Granular experiments of thrust wedges: Insights relevant to methane hydrate exploration at the Nankai accretionary prism

The accumulation mechanism of methane hydrates has been a central issue in previous hydrate research regarding the Nankai accretionary prism, southwest of Japan. Expulsion of formation fluids is significant during the prism accretion process, and the migration of these methane-bearing fluids exerts a strong control on the accumulation of hydrates. Two types of fluid pathways, inter-granular porosity and faults, need to be evaluated to understand hydrate accumulation. Fluid migration along faults can be partly modeled by examining faulting activity. Our study modeled the accretion process by using two granular methods that approximated the geologic body as an assemblage of particles: (1) analog experiments using granular materials, and (2) a numerical simulation based on the distinct element method. The analog experiments closely reproduced the prism geometry observed in seismic profiles across the Nankai accretionary prism. Digital image correlation analysis indicated that the frontal thrust is generally active but older structures are also frequently reactivated. The numerical simulations produced prism geometries similar to those of the analog experiments. The velocity distributions of the particles showed evidence of episodic faulting and reactivation, but the internal stress field exhibited little change in the deeper part of the prism during deformation. The frequent and substantial changes in fault activity displayed by the models indicate episodic fluid flow along fault surfaces. Active frontal thrusting suggests that formation fluids generally migrate from deep within the prism to the deformation front, but may move along reactivated older faults. Inter-granular permeability also fluctuates, as it is controlled by temporal and spatial variations in the internal stress field. However, fluid flow is likely to be relatively stable in the deeper segment of the prism

Safety and Efficacy of Weekly Paclitaxel and Cisplatin Chemotherapy for Ovarian Cancer Patients with Hypersensitivity to Carboplatin

Background: This study aimed to evaluate the safety and efficacy of weekly paclitaxel and cisplatin chemotherapy (wTP) in patients with ovarian cancer who developed carboplatin hypersensitivity reaction (HSR). Methods: We retrospectively investigated 86 patients with ovarian, fallopian tube, and peritoneal carcinoma who developed carboplatin HSR during previous chemotherapy (carboplatin and paclitaxel) at our institution between 2011 and 2019. After premedication was administered, paclitaxel was administered over 1 h, followed by cisplatin over 1 h (paclitaxel 80 mg/m2; cisplatin 25 mg/m2; 1, 8, 15 day/4 weeks). We investigated the incidence of patients who successfully received wTP for at least one cycle, treatments compliance, progression-free survival (PFS), and overall survival (OS). Results: The median number of wTP administration cycles was 4 (Interquartile Range IQR, 3–7), 71 patients (83%) successfully received wTP, and 15 patients (17%) developed cisplatin HSR. The efficacy of treatment was as follows: 55 (64%) patients completed the scheduled wTP, 9 (10%) patients discontinued due to HSR to cisplatin within 6 cycles, 1 (1%) patient discontinued due to renal toxicity (grade 2) at the 6th cycle, and 21 (24%) patients discontinued due to progressive disease within 6 cycles. The median PFS and OS after administration of wTP were 10.9 months (95% CI: 7.7–17.7) and 25.9 months (95% CI: 19.0–50.2), respectively. Conclusions: wTP was safe and well-tolerated in patients who developed carboplatin HSR

Serum FSH as a Useful Marker for the Differential Diagnosis of Ovarian Granulosa Cell Tumors

Background: We evaluated whether the serum hormone levels are useful in the differential diagnosis of granulosa cell tumors (GCTs), regardless of menopausal status. Methods: Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, and progesterone were measured preoperatively in all patients (n = 471) who underwent surgery for ovarian tumors at Chiba University Hospital between 2009 and 2021. These were compared in two groups, a GCT group (n = 13) and a group with other histological types (non-GCT) (n = 458). Results: The GCT group had significantly lower serum LH and FSH (p = 0.03 and p < 0.001, respectively) and significantly higher testosterone, estradiol, and progesterone (p < 0.001, p < 0.001, and p = 0.045, respectively) than the non-GCT group. Multivariate analysis revealed that serum FSH and estradiol were significantly associated with GCT (FSH, odds ratio (OR) = 0.0046, 95% confidence interval (CI) = 0.0026–0.22, p = 0.004; estradiol, OR = 0.98, 95% CI = 0.96–0.998, p = 0.046). Receiver-operating characteristic curve analysis for GCTs showed that the area under the curve of serum FSH was 0.99, with a sensitivity of 100% and a specificity of 98%, when the cutoff level was set at 2.0 IU/L. Conclusions: Preoperative serum FSH level is an extremely useful marker for differentiating GCTs from all ovarian tumors

Bevacizumab in First-Line Chemotherapy Improves Progression-Free Survival for Advanced Ovarian Clear Cell Carcinoma

(1) Background: We investigated survival outcomes following first-line chemotherapy before and after approval of bevacizumab (Bev) for ovarian cancer in Japan to evaluate the efficacy of Bev for advanced clear cell carcinoma (CCC). (2) Methods: We investigated 28 consecutive patients diagnosed with CCC (stages III/IV) at our hospital between 2008 and 2018. Bev was administered for treatment of advanced CCC after approval in Japan in November 2013. Progression-free survival (PFS) was compared between 10 patients treated before Bev approval (2008–2013, Bev- group) and 18 patients treated after Bev approval (2014–2018, Bev+ group) for first-line chemotherapy. (3) Results: No intergroup difference was observed in patient characteristics. The rate of completeness of resection was higher in the Bev − group (9/10, 90%) than in the Bev+ group (15/18, 83%) (p = 0.044). Eleven (61%) patients in the Bev + group received ≥ 21 cycles of Bev. The median PFS increased from 12.0 months before Bev approval to 29.8 months after Bev approval (Wilcoxon test, p = 0.026). Multivariate analysis showed that performance status (p = 0.049), Bev administration (p = 0.023) and completeness of resection (p = 0.023) were independent prognostic factors for PFS. (4) Conclusions: Bev incorporated into first-line chemotherapy might improve PFS in patients with advanced CCC. We hope that our findings will be confirmed in adequate clinical trials