UNASSIGNED: Biology-guided radiotherapy (BgRT) is a novel treatment where the detection of positron emission originating from a volume called the biological tracking zone (BTZ) initiates dose delivery. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is a novel imaging technique that may improve patient selection for metastasis-directed therapy in renal cell carcinoma (RCC). This study aims to determine the feasibility of BgRT treatment for RCC.
UNASSIGNED: All consecutive patients that underwent PSMA PET/CT scan for RCC staging at our institution between 2014 and 2020 were retrospectively considered for inclusion. GTVs were contoured on the CT component of the PET/CT scan. The tumor-to-background ratio was quantified from the normalized standardized uptake value (nSUV), defined as the ratio between SUVmax inside the GTV and SUVmean inside the margin expansion. Tumors were classified suitable for BgRT if (1) nSUV was greater or equal to an nSUV threshold and (2) if the BTZ was free of any PET-avid region other than the tumor.
UNASSIGNED: Out of this cohort of 83 patients, 47 had metastatic RCC and were included in this study. In total, 136 tumors were delineated, 1 to 22 tumors per patient, mostly in lung (40%). Using a margin expansion of 5 mm/10 mm/20 mm and nSUV threshold = 3, 66%/63%/41% of tumors were suitable for BgRT treatment. Uptake originating from another tumor, the kidney, or the liver was typically inside the BTZ in tumors judged unsuitable for BgRT.
UNASSIGNED: More than 60% of tumors were found to be suitable for BgRT in this cohort of patients with RCC. However, the proximity of PET-avid organs such as the liver or the kidney may affect BgRT delivery.

Endothelial cells (ECs) play an important role in tumor progression. Currently, the main target of anti-angiogenic therapy is the vascular endothelial growth factor (VEGF) pathway. Some patients do benefit from anti-VEGF/VEGFR therapy; however, a large number of patients do not have response or acquire drug resistance after treatment. Moreover, anti-VEGF/VEGFR therapy may lead to nephrotoxicity and cardiovascular-related side effects due to its action on normal ECs. Therefore, it is necessary to identify targets that are specific to tumor ECs and could be applied to various cancer types. We integrated single-cell RNA sequencing data from six cancer types and constructed a multi-cancer EC atlas to decode the characteristic of tumor ECs. We found that tip-like ECs mainly exist in tumor tissues but barely exist in normal tissues. Tip-like ECs are involved in the promotion of tumor angiogenesis and inhibition on anti-tumor immune responses. Moreover, tumor cells, myeloid cells, and pericytes are the main sources of pro-angiogenic factors. High proportion of tip-like ECs is associated with poor prognosis in multiple cancer types. We also identified that prostate-specific membrane antigen (PSMA) is a specific marker for tip-like ECs in all the cancer types we studied. In summary, we demonstrate that tip-like ECs are the main differential EC subcluster between tumors and normal tissues. Tip-like ECs may promote tumor progression through promoting angiogenesis while inhibiting anti-tumor immune responses. PSMA was a specific marker for tip-like ECs, which could be used as a potential target for the diagnosis and treatment of non-prostate cancers.

UNASSIGNED: Renal cell carcinoma (RCC) can be complicated by a venous tumor thrombus (TT), of which the optimal management is unknown.
UNASSIGNED: This study sought to assess the prevalence of TT in RCC, its current management, and its association with venous thromboembolism (VTE), arterial thromboembolism (ATE), major bleeding (MB), and mortality.
UNASSIGNED: Patients diagnosed with RCC between 2010 and 2019 in our hospital were included and followed from RCC diagnosis until 2 years after, or until an outcome of interest (VTE, ATE, and MB) or death occurred, depending on the analysis. Cumulative incidences were estimated with death as a competing risk. Cause-specific hazard models were used to identify predictors and the prognostic impact.
UNASSIGNED: Of the 647 patients, 86 had a TT (prevalence 13.3%) at RCC diagnosis, of which 34 were limited to the renal vein, 37 were limited to the inferior vena cava below the diaphragm, and 15 extended above the diaphragm; 20 patients started therapeutic anticoagulation and 45 underwent thrombectomy with/without anticoagulation. During follow-up (median 24.0 [IQR: 7.0-24.0] months), 17 TT patients developed a VTE, 0 developed an ATE, and 11 developed MB. TT patients were more often diagnosed with VTE (adjusted HR: 6.61; 95% CI: 3.18-13.73) than non-TT patients, with increasing VTE risks in more proximal TT levels. TT patients receiving anticoagulation still developed VTE (HR: 0.56; 95% CI: 0.13-2.48), at the cost of more MB events (HR: 3.44; 95% CI: 0.95-12.42) compared with those without anticoagulation.
UNASSIGNED: Patients with RCC-associated TT were at high risk of developing VTE. Future studies should establish which of these patients benefit from anticoagulation therapy.

Xanthogranulomatous pyelonephritis is a rare and aggressive form of chronic pyelonephritis, it can occur at all age groups but is more common in women than in men, supposedly relating to the increased incidence of urinary tract infections and chronic nephrolithiasis in woman. Computed tomography (CT) findings are very helpful in making the correct diagnosis, but the definitive diagnosis is still based on histology, as there are many differential diagnoses such as renal cell carcinoma and renal tuberculosis. The complications of this type of pyelonephritis are due to the involvement of adjacent organs. The most frequent ones are Psoas abscess, perinephric abscess, and sepsis. Nephrocutaneous and renocolic fistulas are less common. We report a case of a 61-year-old male, who presented to emergency for left-sided lumbar pain for whom radiological investigations confirmed a renocolic fistula complicating xanthogranulomatous pyelonephritis. The diagnosis of XGP was proven by histopathological examination of the nephrectomy specimen slides, but there was also association with an underlying malignant squamous differentiation consistent with urothelial carcinoma, which was not evident on CT. XGP is a rare variant of chronic pyelonephritis with known imaging features. The treatment of choice is nephrectomy and histopathological examination is required for final diagnosis, as there may be associated renal malignancy.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare genetic disorder characterised by a germline mutation of the fumarate hydratase (FH) gene, in which affected individuals have a high likelihood of developing cutaneous leiomyomas, uterine leiomyomas and renal cell cancer (RCC). HLRCC-associated RCC is characterised by presentation at a younger age than the sporadic form, its aggressive nature and rapid metastatic potential. We present the case of a 50 year old woman with FH mutation, a history of early onset symptomatic uterine leiomyomas, and RCC with the first reported case of an isolated metastasis to the pituitary gland.

Uterine leiomyomas are common, benign neoplasms of the uterine smooth muscle. Leiomyomatosis is uncommon and causes development of multiple leiomyomas that can manifest as intravascular leiomyomatosis (IVL). We present the case of a 46-year-old female with IVL extending from the right gonadal vein to the right atrium and pulmonary arteries with an independent renal cell carcinoma of the right kidney. She underwent successful open right radical nephrectomy, inferior vena caval tumor thrombectomy and pulmonary embolectomy. While there was initial concern for hereditary renal cell carcinoma, final histologic testing did not support the diagnosis.

UNASSIGNED: Birt-Hogg-Dubé syndrome is a rare genetic tumor syndrome characterized by renal cell cancer, lung bullae, pneumothorax, and fibrofolliculoma. Patients with such orphan tumor disorders are at risk of not receiving a timely diagnosis. In the present, gender-sensitive study, we analyzed the delay between onset of symptoms and diagnosis of Birt-Hogg-Dubé syndrome.
UNASSIGNED: Clinical data of 158 patients from 91 unrelated families were collected. FLCN mutation testing was performed in index patients and family members.
UNASSIGNED: The occurrence of the first symptom (fibrofolliculoma, pneumothorax or renal cell cancer) was rarely followed by a timely diagnosis of Birt-Hogg-Dubé syndrome and did so significantly less often in female (1.3%) compared to male (11.4%) patients (chi-square 6.83, p-value 0.009). Only 17 out of 39 renal cell cancers (7/17 female, 10/22 male patients) were promptly recognized as a symptom of Birt-Hogg-Dubé syndrome. Patients in which renal cell cancer was initially not recognized as a symptom of Birt-Hogg-Dubé syndrome waited 9.7 years (females SD 9.2, range 1-29) and 8.8 years (males, SD 4.1, range 2-11) for their diagnosis, respectively. Four (three female, one male) patients developed renal cell cancer twice before the genetic tumor syndrome was diagnosed. The delay between fibrofolliculoma or pneumothorax as a first symptom and diagnosis of Birt-Hogg-Dubé syndrome was considerable but not significantly different between females and males (18.1/17.19 versus 16.1/18.92 years). Furthermore, 73 patients were only diagnosed due to family history (delay 15.1 years in females and 17.4 years in males).
UNASSIGNED: The delay between onset of symptoms and diagnosis of Birt-Hogg-Dubé syndrome can be substantial and gender-dependent, causing considerable health risks for patients and their families. It is therefore important to create more awareness of Birt-Hogg-Dubé syndrome and resolve gender biases in diagnostic work-up.
UNASSIGNED: None declared.

UNASSIGNED: The risk for major adverse cardiovascular events (MACE) with targeted therapies for patients with advanced renal cell carcinoma (RCC) in real-world practice remains unclear.
UNASSIGNED: The aim of this study was to compare the risk for MACE associated with targeted cancer therapies with that associated with cytokine treatment in patients with advanced RCC.
UNASSIGNED: Using Taiwan\'s National Health Insurance Research Database, a retrospective nationwide cohort study was conducted involving patients with advanced RCC who had received targeted therapy (sunitinib, sorafenib, pazopanib, everolimus, or temsirolimus) or cytokine therapy (interleukin-2 or interferon gamma) from 2007 to 2018. Cox proportional hazards models were used to estimate the risk for MACE (a composite of myocardial infarction, ischemic stroke, heart failure, and cardiovascular death) in the cohort using the propensity score method of stabilized inverse probability of treatment weighting.
UNASSIGNED: In this cohort of 2,785 patients with advanced RCC, 2,257 (81%) and 528 (19%) had received targeted and cytokine therapy, respectively. After stabilized inverse probability of treatment weighting, the incidence rates of MACE were 6.65 and 3.36 per 100 person-years in the targeted and cytokine therapy groups, respectively (HR: 1.80; 95% CI: 1.19-2.74). Baseline history of heart failure (HR: 3.88; 95% CI: 2.25-6.71), atrial fibrillation (HR: 3.60; 95% CI: 2.16-5.99), venous thromboembolism (HR: 2.50; 95% CI: 1.27-4.92), ischemic stroke (HR: 1.88; 95% CI: 1.14-3.11), and age ≥ 65 years (HR: 1.81; 95% CI: 1.27-2.58) were independent risk factors for targeted therapy-associated MACE.
UNASSIGNED: Among patients with advanced RCC, the risk for MACE associated with targeted cancer therapy is higher than that associated with cytokine therapy.

We used aspiration thrombectomy to treat a 66-year-old man with renal cell carcinoma undergoing radical nephrectomy and caval thrombectomy with a massive pulmonary artery tumor embolism. (Level of Difficulty: Intermediate.).

Herein, we report a patient who underwent percutaneous cryoablation for suspected renal cell carcinoma and developed a subcapsular hematoma with numerous pseudoaneurysms and dramatic structural deformity. Despite the severity suggested by the radiologic presentation, a conservative management approach was selected due to the patient\'s favorable hemodynamic status. This resulted in a positive outcome as alternative treatment options would have resulted in loss of the organ.