Surgical Management of Perianal Giant Condyloma Acuminatum of Buschke and Löwenstein: Case Presentation.

INTRODUCTION: The Buschke-Löwenstein tumor (BLT) is an uncommon sexually transmitted ailment attributed to the human papillomavirus (HPV)-usually the 6 or 11 type (90%)-with male predominance and an overall infection rate of 0.1%. BLT or giant condyloma acuminatum is recognized as a tumor with localized aggressiveness, displaying distinctive features: the potential for destructive growth, benign histology, a rate of 56% malignant transformation, and a high rate of recurrence after surgical excision. There are several treatment choices which have been tried, including laser, cryotherapy, radiotherapy, electrocoagulation, immunotherapy, imiquimode, sincatechins, intralesional injection of 5-fluoruracil (5-FU), isolated perfusion, and local or systemic chemotherapy. In the case of an extensive tumor, preoperative chemotherapy or radiotherapy is used for tumor shrinkage, making the debulking procedure safer. HPV vaccines significantly decrease the incidence of genital warts, also decreasing the risk of BLT; HPV-6 and HPV-11 are included in these vaccines. MATERIALS AND METHODS: We present a 53-year-old heterosexual man, hospitalized in our department in June 2021 with a typical cauliflower-like tumor mass involving the perianal region, which progressively increased in size for almost 7 years. The perianal mass was completely removed, ensuring negative surgical margins. The large perianal skin defect which occurred was reconstructed with fascio-cutaneous V-Y advancement flap. There was no need for protective stoma. The literature review extended from January 1980 and December 2022, utilizing Pubmed and Google Scholar as search platforms. RESULTS: Due to the disease's proximity to the anal verge and the limited number of reported cases, arriving at a definitive and satisfactory treatment strategy becomes challenging. The optimal approach entails thorough surgical removal of the lesion, ensuring well-defined surgical margins and performing a wide excision to minimize the likelihood of recurrence. In order to repair the large wound defects, various rotation or advancement flaps can be used, resulting in reduced recovery time and a diminished likelihood of anal stricture or other complications. Our objective is to emphasize the significance of surgical excision in addressing BLT through the presentation of a case involving a substantial perianal condyloma acuminatum, managed successfully with complete surgical removal and the utilization of a V-Y advancement flap technique. In the present case, after 5 months post operation, the patient came back with a buttock abscess, which was incised and drained. After another 5 months, the patient returned for difficult defecation, with an anal stenosis being diagnosed. An anal dilatation and sphincterotomy were carried out, with good postoperative results. CONCLUSIONS: The surgical management of Buschke-Löwenstein tumors needs a multidisciplinary team with specialized expertise. The reconstruction techniques involved can be challenging and may introduce additional complications. We consider aggressive surgery, which incorporates reconstructive procedures, as the standard treatment for Buschke-Löwenstein tumors. This approach aims to achieve optimal surgical outcomes and prevent any recurrence.

CACNA1B gene variants in adult-onset isolated focal dystonia.

BACKGROUND: Isolated focal dystonia (IFD) is a heterogeneous group of potentially invalidating movement disorders. The etiopathogenesis is complex, both genetic and environmental factors playing a role, but remains elusive. The CACNA1B gene codes for the N-type neuronal voltage-gated calcium channels CaV2.2, which may play a role in the development of some IFD. METHODS: We analyzed samples from the GENDYS cohort for mutations in CACNA1B gene, using targeted next-generation sequencing (NGS). RESULTS: The GENDYS cohort consists of 120 people with adult-onset IFD (cervical dystonia 47.5%, blepharospasm 47.2%, others 8.3%). Of these, 35% had subsequent topographical extension. Average age at onset was 42 and average disease durations 8 years. Targeted NGS revealed a novel frameshift mutation c.2291AGG > A, in exon 19, and a previously reported variant, c.6834T > G, in exon 47. CONCLUSION: Our findings suggest that disease-causing mutations in CACNA1B gene may be involved in the development of some adult-onset IFD. To our knowledge, this is the first study that identified a disease-causing CACNA1B gene mutation in association with adult-onset IFD.

Non-Motor Manifestations in Idiopathic Dystonia with Focal Onset - A Pilot Study.

Recent studies emphasize an increased prevalence of non-motor symptoms in idiopathic dystonia with focal onset (IDFO), but their pathophysiological relationship is not clear. We aimed to identify the prevalence of depression and neurocognitive impairment in a group of patients with idiopathic dystonia with focal onset and their impact on the patients' quality of life. This study represents a component of an ongoing research project - GENDYS. From the database of this project, we selected 48 patients 56.62+/-14.16 years old who have been examined clinically and using specific scales: Patient Health Questionnaire-9 (for depression), Montreal Cognitive Assessment - MoCA (for cognitive impairment), and a 5-degree analog scale for subjective perception of the severity of the disease. We conducted a descriptive cross-sectional study on patients with depression and cognition evaluated by the above-mentioned scales. We also performed a nested case-control analysis on 20 IDFO patients with and without at least moderate depression matched for age and gender; the cut-offs for depression were PHQ-9 score ≥10 and PHQ9 <5, for the depression group and the control group, respectively. The cut-off for MoCA was 26 points. 22 IDFO patients (46%) had depression; 54.5% of IDFO patients with depression had cognitive impairment, indicating a slight trend of increased cognitive impairment in those with depression compared to those without; the perception of the severity of disease was the greatest in patients with depression. Depression is more prevalent in patients with IDFO and is associated with a worse perception of the disease severity.

Improving the odds of success in antitumoral drug development using scoring approaches towards heterocyclic scaffolds.

One of the most commonly discussed topics in the field of drug discovery is the continuous search for anticancer therapies, in which small­molecule development plays an important role. Although a number of techniques have been established over the past decades, one of the main methods for drug discovery and development is still represented by rational, ligand­based drug design. However, the success rate of this method could be higher if not affected by cognitive bias, which renders many potential druggable scaffolds and structures overlooked. The present study aimed to counter this bias by presenting an objective overview of the most important heterocyclic structures in the development of anti­proliferative drugs. As such, the present study analyzed data for 91,438 compounds extracted from the Developmental Therapeutics Program (DTP) database provided by the National Cancer Institute. Growth inhibition data from these compounds tested on a panel of 60 cancer cell lines representing various tissue types (NCI­60 panel) was statistically interpreted using 6 generated scores assessing activity, selectivity, growth inhibition efficacy and potency of different structural scaffolds, Bemis­Murcko skeletons, chemical features and structures common among the analyzed compounds. Of the most commonly used rings, the most prominent anti­proliferative effects were produced by quinoline, tetrahydropyran, benzimidazole and pyrazole, while overall, the optimal results were produced by complex ring structures that originate from natural compounds. These results highlight the impact of certain ring structures on the anti­proliferative effects in drug design. In addition, considering that medicinal chemists usually focus their research on simpler scaffolds the majority of the time with no significant pay­off, the present study indicates several unused complex scaffolds that could be exploited when designing anticancer therapies for optimal results in the fight against cancer.

The significance of erythropoietin and insulin administration on survival of fat tissue after autologous fat transplantation in Wistar rats. An experimental study.

Autologous fat transfer is widely used by plastic surgeons for aesthetic and reconstructive purpose, but it has a great disadvantage because of its high variability rate of resorption. Numerous studies have examined the use of different agents to increase the viability of fat grafts. The results were discouraging because the use of a single angiogenic factor to stimulate fat graft angiogenesis may be inappropriate. We proposed to use two pharmacological factors, erythropoietin (EPO) and insulin (INS), in order to decrease the resorption rate, to improve graft vascularization, and to reduce the number of complications. Twenty-four Wistar male rats were randomly divided in four groups (I-IV) of six animals each. The rats belonging to control group were given autologous transfer of simple fat. In group II, the graft was improved with EPO, in group III with INS, and in group IV both pharmacological agents were administered. Histological evaluation of the grafts at two months after injection demonstrated adipocyte survival in all four groups. The volume of the graft has progressively decreased in all groups and the difference in graft volume at one and two months after transplantation was not significant. The highest maintenance of fat graft volume (95%) at two months was observed in group IV, followed by group II and group III. Necrotic cystic changes and increased fibrosis were most extensive in the control group. The combination of INS with EPO may have a synergistic and additive effect. Efficient administration and dose optimization of these growth factors are important things to consider in the future.

Oxidative Stress and the Microbiota-Gut-Brain Axis.

The gut-brain axis is increasingly recognized as an important pathway of communication and of physiological regulation, and gut microbiota seems to play a significant role in this mutual relationship. Oxidative stress is one of the most important pathogenic mechanisms for both neurodegenerative diseases, such as Alzheimer's or Parkinson's, and acute conditions, such as stroke or traumatic brain injury. A peculiar microbiota type might increase brain inflammation and reactive oxygen species levels and might favor abnormal aggregation of proteins. Reversely, brain lesions of various etiologies result in alteration of gut properties and microbiota. These recent hypotheses could open a door for new therapeutic approaches in various neurological diseases.