Taxol, a type of antimitotic agent, could modulate local inflammatory conditions in peripheral nerves, which may impair their regeneration and recovery when injured. This study provided in vivo trials of silicone rubber chambers to bridge a long 10 mm sciatic nerve defect in taxol-treated rats. It was aimed to determine the effects of electrical stimulation at various frequencies on regeneration of the sciatic nerves in the bridging conduits. Taxol-treated rats were divided into four groups (n = 10/group): sham control (no current delivered from the stimulator); and electrical stimulation (3 times/week for 3 weeks at 2, 20, and 200 Hz with 1 mA current intensity). Neuronal electrophysiology, animal behavior, neuronal connectivity, macrophage infiltration, calcitonin gene-related peptide (CGRP) expression levels, and morphological observations were evaluated. At the end of 4 weeks, animals in the low- (2 Hz) and medium-frequency (20 Hz) groups had dramatic higher rates of successful regeneration (90% and 80%) across the wide gap as compared to the groups of sham and high-frequency (200 Hz) (60% and 50%). In addition, the 2 Hz group had significantly larger amplitudes and evoked muscle action potentials compared to the sham and the 200 Hz group, respectively (P < 0.05). Heat, cold plate licking latencies, motor coordination, and neuronal connectivity were unaffected by the electrical stimulation. Macrophage density, CGRP expression level, and axon number were all significantly increased in the 20 Hz group compared to the sham group (P < 0.05). This study suggested that low- (2 Hz) to medium-frequency (20 Hz) electrical stimulation could ameliorate local inflammatory conditions to augment recovery of regenerating nerves by accelerating their regrowth and improving electrophysiological function in taxol-treated peripheral nerve injury repaired with the silicone rubber conduit.

Background: We describe a DNA methylation assay, named MPap test, using cervical scraping as an alternative technique for endometrial cancer detection. Methods: A multicenter hospital-based, two-stage validation study was conducted to validate the cancer detection performance of the MPap test. The MPap value was determined from the DNA methylation status of two genes (BHLHE22, CDO1) and combined with two other clinical variables (age, BMI). The cutoff threshold of the MPap value was established in stage 1 and validated in stage 2. A total of 592 women with abnormal uterine bleeding were enrolled from five medical centers throughout Taiwan. Results: In stage 1, the sensitivity, specificity, and positive and negative predictive values of the MPap test for detecting endometrial cancer were 92.9%, 71.5%, 39.8%, and 98.0%, respectively. These values were validated in stage 2, being 92.5%, 73.8%, 40.2%, and 98.1%. Moreover, MPap outperformed transvaginal ultrasound in sensitivity and negative predictive values for detecting endometrial cancer. When we applied the algorithm for triage of endometrial cancer detection by MPap in the Taiwan National Health Insurance dataset, we found that it may reduce invasive procedures by 69~73%. Conclusions: MPap may provide a feasible alternative for endometrial cancer detection and can be considered as a triage test to reduce unnecessary invasive procedures.

Treatment of bulky cervical cancer is associated with both high adverse effects and local recurrence rates with traditional box method radiotherapy. Intensity-modulated radiotherapy (IMRT) has been adopted for the treatment of cervical cancer in order to deliver more precise radiation doses to the target region. We retrospectively enrolled a total of 98 patients with cervical cancer ≥4 cm who completed IMRT and point A-based brachytherapy treatment. The median follow-up time of the cohort was 6.84 years, with the 5-year OS and DFS being 66.33% and 75.12%, respectively. In addition, 7.14% of patients experienced local recurrence, 12.24% had distant recurrence, 6.12% had both local and distant recurrence, and 3.06% had persistent disease. In the univariate analysis, lymph node metastasis, higher creatinine levels, higher initial CA-125 and receiving chemotherapy other than cisplatin were all associated with a worse PFS. A tumor size ≥6 cm was associated with an increased incidence of higher grade of acute diarrhea. Grade 3 late radiation proctitis and cystitis developed in 11.22% and 13.27% of patients, respectively. The local recurrence rates and overall efficiencies were not inferior to other studies involving traditional pelvic external beam radiation therapy with concurrent chemotherapy. The safety and efficacy of IMRT for bulky cervical cancer were acceptable.

Background: Endometrial cancer is the most common gynecological cancer in developed countries. With recent advances in equipment and knowledge, minimally invasive surgery (MIS) is widely accepted for the treatment of endometrial cancer. This study had the largest number of cases to date in Taiwan, comparing outcomes between MIS and laparotomy staging surgery using real-world data with long-term follow-up. Methods: We retrospectively reviewed patients with clinical stage 1 endometrial cancer from 2009 to 2020 in our institute. All patients underwent comprehensive surgical staging procedures by MIS or laparotomy. The safety, morbidity, progression-free survival (PFS), and overall survival (OS) rates of the two groups were compared. Clinical and pathologic factors were compared with Chi-square and Fisher Exact test. PFS and OS were estimated by the Kaplan-Meier method. Differences between survival curves were analyzed using the log-rank test. A p value of <0.05 was considered statistically significant. Using Cox proportional hazards models, all factors found to be significantly associated with risk of recurrence on univariate analyses were then assessed together through multivariable models, resulting in a final oncologic outcome between MIS and laparotomy. Results: A total of 665 cases (412 cases in MIS group and 253 cases in laparotomy group) were enrolled for data analysis. Median operation time was shorter in MIS group (244 and 265 minutes, p < 0.001). Median blood loss was also less (75 and 430 mL, p < 0.001). Median postoperative hospitalization duration was longer in the laparotomy group (2 and 7 days, p = 0.001). After adjusting presurgery risk factors, the PFS and OS were no significant difference in MIS and laparotomy groups. Conclusion: Using real-world data with long-term follow-up, we could confirm excellent PFS and OS in selective patients with clinical stage 1 endometrial carcinoma who received MIS, and the surgical time, hospital day, and blood loss were also less.

Tumor-infiltrating lymphocytes (TILs) have emerged as a prognostic marker in endometrial cancer (EC). However, the role of TILs in EC with distinct histology grades and molecular types (such as mismatch repair [MMR] deficiency) has not yet been made clear. We retrospectively included 237 patients with primary EC who underwent a standard staging operation of laparoscopic or laparotomy total hysterectomy and bilateral salpingo-oophorectomy for analyses. An independent pathologist who was blind to the study patients’ information reviewed the pathologic slides to assess TILs according to the method introduced by the International Immuno-Oncology Biomarkers Working Group in 2017. The outcomes of interest included both progression-free survival (PFS) and overall survival (OS). The Kaplan–Meier method was used to determine the curves of PFS and OS according to TILs, and also in the relevant subgroups (low-grade vs. high-grade, MMR-proficient vs. MMR-deficient). After a median follow-up duration of 1.82 years, 18 patients had experienced either disease progression or death. Overall, TILs (+) were not associated with PFS or OS. We did observe, however, that TILs (+) were associated with a better PFS (p = 0.045) in patients with high-grade EC, but not in those with low-grade tumors (p = 0.733). The effect of TILs on PFS was not observed in patients with MMR-proficient (p = 0.347) or MMR-deficient (p = 0.168) EC. TILs were associated with a better PFS in patients with high-grade EC. Our results suggest that TILs may be a potential prognostic marker in these patients.

The overall five-year survival rate for patients with esophageal cancer is low (15 to 25%) because of the poor prognosis at earlier stages. Rutaecarpine (RTP) is a bioalkaloid found in the traditional Chinese herb Evodia rutaecarpa and has been shown to exhibit anti-proliferative effect on tumor cells. However, the mechanisms by which RTP confer these effects and its importance in esophageal squamous cell carcinoma treatment remain unclear. Thus, in the present study, we first incubated human esophageal squamous cell carcinoma cell line, CE81T/VGH, with RTP to evaluate RTP’s effects on tumor cell growth and apoptosis. We also performed a xenograft study to confirm the in vitro findings. Furthermore, we determined the expression of p53, Bax, bcl-2, caspase-3, caspase-9, and PCNA in CE81T/VGH cells or the tumor tissues to investigate the possible mechanisms. All the effects of TRP were compared with that of cisplatin. The results showed that RTP significantly inhibits CE81T/VGH cell growth, promotes arrest of cells in the G₂/M phase, and induces apoptosis. Consistently, the in vivo study showed that tumor size, tumor weight, and proliferating cell nuclear antigen protein expression in tumor tissue are significantly reduced in the high-dose RTP treatment group. Furthermore, the in vitro and in vivo studies showed that RTP increases the expression of p53 and Bax proteins, while inhibiting the expression of Bcl-2 in cancer cells. In addition, RTP significantly increases the expression of cleaved caspase-9 and cleaved caspase-3 proteins in tumor tissues in mice. These results suggest that RTP may trigger the apoptosis and inhibit growth in CE81T/VGH cells by the mechanisms associated with the regulation of the expression of p53, Bax, Bcl-2, as well as caspase-9 and caspase-3.