A Unique Case of the Transformation of a Hepatic Leiomyoma into Leiomyosarcoma with Pancreatic Metastases: Review of the Literature with Case Presentation

Primary hepatic leiomyoma (PHL) is a rare entity, with very few cases reported in the literature. Even more rarely, until now practically undescribed, is the transformation of a hepatic leiomyoma into leiomyosarcoma with pancreatic metastases. Here, we report a single case of the progression of PHL in primary hepatic leiomyosarcoma, with clinical–surgical and histopathological features, and we conducted a review of the literature of related cases that can be found

Video-Laparoscopic versus Open Surgery in Obese Patients with Colorectal Cancer: A Propensity Score Matching Study

Background: Minimally invasive surgery in obese patients is still challenging, so exploring one more item in this research field ranks among the main goals of this research. We aimed to compare short-term postoperative outcomes of open and video-laparoscopic (VL) approaches in CRC obese patients undergoing colorectal resection. Methods: We performed a retrospective analysis of a surgical database including 138 patients diagnosed with CRC, undergoing VL (n = 87, 63%) and open (n = 51, 37%) colorectal surgery. As a first step, propensity score matching was performed to balance the comparison between the two intervention groups (VL and open) in order to avoid selection bias. The matched sample (N = 98) was used to run further regression models in order to analyze the observed VL surgery advantages in terms of postoperative outcome, focusing on hospitalization and severity of postoperative complications, according to the Clavien–Dindo classification. Results: The study sample was predominantly male (N = 86, 62.3%), and VL was more frequent than open surgery (63% versus 37%). The two subgroup results obtained before and after the propensity score matching showed comparable findings for age, gender, BMI, and tumor staging. The specimen length and postoperative time before discharge were longer in open surgery (OS) patients; the number of harvested lymph nodes was higher than in VL patients as well (p < 0.01). Linear regression models applied separately on the outcomes of interest showed that VL-treated patients had a shorter hospital stay by almost two days and about one point less Clavien–Dindo severity than OS patients on average, given the same exposure to confounding variables. Tumor staging was not found to have a significant role in influencing the short-term outcomes investigated. Conclusion: Comparing open and VL surgery, improved postoperative outcomes were observed for VL surgery in obese patients after surgical resection for CRC. Both postoperative recovery time and Clavien–Dindo severity were better with VL surgery

Predictors of Long-Term Outcomes of Video-Laparoscopic Versus Open Surgery in Obese Patients with Colorectal Cancer: A Propensity Score Matching Study

Background: Minimally invasive methods in colorectal surgery offer unquestionable advantages, especially in the context of obesity. The current study addresses the lack of scientific evidence on the long-term oncologic safety of video-laparoscopic (VL) approaches in excess-weight CRC patients undergoing surgery. Methods: We retrospectively analyzed a surgical database consisting of 138 CRC patients undergoing VL (n = 87, 63%) and open CRC surgery (n = 51, 37%). To reduce selection bias, a propensity score matching was applied as a preliminary step to balance the comparison between the two surgery groups, i.e., VL and open surgery. Data from patients treated by the same surgeon were used.to minimize bias. Additional Cox regression models were run on the matched sample (N = 98) to explore the observed benefits of VL surgery in terms of overall and cancer-free survival. The nonparametric Kaplan-Meier method was used to compare the two surgical approaches and assess the likelihood of survival and cancer relapse. Results: The study sample was mostly male (N = 86, 62.3%), and VL outnumbered open surgery (63% versus 37%). Both before and after the matching, the VL-allocated group showed better overall survival (p < 0.01) with comparable cancer-free survival over more than five years of median observation time (66 months). Kaplan Meier survival probability curves corroborated the VL significant protective effect on survival (HR of 0.32; 95% CI: 0.13 to 0.81) even after adjusting for major confounding factors (age, gender, comorbidity index, BMI, tumor localization, tumor staging, tumor grading, clearance, CRM). Findings on oncologic performance by tumor relapse were comparable but lacked significance due to the small number of events observed. Conclusions: Comparing CRC surgical approaches, VL allocation showed comparable cancer-free survival but also a better performance on overall mortality than open surgery over more than five years of median observation

Metabolomic Approaches for Detection and Identification of Biomarkers and Altered Pathways in Bladder Cancer

Metabolomic analysis has proven to be a useful tool in biomarker discovery and the molecular classification of cancers. In order to find new biomarkers, and to better understand its pathological behavior, bladder cancer also has been studied using a metabolomics approach. In this article, we review the literature on metabolomic studies of bladder cancer, focusing on the different available samples (urine, blood, tissue samples) used to perform the studies and their relative findings. Moreover, the multi-omic approach in bladder cancer research has found novel insights into its metabolic behavior, providing excellent start-points for new diagnostic and therapeutic strategies. Metabolomics data analysis can lead to the discovery of a “signature pathway” associated with the progression of bladder cancer; this aspect could be potentially valuable in predictions of clinical outcomes and the introduction of new treatments. However, further studies are needed to give stronger evidence and to make these tools feasible for use in clinical practice

Renal Cell Carcinoma as a Metabolic Disease: An Update on Main Pathways, Potential Biomarkers, and Therapeutic Targets

: Clear cell renal cell carcinoma (ccRCC) is the most frequent histological kidney cancer subtype. Over the last decade, significant progress has been made in identifying the genetic and metabolic alterations driving ccRCC development. In particular, an integrated approach using transcriptomics, metabolomics, and lipidomics has led to a better understanding of ccRCC as a metabolic disease. The metabolic profiling of this cancer could help define and predict its behavior in terms of aggressiveness, prognosis, and therapeutic responsiveness, and would be an innovative strategy for choosing the optimal therapy for a specific patient. This review article describes the current state-of-the-art in research on ccRCC metabolic pathways and potential therapeutic applications. In addition, the clinical implication of pharmacometabolomic intervention is analyzed, which represents a new field for novel stage-related and patient-tailored strategies according to the specific susceptibility to new classes of drugs

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible

A challenging surgical approach to locally advanced primary urethral carcinoma: A case report and literature review

Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches. A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and "en bloc" removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy. The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery. Patients with advanced stage tumors of the bulbomembranous urethra should be managed with radical surgery including the corporas up to the ischiatic tuberosity attachment, and membranous urethra in continuity with the prostate and bladder. Neo-adjuvant treatment may be advisable with the aim of improving the poor prognosis, even if the efficacy is not certain while it can delay the radical treatment of the disease

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19