Transperineal excision of malignant peripheral nerve sheath tumors of the ischiorectal fossa: Case report of a rare tumor in a frequently forgotten anatomical region

Introduction and importance: Malignant peripheral nerve sheath tumor is an aggressive tumor that arises from peripheral nerves. Frequently associated with neurofibromatosis, its common localization is in the extremities, trunk (with paravertebral regions), neck and head. Some cases have been found in the pelvis or uterus. In this case report we illustrate one of the rarest localization of this type of tumor in the ischiorectal fossa, with the full recovery of the patient after surgical excision and radiotherapy. Case presentation: A 61-year-old woman showed a lump near the anus which was initially diagnosed as a lipoma of the right ischiorectal fossa, by Computed Tomography scan. The tumor was completely removed with a minimal skin incision, and the patient had a complete recovery. Only the pathological examination determined the diagnosis of malignant peripheral nerve sheath tumor, in this unusual localization. In consideration of its high aggressiveness the patient underwent radiotherapy. After more than two years of follow-up there is no sign of recurrence. Discussion: In sites far from branches of nerves, malignant peripheral nerve sheath tumors can be considered episodic. Ischiorectal fossa is a rare localization, and the differential diagnosis from benign mesenchymal cell tumors can be challenging. When possible, a biopsy should be performed before surgery. Conclusion: Surgical excision of tumors in ischiorectal fossa should be always complete, in consideration of possible histological surprise

Perirectal hematoma after stapled surgery for hemorrhoidal prolapse and obstructed defecation syndrome: case series management to avoid panic-guided treatment

Perirectal hematoma (PH) is one of the most feared complications of stapling procedures. Literature reviews have reported only a few works on PH, most of them describing isolated treatment approaches and severe outcomes. The aim of this study was to analyze a homogenous case series of PH and to define a treatment algorithm for huge postoperative PHs. A retrospective analysis of a prospective database of three high-volume proctology units was performed between 2008 and 2018, and all PH cases were analyzed. In all, 3058 patients underwent stapling procedures for hemorrhoidal disease or obstructed defecation syndrome with internal prolapse. Among these, 14 (0.46%) large PH cases were reported, and 12 of these hematomas were stable and treated conservatively (antibiotics and CT/laboratory test monitoring); most of them were resolved with spontaneous drainage. Two patients with progressive PH (signs of active bleeding and peritonism) were submitted to CT and arteriography to evaluate the source of bleeding, which was subsequently closed by embolization. This approach helped ensure that no patients with PH were referred for major abdominal surgery. Most PH cases are stable and treatable with a conservative approach, evolving with self-drainage. Progressive hematomas are rare and should undergo angiography with embolization to minimize the possibility of major surgery and severe complications

Aurora Kinases: New Molecular Targets for the Therapy of Aggressive Thyroid Cancers

Epithelial thyroid carcinomas (TC) account for more than 90% of all endocrine malignancies and represent one of the most frequent cancers in women. They include the well-differentiated TC (DTC), comprising the papillary (PTC) and follicular (FTC) histotypes, the poorly differentiated (PDTC), and the undifferentiated or anaplastic TC (ATC). Both PDTC and ATC are aggressive human neoplasms with a dire prognosis due to the absence of effective therapies, which makes mandatory the identification of novel therapeutic strategies. Intrinsic chromosomal instability (CIN, an increased rate of gain or losses of chromosomes during cell division) is a common feature of solid tumors and represents a major driving force in thyroid cancer progression, thought to be responsible for the acquisition by malignant cells of novel functional capabilities. Different mitotic kinases, whose expression or function has been found altered in human cancer tissues, are major drivers of thyroid tumor aneuploidy. Among these are the three members of the Aurora family (Aurora-A, Aurora-B and Aurora-C), serine/threonine kinases that regulate multiple aspects of chromosome segregation and cytokinesis. Over the last few years, several small molecule inhibitors targeting Aurora kinases were developed with promising antitumor effects in preclinical and clinical studies against different human cancers, including TC. Here, we will focus on the Aurora mitotic functions in normal cells; we shall then describe the main implications of their overexpression in the onset of genetic instability and aneuploidy. We will finally describe the consequences of Aurora kinase inhibition on TC cell growth and tumorigenicity

"Water or not water: That is the question." Analysis of costs and consumption of the operating theaters in a greener perspective

Objective: To compare the amounts of water and plastic used in surgical hand washing with medicated soaps and with alcohol-based products and to compare costs and consumption in a year, based on scheduled surgical activity. Method: This retrospective study was carried out at Udine's Gynecology Operating Block from October to November 2022. We estimated the average amount of water with a graduated cylinder and the total cost of water usage based on euros/m3 indicated by the supplier; for each antiseptic agent we collected the data relevant to wash time, amount of water and product used per scrub, number of handscrubs made with every 500 mL bottle and cost of a single bottle. We put data into two hypothetical contexts, namely WHO guidelines and manufacturers' recommendations. Data were subjected to statistical analysis. Results: The daily amount of water using povidone-iodine, chlorhexidine-gluconate and alcohol-based antiseptic agents was 187.6, 140.7 and 0 L/day (P value = 0.001), respectively; A total of 69 000 L/year of water would be saved if alcohol-based products were routinely used. A single unit of an alcohol-based product allows three times as many handscrubs as any other product (P value = 0.001) with consequent reduction in plastic packaging. Conclusion: Despite the cost saving being negligible, choosing alcohol-based handrub over medicated soap handrub - on equal antiseptic efficacy grounds - could lead to a significant saving of water and plastic, thus making our operating theaters more environmentally friendly

CD28 Individual Signaling Up-regulates Human IL-17A Expression by Promoting the Recruitment of RelA/NF-κB and STAT3 Transcription Factors on the Proximal Promoter

CD28 is an important co-stimulatory receptor for T lymphocytes that, in humans, delivers TCR-independent signal leading to the up-regulation of pro-inflammatory cytokines. We have recently reported that CD28 autonomous signaling induces the expression of IL-17A in peripheral CD4+ T lymphocytes from healthy donors, multiple sclerosis, and type 1 diabetes patients. Due to the relevance of IL-17A in the pathophysiology of several inflammatory and autoimmune diseases, we characterized the mechanisms and signaling mediators responsible for CD28-induced IL-17A expression. Here we show that CD28-mediated up-regulation of IL-17A gene expression depends on RelA/NF-κB and IL-6-associated STAT3 transcriptions factors. In particular, we found that CD28-activated RelA/NF-κB induces the expression of IL-6 that, in a positive feedback loop, mediates the activation and nuclear translocation of tyrosine phosphorylated STAT3 (pSTAT3). pSTAT3 in turn cooperates with RelA/NF-κB by binding specific sequences within the proximal promoter of human IL-17A gene, thus inducing its expression. Finally, by using specific inhibitory drugs, we also identified class 1A phosphatidylinositol 3-kinase (PI3K) as a critical upstream regulator of CD28-mediated RelA/NF-κB and STAT3 recruitments and trans-activation of IL-17A promoter. Our findings reveal a novel mechanism by which human CD28 may amplify IL-17A expression in human T lymphocytes and provide biological bases for immunotherapeutic approaches targeting CD28-associated class 1A PI3K to dampen IL-17A-mediated inflammatory response in autoimmune/inflammatory disorders

Moderni orientamenti nella chirurgia della parotide

La scelta del tipo di approccio nella chirurgia parotidea è di fondamentale importanza per condurre al meglio l’atto curativo pur preservando le delicate strutture del compartimento parotideo. Lo scopo di questo lavoro è di dimostrare come un’approfondita conoscenza dell’anatomia ed una scrupolosa esecuzione dell’atto chirurgico permettano di conciliare radicalità chirurgica e salvaguardia delle strutture nobili. Descriveremo quindi osservazioni anatomo-chirurgiche alla luce delle patologie di nostra pertinenza, ricordando le diverse tipologie di interventi eseguibili. Queste considerazioni saranno lo spunto per discutere ed analizzare alcune strategie chirurgich

CTLA-4 and PD-1 ligand gene expression in epithelial thyroid cancers

The dysregulation of PD-1 ligands (PD-L1 and PD-L2) and CTLA-4 ligands (CD80 and CD86) represents a tumor strategy to escape the immune surveillance. Here, the expression of PD-L1, PD-L2, CD80 and CD86 was evaluated at mRNA level in 94 patients affected by papillary thyroid carcinoma (PTC) and 11 patients affected by anaplastic thyroid carcinoma (ATC). Variations in the mRNAs in PTC patients were then correlated with clinicopathological features. The expression of all genes was deregulated in PTC and ATC tissues compared to normal tissues. In particular, the down-regulation of CD80 was observed in above all ATC. In addition, the increased expression of CD80 associated to longer disease-free survival in PTC. Higher expression of PD-L1 associated with the classical histological variant and with the presence of BRAFV600E mutation in PTC. The increased PD-L2 expression correlated with BRAFV600E mutation and lymph node metastasis, while its lower expression correlated with the follicular PTC variant. The latter was also associated with the CD80 down-regulation, which was also related to the absence of lymph node metastasis. In conclusion, we documented the overall dysregulation of PD-1 and CTLA-4 ligands in PTC and ATC tissues and a possible prognostic value for CD80 gene expression in PTC

Does Sexual Function and Quality of Life Improve after Medical Therapy in Women with Endometriosis? A Single-Institution Retrospective Analysis

Background: Endometriosis is a gynecological condition affecting up to 10% of women of reproductive age and characterized by chronic pain. Pain is the major cause of the impairment of quality of life in all aspects of these patients. Previous studies have shown that endometriosis treatment, hormonal or surgical, has proven effective not only in controlling the disease but also in improving symptoms, and we can assume also effective in improving quality of life. Methods: This study evaluates quality of life and sexual function in patients with endometriosis at the time of diagnosis and after 6 months of medical therapy, to assess the impact of treatment on these aspects. We evaluated retrospectively patients with a diagnosis of endometriosis between 2018 and 2020. All patients underwent gynecological examination and transvaginal ultrasound and filled in three questionnaires. The same evaluation was provided after taking medical hormonal therapy. Results: The improvement of dysmenorrhea, chronic pelvic pain, and dyspareunia after medical treatment were statistically significant. Instead, items concerning arousal, lubrication, and sexual satisfaction showed a statistically significant worsening after therapy. Conclusions: We can state that hormone therapy alone is not sufficient to achieve an improvement in the patient's quality of life and sexual function. Emerging evidence suggests that most of these patients showed a central sensibilization phenomenon characterized by an amplification of the response to a peripheral and/or neuropathic nociceptive trigger, which is expressed by hyperalgesia and allodynia. For this reason, in these patients, it is better to adopt a multimodal and multidisciplinary approach, including other professional figures, that acts on pain and also intervenes in all those conditions that contribute to worsening quality of life

L’adenocarcinoma dell’appendice ileo-ciecale: presentazione di un caso clinico e revisione della letteratura

L’adenocarcinoma dell’appendice ileo-ciecale è una neoplasia di rara osservazione rappresentando meno dello 0,5% di tutti i tumori dell’apparato gastrointestinale. Nella maggior parte dei casi viene diagnosticato all’esame istologico definitivo di un’appendice asportata per flogosi, talora invece rappresenta un reperto del tutto inatteso, documentato da biopsie estemporanee, in corso di intervento chirurgico eseguito per sospetta appendicite acuta o altra patologia non appendicolare. La storia naturale di tale neoplasia è fortemente condizionata dalle peculiari caratteristiche anatomiche del viscere che ne favoriscono la precoce diffusione e una notevole tendenza alla perforazione. Si associa frequentemente ad altre neoplasie primitive, sincrone o metacrone, a localizzazione colo-rettale o extraintestinale. Il trattamento chirurgico oncologicamente corretto è l’emicolectomia destra che può essere eseguita come prima procedura, nei casi in cui la neoplasia venga diagnosticata pre- o intraoperatoriamente, o come seconda procedura, due-tre settimane dopo l’appendicectomia, qualora soltanto l’esame istologico dell’appendice asportata riveli la presenza dell’adenocarcinoma. L’emicolectomia destra è il trattamento chirurgico più idoneo in tutti gli istotipi (colico, mucinoso, adenocarcinoide), in presenza di perforazione ed anche nelle neoplasie allo stadio A di Dukes. Durante l’atto operatorio è necessario effettuare un’accurata esplorazione della cavità addominale per la ricerca di neoplasie sincrone, mentre dopo l’intervento i pazienti dovranno essere sottoposti ad un follow-up regolare e prolungato nel tempo onde diagnosticare precocemente eventuali neoplasie metacrone. Riportiamo il caso di una donna di 78 anni con adenocarcinoma dell’appendice scoperto casualmente in corso di intervento chirurgico eseguito per un quadro di occlusione intestinale da sospetta neoplasia del cieco

Thyroglobulin measurement in the washout of fine needle aspirates for the diagnosis of suspicious cervical lymph nodes

Ultrasound-guided fine-needle aspiration cytology (FNAC) for suspicious cervical lymph nodes (CLN) is the gold standard technique for the identification of metastases from differentiated thyroid carcinomas. Thyroglobulin protein (Tgp) assay in the washout of needles employed for FNA biopsies (FNAB) has been reported to refine and support FNAC performances, especially in cases of inadequate sampling or cystic lymph nodes. In the present work, we evaluated the usefulness of routine measurement of Tgp in the FNAB washout of suspicious cervical lymph nodes (CLN), and its ability to increase the FNAC accuracy in the diagnosis of metastatic CLN. A case study of 45 CLN with histological diagnosis from 36 patients was analyzed. Histology showed metastases from papillary thyroid carcinomas (PTC) in 31 CLN, from anaplastic thyroid cancer (ATC) in 3 CLN, from medullary thyroid cancer (MTC) in 4 CLN, and metastases from extrathyroidal malignancies in 5 CLN. Two CLN analyzed were found to be non-neoplastic. The overall accuracy of FNAC was 82.9%, and that of Tgp was 91.1%, not statistically different. However, Tgp determination was found essential in 4 cases of metastatic CLN from DTC with inadequate cytology, and in 1 case in which the FNAC provided a false negative result. We demonstrated that FNAC and Tgp assay show similar diagnostic accuracies, and that Tgp measurement may represent the only available information in case of inadequate lymph node sampling or cystic lymph nodes