Cervical cancer is the fourth most lethal women's cancer worldwide. Current treatments against cervical cancer include surgery, radiotherapy, chemotherapy, and anti-angiogenic agents. However, despite the various treatments utilized for the treatment of cervical cancer, its disease burden remains a global issue. Persistent infection of human papillomavirus (HPV) has been identified as an essential step of pathogenesis of cervical cancer and many other cancers, and nation-wide HPV screening as well as preventative HPV vaccination program have been introduced globally. However, even though the commercially available prophylactic HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are effective in blocking the entry of HPV into the epithelium of cervix through generation of HPV-specific neutralizing antibodies, they cannot eliminate the pre-existing HPV infection. For these reason, other immunotherapeutic options against HPV-associated diseases, including therapeutic vaccines, have been continuously explored. Therapeutic HPV vaccines enhance cell-mediated immunity targeting HPV E6 and E7 antigens by modulating primarily dendritic cells and cytotoxic T lymphocyte. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we will discuss the potential of immune checkpoint inhibitors that have recently been adopted and tested for their treatment efficacy against HPV-induced cervical cancer.
Dendritic Cells/immunology ; Female ; Genetic Vectors ; Humans ; *Immunotherapy ; Papillomavirus Infections/*complications/therapy ; Papillomavirus Vaccines/therapeutic use ; *Translational Medical Research ; Uterine Cervical Neoplasms/*therapy ; Vaccines, DNA/therapeutic use ; Vaccines, Subunit/therapeutic use

More than 99% of cervical cancers have been associated with human papillomaviruses (HPVs), particularly HPV type 16. The clear association between HPV infection and cervical cancer indicates that HPV serves as an ideal target for development of preventive and therapeutic vaccines. Although the recently licensed preventive HPV vaccine, Gardasil, has been shown to be safe and capable of generating significant protection against specific HPV types, it does not have therapeutic effect against established HPV infections and HPV-associated lesions. Two HPV oncogenic proteins, E6 and E7, are consistently co-expressed in HPV-expressing cervical cancers and are important in the induction and maintenance of cellular transformation. Therefore, immunotherapy targeting E6 and/or E7 proteins may provide an opportunity to prevent and treat HPV-associated cervical malignancies. It has been established that T cell-mediated immunity is one of the most crucial components to defend against HPV infections and HPV-associated lesions. Therefore, effective therapeutic HPV vaccines should generate strong E6/E7-specific T cell-mediated immune responses. DNA vaccines have emerged as an attractive approach for antigen-specific T cell-mediated immunotherapy to combat cancers. Intradermal administration of DNA vaccines via a gene gun represents an efficient way to deliver DNA vaccines into professional antigen-presenting cells in vivo. Professional antigen-presenting cells, such as dendritic cells, are the most effective cells for priming antigen-specific T cells. Using the gene gun delivery system, we tested several DNA vaccines that employ intracellular targeting strategies for enhancing MHC class I and class II presentation of encoded model antigen HPV-16 E7. Furthermore, we have developed a strategy to prolong the life of DCs to enhance DNA vaccine potency. More recently, we have developed a strategy to generate antigen-specific CD4+ T cell immune responses to further enhance DNA vaccine potency. The impressive pre- clinical data generated from our studies have led to several HPV DNA vaccine clinical trials.
Female ; Humans ; Oncogene Proteins, Viral/genetics/immunology ; Papillomaviridae/*genetics/immunology ; Papillomavirus Infections/immunology/*prevention & control ; Papillomavirus Vaccines/*administration & dosage ; Repressor Proteins ; Uterine Cervical Neoplasms/*prevention & control ; Vaccines, DNA/*administration & dosage ; Viral Vaccines/administration & dosage

AIMTo determine the incidence of adenocarcinoma of the prostate for patients undergoing radical cystoprostatectomy for bladder cancer in Taiwan.

METHODSA total of 248 patients in Taiwan who were histologically confirmed for transitional cell carcinoma of the bladder underwent cystoprostatectomy. Histopathologic evaluation of the prostate specimens sectioned at 5 mm intervals was performed.

RESULTSOf the 248 patients, 10 (4.03%) were found to have prostate cancer. Of the 10 cases of unsuspected prostate cancer, eight proved to be at stage T1 or T2, and two at T3 and T4, respectively. This rate of incidentally found prostate cancer amongst our bladder cancer patients appeared to be lower than that found in bladder cancer patients in similar studies in USA.

CONCLUSIONAlthough the incidence of incidental prostate cancer in patients in Taiwan with bladder cancer is not high compared with that in Western countries, we suggest that digital rectal examination and prostate-specific antigen (PSA) are important screening tools for men with bladder cancer, especially for those aged 60 years and older in Taiwan.

Carcinoma, Transitional Cell ; pathology ; surgery ; Humans ; Male ; Neoplasm Staging ; Prostatectomy ; Prostatic Neoplasms ; complications ; surgery ; Urinary Bladder Neoplasms ; complications ; pathology ; surgery

Atopic dermatitis (AD) is a chronic inflammatory skin disease, and its prevalence is increasing. AD usually elicits skin barrier dysfunction, dry skin and itching. As the mechanisms of AD remain unknown, there is an urgent need to find effective therapies. Because of the diversity and complexity of marine environments, the discovery of drugs from marine organisms as novel therapeutic agents for human diseases has seen renewed interest. Dihydroaustrasulfone alcohol (WA-25), the synthetic precursor of austrasulfone, which is a natural product isolated from a Formosan soft coral, has been shown to possess many therapeutic effects in our previous studies. However, the detailed mechanisms and therapeutic effects of WA-25 on AD are incompletely understood. We performed in vitro and in vivo studies to examine the effects of WA-25 on AD. We showed that WA-25 blocks inflammation and oxidative stress. Simultaneously, we also found that WA-25 reduces the AD scores and AD-induced transepidermal water loss (TEWL), scratching behavior, and alloknesis. WA-25 is more effective in cases of AD than are the drugs that are currently used clinically. Importantly, we also found that when nucleophosmin (NPM) was inhibited or when its expression was reduced, the anti-inflammatory and anti-AD effects of WA-25 were blocked. These data suggest that NPM plays dual roles in inflammation and AD. Overall, these results suggest that WA-25 is a potential anti-inflammatory and AD therapeutic agent that is modulated by NPM.

This video presents a case of L4–5 unstable spondylolisthesis treated with full-endoscopic transforaminal lumbar interbody fusion (Endo-TLIF), emphasizing the GUARD (Glider Used as a Rotary Device) technique for nerve root protection. This innovative approach involves controlled rotation of the cage glider before cage insertion to minimize the risk of nerve root injury, a significant complication in Endo-TLIF procedures. The GUARD technique, validated in previous cadaveric studies, provides enhanced safety during cage insertion by protecting the nerve root. A 48-year-old woman with a 3-year history of progressive low back pain and bilateral lower extremity radiculopathy (right-sided predominance) was diagnosed with L4–5 unstable spondylolisthesis and spinal stenosis. After failure of conservative management, she underwent uniportal full-endoscopic facet-resecting transforaminal lumbar interbody fusion using the GUARD technique. Postoperatively, the patient experienced significant symptomatic improvement and resolution of radiculopathy, without any intraoperative nerve root injury or postoperative neurological deficits. This case demonstrates the effectiveness of the GUARD technique in reducing neurological complications and improving patient outcomes.

Objective: Uniportal full-endoscopic transforaminal lumbar interbody fusion (FE-TLIF) carries a unique risk of nerve traction and abrasion injury during cage insertion. This study aims to evaluate the clinical efficacy of the GUARD technique and delayed ligamentum flavectomy in reducing postoperative radicular pain and neurapraxia in patients undergoing uniportal FE-TLIF. Methods: A retrospective analysis was conducted on 45 patients with an average age of 53.9±12.4 years who underwent either FE facet-sparing TLIF (FE fs-TLIF) or FE facet-resecting TLIF (FE fr-TLIF). Patients were divided into 2 groups: the sentinel group (21 patients) using traditional sentinel pin techniques, and the GUARD group (24 patients) using the GUARD technique with delayed ligamentum flavectomy. Patient-reported outcomes included the visual analogue scale (VAS) for leg and back pain, and Oswestry Disability Index. Complication rates, including incidental durotomy, postoperative neurapraxia, and hematoma, were also documented. Results: Postoperative radicular pain in the legs was significantly reduced at 6 weeks in the GUARD group compared to the sentinel group (VAS: 2.201 vs. 3.267, p=0.021). The incidence of postoperative neurapraxia was markedly lower in the GUARD group (0% vs. 19%, p=0.047). Both groups showed similar improvements in disc height, segmental lordosis, and lumbar lordosis at the 1-year follow-up, with no significant differences in endplate injury or fusion rates. Conclusion The GUARD technique and delayed ligamentum flavectomy significantly enhance patient safety by reducing postoperative radicular pain and neurapraxia without incurring additional costs. These techniques are easy to learn and integrate into existing surgical workflows, offering a valuable improvement for surgeons performing FE-TLIF procedures.

This video presents a case of L4–5 unstable spondylolisthesis treated with full-endoscopic transforaminal lumbar interbody fusion (Endo-TLIF), emphasizing the GUARD (Glider Used as a Rotary Device) technique for nerve root protection. This innovative approach involves controlled rotation of the cage glider before cage insertion to minimize the risk of nerve root injury, a significant complication in Endo-TLIF procedures. The GUARD technique, validated in previous cadaveric studies, provides enhanced safety during cage insertion by protecting the nerve root. A 48-year-old woman with a 3-year history of progressive low back pain and bilateral lower extremity radiculopathy (right-sided predominance) was diagnosed with L4–5 unstable spondylolisthesis and spinal stenosis. After failure of conservative management, she underwent uniportal full-endoscopic facet-resecting transforaminal lumbar interbody fusion using the GUARD technique. Postoperatively, the patient experienced significant symptomatic improvement and resolution of radiculopathy, without any intraoperative nerve root injury or postoperative neurological deficits. This case demonstrates the effectiveness of the GUARD technique in reducing neurological complications and improving patient outcomes.

Objective: Uniportal full-endoscopic transforaminal lumbar interbody fusion (FE-TLIF) carries a unique risk of nerve traction and abrasion injury during cage insertion. This study aims to evaluate the clinical efficacy of the GUARD technique and delayed ligamentum flavectomy in reducing postoperative radicular pain and neurapraxia in patients undergoing uniportal FE-TLIF. Methods: A retrospective analysis was conducted on 45 patients with an average age of 53.9±12.4 years who underwent either FE facet-sparing TLIF (FE fs-TLIF) or FE facet-resecting TLIF (FE fr-TLIF). Patients were divided into 2 groups: the sentinel group (21 patients) using traditional sentinel pin techniques, and the GUARD group (24 patients) using the GUARD technique with delayed ligamentum flavectomy. Patient-reported outcomes included the visual analogue scale (VAS) for leg and back pain, and Oswestry Disability Index. Complication rates, including incidental durotomy, postoperative neurapraxia, and hematoma, were also documented. Results: Postoperative radicular pain in the legs was significantly reduced at 6 weeks in the GUARD group compared to the sentinel group (VAS: 2.201 vs. 3.267, p=0.021). The incidence of postoperative neurapraxia was markedly lower in the GUARD group (0% vs. 19%, p=0.047). Both groups showed similar improvements in disc height, segmental lordosis, and lumbar lordosis at the 1-year follow-up, with no significant differences in endplate injury or fusion rates. Conclusion The GUARD technique and delayed ligamentum flavectomy significantly enhance patient safety by reducing postoperative radicular pain and neurapraxia without incurring additional costs. These techniques are easy to learn and integrate into existing surgical workflows, offering a valuable improvement for surgeons performing FE-TLIF procedures.

This video presents a case of L4–5 unstable spondylolisthesis treated with full-endoscopic transforaminal lumbar interbody fusion (Endo-TLIF), emphasizing the GUARD (Glider Used as a Rotary Device) technique for nerve root protection. This innovative approach involves controlled rotation of the cage glider before cage insertion to minimize the risk of nerve root injury, a significant complication in Endo-TLIF procedures. The GUARD technique, validated in previous cadaveric studies, provides enhanced safety during cage insertion by protecting the nerve root. A 48-year-old woman with a 3-year history of progressive low back pain and bilateral lower extremity radiculopathy (right-sided predominance) was diagnosed with L4–5 unstable spondylolisthesis and spinal stenosis. After failure of conservative management, she underwent uniportal full-endoscopic facet-resecting transforaminal lumbar interbody fusion using the GUARD technique. Postoperatively, the patient experienced significant symptomatic improvement and resolution of radiculopathy, without any intraoperative nerve root injury or postoperative neurological deficits. This case demonstrates the effectiveness of the GUARD technique in reducing neurological complications and improving patient outcomes.

Objective: Uniportal full-endoscopic transforaminal lumbar interbody fusion (FE-TLIF) carries a unique risk of nerve traction and abrasion injury during cage insertion. This study aims to evaluate the clinical efficacy of the GUARD technique and delayed ligamentum flavectomy in reducing postoperative radicular pain and neurapraxia in patients undergoing uniportal FE-TLIF. Methods: A retrospective analysis was conducted on 45 patients with an average age of 53.9±12.4 years who underwent either FE facet-sparing TLIF (FE fs-TLIF) or FE facet-resecting TLIF (FE fr-TLIF). Patients were divided into 2 groups: the sentinel group (21 patients) using traditional sentinel pin techniques, and the GUARD group (24 patients) using the GUARD technique with delayed ligamentum flavectomy. Patient-reported outcomes included the visual analogue scale (VAS) for leg and back pain, and Oswestry Disability Index. Complication rates, including incidental durotomy, postoperative neurapraxia, and hematoma, were also documented. Results: Postoperative radicular pain in the legs was significantly reduced at 6 weeks in the GUARD group compared to the sentinel group (VAS: 2.201 vs. 3.267, p=0.021). The incidence of postoperative neurapraxia was markedly lower in the GUARD group (0% vs. 19%, p=0.047). Both groups showed similar improvements in disc height, segmental lordosis, and lumbar lordosis at the 1-year follow-up, with no significant differences in endplate injury or fusion rates. Conclusion The GUARD technique and delayed ligamentum flavectomy significantly enhance patient safety by reducing postoperative radicular pain and neurapraxia without incurring additional costs. These techniques are easy to learn and integrate into existing surgical workflows, offering a valuable improvement for surgeons performing FE-TLIF procedures.