Management of Upper Tract Urothelial Carcinoma in a Double Collecting System Kidney.

Upper tract urothelial carcinoma (UTUC) in a duplex collecting system (DCS) is a relatively uncommon presentation with unclear management guidelines. Herein, we retrospectively reviewed all published cases of DCS with UTUC aiming to suggest personalized clinical care options for future cases. We conducted a systematic search for all cases of UTUC in DCS from published literature using the following keywords: UTUC, urothelial carcinoma (UC), collecting duct carcinoma, and DCS. The cases were summarized based on demographics, clinical presentation, predisposing risk factors, tumor location, management, and follow-up. We present an additional case based on our experience with a 69-year-old female with high-grade (HG) UTUC of the upper moiety in complete DCS. The patient underwent a robotic upper pole hemi-nephroureterectomy (hemi-NU) with a common sheath distal ureterectomy and a bladder cuff, followed by lower pole ureteral reimplantation. Overall, 34 patients with 35 renal units of UTUC in DCS were included and analyzed. To conclude, UTUC of DCS is rare and underreported. Hence, it is difficult to define a standard treatment. Although hemi-NU has been previously described, to the best of our knowledge, this is the first case report of robot-assisted hemi-NU for complete DCS with single-moiety UC.

Cemiplimab as First Line Therapy in Advanced Penile Squamous Cell Carcinoma: A Real-World Experience.

In the treatment of cancer, immune checkpoint inhibitors (ICIs) have demonstrated significantly greater effectiveness compared to conventional cytotoxic or platinum-based chemotherapies. To assess the efficacy of ICI's in penile squamous cell carcinoma (pSCC) we performed a retrospective observational study. We reviewed electronic medical records of patients with penile squamous cell carcinoma (SCC), diagnosed between January 2020 and February 2023. Nine patients were screened, of whom three were ineligible for chemotherapy and received immunotherapy, cemiplimab, in a first-line setting. Each of the three immunotherapy-treated patients achieved almost a complete response (CR) after only a few cycles of therapy. The first patient had cerebral arteritis during treatment and received a high-dose steroid treatment with resolution of the symptoms of arteritis. After tapering down the steroids dose, the patient continued cemiplimab without further toxicity. The other two patients did not have any toxic side effects of the treatment. To the best of our knowledge, this is the first real world report of near CR with cemiplimab as a first-line treatment in penile SCC.

Carpal Tunnel Syndrome Associated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) have transformed the therapeutic approach to diverse malignancies, leading to substantial enhancements in patient prognosis. However, along with their benefits, ICIs also increase the incidence of immune-related adverse events (irAEs). In the present paper, we highlight four cases of carpal tunnel syndrome (CTS) as an uncommon manifestation of toxicity induced by ICIs. Although diagnosed with different malignancies, the patients were undergoing ICI therapy when they developed CTS-consistent side effects accompanied by severe neuropathy. Prompt treatment with corticosteroids, intravenous immunoglobulins, or methotrexate resulted in complete symptomatic relief for all patients. This article therefore emphasizes the importance of recognizing and managing rare adverse events associated with ICI use to ensure optimal patient care.

Modified Citrus Pectin Treatment in Non-Metastatic Biochemically Relapsed Prostate Cancer: Long-Term Results of a Prospective Phase II Study.

The optimal therapy for patients with non-metastatic biochemically relapsed prostate cancer (BRPC-M0) after local therapy is elusive. Thus, the evaluation of new non-toxic compounds in BRPC-M0 patients is warranted. PectaSol®-Modified citrus pectin (P-MCP) is a food supplement categorized as GRAS (Generally Recognized As Safe) by the FDA. It is a competitive inhibitor of the galectin-3 protein, which is involved in cancer pathogenesis. In an early report of the present phase 2 study, P-MCP treatment for 6 months led to prostate-specific antigen doubling time (PSADT) improvement in 75% of patients with BRPC-M0. Herein, we report the second long-term treatment phase of an additional 12 months of P-MCP therapy (4.8 g × 3/day orally) in patients without disease progression after the initial 6 months of therapy. Of the 46 patients that entered the second treatment phase, 7 patients withdrew consent and decided to continue therapy out of pocket, and 39 initiated the second treatment phase. After a total of 18 months of P-MCP treatment, 85% (n = 33) had a durable long-term response, with 62% (n = 24) showing decreased/stable PSA, 90% (n = 35) PSADT improvement, and all with negative scans. No patient had grade 3/4 toxicity. In conclusion, P-MCP may have long-term durable efficacy and is safe in BRPC-M0.

Unexpected Adverse Events of Immune Checkpoint Inhibitors.

The introduction of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment standards and significantly enhanced patient prognoses. However, the utilization of these groundbreaking therapies has led to the observation and reporting of various types of adverse events, commonly known as immune-related adverse events (irAEs). In the following article, we present four patients who encountered uncommon toxicities induced by ICIs. The first patient was a 59-year-old female diagnosed with stage 4 lung adenocarcinoma. She received immunotherapy (pembrolizumab) together with chemotherapy and subsequently developed autonomic neuropathy (AN). The next two patients also received chemo-immunotherapy (pembrolizumab) and were both 63-year-old males with stage 4 lung adenocarcinoma. One of the two experienced palmoplantar keratoderma, while the other presented with Reiter's syndrome (urethritis, conjunctivitis and arthritis). The 4th patient, an 80-year-old male with stage 4 squamous cell carcinoma of the lung, received chemo-immunotherapy (pembrolizumab) and developed myasthenia gravis.

Radiotherapy-Induced Atrial Myxoma: A Case Report and Literature Review.

In this particular case study, we present a 66-year-old male who was diagnosed with an atrial myxoma eight years after receiving treatment for non-small cell lung cancer. The patient underwent chemo-radiotherapy (mediastinal area) in 2012 to address stage III-A adenocarcinoma of the lung. During follow-up imaging in 2020, a left atrial mass displaying characteristic features of a cardiac myxoma was detected. Upon reviewing a computed tomographic (CT) scan from 2017 within the previously irradiated mediastinal region, the cardiac mass was retrospectively identified. The surgical excision of the cardiac mass was performed, and a subsequent pathological examination confirmed the diagnosis of myxoma. To the best of our knowledge, this is the first reported case of a left atrial myxoma in a patient previously treated for adenocarcinoma of the lung and the first instance of an atrial myxoma occurring in a site that had undergone prior radiation therapy.

Erdafitinib treatment in metastatic urothelial carcinoma: a real-world analysis.

Background: Erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor is a standard post chemotherapy advanced treatment line for metastatic urothelial carcinoma harboring FGFR2/3 genomic alterations. It was approved based on a phase 2 clinical trial, revealing a 40% response rate, and 13.8 months overall survival. These FGFR genomic alterations are uncommon. Thus, real-world data on erdafitinb use is scant. We herein describe erdafitinib treatment outcome in a real world patient cohort. Methods: We retrospectively reviewed the data of patients treated with erdafitinib from 9 Israeli medical centers. Results: Twenty-five patients with metastatic urothelial carcinoma (median age 73, 64% male, 80% with visceral metastases) were treated with erdafitinib between January 2020 to October 2022. A clinical benefit (complete response 12%, partial response 32%, stable disease 12%) was seen in 56%. Median progression-free survival was 2.7 months, and median overall survival 6.73 months. Treatment related toxicity ≥ grade 3 occurred in 52%, and 32% discontinued therapy due to adverse events. Conclusions: Erdafitinib therapy is associated with a clinical benefit in the real world setting, and associated with similar toxicity as reported in prospective clinical trials.

Evaluation of the optimal strategy in men with a single unilateral suspicious lesion on MRI undergoing transperineal MRI/ultrasound fusion prostate biopsy.

BACKGROUND: Targeting biopsy (TBx) of suspicious lesions combined with random systematic biopsy (SBx) improves detection rates of prostate cancer (PCa) during magnetic resonance imaging (MRI)/ultrasound (US) fusion prostate biopsy. However, this combination increases the number of biopsy cores, prolongs the procedure time, and increases complications and costs, leading to the overdiagnosis of clinically insignificant PCa (ciPCa). This study aims to evaluate the optimal sampling design to achieve a detection rate of clinically significant PCa (csPCa) equal to standard TBx with SBx with fewer biopsy cores. MATERIALS AND METHODS: Of 508 consecutive men who underwent transperineal MRI/US fusion prostate biopsy at our center between January 2020 and December 2022, 364 patients with a single unilateral suspicious lesion on MRI were included in the study. Three biopsy strategies were randomly selected to evaluate the diagnostic accuracy of PCa detection: (1) TBx with ipsilateral SBx, (2) TBx with contralateral SBx, and (3) TBx only. The PCa detection sensitivity for selected biopsy strategies was compared with the reference standards. The significance of differences in cancer detection between sampling schemes was determined using McNemar's test. RESULTS: PCa was diagnosed in 182 of 364 men using TBx with bilateral SBx. International Society of Urological Pathology grade group (ISUP GG) ≥ 2 and ISUP GG ≥ 3 PCa was detected in 84/364 (23.1%) and 42/364 (11.5%), respectively, while ISUP GG 1 PCa was diagnosed in 98/364 (26.9%). Combining TBx with ipsilateral SBx detected 94.5% of all, 98.8% of ISUP GG ≥ 2, 100% of ISUP GG ≥ 3, and 89.8% of ISUP GG 1 PCa. TBx with contralateral SBx detected fewer csPCa (91.7% vs. 98.8%, p = 0.03), as did TBx alone (90.5 vs. 98.8, p = 0.008). CONCLUSIONS: Our study demonstrates that TBx with ipsilateral SBx performed around the multiparametric MRI-suspected lesion in transperineal MRI/US biopsy of the prostate achieves a very high detection rate for csPCa (ISUP ≥ 2) without compromising the detection of increased risk PCa (ISUP ≥ 3). In addition, this strategy reduces the number of biopsy cores by 8-10 per patient, procedure time, and pathology processing costs and decreases ciPCa detection.

Functional binding of PD1 ligands predicts response to anti-PD1 treatment in patients with cancer.

Accurate predictive biomarkers of response to immune checkpoint inhibitors (ICIs) are required for better stratifying patients with cancer to ICI treatments. Here, we present a new concept for a bioassay to predict the response to anti-PD1 therapies, which is based on measuring the binding functionality of PDL1 and PDL2 to their receptor, PD1. In detail, we developed a cell-based reporting system, called the immuno-checkpoint artificial reporter with overexpression of PD1 (IcAR-PD1) and evaluated the functionality of PDL1 and PDL2 binding in tumor cell lines, patient-derived xenografts, and fixed-tissue tumor samples obtained from patients with cancer. In a retrospective clinical study, we found that the functionality of PDL1 and PDL2 predicts response to anti-PD1 and that the functionality of PDL1 binding is a more effective predictor than PDL1 protein expression alone. Our findings suggest that assessing the functionality of ligand binding is superior to staining of protein expression for predicting response to ICIs.

Safety and rapid response of dabrafenib and trametinib therapy during hyperbilirubinemia in metastatic melanoma.

This case report describes the occurrence of hyperbilirubinemia as a complication of metastatic melanoma. A 72-year-old male patient was diagnosed with BRAF V600E-mutated melanoma with metastases in the liver, lymph nodes, lungs, pancreas, and stomach. Due to a lack of clinical data and specific guidelines for the treatment of mutated metastatic melanoma patients with hyperbilirubinemia, a conference of specialists debated between initiating treatment or providing supportive care. Ultimately, the patient was started on the combination therapy of dabrafenib and trametinib. This treatment resulted in a significant therapeutic response via normalization of bilirubin levels and an impressive radiological response of metastases just one month post-treatment initiation.

Prophylactic Breast Irradiation for Prevention of Bicalutamide-induced Painful Gynecomastia in Patients with Low- and Intermediate-risk Prostate Cancer.

BACKGROUND: Bicalutamide monotherapy (BMT) is an option for androgen deprivation therapy (ADT) in patients with low- and intermediate-risk prostate cancer (LIR-PC). Painful gynecomastia (PG) is a common side effect of BMT. Few therapeutic options are available for preventing BMT-induced PG. OBJECTIVES: To assess the efficacy and side effects of single fraction (SF) prophylactic breast irradiation (PBI) to prevent painful gynecomastia (PG) in patients LIR-PC treated with BMT. METHODS: We reviewed the results of bilateral PBI in a prospective cohort of LIR-PC patients who received 150 mg bicalutamide daily as a first-line treatment for at least 12 months. A single fraction of 8 Gy was administered to both breasts by a stationary field of 10 × 10 cm, using 10-15 MeV electron beam. PBI was commenced on the same day as BMT, but prior to the first dose of bicalutamide. A radiotherapy treatment plan was designed to cover breast tissue by the 90% isodose line. Subsequent monthly physical examinations were scheduled for all patients during the first year of BMT to evaluate any PG symptoms. RESULTS: Seventy-six patients received BMT and PBI, 80% (61/76) showed no signs of PG; 20% (15/76) experienced mild gynecomastia. The main adverse effect of PBI was grade 1 radiation dermatitis. CONCLUSIONS: PBI using a SF of 8 Gy is an effective, safe, and low-cost strategy for the prevention of BMT-induced PG in LIR-PC patients.

A Retrospective, Single-Institution Experience of Bullous Pemphigoid as an Adverse Effect of Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors are a class of cancer treatment drugs that stimulate the immune system's ability to fight tumor cells. These drugs are monoclonal antibodies targeting im-mune-inhibiting proteins on cancer cells, such as CTLA-4 and PD-1/PD-L1. Immune checkpoint inhibitors cause many immune-related adverse events. Cutaneous toxicities are of the most common adverse effects and occur with a range of severity. Bullous Pemphigoid is a rare adverse event with a high impact on quality of life that may occur after immune checkpoint inhibitor treatment. In this article, we investigate current research on immune checkpoint inhibitors, cutaneous adverse events, and common presentations and treatments, with a specific focus on Bullous Pemphigoid, its characteristics, onset timing, and treatment. Significant findings include a negative skew in the onset of presentation. Furthermore, we describe exclusive cases.

The impact of the COVID-19 pandemic on colorectal and gastric cancer diagnosis, disease stage and mortality.

Background: Since the outbreak of COVID-19, a significant decline in endoscopic procedures has been observed. Aims: We investigated the change of incidence, clinical characteristics, disease stage and mortality of patients with gastric cancer (GC) or colorectal cancer (CRC) diagnosed in 2020 compared to the pre-pandemic year 2019. Methods: Demographic, clinical and laboratory data on all patients diagnosed with GC or CRC at the Soroka University Medical Center were retrospectively collected and compared. Number of cases, time of diagnosis, clinical presentation, staging at diagnosis and mortality rates were compared. Results: Two hundred sixteen patients were diagnosed with CRC in 2019, whereas only 162 were diagnosed in 2020 (25% reduction), while 36 GC diagnoses were made in 2019 compared to 24 in 2020 (33% reduction). The age-adjusted incidence was calculated to be 24.28 for CRC and 5.0 for GC in 2020 compared to 29.93 and 5.32 in 2019, respectively. CRC patients had a significantly lower rate of rectal bleeding as their presenting symptom in 2020 compared with 2019, 8.1 vs. 19% (p = 0.003), but higher rate of diarrhea as their presenting symptom, 4.3 vs. 1% (p = 0.044). No significant differences regarding other presenting symptoms, comorbidities, surgery or mortality rates were found between the groups diagnosed in 2019 or 2020. Conclusion: A decrease in GC and CRC incidence was observed during the year 2020; lower rate of rectal bleeding and higher rate of diarrhea as presenting symptoms were noted in 2020, but no significant difference was found regarding other presenting symptoms, disease stage, surgery or mortality.

Metabolic Activity Assessment by 18F-Fluorodeoxyglucose Positron Emission Tomography in Patients after COVID-19 Vaccination.

In the following report, we describe 11 patients with various diagnoses and different treatment statuses (newly diagnosed, receiving treatment, or follow-up) of oncological diseases (breast, lymphoma, melanoma, and head and neck cancers). The patients underwent PET-CT for disease staging or follow-up and it was noted that all patients had areas of hypermetabolic uptake in the axillary lymph-nodes of the ipsilateral upper extremity where the Pfizer-BioNTech coronavirus (COVID-19) vaccine was administered. Following further investigations, including an ultrasound (US), biopsies and an examination of medical records, it was concluded that these findings were the result of the vaccination and not a progression of pre-existing disease.

Safety of the BNT162b2 mRNA COVID-19 vaccine in oncologic patients undergoing numerous cancer treatment options: A retrospective single-center study.

ABSTRACT: The COVID-19 pandemic, caused by the SARS-CoV2 virus, has infected millions worldwide with cancer patients demonstrating a higher prevalence for severe disease and poorer outcomes. Recently, the BNT162b2 mRNA COVID-19 vaccine was released as the primary means to combat COVID-19. The currently reported incidence of local and systemic side effects was 27% in the general public. The safety of the BNT162b2 mRNA COVID-19 vaccine has not been studied in patients with an active cancer diagnosis who are either ongoing or plan to undergo oncologic therapy.This single center study reviewed the charts of 210 patients with active cancer diagnoses that received both doses of the BNT162b2 mRNA COVID-19 vaccine. The development of side effects from the vaccine, hospitalizations or exacerbations from various oncologic treatment were documented. Type of oncologic treatment (immunotherapy, chemotherapy, hormonal, biologic, radiation or mixed) was documented to identify if side effects were related to treatment type. The time at which the vaccine was administered in relation to treatment onset (on long term therapy, within 1 month of therapy or prior to therapy) was also documented to identify any relationships.Sixty five (31%) participants experienced side effects from the BNT162b2 mRNA COVID-19 vaccine, however most were mild to moderate. Treatment protocol was not linked to the development of vaccine related side effects (P = .202), nor was immunotherapy (P = .942). The timing of vaccine administered in relation to treatment onset was also not related to vaccine related side effects (P = .653). Six (2.9%) participants were hospitalized and 4 (2%) died.The incidence of side effects in cancer patients is similar to what has been reported for the general public (31% vs 27%). Therefore, we believe that the BNT162b2 mRNA COVID-19 vaccine is safe in oncologic patients undergoing numerous cancer treatments.

Intravenous immunoglobulin efficacy on pembrolizumab induced severe toxic epidermal necrolysis.

Pembrolizumab is an immune checkpoint inhibitor used in many different cancers. Several immune-related adverse events (irAEs) have been associated with pembrolizumab, including toxic epidermal necrolysis. Here, we are presenting a patient with non-small cell lung cancer that developed toxic epidermal necrolysis 3-days following initiation of pembrolizumab. Following high-dose steroid therapy, intravenous immunoglobulin 2 g/kg was initiated and resulted in complete resolution of all his irAEs. To our knowledge, this is the first reported case of total re-epithelialization and resolution of immune checkpoint inhibitor-induced toxic epidermal necrolysis following the use of intravenous immunoglobulin.

Modified Citrus Pectin Treatment in Non-Metastatic Biochemically Relapsed Prostate Cancer: Results of a Prospective Phase II Study.

Optimal therapy of biochemically relapsed prostate cancer (BRPC) after local treatment is elusive. An established modified citrus pectin (PectaSol®, P-MCP), a dietary polysaccharide, is an established antagonist of galectin-3, a carbohydrate-binding protein involved in cancer pathogenesis. Based on PSA dynamics, we report on the safety and the primary outcome analysis of a prospective phase II study of P-MCP in non-metastatic BRPC based. Sixty patients were enrolled, and one patient withdrew after a month. Patients (n = 59) were given P-MCP, 4.8 grams X 3/day, for six months. The primary endpoint was the rate without PSA progression and improved PSA doubling time (PSADT). Secondary endpoints were the rate without radiologic progression and toxicity. Patients that did not progress by PSA and radiologically at six months continued for an additional twelve months. After six months, 78% (n = 46) responded to therapy, with a decreased/stable PSA in 58% (n = 34), or improvement of PSADT in 75% (n = 44), and with negative scans, and entered the second twelve months treatment phase. Median PSADT improved significantly (p = 0.003). Disease progression during the first 6 months was noted in only 22% (n = 13), with PSA progression in 17% (n = 10), and PSA and radiologic progression in 5% (n = 3). No patients developed grade 3 or 4 toxicity.

Metastatic small cell lung cancer - an aggressive disease: a case report and literature review.

In the present case study, we describe a 53-year-old male with an aggressive small cell lung cancer (SCLC) that was diagnosed in January 2019. Our patient was treated as first line of systemic chemotherapy consisting of cisplatin and etoposide followed by mediastinal prophylactic radiotherapy with good response later he received for his metastatic disease (M-SCLC) a rechallenge of systemic chemotherapy consisting of carboplatin, etoposide and dulvalumab with stable disease and after progression his disease he was treated with lurbinectedin and after four cycles he reached a complete radiologic response. To the best of our knowledge, this is the first case to be reported of M-SCLC patient treated with prior of two types of platinum combination with immunotherapy and reaching a complete radiologic response.

Pulmonary toxicity following administration of granulocyte colony-stimulating factor during chemotherapy for breast cancer: a case report and literature review.

In this report, we aim to present a case of pulmonary toxicity in a patient that received neoadjuvant chemotherapy treatment with doxorubicin and cyclophosphamide for triple-negative breast cancer that was followed with granulocyte colony-stimulating factor (G-CSF) for prevention neutropenia, our patient presented with chest discomfort and dyspnea, with radiologic evidence of radiologic investigations showed acute respiratory distress syndrome, after investigation and follow up we came to the conclusion that it was G-CSF adverse effect.

Nivolumab-induced systemic capillary leak syndrome as an ultra rare life-threatening phenomenon of late toxicity and intravenous immunoglobulin efficacy.

Systemic capillary leak syndrome (SCLS) is a life-threatening disease. It is characterized by severe capillary hyperpermeability to proteins resulting in hemoconcentration, hypoalbuminemia and hypovolemic shock. Its treatment remains supportive, and the prognosis is generally poor. We report on a 51-year old male with melanoma treated with nivolumab for 1 year. 1 month following the completion of the treatment, the patient presented with signs of hypovolemic shock, anasarca, hemoconcentration and hypoalbuminemia. After excluding other diseases, a diagnosis of nivolumab-induced systemic capillary leak syndrome was made. A high dose of intravenous steroid therapy was promptly initiated without any significant clinical improvement. Intravenous immunoglobulin therapy was then administered with normalization of blood pressure, hemoconcentration and complete resolution of anasarca. Intravenous immunoglobulin should be considered a first-line treatment option for this rare phenomenon.

Lay abstract Systemic capillary leak syndrome (SCLS) is a life-threatening disease with a high fatality rate. Patients present with low blood pressure, widespread edema and rapid weight gain. Labs show low albumin levels with highly concentrated blood, seen as high hematocrit and hemoglobin levels. Current treatments aim to support the acute crisis. We are presenting on a 51-year old patient with melanoma, treated with nivolumab for 1 year who developed signs of SCLS 1-month following medication discontinuation. He was first treated with high-dose steroids without symptom resolution. He was then administered immune proteins called intravenous immunoglobulins, resolving all his symptoms. Due to the patient's complete response, we suggest intravenous immunoglobulins as the initial treatment in patients taking nivolumab presenting with SCLS.