A novel variant in the FLCN gene in a Chinese family with Birt-Hogg-Dubé syndrome.

BACKGROUND: This study aimed to identify disease-causing variants within a Chinese family affected by Birt-Hogg-Dubé syndrome (BHDS), which arises from an autosomal dominant inheritance pattern attributed to variants in the folliculin (FLCN) gene, recognized as a tumor suppressor gene. METHODS: A Chinese proband diagnosed with BHDS due to renal tumors underwent next-generation sequencing (NGS), revealing a novel variant in the FLCN gene. Sanger sequencing was subsequently performed on blood samples obtained from family members to confirm the presence of this variant. RESULTS: A novel germline frameshift variant (NM_144997.5:c.977dup) was identified in five individuals among the screened family members, marking the first report of this variant. Additionally, a somatic frameshift variant (NM_144997.5:c.1252del) was detected in the renal tumors of the proband. No variant was detected in unaffected family members. CONCLUSIONS: A novel heterozygous variant was identified in exon 9 of the FLCN gene, which broadens the spectrum of FLCN variants. We recommend that molecular analysis of the FLCN gene be performed in patients with suspected BHDS and their families.

Lesion-aware cross-phase attention network for renal tumor subtype classification on multi-phase CT scans.

Multi-phase computed tomography (CT) has been widely used for the preoperative diagnosis of kidney cancer due to its non-invasive nature and ability to characterize renal lesions. However, since enhancement patterns of renal lesions across CT phases are different even for the same lesion type, the visual assessment by radiologists suffers from inter-observer variability in clinical practice. Although deep learning-based approaches have been recently explored for differential diagnosis of kidney cancer, they do not explicitly model the relationships between CT phases in the network design, limiting the diagnostic performance. In this paper, we propose a novel lesion-aware cross-phase attention network (LACPANet) that can effectively capture temporal dependencies of renal lesions across CT phases to accurately classify the lesions into five major pathological subtypes from time-series multi-phase CT images. We introduce a 3D inter-phase lesion-aware attention mechanism to learn effective 3D lesion features that are used to estimate attention weights describing the inter-phase relations of the enhancement patterns. We also present a multi-scale attention scheme to capture and aggregate temporal patterns of lesion features at different spatial scales for further improvement. Extensive experiments on multi-phase CT scans of kidney cancer patients from the collected dataset demonstrate that our LACPANet outperforms state-of-the-art approaches in diagnostic accuracy.

Esophageal squamous cell carcinoma metastases to kidney and renal hilar lymph nodes through epithelial-mesenchymal transition: a case report and literature review.

BACKGROUND: Esophageal cancer (EC) metastasized to the kidney is extremely rare clinically. Here, we present a case of metachronous renal metastasis of esophageal squamous cell carcinoma (ESCC) through epithelial-mesenchymal transition (EMT). CASE PRESENTATION: A 60-year-old patient, male, complained of left waist pain for 5 days, 11 months after radical esophagectomy. Laboratory tests revealed haematuria. Both CT and PET-CT scan showed retroperitoneal lymph nodes and left renal masses. Subsequently the patient received a left nephrectomy and lymph nodes resection, and squamous cell carcinoma of kidney and renal hilar lymph nodes was diagnosed, combined with morphology, medical history and immunophenotype, it was presumed to be metastasis of ESCC through the EMT pathway. CONCLUSIONS: The renal metastasis of squamous cell carcinoma should be considered in patients with history of EC, although this is very rare. Histopathological examination combined with immunochemical detection is helpful in differential diagnosis.

Renomedullary Interstitial Cell Tumor in the Background of a Renal Oncocytoma: A Case Report.

Renomedullary interstitial cell tumors (RMICTs) are rare benign renal tumors that arise from the renal medulla. They are rarely symptomatic and are mostly discovered incidentally. Radiologically, their co-presence ipsilaterally in the background of a larger mass introduces a miscellaneous presentation that raises the suspicion of metastatic disease. A characteristic presentation does not exist. Therefore, an individualized, patient-centered approach should be tailored depending on the nature of the presentation. We report the clinical, radiological, and histopathological presentation of a 46-year-old woman presenting with an RMICT in the background of a renal oncocytoma.

Contrast-enhanced ultrasound (CEUS) as a follow-up method after the focal treatment of renal tumors: systematic review and meta-analysis.

CONTEXT: Contrast-enhanced ultrasound (CEUS) is a cost-effective radiation-free diagnostic method that can be used for renal tumor postoperative visualization after ablative treatment. OBJECTIVE: To assess CEUS diagnostic accuracy comparing with CT and MRI as a follow-up method in short-term and long-term postoperative periods after renal tumor ablation. MATERIALS AND METHODS: A systematic review and meta-analysis were performed in Scopus and Medline databases using the query "(kidney OR rena* OR RCC) AND (ablation OR RFA OR MWA OR cryo*) AND CEUS". The endpoint of the study was the evaluation of the overall accuracy of CEUS. RESULTS: Twelve trials were included in the review. With CT or MRI as a reference, for a short-term group (< 6 weeks after ablation) pooled sensitivity was 90.2%, I2 = 0%; pooled specificity was 99.3%, I2 = 0%; pooled NPV was 98.6%, I2 = 0%; pooled PPV was 94.6%, I2 = 0%; the AUC on the SROC curve was 0.971. For the long-term group (> 6 weeks after ablation), pooled sensitivity was 95.3%, I2 = 0%; pooled specificity was 97.6%, I2 = 0%; PPV was 74.2%, I2 = 4%; NPV was 99.4%, I2 = 5%; AUC = 0.93. CONCLUSION: CEUS has high sensitivity and specificity in ruling out the presence of local recurrence after renal tumor ablation with a higher risk of false-positive results within follow-up > 6 weeks compared with that for CT or MRI. Further studies with a unified protocol and morphological control of local renal tumor recurrence after ablation are needed.

Current surgical approaches to pediatric renal tumors.

Pediatric renal tumors are among the most common pediatric solid malignancies. Surgical resection is a key component in the multidisciplinary therapy for children with kidney tumors. Therefore, it is imperative that surgeons caring for children with renal tumors fully understand the current standards of care in order to provide appropriate surgical expertise within this multimodal framework. Fortunately, the last 60 years of international, multidisciplinary pediatric cancer cooperative group studies have enabled high rates of cure for these patients. This review will highlight the international surgical approaches to pediatric patients with kidney cancer to help surgeons understand the key differences and similarities between the European (International Society of Pediatric Oncology) and North American (Children's Oncology Group) recommendations.

Intraoperative Ultrasound: Bridging the Gap between Laparoscopy and Surgical Precision during 3D Laparoscopic Partial Nephrectomies.

The use of 3D laparoscopic partial nephrectomy has emerged as a cornerstone in the surgical arsenal for addressing renal tumors, particularly in managing challenging cases characterized by deeply seated tumors embedded within the renal parenchyma. In these intricate scenarios, the utilization of intraoperative ultrasound (IOUS) acquires paramount importance, serving as an indispensable tool for guiding and meticulously monitoring the surgical process in real time. To further explore the efficacy of IOUS-guided techniques, we conducted a retrospective study comparing outcomes in patients who underwent partial nephrectomy with IOUS guidance (n = 60) between 2020 and 2022 with a cohort from 2018 to 2019 without IOUS guidance (n = 25). Our comprehensive analysis encompassed various post-operative parameters, including the duration until food resumption, analgesia requirements, and length of the hospital stay. While these parameters exhibited comparable outcomes between the two groups, notable distinctions emerged in the intraoperative metrics. The IOUS-guided cohort demonstrated significantly reduced blood loss, a shorter median operative duration, and diminished ischemia time (p = 0.001). These compelling findings underscore the undeniable benefits of IOUS-guided techniques in not only facilitating the attainment of negative surgical margins but also in enhancing procedural safety and precision, thereby contributing to improved patient outcomes in the management of renal tumors.

Effects of percutaneous cryoablation for renal tumor on overall and split renal function.

PURPOSE: To evaluate retrospectively the influence of percutaneous cryoablation for small renal tumors on total and affected kidney function and risk factors associated with worsening function of the affected kidney. MATERIALS AND METHODS: Between April 2016 and March 2022, 27 patients who underwent cryoablation for small renal tumors at our institution participated in this study, which investigated time-dependent changes in postoperative renal function. We evaluated estimated glomerular filtration rates (eGFRs) and split renal function revealed by scintigraphy using 99 m technetium-mercaptoacetyltriglycine (99mTc-MAG3) before cryoablation and at 1 week, 1 month, and 6 months after cryoablation. Numerous variables were analyzed to assess risk factors for worsening renal function. RESULTS: Baseline eGFR (mean ± standard deviation) was 56.5 ± 23.7 mL/min/1.73 m2 (mean ± SD; range, 20.5-112.5). Mean eGFRs at 1 week, 1 month, and 6 months after cryoablation were 57.4 ± 24.5 (19.1-114.9), 57.1 ± 25.1 (21.5-114.9), and 53.8 ± 23.9 mL/min/1.73 m2 (20.0-107.5), respectively. Changes were statistically insignificant (p = 1.0000, = 0.6749, and = 0.0761, respectively). Regarding split renal function, mean baseline contribution of the affected kidney determined by 99mTc-MAG3 was 49.7% ± 6.0% (38.8-63.3%); these rates at 1 week, 1 month, and 6 months after cryoablation were 43.7% ± 8.8 (29.1-70.6%), 46.2% ± 7.7% (32.6-70.3%), and 46.0% ± 8.5% (32.5-67.6%), respectively. Differences from baseline were significant for all periods (p < 0001, < 0001, = 0.0001, respectively). Serum C reactive protein and lactate dehydrogenase at 1 day following cryoablation, tumor's nearness to the collecting system or sinus, and volume of ablated normal renal parenchyma were significantly correlated with decreased contributions of the affected kidney by > 10% after cryoablation. CONCLUSION: Unlike total renal function, affected kidney function could worsen after cryoablation.

Papillary renal neoplasm with reverse polarity: an observational study of histology, immunophenotypes, and molecular variation.

Background: Papillary renal neoplasm with reverse polarity (PRNRP) is a novel entity with unique clinicopathological characteristics, and only a small number of patients with PRNRP have been described. Methods: We retrospectively analyzed the data for nine patients with PRNRP and evaluated differences in the clinical, histomorphological, immunohistochemical, and molecular features; prognosis; and differential diagnosis of PRNRP from other renal tumors with papillary structure. Results: There were six males and three females aged 36 to 74 years (mean: 62.33 years; median: 68 years). All the tumors were solitary and ranged from 1 to 3.7 cm (mean: 2.17 cm; median: 2 cm), with three and six tumors arose in the left and right renal tract, respectively. Pathologically, PRNRP is a small, well-circumscribed neoplasm with predominant papillary formations. The lining epithelium is composed of a monolayer of cuboidal to low-columnar cells with low-grade nuclei arranged against the apical pole of the tumor cells. Edema, mucinous degeneration, and hyaline degeneration are found in the fibrovascular cores. Foamy macrophages, psammoma bodies, hemosiderin deposition, and infiltrative tumor boundaries were present in some patients. Immunohistochemically, all tumors showed diffuse positive staining for GATA3. Sanger sequencing confirmed the presence of KRAS mutation in seven patients. All patients had a good prognosis after surgery and were relapse free. Positive staining for GATA3 and negative staining for vimentin were the most significant markers for differentiating PRNRP from other renal tumors with analogous structure. Conclusions: These findings suggested that PRNRP is a distinctive subtype of renal tumor with specific pathological features and indolent behaviors that should be distinguished from other renal tumors, especially papillary renal cell carcinoma. A monolayer of tumor cells with an inverted nuclear pattern, positive staining for GATA3, and KRAS mutation are essential for pathological diagnosis. Owing to its satisfactory prognosis, the surveillance and follow-up of patients with PRNRP should be additionally formulated.

Case report: Isolated eyelid metastasis of ccRCC 5 years after receiving radical nephrectomy.

Introduction: The most common sites of clear cell renal cell carcinoma(ccRCC) metastasis are the lung, bones, liver and brain; eyelid metastasis is a rare occurrence. Case presentation: We report a case of ccRCC metastasis to the left eyelid after radical nephrectomy, and remission after sunitinib treatment. Conclusions: Although the probability of eyelid metastasis rate is very low, tumor metastasis to the eyelid skin is possible after radical nephrectomy. Therefore, any rash like changes on the skin during the review procedure cannot be ignored by the physician.

An Uncommon Presentation of Renal Angiomyolipoma: A Case Report.

Renal angiomyolipoma (AML) is a rare benign tumor of the kidney that can occur as a sporadic lesion or a part of tuberous sclerosis. A 77-year-old female patient with a history of hypertension, hyperlipidemia, and an unclear history of left nephrectomy in 1999 presented with progressive shortness of breath and palpitations. Her vital signs showed elevated blood pressure, and the examination was benign and non-focal. A work-up showed multiple lesions in her lungs and right kidney, representing lymphangioleiomyomatosis. The patient was diagnosed with tuberous sclerosis and was followed up by pulmonology and nephrology. She underwent embolization of the renal AML, after which her blood pressure (BP) was more controlled, and she reported feeling well and symptom-free. Renal AML, as a part of tuberous sclerosis, is a rare cause of secondary hypertension. Embolization of AML is effective in controlling BP.

Ossifying renal tumor of infancy: A case report.

Ossifying Renal Tumor of Infancy (ORTI) represents an extremely rare and benign renal neoplasm, with limited cases published in the literature. Predominantly characterized by painless and intermittent gross hematuria, the diagnostic evaluation is effectively facilitated through ultrasound, computed tomography, and magnetic resonance imaging. Despite progress, its etiology has not yet been elucidated. We report an additional case with an unusual clinical presentation.

Actual encounters of the kidney kind: Exploring 48 cases of renal collision tumors through the lens of literature.

Multiple tumors of different lineages merging into a single mass, termed collision tumors, are considered a rare phenomenon in the kidney. Tumor components, or partners, may be malignant (including metastatic disease), borderline, or benign. We report the largest cohort to date of 48 cases. The cases were identified from the archives of three institutions in the last 16 years, including 43 (90%) with 2 tumor partners (dyad) and 5 (10%) with 3 partners (triad), totaling 101 individual neoplasms. The majority of cases involved immunohistochemical workup, and 5 underwent FISH or molecular studies. Forty (83%) cases featured a malignant entity, including all triads. Twenty dyads and two triads were composed entirely of malignant tumors. The most common malignant partner was clear cell renal cell carcinoma (RCC) (N = 19) followed by papillary RCC (N = 17). Nine (19%) cases featured borderline entities, including 5 multilocular cystic neoplasms of low malignant potential and 6 clear cell papillary renal cell tumors. Twenty one (44%) cases contained a benign partner, including 6 benign dyads. Papillary adenoma (N = 13) and oncocytoma (N = 8) were most common. Epithelial tumors were present in all 48 cases, and non-epithelial neoplasms in 9 cases (19%). Our cohort includes many novel combinations and collision partners with rare entities such as SDH-deficient RCC, TFE3-rearranged RCC, eosinophilic solid and cystic RCC, and acquired cystic disease associated RCC. A comprehensive literature review and analysis of collision tumor phenomenon in kidney placed these cases in context suggesting that collision tumors of the kidney are more common than previously recognized.

Hydrodissection During Computed Tomography-Guided Cryoablation for Renal Tumors: Where is the Effective Fluid Accumulation Space in the Retroperitoneum?

PURPOSE: This study was performed to investigate the effectiveness of hydrodissection during computed tomography-guided renal cryoablation by evaluation of the fluid distribution based on the retroperitoneal anatomy with the interfascial plane. MATERIALS AND METHODS: Between March 2014 and March 2021, 52 renal tumors were treated by cryoablation with hydrodissection (36 men; mean age 72.5 years). The hydrodissection needle was located in perirenal space. The spreading fluid space based on the retroperitoneal anatomy with the interfascial plane was retrospectively evaluated. The fluid space that most effectively separated the tumor from the adjacent organs was defined. The relationship of the needle tip position in the perirenal space (renal capsule or fascia side) and the most effective fluid space was also evaluated. RESULTS: Cryoablation was successfully completed in all cases with no major complications. Hydrodissection was effective in all cases. The distance between the tumors and the adjacent organs was significantly longer after hydrodissection (from 7.50 ± 7.43 to 22.6 ± 9.86 mm) (P < 0.0001). Although fluid spreading through multiple retroperitoneal spaces was frequently observed, the retromesenteric plane was observed more frequently as the most effective fluid space (67.3%) than the perirenal space (21.2%) (P < 0.0001). Regardless of the needle tip position, the most effective fluid space was also commonly the retromesenteric plane. CONCLUSIONS: The retromesenteric plane could be the most effective fluid space to separate the tumor from the adjacent organ, regardless of where the hydrodissection needle tip is positioned in the perirenal space. LEVEL OF EVIDENCE: 3b.

Ultrasound image segmentation of renal tumors based on UNet++ with fusion of multiscale residuals and dual attention.

Objective. Laparoscopic renal unit-preserving resection is a routine and effective means of treating renal tumors. Image segmentation is an essential part before tumor resection. The current segmentation method mainly relies on doctors manual delineation, which is time-consuming, labor-intensive, and influenced by their personal experience and ability. And the image quality of segmentation is low, with problems such as blurred edges, unclear size and shape, which are not conducive to clinical diagnosis.Approach. To address these problems, we propose an automated segmentation method, i.e. the UNet++ algorithm fusing multiscale residuals and dual attention (MRDA_UNet++). It replaces two consecutive 3 × 3 convolutions in UNet++ with the 'MultiRes block' module, which incorporates coordinate attention to fuse features from different scales and suppress the impact of background noise. Furthermore, an attention gate is also added at the short connections to enhance the ability of the network to extract features from the target area.Main results. The experimental results show that MRDA_UNet++ achieves 93.18%, 92.87%, 93.66%, and 92.09% on the real-world dataset for MIoU, Dice, Precision, and Recall, respectively. Compared to the baseline model UNet++ on three public datasets, the MIoU, Dice, and Recall metrics improved by 6.00%, 7.90% and 18.09% respectively for BUSI, 0.39%, 0.27% and 1.03% for Dataset C, and 1.37%, 1.75% and 1.30% for DDTI.Significance. The proposed MRDA_UNet++ exhibits obvious advantages in feature extraction, which can not only significantly reduce the workload of doctors, but also further decrease the risk of misdiagnosis. It is of great value to assist doctors diagnosis in the clinic.

Imaging-based deep learning in kidney diseases: recent progress and future prospects.

Kidney diseases result from various causes, which can generally be divided into neoplastic and non-neoplastic diseases. Deep learning based on medical imaging is an established methodology for further data mining and an evolving field of expertise, which provides the possibility for precise management of kidney diseases. Recently, imaging-based deep learning has been widely applied to many clinical scenarios of kidney diseases including organ segmentation, lesion detection, differential diagnosis, surgical planning, and prognosis prediction, which can provide support for disease diagnosis and management. In this review, we will introduce the basic methodology of imaging-based deep learning and its recent clinical applications in neoplastic and non-neoplastic kidney diseases. Additionally, we further discuss its current challenges and future prospects and conclude that achieving data balance, addressing heterogeneity, and managing data size remain challenges for imaging-based deep learning. Meanwhile, the interpretability of algorithms, ethical risks, and barriers of bias assessment are also issues that require consideration in future development. We hope to provide urologists, nephrologists, and radiologists with clear ideas about imaging-based deep learning and reveal its great potential in clinical practice.Critical relevance statement The wide clinical applications of imaging-based deep learning in kidney diseases can help doctors to diagnose, treat, and manage patients with neoplastic or non-neoplastic renal diseases.Key points• Imaging-based deep learning is widely applied to neoplastic and non-neoplastic renal diseases.• Imaging-based deep learning improves the accuracy of the delineation, diagnosis, and evaluation of kidney diseases.• The small dataset, various lesion sizes, and so on are still challenges for deep learning.

Folliculin gene-negative Birt-Hogg-Dube syndrome: a case report.

Introduction and importance: Birt-Hogg-Dube (BHD) is a rare genetic disorder that results from a mutation in the folliculin (FLCN) gene. Manifestations include pulmonary cysts, fibrofolliculomas, renal tumors, and pneumothoraces. Genetic testing can be used to confirm the diagnosis when suspected. BHD syndrome is diagnosed in patients with negative FLCN gene results using diagnostic criteria. Case presentation: A male in his 20s presented with recurrent pneumothoraces. A physical examination revealed bumps on his face and upper body. A chest computed tomography scan revealed cystic lesions. Blood tests, ESR, and CRP levels were unremarkable. Punch skin biopsy revealed fibrofolliculomas. Genetic testing for the FLCN mutation returned negative. His history, physical exam, imaging, and histopathology suggested BHD syndrome despite having a negative family history and genetic analysis. Eventually, the patient was diagnosed with FLCN gene-negative BHD syndrome. Clinical discussion: More than a hundred families have been identified to have BHD worldwide. There are a few cases in the literature describing patients phenotypically presenting with BHD despite having a negative genetic analysis. One study in Japan found 16 out of 157 individuals having a clinical presentation of BHD with no mutations. Also, decreased expression of the FLCN mRNA may lead to BHD. Conclusion: BHD syndrome can present with a negative FLCN gene mutation; however, patients must meet the known diagnostic criteria such as criteria made by Menko et al., Gupta et al., and Schmidt et al. in order to have a diagnosis of BHD syndrome. Also, a qualitative decrease of FLCN with the absence of mutations may also lead to BHD.