Potentially actionable targets in synovial sarcoma: A tissue microarray study.

BACKGROUND: Synovial sarcoma (SynSa) is one of the most common translocation-related soft tissue sarcomas. Patients with metastatic SynSa have limited treatment options and a very poor prognosis. Several novel experimental therapies are currently being explored in clinical trials, including T cell-based therapies targeting cancer testis antigens such as New York esophageal squamous cell carcinoma 1 (NY-ESO-1) or melanoma-associated antigen A4 (MAGE-A4), and degraders targeting bromodomain-containing protein 9 (BRD9). Preclinical studies investigate inhibitors of Yes associated protein 1 (YAP1), transcriptional co-activator with PDZ-binding motif (TAZ) and inhibitors of chemokine receptor 4 (CXCR4). METHODS: We explored the immunohistochemical expression of these targets using a tissue microarray (TMA) constructed from 91 clinical SynSa samples and correlated these findings with corresponding clinicopathological data. RESULTS: Expression of MAGE-A4 and NY-ESO-1 was found in 69 % and 56 % of the samples, respectively. NY-ESO-1 was statistically higher expressed in samples from metastatic lesions as compared to samples from primary tumors. Nuclear expression of YAP1 and TAZ was observed in 92 % and 51 % of the samples, respectively. CXCR4 was expressed in the majority of the samples (82 %). BRD9 was highly expressed in all specimens. No prognostic role could be identified for any of the investigated proteins. CONCLUSION: This study is a comprehensive study providing real-world data on the expression of several actionable proteins in a large proportion of SynSa samples. All evaluated markers were expressed in a clinically meaningful proportion of cases represented in our TMA, supporting the relevance of ongoing preclinical and clinical research with novel agents directed against these targets.

Fissurectomy versus lateral internal sphincterotomy in the treatment of chronic anal fissures: no advantages in terms of post-operative incontinence.

PURPOSE: The standard treatment for chronic anal fissures that have failed non-operative management is lateral internal sphincterotomy. Surgery can cause de novo incontinence. Fissurectomy has been proposed as a sphincter/saving procedure, especially in the presence of a deep posterior pouch with or without a crypt infection. This study investigated whether fissurectomy offers a benefit in terms of de novo post-operative incontinence. METHODS: Patients surgically managed with fissurectomy or lateral internal sphincterotomy for chronic anal fissures from 2013 to 2019 have been included. Healing rate, changes in continence and patient satisfaction were investigated at long-term follow-up. RESULTS: One hundred twenty patients (55 females, 65 males) were analysed: 29 patients underwent fissurectomy and 91 lateral internal sphincterotomy. Mean follow-up was 55 months [confidence interval (CI) 5-116 months]. Both techniques showed some rate of de novo post-operative incontinence (> +3 Vaizey score points): 8.9% lateral internal sphincterotomy, 17.8% fissurectomy (p = 0.338). The mean Vaizey score in these patients was 10.37 [standard deviation (sd) 6.3] after lateral internal sphincterotomy (LIS) and 5.4 (sd 2.3) after fissurectomy Healing rate was 97.8% in the lateral internal sphincterotomy group and 75.8% in the fissurectomy group (p = 0.001). In the lateral internal sphincterotomy group, patients with de novo post-op incontinence showed a statistically significant lower satisfaction rate (9.2 ± 1.57 versus 6.13 ± 3; p = 0.023) while no differences were present in the fissurectomy group (8.87 ± 1.69 versus 7.4 ± 1.14; p = 0.077). CONCLUSIONS: Lateral internal sphincterotomy is confirmed as the preferred technique in term of healing rate. Fissurectomy did not offer a lower rate of de novo post-operative incontinence, but resulted in lower Vaizey scores in patients in whom this occurred. Satisfaction was lower in patients suffering a de novo post-operative incontinence after lateral internal sphincterotomy.

How I Treat Localized Soft Tissue Sarcomas: Update on Diagnosis, Risk Stratification, and Treatment.

BACKGROUND: Adult-type soft tissue sarcomas (STSs) are rare tumors representing about 1% of all adult malignant tumors. Their extreme histological heterogeneity places them among the most challenging fields of diagnostic pathology. The variability of clinical and prognostic presentation between the various histotypes reflects the different management that should be followed on a case-by-case basis. These features make STSs the case in point of how important it is a centralized and multidisciplinary approach. SUMMARY: Surgery represents the mainstay in the treatment of localized STSs. Recently, more and more studies are making efforts to understand what the contribution of chemotherapy and radiotherapy with neoadjuvant and adjuvant intent may be both in unselected and selected histological subgroups. In fact, despite the improvement in overall survival seen in the past few years thanks to the adoption of a more radical surgical approach, mortality remains relatively high and the 5-year overall survival is around 65%. KEY MESSAGES: In this review, we comment upon the treatment of localized STSs of the extremity, trunk wall, and retroperitoneum and how surgery, radiotherapy, and chemotherapy can be integrated with each other and individually tailored. Nomograms can assist clinicians in this complex therapeutic decision-making process, through the identification of patients at higher risk of death or disease relapse.

Impact of adjuvant imatinib on bone and muscle density in patients with resected gastrointestinal stromal tumors.

Adjuvant treatment with Imatinib is the standard of care for high-risk resected GISTs. Imatinib is known to have an impact on bone mineral density in patients affected by chronic myeloid leukemia, however this effect has never been investigated in GISTs. We retrospectively evaluated, on CT scans, the effect of adjuvant Imatinib (400 mg/die) on bone mineral density and muscle composition in 14 patients with surgically resected GISTs and in a control group of 8 patients who did not received any treatment. The effect of bone and muscle composition on Imatinib-tolerance was assessed as well. Overall patients receiving Imatinib experienced an increase in bone mineral density during treatment (p = 0.021); with higher increase in patients with basal values < 120 mg/cm3 (p = 0.002). No changes were observed in the control group (p = 0.918). Skeletal muscle index and lean body mass did not change over time during Imatinib therapy; however, patients with lower lean body mass and lower body mass index experienced more grade 3 treatment related toxicities (p = 0.024 and p = 0.014 respectively). We also found a non-significant trend between basal BMD and grade 3 toxicities (p = 0.060).