Role of MRI to confirm healing in complex high cryptoglandular anal fistulas: long-term follow-up of 151 cases.

AIM: Complex fistula-in-ano can recur even after complete clinical healing has occurred. 'Radiological healing' of fistula on MRI correlates well with long-term healing rates but no study has yet objectively quantified this. The aim of this study was to assess the accuracy of anal fistula healing as documented on MRI and to correlate it with long-term healing as evidenced on long-term follow-up. METHODS: Patients with clinically healed anal fistulas who also had radiological healing checked by postoperative MRI were included in the study. RESULTS: Three hundred and twenty-five patients operated for high complex fistula-in-ano were followed up for 14-68 months (median 38 months). Postoperative MRI was done to assess radiological healing of the fistula in 151 patients, and they were included in the study. The mean age was 39.4 ± 10.5 years (116 men). Five patients were lost to follow-up. The fistulas did not heal radiologically (on MRI) in 20 patients and recurred in all these patients. The fistulas healed radiologically (on MRI) in 126 patients. On long-term follow-up, 124/126 patients remained healed while 2/126 had a recurrence. In the first patient, the fistula recurred 40 months after complete radiological healing. In the second patient, the fistula recurred 10 months after complete radiological healing but pus from the fistula tested positive for tuberculosis (by real-time polymerase chain reaction) and he was excluded from the analysis. Thus, there was only one (1/125) recurrence on long-term follow-up. CONCLUSIONS: Radiological healing on MRI correlates well with long-term healing in complex fistula-in-ano.

Transanal opening of the intersphincteric space (TROPIS): a novel procedure on the horizon to effectively manage high complex anal fistulas.

Anal fistulas, especially complex and high fistulas, are difficult to manage. The transanal opening of the intersphincteric space (TROPIS) procedure was first described in 2017, and a high success rate of over 90% was reported in high complex fistulas. Since then, more studies and even a meta-analysis have corroborated the high efficacy of this procedure in high fistulas. Conventionally, the main focus was to close the internal (primary) opening for the fistula to heal. However, most complex fistulas have a component of the fistula tract in the intersphincteric plane. This component is like an abscess (sepsis) in a closed space (2 muscle layers). It is a well-known fact that in the presence of sepsis, healing by secondary intention leads to better results than attempting to heal by primary intention. Therefore, TROPIS is the first procedure in which, instead of closing the internal opening, the opening is widened by laying open the fistula tract in the intersphincteric plane so that healing can occur by secondary intention. Although the drainage of high intersphincteric abscesses through the transanal route was described 5 decades ago, the routine utilization of TROPIS for the definitive management of high complex fistulas was first described in 2017. The external anal sphincter (EAS) is completely spared in TROPIS, as the fistula tract on either side of the EAS is managed separately-inner (medial) to the EAS by laying open the intersphincteric space and outer (lateral) to the EAS by curettage or excision.

Immune responses, therapeutic anti-tumor effects, and tolerability upon therapeutic HPV16/18 E6/E7 DNA vaccination via needle-free biojector.

IMPORTANCE: Respectively, HPV16 and HPV18 cause 50% and 20% of cervical cancer cases globally. Viral proteins E6 and E7 are obligate drivers of oncogenic transformation. We recently developed a candidate therapeutic DNA vaccine, pBI-11, that targets HPV16 and HPV18 E6 and E7. Single-site intramuscular delivery of pBI-11 via a needle elicited therapeutic anti-tumor effects in mice and is now being tested in high-risk human papillomavirus+ head and neck cancer patients (NCT05799144). Needle-free biojectors such as the Tropis device show promise due to ease of administration, high patient acceptability, and the possibility of improved delivery. For example, vaccination of patients with the ZyCoV-D DNA vaccine using the Tropis device is effective against COVID19, well tolerated, and licensed. Here we show that split-dose, multi-site administration and intradermal delivery via the Tropis biojector increase the delivery of pBI-11 DNA vaccine, enhance HPV antigen-specific CD8+ T-cell responses, and improve anti-tumor therapeutic effects, suggesting its translational potential to treat HPV16/18 infection and disease.

Small animal jet injection technique results in enhanced immunogenicity of hantavirus DNA vaccines.

DNA vaccine evaluation in small animals is hampered by low immunogenicity when the vaccines are delivered using a needle and syringe. To overcome this technical hurdle we tested the possibility that a device developed for human intradermal medicine delivery might be adapted to successfully deliver a DNA vaccine to small animals. Disposable syringe jet injection (DSJI) does not currently exist for small animals. However, a commercialized, human intradermal device used to to administer medicines to the human dermis in a 0.1 mL volume was evaluated in Syrian hamsters. Here, we found that hantavirus DNA vaccines administered to hamsters using DSJI were substantially more immunogenic than the same vaccines delivered by needle/syringe or particle mediated epidermal delivery (gene gun) vaccination. By adjusting how the device was used we could deliver vaccine to either subcutaneous tissues, or through the skin into the muscle. RNA and/or antigen expression was detected in epidermal, subepidermal and fibroblast cells. We directly compared six optimized and non-optimized hantavirus DNA vaccines in hamsters. Optimization, including codon-usage and mRNA stability, did not necessarily result in increased immunogenicity for all vaccines tested; however, optimization of the Andes virus (ANDV) DNA vaccine protected vaccinated hamsters from lethal disease. This is the first time active vaccination with an ANDV DNA vaccine has shown protective efficacy in the hamster model. The adaptation of a human intradermal jet injection device for use as a method of subcutaneous and intramuscular jet injection of DNA vaccines will advance the development of nucleic acid based medical countermeasures for diseases modeled in hamsters.

Treating highly complex anal fistula with a new method of combined intraoperative endoanal ultrasonography (IOEAUS) and transanal opening of intersphincteric space (TROPIS).

INTRODUCTION: Treatment of highly complex anal fistula is still a profound test for a specialist colorectal surgeon. The reasons are directly related to recurrence and incontinence. AIM: To evaluate the clinical results of a combined method of intraoperative endoanal ultrasonography (IOEAUS) and transanal opening of the intersphincteric space (TROPIS). MATERIAL AND METHODS: This study retrospectively included 48 patients with complex anal fistula, all of whom underwent new surgical methods. This operation mainly consists of two steps. Firstly, the type of anal fistula was determined by endoanal ultrasonography (EAUS) or magnetic resonance imaging (MRI) before the operation. Then the TROPIS procedure was performed with the help of EAUS, and the decision on whether a drainage seton should be placed depended on the condition of the tract. If there were secondary tracts, they were found and the same was done. RESULTS: The median follow-up was 12 months. Two (4.1%) patients experienced recurrence. Four (8.3%) patients did not have primary healing. All 6 patients underwent the same procedure again, and three recovered completely. So total successful fistula healing was observed in 45 (93.7%). There were no major complications and no significant deterioration in anal function and incontinence postoperatively. CONCLUSIONS: Combined IOEAUS and TROPIS is an effective procedure in the treatment of highly complex anal fistula, and it may offer a new means for other operations.