Unlocking Precision Medicine: Liquid Biopsy Advancements in Renal Cancer Detection and Monitoring.

Renal cell carcinoma (RCC) remains a formidable diagnostic challenge, especially in the context of small renal masses. The quest for non-invasive screening tools and biomarkers has steered research towards liquid biopsy, focusing on microRNAs (miRNAs), exosomes, and circulating tumor cells (CTCs). MiRNAs, small non-coding RNAs, exhibit notable dysregulation in RCC, offering promising avenues for diagnosis and prognosis. Studies underscore their potential across various biofluids, including plasma, serum, and urine, for RCC detection and subtype characterization. Encouraging miRNA signatures show correlations with overall survival, indicative of their future relevance in RCC management. Exosomes, with their diverse molecular cargo, including miRNAs, emerge as enticing biomarkers, while CTCs, emanating from primary tumors into the bloodstream, provide valuable insights into cancer progression. Despite these advancements, clinical translation necessitates further validation and standardization, encompassing larger-scale studies and robust evidence generation. Currently lacking approved diagnostic assays for renal cancer, the potential future applications of liquid biopsy in follow-up care, treatment selection, and outcome prediction in RCC patients are profound. This review aims to discuss and highlight recent advancements in liquid biopsy for RCC, exploring their strengths and weaknesses in the comprehensive management of this disease.

SARS-CoV-2 infection affects the lower urinary tract and male genital system: A systematic review.

PubMed, Scopus, and ISI Web of Knowledge databases were searched to identify studies published up to December 2020 on the involvement of urinary and male genital systems in COVID-19. Sixteen studies involving a total of 575 patients (538 males and 37 females) were included in this systematic review. The COVID-19 phase was available for 479 patients: 426 in the acute and 53 in the recovery phase. De novo lower urinary tract symptoms (LUTS) were observed in 43 patients and deterioration of pre-existing LUTS in 7. Bladder hemorrhage was observed in three patients and acute urinary retention in one. Regarding the male genital system, scrotal discomfort was observed in 8 patients, swelling in 14, pain in 16, and erythema in 1; low flow priapism was observed in 2 patients. Ultrasound examination identified acute orchitis in 10 patients, acute epididymitis in 7, and acute epididymo-orchitis in 16. A case-control study reported that patients with moderate COVID-19 show a significant reduction in sperm concertation, the total number of sperms per ejaculate, progressive motility, and complete motility. In contrast to what is known from the first studies on the subject, this review also includes subsequent studies that give evidence of the involvement of the lower urinary tract and male genital system in COVID-19.

Renal involvement in COVID-19: focus on kidney transplant sector.

INTRODUCTION: Kidney transplant recipients and patients on the waiting list for kidney transplant who acquire SARS-CoV-2 infection are at serious risk of developing severe COVID-19, with an increased risk of mortality for the their immunosuppressive state; other risk factors for mortality have been identified in some comorbidities such as obesity, diabetes, asthma and chronic lung disease. MATERIALS AND METHODS: The COVID-19 pandemic has led to a sharp reduction in kidney transplants in most countries, mainly due to the concern of patients on the waiting list for their potential increased susceptibility to acquire SARS-CoV-2 infection in healthcare facilities and for the difficulties of transplant centers to ensure full activity as hospitals have had to focus most of their attention on COVID-19 patients. Indeed, while the infection curve continued its exponential rise, there was a vertical decline in kidney donation/transplant activity. CONCLUSION: This review article focuses on the damage induced by SARS-CoV-2 infection on kidney and on the adverse effect of this pandemic on the entire kidney transplant sector.

Bowel obstruction and peritoneal carcinomatosis in the elderly. A systematic review.

BACKGROUND: There are not guidelines for surgical management of malignant bowel obstruction (MBO) caused by peritoneal carcinomatosis (PC), mainly when it involves elderly; so its treatment is still debated. AIM: To outline indications and benefits of palliative surgery for obstructive carcinomatosis and determine what prognostic factors, including age, have independent and significant association with outcome. METHODS: We conducted English-language MEDLINE and EMBASE searches of articles published between 1998 and 2016, which reported outcome data after palliative surgery for MBO due to PC. We excluded all articles lacking of surgical cohort and those with main interest in conservative treatment. Of 1275 articles identified, 12 satisfied selection criteria and were included in our analysis. RESULTS: Overall, these studies involved 548 patients undergoing palliative surgery for MBO caused by PC. The median age was 58 (range 19-93). Relief of symptoms was achieved in 26.5-100% of cases. Postoperative morbidity ranged between 7 and 44%. Mortality was high (6-22%). The median survival was longer in surgical patients than in those receiving conservative therapy (8-34 vs 4-5 weeks). Factors associated with surgery failure were poor performance status, diffuse carcinomatosis, previous radiotherapy, and obstruction of small bowel. Old age was significantly associated with a poor prognosis upon univariate analysis, while this association vanished upon multivariate analysis. CONCLUSIONS: Surgical palliation can provide relief of obstructive symptoms as well as improved survival in well-selected patients, even if elderly.

Early and late post-procedural complications in different orthotopic neobladder surgical approaches: A systematic review.

Bladder cancer (BCa) represents the second most common malignancy of the genitourinary tract. The major risk factors include age, gender, smoking attitude, and occupational exposure, while the exact etiopathogenesis is still uncertain. Patients diagnosed with a BCa showing invasion of the muscle layer below the submucosa must undergo radical cystectomy (RC) with urinary diversion (UD). Many different surgical approaches to UD have been developed. Packaging an orthotopic neobladder (ON) with a bowel tract represents the gold standard when certain patient selection criteria are satisfied. Using PRISMA guidelines, we performed a systematic review assessing early (within 90 days) and late (beyond 90 days) post-procedural complications of different ON surgical approaches. A comprehensive systematic search was conducted in PubMed, Scopus, and Google Scholar databases to identify papers starting from 2012 using dedicated keywords ("neobladder", "orthotopic neobladder", "complications'' and "outcomes"). A total of 27 articles were found to satisfy the inclusion criteria and selected. Although the ON is a safe procedure that guarantees the patient the best quality of life (QoL), it is not free from risks. Many complications could occur during and after the surgical time which imposes the necessity of strict follow-up and careful checks over time, which should be properly discussed with patients before.

Advances in Urinary Diversion: From Cutaneous Ureterostomy to Orthotopic Neobladder Reconstruction-A Comprehensive Review.

Bladder cancer ranks as the 10th most prevalent cancer globally with an increasing incidence. Radical cystectomy combined with urinary diversion represents the standard treatment for muscle-invasive bladder cancer, offering a range of techniques tailored to patient factors. Overall, urinary diversions are divided into non-continent and continent. Among the first category, cutaneous ureterostomy and ileal conduit represent the most common procedures while in the second category, it could be possible to describe another subclassification which includes ureterosigmoidostomy, continent diversions requiring catheterization and orthotopic voiding pouches and neobladders. In this comprehensive review, urinary diversions are described in their technical aspects, providing a summary of almost all alternatives to urinary diversion post-radical cystectomy.

Intraperitoneal dedifferentiated liposarcoma showing MDM2 amplification: case report.

BACKGROUND: Liposarcoma is the most common type of soft tissue sarcoma (STS). It is divided into five groups according to histological pattern: well-differentiated, myxoid, round cell, pleomorphic, and dedifferentiated. Dedifferentiated liposarcoma most commonly occurs in the retroperitoneum, while an intraperitoneal location is extremely rare. Only seven cases have been reported in literature. Many pathologists recognize that a large number of intra-abdominal poorly differentiated sarcomas are dedifferentiated liposarcomas. We report a case initially diagnosed as undifferentiated sarcoma that was reclassified as intraperitoneal dedifferentiated liposarcoma showing an amplification of the MDM2 gene. CASE PRESENTATION: A 59-year-old woman with abdominal pain and constipation was referred to the Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy, in November 2012. On physical examination, a very large firm mass was palpable in the meso-hypogastrium. Computed tomography (CT) scan showed a heterogeneous density mass (measuring 10 × 19 cm) that was contiguous with the mesentery and compressed the third part of the duodenum and jejunum.At laparotomy, a large mass occupying the entire abdomen was found, adhering to the first jejunal loop and involving the mesentery. Surgical removal of the tumor along with a jejunal resection was performed because the first jejunal loop was firmly attached to the tumor.Macroscopic examination showed a solid, whitish, cerebroid, and myxoid mass, with variable hemorrhage and cystic degeneration, measuring 26 × 19 × 5 cm. Microscopic examination revealed two main different morphologic patterns: areas with spindle cells in a myxoid matrix and areas with pleomorphic cells. The case was initially diagnosed as undifferentiated pleomorphic sarcoma. Histological review showed areas of well-differentiated liposarcoma. Fluorescence in situ hybridization (FISH) analysis was performed and demonstrated an amplification of the MDM2 gene. Definitive diagnosis was intraperitoneal dedifferentiated liposarcoma.No adjuvant therapy was given, but 5 months after laparotomy, the patient presented with a locoregional recurrence and chemotherapy with high-dose ifosfamide was started. CONCLUSIONS: No guidelines are available for the management of intraperitoneal dedifferentiated liposarcoma. We report this case to permit the collection of a larger number of cases to improve understanding and management of this tumor. Moreover, this study strongly suggests that poorly differentiated sarcomas should prompt extensive sampling to demonstrate a well-differentiated liposarcoma component and, if possible, FISH analysis.

Multidisciplinary Approach to the Diagnosis and Therapy of Mycosis Fungoides.

Mycosis fungoides is the most common primary cutaneous T-cell lymphoma, characterized by skin-homing CD4+ T cells derivation, indolent course, and low-grade of malignancy. Mycosis fungoides's classic type typically onsets with cutaneous erythematous patches, plaque, and tumor. In WHO-EORTC classification, folliculotropic mycosis fungoides, pagetoid reticulosis, and granulomatous slack skin are recognized as distinct variants of mycosis fungoides, because of their clinical and histological features, behavior, and /or prognosis. Mycosis fungoides often shows diagnostic difficulties, due to its absence of specific features and lesional polymorphism. A patient's treatment requires staging. In about 10% of cases, mycosis fungoides can progress to lymph nodes and internal organs. Prognosis is poor at advanced stage and management needs a multidisciplinary team approach. Advanced stage disease including tumors, erythroderma, and nodal, visceral, or blood involvement needs skin directed therapy associated with systemic drugs. Skin directed therapy includes steroids, nitrogen mustard, bexarotene gel, phototherapy UVB, and photochemiotherapy, i.e., total skin electron radiotherapy. Systemic therapies include retinoids, bexarotene, interferon, histone deacetylase inhibitors, photopheresis, targeted immunotherapy, and cytotoxic chemotherapy. Complexity of mycosis fungoides associated with long-term chronic evolution and multiple therapy based on disease stage need a multidisciplinary team approach to be treated.

Comparing cardiovascular adverse events in cancer patients: A meta-analysis of combination therapy with angiogenesis inhibitors and immune checkpoint inhibitors versus angiogenesis inhibitors alone.

Anti-VEGF (vascular endothelial growth factor) agents were associated with increased risk of several cardiovascular events, while one meta-analysis did not show any significantly increased risk of cardiotoxicity associated with the use of immune checkpoint inhibitors (ICIs). This meta-analysis of randomized-controlled trials (RCTs) was designed to compare cardiovascular toxicity of anti-VEGF agents plus ICI vs anti-VEGF agents without ICIs. A systematic search of the literature was conducted to include all full papers reporting about phase II and III randomized controlled trials (RCTs) conducted in patients with solid malignancies randomized to an anti-VEGF agent plus an ICI vs. an anti-VEGF agent without an ICI. Overall incidences of cardiovascular events were compared between these two treatment groups estimating the corresponding odds ratios. This analysis suggests that ICIs may increase the risk of cardiovascular toxicities associated with anti-VEGF therapies. Further research, including real world studies, is warranted.

Epidemiological and clinical aspects of hepatitis B virus infection in Italy over the last 50 years.

A relevant gradual reduction of both the incidence rate of acute hepatitis B (AHB) and prevalence of chronic hepatitis B has occurred in Italy in the last 50 years, due to substantial epidemiological changes: Improvement in socioeconomic and hygienic conditions, reduction of the family unit, accurate screening of blood donations, abolition of re-usable glass syringes, hepatitis B virus (HBV)-universal vaccination started in 1991, use of effective well tolerated nucleo(t)side analogues able to suppress HBV replication available from 1998, and educational mediatic campaigns against human immunodeficiency virus infection focusing on the prevention of sexual and parenteral transmission of infections. As an example, AHB incidence has gradually decreased from 10/100000 inhabitants in 1985 to 0.21 in 2020. Unfortunately, the coronavirus disease 2019 (COVID-19) pandemic has interrupted the trend towards HBV eradication. In fact, several HBV chronic carriers living in the countryside have become unable to access healthcare facilities for screening, diagnosis, clinical management, and nucleo(t)side analogue therapy in the COVID-19 pandemic, mainly for anxiety of becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), movement restrictions, and reduced gains from job loss. In addition, one-third of healthcare facilities and personnel for HBV patients have been devolved to the COVID-19 assistance.

Epithelioid Hemangioma of the Nose: A Challenging Diagnosis.

Epithelioid hemangioma is a rare reactive vasoproliferative disease presenting with painless vascular nodules in the dermal and subcutaneous tissues of the head and neck. Clinical diagnosis can be difficult as, in most cases, the only symptom is a progressively tender swelling next to a vessel course. Thus far, few cases of epithelioid hemangioma localized to the nose have been described in the literature. Herein, we present a case of a 47-year-old woman with just such a lesion of the nose, focusing on its diagnosis and treatment.

One-stage resection of primary colorectal cancer and hepatic metastases using the Habib Device: analysis of 40 consecutive cases treated in a Unit of general surgery.

BACKGROUND: More than 50% of patients with colorectal cancer (CRC) present or develop hepatic metastases (HM). The intraoperative use of the Habib 4X® radio frequency probe device is safe in resetting HM and allows a one-stage resection of both CRC and HM with a similar mortality rate than a two-stage surgical treatment. METHODS: After an exhaustive residential training at the reference center for hepato-biliary surgery of the Imperial College of London, we treated at our unit of general surgery 40 consecutive patients with CRC and HM with the one-stage resection, using the Habib 4X® intraoperative radiofrequency probe device to reset HM. RESULTS: None of the 40 patients died during the intra-operatory and post-operatory periods, none presented liver failures during the postoperative course nor complication related to the Habib's resection procedure (e.g. bleeding, abscess, bile leak). The amount of intra-operative liver bleeding was minimal. New HM arose in 10 (25%) cases, with a mean disease-free interval of 13 months, but the hepatic tissue close to previous resections remained cancer-free. The 69.7% of patients were disease-free at month 24 of the post-operative follow-up and 5-year rate was about 70%. CONCLUSIONS: The data suggest that surgeons well trained at a reference center for hepato-biliary surgery may perform with excellent results the one-stage CRC and HM resection with the Habib 4X® device even in a Unit of general surgery.

Immune Checkpoint Inhibitors as a Neoadjuvant/Adjuvant Treatment of Muscle-Invasive Bladder Cancer: A Systematic Review.

Bladder cancer is the ninth most common cancer worldwide. Over 75% of non-muscle invasive cancer patients require conservative local treatment, while the remaining 25% of patients undergo radical cystectomy or radiotherapy. Immune checkpoint inhibitors represent a novel class of immunotherapy drugs that restore natural antitumoral immune activity via the blockage of inhibitory receptors and ligands expressed on antigen-presenting cells, T lymphocytes and tumour cells. The use of immune checkpoint inhibitors in bladder cancer has been expanded from the neoadjuvant setting, i.e., after radical cystectomy, to the adjuvant setting, i.e., before the operative time or chemotherapy, in order to improve the overall survival and to reduce the morbidity and mortality of both the disease and its treatment. However, some patients do not respond to checkpoint inhibitors. As result, the capability for identifying patients that are eligible for this immunotherapy represent one of the efforts of ongoing studies. The aim of this systematic review is to summarize the most recent evidence regarding the use of immune checkpoint inhibitors, in a neoadjuvant and adjuvant setting, in the treatment of muscle-invasive bladder cancer.

Promoting Laparoscopic Anterior Approach for a Very Low Presacral Primary Neuroendocrine Tumor Arising in a Tailgut Cyst.

BACKGROUND: Tailgut cysts are rare congenital lesions that develop in the presacral space. As they can potentially conceal primary neuroendocrine tumors, surgical excision is suggested as the treatment of choice. However, specific management guidelines have yet to be developed. A posterior approach is usually preferred for cysts extending to the third sacral vertebral body. Conversely, a transabdominal approach is preferred for lesions extending upward to achieve an optimal view of the surgical field and avoid injuries. CASE REPORT: Here, we report a case of a 48-year-old man suffering from perianal pain and constipation. Digital rectal examination and magnetic resonance imaging revealed a presacral mass below the third sacral vertebral body. A laparoscopic transabdominal presacral tumor excision was performed. The final histological diagnosis was a rare primary neuroendocrine tumor arising from a tailgut cyst. The postoperative course was uneventful, and no signs of recurrence were observed at the six-month follow-up. CONCLUSIONS: This study may help establish more well-grounded recommendations for the surgical management of rectal tumors, demonstrating that the laparoscopic transabdominal technique is safe and feasible, even for lesions below the third sacral vertebral body. This approach provided an adequate view of the presacral space, facilitating the preservation of cyst integrity, which is essential in cases of malignant pathologies.

Dyslipidemia in Transplant Patients: Which Therapy?

Cardiovascular disease is the most important cause of death worldwide in recent years; an increasing trend is also shown in organ transplant patients subjected to immunosuppressive therapies, in which cardiovascular diseases represent one of the most frequent causes of long-term mortality. This is also linked to immunosuppressant-induced dyslipidemia, which occurs in 27 to 71% of organ transplant recipients. The aim of this review is to clarify the pathophysiological mechanisms underlying dyslipidemia in patients treated with immunosuppressants to identify immunosuppressive therapies which do not cause dyslipidemia or therapeutic pathways effective in reducing hypercholesterolemia, hypertriglyceridemia, or both, without further adverse events.

Metastasis-Directed Radiation Therapy with Consolidative Intent for Oligometastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis.

The management of patients with oligometastatic urothelial carcinoma (UC) represents an evolving field in uro-oncology, and the role of metastasis-directed therapies, including metastasectomy and metastasis-directed radiation therapy (MDRT), is gaining increasing attention. Herein, we summarize available evidence about the role of MDRT with consolidative intent in oligometastatic UC patients. A systematic review was performed in December 2021. Six studies involving 158 patients were identified. Most patients (n = 120, 90.2%) had a history of bladder cancer and the most frequent sites of metastases were lymph nodes (n = 61, 52.1%) followed by the lungs (n = 34, 29%). Overall, 144 metastases were treated with MDRT. Median follow-up ranged from 17.2 to 25 months. Local control rates ranged from 57% to 100%. Median Overall Survival (OS) ranged from 14.9 to 51.0 months and median progression-free survival ranged from 2.9 to 10.1 months. Rates of OS at one and two years ranged from 78.9% to 96% and from 26% to 63%, respectively. Treatment-related toxicity was recorded in few patients and in most cases a low-grade toxicity was evident. MDRT with consolidative intent represents a potential treatment option for selected patients with oligometastatic UC.

Prostate Cancer Diagnosis, Treatment and Outcomes in Patients with Previous or Synchronous Colorectal Cancer: A Systematic Review of Published Evidence.

The management of patients with prostate cancer (PCa) and previous or synchronous colorectal cancer (CRC) represents a challenging issue. A systematic review was performed in May 2022 to summarize available evidence about the diagnosis, management, and outcomes of these patients. Twenty-seven studies involving 252 patients were identified. Overall, 163 (64.7%) and 89 (35.3%) patients had synchronous and metachronous PCa and CRC, respectively. In patients with synchronous diseases, PCa treatment involved active surveillance in 1 patient, radical prostatectomy (RP) in 36 patients, radiotherapy (RT) in 60 patients, RP plus RT in 1 patient, proton beam therapy in 1 patient, and cryoablation in 1 patient. In patients with previous CRC treatment, prostate biopsy was mostly performed by transrectal approach (n = 24). The trans-perineal and suprapubic approaches were adopted in 12 and 6 cases, respectively. Surgical PCa treatment in these cases involved endoscopic extraperitoneal RP, robot-assisted RP, and not otherwise specified RP in 30, 15, and 2 cases, respectively. Biochemical recurrence rates ranged from 20% to 28%. Non-surgical PCa treatment options included brachytherapy, RT plus androgen deprivation therapy, and RT alone in 23, 2 and 4 patients, respectively. PCa specific survival was reported by one study and was 100%.

Physical activity in elderly kidney transplant patients with multiple renal arteries.

BACKGROUND: Kidney transplantation (KT) is the gold standard for treatment of patients with end-stage-renal disease. To expand the donor reserve, it is necessary to use marginal/suboptimal kidneys. METHODS: We retrospectively evaluated the short/long-term outcome of 34 KT elderly patients who received allografts with vascular abnormalities (MRA group), in comparison with 34 KT patients who received a kidney with a single renal artery (SRA group) pair-matched by age, length of time on dialysis, comorbidity and donor age. RESULTS: All participants completed the International Physical Activity Questionnaire at KT, and then 4, 8, and 12 weeks after transplantation. Our data indicate that kidney with vascular anatomical variants may be successfully transplanted, since the overall rate of surgical complications was 20.6% in the SRA group and 17.6% in the MRA group and that the 5-year survival rate after KT was 100% in both groups. CONCLUSIONS: The data also underlined that individualized physical activity programs induced similar excellent results in both groups, improving physical capacities, arterial pressure, lipid metabolism, insulin sensitivity, quality of life and physical and mental status.

How Fear of COVID-19 Can Affect Treatment Choices for Anaplastic Large Cell Lymphomas ALK+ Therapy: A Case Report.

BACKGROUND: The t (2; 5) chromosomal rearrangement of the ALK gene with nucleophosmin 1 gene (NPM1), resulting in an NPM1-ALK fusion, was first demonstrated in 1994 in anaplastic large cell lymphoma, (ALCL), a T-cell lymphoma responsive to cyclophosphamide, abriblastine, vincristine and prednisone in approximately 80% of cases; refractory cases usually respond favorably to brentuximab vedotin. These treatments are regarded as a bridge to allogeneic hematopoietic stem cell transplantation (allo-SCT). Nowadays, transplant procedures and the monitoring of chemotherapy patients proceed very slowly because the SARS-CoV-2 pandemic has heavily clogged the hospitals in all countries. RESULTS: A 40-year-old Caucasian woman was first seen at our clinical center in June 2020. She had ALCL ALK+, a history of failure to two previous therapeutic lines and was in complete remission after 12 courses of brentuximab, still pending allo-SCT after two failed donor selections. Facing a new therapeutic failure, we requested and obtained authorization from the Italian drug regulatory agency to administer 250 mg of crizotinib twice a day, a drug incomprehensibly not registered for ALCL ALK +. CONCLUSIONS: The response to crizotinib was optimal since no adverse event occurred, and CT-PET scans persisted negative; this drug has proved to be a valid bridge to allo-SCT.

Fournier's Gangrene in Patients with Oncohematological Diseases: A Systematic Review of Published Cases.

Patients suffering from hematological malignancies are at increased risk of Fournier's gangrene (FG) due to immunosuppression caused by the disease itself or by disease-related treatments. A systematic review of PubMed, ISI Web of Knowledge, and Scopus databases was performed in June 2021. We included full papers that met the following criteria: original research, human studies, and describing clinical presentation, treatment, and outcomes of FG in patients with oncohematological diseases. We identified 35 papers published from 1983 to 2021 involving 44 patients (34 males, 8 females) aged between 4 days and 83 years. The most common malignant hematological disorders were acute myeloid leukemia (n = 21) and acute lymphocytic leukemia (n = 9). In 10 patients FG represented the first presentation of hematological malignancy. Scrotum (n= 27) and perineum (n = 11) were the sites most commonly involved. Pseudomonas aeruginosa (n = 21) and Escherichia coli (n = 6) were the most commonly isolated microorganisms. Surgery was performed in 39 patients. Vacuum-assisted closure and hyperbaric oxygen therapy were adopted in 4 and in 3 patients, respectively. Recovery was achieved in 30 patients. FG-related mortality was observed in 11 patients. FG should be carefully considered in patients with oncohematological diseases.