIVE: To investigate the effectiveness and safety of pembrolizumab and lenvatinib (PEMBRO+LEN) for recurrent endometrial cancer (EC) in a real-world setting. METHODS: This multicenter retrospective cohort study included patients with recurrent EC who received PEMBRO+LEN between March 2020 and May 2021 at three tertiary hospitals in Korea. We summarized patient characteristics and evaluated the response rates, survival outcomes, and treatment-related adverse events (AEs). RESULTS: In total, 48 patients were included in the study. The median age of the patients was 62.5 (range, 42-78) years. The most common histologic subtype was endometrioid adenocarcinoma (43.8%), followed by serous adenocarcinoma (25.0%). Most patients (91.7%) had mismatch repair-proficient tumors. Patients received PEMBRO+LEN for a median of 4.5 cycles, during which the best objective response rate and disease control rate were 23.8% (95% CI, 11.9-38.1) and 76.2% (95% CI, 61.9-88.1), respectively. Overall, 56.2% of patients experienced LEN dose reduction once or more and 16.7% experienced LEN interruption. The most common treatment-related AEs were fatigue (18.8%), hypertension (16.7%), and hypothyroidism (14.6%). Total of 8 patients (16.7%) discontinued LEN during the treatment because of treatment-related AEs. Serum CA-125 level was the only prognostic factor for progression-free survival (adjusted hazard ratio, 4.41; 95% confidence interval, 1.19-16.36; p = 0.03). CONCLUSIONS: In our real-world study, Korean patients with recurrent EC who received PEMBRO+LEN showed lower treatment response rate and similar treatment discontinuation rate, compared to clinical trials.

Impact of bevacizumab and secondary cytoreductive surgery on survival outcomes in platinum-sensitive relapsed ovarian clear cell carcinoma: A multicenter study in Korea.

OBJECTIVE: This study investigated survival outcomes for platinum-sensitive relapsed ovarian clear cell carcinoma (OCCC) by treatment method. METHODS: OCCC patients with platinum-sensitive recurrence that received secondary treatment at five institutions between July 2007 and June 2021 were included. Patient characteristics and survival outcomes were compared according to the use of bevacizumab (BEV) during second-line chemotherapy and secondary cytoreductive surgery (CRS). RESULTS: 138 patients were included. The BEV (n = 36) and non-BEV (n = 102) groups had similar initial FIGO stages and proportions of secondary CRS. The BEV group showed improved progression-free survival (PFS; median, 15.4 vs. 7.5 months; P = 0.042) and overall survival (OS; P = 0.043) compared to the non-BEV group. In multivariate analyses, BEV was identified as an independent prognostic factor for PFS (adjusted hazard ratio [aHR], 0.571; 95% confidence interval [CI], 0.354-0.921; P = 0.022) and OS (aHR, 0.435; 95%CI, 0.195-0.970; P = 0.042). The secondary CRS group (n = 42) had early-stage disease at diagnosis more frequently (P = 0.009) and multi-site metastasis (P < 0.001) at recurrence less frequently than the no surgery group (n = 96). The secondary CRS group showed significantly better PFS (median, 33.7 vs. 7.2 months; P < 0.001) and OS (P < 0.001). Secondary CRS was associated with a significantly improved PFS (aHR, 0.297; 95% CI, 0.183-0.481; P < 0.001) and OS (aHR, 0.276; 95% CI, 0.133-0.576; P = 0.001). The BEV and non-BEV groups showed similar PFS and OS among the patients who underwent secondary CRS. In contrast, the BEV group showed improved PFS and OS among patients who did not undergo surgery. CONCLUSIONS: The use of BEV during second-line chemotherapy and secondary CRS may improve PFS and OS in patients with platinum-sensitive relapsed OCCC. Further prospective studies are warranted.

Combination effect of poly (ADP-ribose) polymerase inhibitor and DNA demethylating agents for treatment of epithelial ovarian cancer.

OBJECTIVE: Poly (ADP)-ribose polymerase inhibitors (PARPi) are effective clinical agents for treatment of epithelial ovarian cancer (EOC) harboring BRCA mutations as well as those without BRCA mutations. In this study, we evaluate the efficacy of combined PARPi and DNA methyltransferase inhibitor (DNMTi) in EOCs. METHODS: Expression levels of DNMT1 and PARP1 proteins in EOC cells were assessed using western blot analysis and immunohistochemistry. To evaluate the effects of co-treatment of PARPi (olaparib) and DNMTi (5-azacitidine, 5-AZA), we performed cell proliferation, apoptosis, and wound-healing assays in EOC cells. In addition, we performed in vivo experiments using both cell-line and patient-derived xenograft (PDX) models of EOC. RESULTS: The combination of olaparib and 5-AZA significantly inhibited cell proliferation and migration and induced apoptosis compared with olaparib or 5-AZA alone in EOC cell lines including A2780, HeyA8, A2780-CP20, and HeyA8-MDR. Moreover, in vivo experiments with this combination showed significantly decreased weight and nodule numbers of tumors in cell-line xenograft models with A2780 cells and a PDX model compared with control, olaparib, and 5-AZA groups. As a potential mechanism, the expression of intracellular reactive oxygen species (ROS) and its related proteins, including p-ERK, NRF2, p-p38, HO-1, and γH2AX, was affected in EOC cells. CONCLUSIONS: Co-treatment with PARPi and DNMTi had a significant anti-tumor effect in EOC cells. This combination might be a potential therapeutic strategy for EOCs.

Impact of no residual disease on postoperative computed tomography on survival in patients with optimally debulked advanced high-grade serous ovarian cancer during upfront surgery.

OBJECTIVE: We sought to investigate the impact of size of residual tumors as determined by postoperative computed tomography (CT) on survival of patients with advanced, high-grade serous ovarian carcinoma (HGSC) who achieved residual disease less than 1 cm after primary debulking surgery (PDS). METHODS: We collected data of patients with stage III HGSC who had residual tumor less than 1 cm after PDS between 2013 and 2018. Surgeon-assessed residual disease during surgery was defined as sR0 (no gross residual) or sR1 (gross residual <1 cm), and radiologist-assessed residual disease on postoperative CT was defined as rR0 (no evidence of disease) or rRany (existing residual disease). All patients were classified into the following groups: sR0/rR0, sR1/rR0, sR0/rRany, and sR1/rRany. RESULTS: A total of 436 patients was placed into the sR0/rR0 (n = 187, 42.9%), sR1/rR0 (n = 59, 13.5%), sR0/rRany (n = 79, 18.1%), or sR1/rRany group (n = 111, 25.5%). Discrepancies between surgical and radiological assessments were recorded for 176 patients (40.4%) including 38 cases of sR1/rRany group with discordant residual tumor location indicated between two methods. During multivariate analysis, patients with ascites on preoperative CT, sR0/rRany group inclusion, and sR1/rRany group inclusion showed unfavorable progression-free and overall survival. CONCLUSIONS: The incorporation of surgical and radiological evaluations for determining the size of residual tumors was more accurate than surgical evaluation only for predicting survival among patients with advanced ovarian cancer who underwent PDS to residual disease less than 1 cm.

Patterns and risk factors of recurrence in low-risk early-stage cervical adenocarcinoma treated with surgery alone: implications on risk group stratification.

OBJECTIVE: Cervical adenocarcinoma has poorer outcomes compared with squamous cell carcinoma; however, treatment is identical irrespective of histologic sub-types. This study aimed to investigate the patterns and risk factors of recurrence following surgery alone for low-risk early-stage cervical adenocarcinoma. METHODS: We retrospectively reviewed patients who underwent surgery alone for low-risk early-stage cervical adenocarcinoma between January 2001 and December 2018 in a single institution. Baseline clinicopathological characteristics were collected to identify the factors associated with recurrence-free survival. RESULTS: A total of 252 patients met the inclusion criteria. Most patients underwent radical hysterectomy (218 patients, 86.5%) and had usual type endocervical adenocarcinoma (190 patients, 75.4%). The International Federation of Gynecology and Obstetrics 2018 stage was IA1 in 72 patients (27.4%), IA2 in 58 (22.1%), IB1 in 51 (19.4%), and IB2 in 71 patients (27.0%). With a median follow-up of 70.4 months (range 6.2-252.5 months), 5-year survival rates were as follows: locoregional recurrence-free survival, 93.0%; recurrence-free survival, 89.6%; overall survival, 94.7%. The recurrence patterns were local in nine patients (32.1%), regional in five patients (17.8%), distant in 10 patients (35.7%), local and distant in one patient (3.6%), regional and distant in two patients (7.2%), and locoregional and distant in one patient (3.6%). In multivariable analysis, negative human papillomavirus (HPV) status (HR 7.314; p<0.001) and deep cervical stromal invasion (HR 5.110; p=0.003) were associated with poor locoregional recurrence-free survival. Patients were stratified based on the number of risk factors and a statistically significant difference in locoregional recurrence-free survival was observed: 5-year survival rates of 99.0%, 84.2%, and 50.0% for patients with 0, 1, and 2 risk factors (0 vs 1, p=0.001; 1 vs 2, p=0.011). CONCLUSION: Surgery alone for low-risk early-stage cervical adenocarcinoma was associated with favorable outcomes over a long follow-up period. Patients with the highest risk of recurrence were those with a negative HPV status and deep cervical stromal invasion. Additional management following surgery may be considered in patients with these risk factors.

Predicting the Recurrence of Gastric Cancer Using the Textural Features of Perigastric Adipose Tissue on [18F]FDG PET/CT.

This study aimed to assess the relationship between the histopathological and textural features of perigastric adipose tissue (AT) on 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) and to evaluate the prognostic significance of perigastric AT textural features in predicting recurrence-free survival (RFS) in patients with gastric cancer. Sixty-nine patients with gastric cancer who underwent staging [18F]FDG PET/CT and subsequent curative surgery were retrospectively reviewed. Textural features of perigastric AT were extracted from PET images. On histopathological analysis, CD4, CD8, and CD163 cell infiltration and matrix metalloproteinase-11 and interleukin-6 (IL-6) expression in perigastric AT were graded. The degree of CD163 cell infiltration in perigastric AT was significantly correlated with the mean standardized uptake value (SUV), SUV histogram entropy, grey-level co-occurrence matrix (GLCM) energy, and GLCM entropy of perigastric AT. The degree of IL-6 expression in the perigastric AT was significantly correlated with the mean and median SUVs of perigastric AT. In multivariate survival analysis, GLCM entropy, GLCM dissimilarity, and GLCM homogeneity of perigastric AT were significant predictors of RFS. The textural features of perigastric AT on [18F]FDG PET/CT significantly correlated with inflammatory response in perigastric AT and were significant prognostic factors for predicting RFS in patients with gastric cancer.

Production of a Bacteria-like Particle Vaccine Targeting Rock Bream (Oplegnathus fasciatus) Iridovirus Using Nicotiana benthamiana.

Viral diseases are extremely widespread infections that change constantly through mutations. To produce vaccines against viral diseases, transient expression systems are employed, and Nicotiana benthamiana (tobacco) plants are a rapidly expanding platform. In this study, we developed a recombinant protein vaccine targeting the major capsid protein (MCP) of iridovirus fused with the lysine motif (LysM) and coiled-coil domain of coronin 1 (ccCor1) for surface display using Lactococcus lactis. The protein was abundantly produced in N. benthamiana in its N-glycosylated form. Total soluble proteins isolated from infiltrated N. benthamiana leaves were treated sequentially with increasing ammonium sulfate solution, and recombinant MCP mainly precipitated at 40-60%. Additionally, affinity chromatography using Ni-NTA resin was applied for further purification. Native structure analysis using size exclusion chromatography showed that recombinant MCP existed in a large oligomeric form. A minimum OD600 value of 0.4 trichloroacetic acid (TCA)-treated L. lactis was required for efficient recombinant MCP display. Immunogenicity of recombinant MCP was assessed in a mouse model through enzyme-linked immunosorbent assay (ELISA) with serum-injected recombinant MCP-displaying L. lactis. In summary, we developed a plant-based recombinant vaccine production system combined with surface display on L. lactis.

Prognostic significance of liver CT-attenuation and 18F-FDG uptake for predicting hepatic recurrence following curative resection of colorectal cancer.

OBJECTIVE: This study investigated the predictive values of computed tomography (CT)-attenuation and fluorine-18-fluorodeoxyglucose (18F-FDG) uptake in the liver for the hepatic recurrence of colorectal cancer. SUBJECT AND METHODS: This study retrospectively included 257 colorectal cancer patients who underwent staging 18F-FDG positron emission tomography (PET)/CT and were subsequently treated with curative surgical resection. Using non contrast-enhanced CT images in PET/CT, the liver-spleen ratio and liver-spleen difference of CT-attenuation and CT-attenuation of the liver were calculated. The maximum and mean 18F-FDG uptake in the liver was measured using the PET images. The relationship of these five liver parameters to recurrence-free survival (RFS), hepatic RFS, and extrahepatic RFS was assessed. RESULTS: In univariate survival analysis, the liver-spleen ratio, liver-spleen difference, and maximum 18F-FDG uptake of the liver were significant predictors of both RFS and hepatic RFS (P<0.05), whereas none of the five liver parameters were significantly associated with extrahepatic RFS (P>0.05). Patients with a low liver-spleen ratio and liver-spleen difference and a high maximum 18F-FDG uptake showed better hepatic RFS than those with a high liver-spleen ratio and liver-spleen difference and a low maximum 18F-FDG uptake. In multivariate analysis, the liver-spleen ratio, liver-spleen difference, and maximum 18F-FDG uptake of liver remained significant predictors for hepatic RFS after adjusting for age, sex, obesity, andstage (P<0.05). CONCLUSION: Computed tomography-attenuation and maximum 18F-FDG uptake in the liver on 18F-FDG PET/CT were significant predictive factors for hepatic RFS in patients with colorectal cancer after curative resection.