Activation of toll-like receptor 4 (TLR4) in the dorsal root ganglion (DRG) and spinal cord contributes to the generation of paclitaxel-related chemotherapy-induced peripheral neuropathy (CIPN). Generalizability of TLR4 signaling in oxaliplatin-induced CIPN was tested here. Mechanical hypersensitivity developed in male SD rats by day 1 after oxaliplatin treatment, reached maximum intensity by day 14, and persisted through day 35. Western blot revealed an increase in TLR4 expression in the DRG of oxaliplatin at days 1 and 7 after oxaliplatin treatment. Cotreatment of rats with the TLR4 antagonist lipopolysaccharide derived from Rhodobacter sphaeroides ultrapure or with the nonspecific immunosuppressive minocycline with oxaliplatin resulted in significantly attenuated hyperalgesia on day 7 and 14 compared with rats that received oxaliplatin plus saline vehicle. Immunostaining of DRGs revealed an increase in the number of neurons expressing TLR4, its canonical downstream signal molecules myeloid differentiation primary response gene 88 (MyD88) and TIR-domain–containing adapter-inducing interferon-β, at both day 7 and day 14 after oxaliplatin treatment. These increases were blocked by cotreatment with either lipopolysaccharide derived from Rhodobacter sphaeroides or minocycline. Double staining showed the localization of TLR4, MyD88, and TIR-domain–containing adapter-inducing interferon-β in subsets of DRG neurons. Finally, there was no significant difference in oxaliplatin-induced mechanical hypersensitivity between male and female rats when observed for 2 weeks. Furthermore, upregulation of TLR4 was detected in both sexes when tested 14 days after treatment with oxaliplatin. These findings suggest that the activation of TLR4 signaling in DRG neurons is a common mechanism in CIPN induced by multiple cancer chemotherapy agents.
Objectives: To investigate whether PET–CT or PET–MRI is more appropriate for imaging prostate cancer, in terms of primary tumor detection, local staging and recurrence, as well as lymph nodes and distant metastases. Methods: A systematic literature search was conducted on Embase, PubMed/MEDLINE, and the Cochrane Library database. Studies evaluating the diagnostic performance of PET–CT vs PET–MRI in prostate cancer patients were emphasized. Results: We reviewed 57 original research articles during the period 2016–2021: 14 articles regarding the radiotracer PSMA; 18 articles regarding the primary tumor detection, local tumor staging, managing local recurrence; 17 articles for managing lymph node metastases; and eight articles for managing bone and other distant metastases. PSMA PET could be complementary to mpMRI for primary prostate cancer localization and is particularly valuable for PI-RADS three lesions. PET–MRI is better than PET–CT in local tumor staging due to its specific benefit in predicting extracapsular extension in MRI-occult prostate cancer patients. PET–MRI is likely superior as compared with PET–CT in detecting local recurrence, and has slightly higher detection rates than PET–CT in lymph node recurrence. PET–CT and PET–MRI seem to have equivalent performance in detecting distant bony or visceral metastases. Conclusion: In conclusion, PET–MRI is suitable for local and regional disease, either primary staging or restaging, whereas PET–CT is valuable for managing distant bony or visceral metastasis. Advances in knowledge: We reviewed the emerging applications of PET–MRI and PET–CT in clinical aspects. Readers will gain an objective overview on the strength and shortfalls of PET–MRI or PET–CT in the management of prostate cancer.
Over the past decades, the incidence of prostate cancer in Taiwan kept rising. Many possible factors including the utility of prostate specific antigen tests, lifestyle remodeling, and patient's comorbidities may contribute to the increasing of incidence or prostate cancer. We aim to use the nationwide Health and Welfare Database (HWD) to investigate possible associated factors. We used HWD, a nationwide database of medical information, to assess the incidence of prostate cancer, utilization of prostate-specific antigen (PSA) test, and underlying diseases of patients and to evaluate whether there was a common trend among these factors. In total, 32,508 patients with newly diagnosed prostate cancer from 2006 to 2013 were identified. The incidence rate of prostate cancer per 100,000 men increased from 35.47 in 2006 to 52.87 in 2012. The number of patients with prostate cancer and underlying diseases related to metabolic syndrome increased every year. The number of total PSA tests and patients undergoing PSA testing, as well as average times of PSA testing per person in the whole population, increased every year. The average PSA test times of patients with newly diagnosed prostate cancer within 3 years before the diagnosis of prostate cancer also increased every year. There was a high correlation between the average PSA test times and the number of patients with newly diagnosed prostate cancer (r2 = 0.9734). The trends of incidence of prostate cancer, utilization of PSA testing, and underlying diseases related to metabolic syndrome at the diagnoses of cancer were similar, increasing every year in the study period. The results suggested that increasing use of PSA tests may increase the diagnosis of prostate cancers. Underlying diseases related to metabolic syndrome might also affect the incidence of prostate cancer.
Background: To compare the intraoperative and postoperative outcomes of indocyanine green (ICG) administration in robot-assisted partial nephrectomy (RAPN) and report the differences in the results between patients with benign and malignant renal tumors. Methods: From 2017 to 2020, 132 patients underwent RAPN at our institution, including 21 patients with ICG administration. Clinical data obtained from our institution’s RAPN database were retrospectively reviewed. Intraoperative, postoperative, pathological, and functional outcomes of RAPN were assessed. Results: The pathological results indicated that among the 127 patients, 38 and 89 had received diagnoses of benign and malignant tumors, respectively. A longer operative time (311 vs. 271 min; p = 0.006) but superior preservation of estimated glomerular filtration rate (eGFR) at 3-month follow-up (90% vs. 85%; p = 0.031) were observed in the ICG-RAPN group. Less estimated blood loss, shorter warm ischemia time, and superior preservation of eGFR at postoperative day 1 and 6-month follow-up were also noted, despite no significant differences. Among the patients with malignant tumors, less estimated blood loss (30 vs. 100 mL; p < 0.001) was reported in the ICG-RAPN subgroup. Conclusions: Patients with ICG-RAPN exhibited superior short-term renal function outcomes compared with the standard RAPN group. Of the patients with malignant tumors, ICG-RAPN was associated with less blood loss than standard RAPN without a more positive margin rate. Further studies with larger cohorts and prospective designs are necessary to verify the intraoperative and functional advantages of the green dye.
Purpose: The purpose of this pilot prospective study is to examine the gallium-68-prostate-specific membrane antigen-11 ([68Ga]Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) imaging response in patients with advanced or metastatic hormone-naïve prostate cancer (PC) after 3 months of androgen deprivation therapy (ADT). Methods: We prospectively included men with untreated, clinical stage III or IV PC scheduled to receive ADT for at least 6 months. [68Ga]Ga-PSMA-11 PET/CT images were obtained before the start of ADT and 10–14 weeks thereafter. The following indices were examined: maximum standardized uptake value (SUVmax), mean SUV, PSMA total volume, and PSMA total lesion values of the prostate, nodes, bones, and whole-body. The therapeutic response was assessed using the modified PET response criteria in solid tumors 1.0. A subgroup analysis of patients with the International Society of Urological Pathology (ISUP) grade group 5 versus <5 was also performed. Results: A total of 30 patients were eligible. All PSMA PET/CT indices were significantly reduced (p < 0.001) after 3 months of ADT. Twenty-four (80%) patients showed partial response. Complete response, stable disease, and disease progression were observed in two patients each. Sixteen patients with ISUP grade group 5 showed a less prominent SUVmax reduction (p = 0.006), and none of them reached complete response. Conclusions: Three months of ADT in patients with untreated, advanced PC significantly reduced PSMA PET/CT indices. While most participants partially responded to ADT, patients with ISUP grade group 5 showed a less prominent SUVmax reduction. Collectively, our pilot results indicate that [68Ga]Ga-PSMA-11 PET/CT imaging holds promise to monitor treatment response after the first three months of ADT.