Doppler ultrasound (pre‐ and post‐contrast enhancement) for detection of recurrent stenosis in stented renal arteries: Preliminary results

The purpose of the present paper was to assess whether conventional renal Doppler ultrasound and the commonly used parameters of peak systolic velocity and renal aortic ratio may be an appropriate modality for the follow‐up of renal artery stents. A total of 19 arteries in 15 patients was examined with both renal Doppler ultrasound and angiography for the presence or absence of recurrent renal artery stenosis. Disease was considered present on angiography if the arterial diameter was more than 60% stenotic. Doppler criteria for stenosis were either a peak systolic velocity of > 180 cm/s or a renal aortic ratio of > 3.0. Echo enhancement with Levovist (Schering, Berlin, Germany) was used if studies were technically unsuccessful or to improve diagnostic confidence. Renal Doppler ultrasound detected 100% of renal artery stenoses. The specificity was 75%, the positive predictive value was 67% and the negative predictive value was 100%. Echo enhancement improved the technical success rate from 89 to 95% and also increased diagnostic confidence in six examinations. The present limited study suggests that similar renal Doppler parameters as used for the study of unstented renal arteries may be applied to the examination of renal arteries with renal stents in situ. It therefore suggests that Doppler ultrasound may provide an adequate non‐invasive means of renal artery stent follow‐up, particularly when combined with echo‐enhancing agents. Further study is warranted to confirm these initial conclusions.     

Lumbar artery pseudoaneurysm following renal biopsy: Treatment with ultrasound‐guided thrombin injection

latrogenic pseudoaneurysms are usually seen following arterial catheterization. However, we describe a case of a 23‐year‐old woman who developed a pseudoaneurysm of a lumbar artery following renal biopsy. In view of her progressing renal failure, arterial embolization was felt to be inappropriate, and although the pseudoaneurysm could be seen ultrasonically, guided compression could not be applied because of the location of the aneurysm deep to the lumbar musculature. Hence, the pseudoaneurysm was thrombosed by percutaneous ultrasound‐guided injection of thrombin directly into the pseudoaneurysm sac. This resulted in immediate thrombosis of the aneurysm and no recurrence on follow‐up imaging. Thrombin injection for femoral artery pseudoaneurysms following catheterization is becoming more widely accepted, and our case demonstrates that this technique might be applied to pseudoaneurysms elsewhere in the body.     

Treatment of renovascular disease with percutaneous stent insertion: Long‐term outcomes

Renal artery stenosis is a common, progressive cause of hypertension and renal impairment, and is frequently treated with percutaneous transluminal dilatation and stenting. The outcome of this procedure is still being evaluated. The records of 198 consecutive patients who had stents inserted at the Royal Melbourne Hospital were analysed retrospectively, and adequate follow‐up information on 148 (75%), in whom a total of 182 renal arteries had been treated was obtained. Technical success was achieved in 144 patients (97%). Complications occurred in 19 patients (13.3%), with major complications occurring in 10 (7.0%) and one death occurring in relation to the procedure. A fall in average systolic blood pressure of 13.2 mmHg (12.1–14.3 mmHg) was seen and a fall in diastolic blood pressure of 10.1 mmHg (9.3–10.9 mmHg), without an increase in the number of antihypertensive drugs used. Renal function remained stable in the majority of patients, particularly those who had minimal baseline renal impairment. Restenosis was common after 6 months, occurring eventually in 29% of screened patients, but was not shown to affect clinical outcomes. Insertion of renal artery stents is a safe and effective treatment for renal artery stenosis.     

Unusual clinical manifestations of the Nutcracker Syndrome

The Nutcracker Syndrome, caused by compression of the left renal vein as it passes in a tight angle between the aorta and the superior mesenteric artery, usually presents with unexplained haematuria localized to the left ureteric orifice. We report on a series of cases where compression of the left renal vein caused prominent left‐gonadal‐vein reflux, which in turn resulted in lower‐limb varices and varicocele formation.     

Use of intra‐arterial multi‐detector row CT angiography for the evaluation of an ischaemic limb in a patient with renal impairment

The vastly improved scanning speed and z‐axis resolution afforded by multi‐detector technology has allowed CT to refine its traditional roles and to explore many new applications in imaging. We present a case report of a patient with renal failure and an ischaemic leg, which illustrates a useful new CT vascular imaging application. By carrying out 16‐channel multi‐detector row CT angiography through a sheath introduced into the common femoral artery, we obtained a high‐quality angiographic image of the affected leg, using only 30 mL of iodinated contrast material. The examination definitively showed the number, distribution and patency of the tibial run‐off arteries, with significant influence on the patient‘s subsequent clinical management. This simple and relatively minimally invasive technique is useful in peripheral vascular imaging, when conventional CT angiography using a large volume of i.v. contrast and MR angiography are unsuitable or unavailable.     

Birt‐Hogg‐Dubé syndrome‐associated renal cell carcinoma: Histopathological features and diagnostic conundrum

Birt‐Hogg‐Dubé (BHD) syndrome is associated with the development of hereditary renal cell carcinoma (RCC) and is caused by a germline mutation in the folliculin gene. Most cases of BHD syndrome‐associated RCC (BHD‐RCC) are less aggressive than sporadic clear cell RCC and multifocal. Therefore, it is critical to distinguish BHD‐RCC from its sporadic counterparts to identify and monitor affected families and to preserve renal function for as long as possible. The World Health Organization/International Society of Urological Pathology consensus classification defined distinct entities for certain hereditary RCC; however, BHD‐RCC was not included in this classification. Although the clinical features and molecular mechanisms of BHD‐RCC have been investigated intensively over the last two decades, pathologists and urologists occasionally face difficulties in the diagnosis of BHD‐RCC that require genetic testing. Affected patients usually have miscellaneous benign disorders that often precede renal carcinogenesis. In the present review, we summarize the current understanding of the histopathological features of BHD‐RCC based on our epidemiological studies of Japanese families and a literature review. Pathological diagnostic clues and differential diagnosis of BHD‐RCC from other hereditary RCC are also briefly discussed.     

Contrast‐enhanced three‐dimensional fast‐spoiled gradient magnetic resonance angiography of the renal arteries for potential living renal transplant donors: A comparative study with digital subtraction angiography

Preoperative assessment of the arterial anatomy of prospective renal donors is essential. Various non‐invasive techniques are used for such evaluation. We conducted this study using contrast‐enhanced 3‐D fast‐spoiled gradient (CE 3‐D FSPGR) magnetic resonance angiography (MRA) on a 1.0 Tesla magnet, for preoperative definition of the renal arteries. Forty‐five preoperative living renal donors underwent CE 3‐D FSPGR MRA of the renal vessels and the results were compared with conventional digital subtraction angiography (DSA). The renal vascular anatomy, both normal and with variations, was satisfactorily defined in all 45 cases with CE 3‐D FSPGR MRA. Fifteen cases showed an accessory or aberrant arterial supply. A small aneurysm was shown in one case. All cases compared well with conventional DSA. Our study revealed that CE 3‐D FSPGR MRA on a lower field strength magnet is accurate in defining the renal vascular anatomy and its variations.     

Blunt renal vascular trauma resulting in arterial avulsion injury with a nephron‐sparing outcome

Blunt renal vascular traumatic injury is uncommon, and most injuries can be managed conservatively in a patient who is clinically stable. Pseudoaneurysm or active bleeding at presentation is rare and in an unstable patient, endovascular techniques offer a low morbidity option for rapid treatment. We present an unusual case of avulsion of a second order renal artery from the main renal artery, with active bleeding at presentation treated by excluding the bleed with a stent graft. This was complicated by delayed pseudoaneurysm formation, treated with a larger stent graft. This resulted in preservation of renal parenchyma and renal function in a young patient.     

Fluoroscopic‐guided balloon dilatation and stenting in tracheal stenosis with metallic self‐expandable stents and long‐term follow‐up results

The purpose of this study was to assess the safety and long‐term efficacy of self‐expandable stents in the treatment of benign tracheal stenosis. Nine patients (seven men) with tracheal stenosis (including one with fistula) of varied cause were treated by fluoroscopically guided balloon dilatation and stenting with self‐expandable metallic stents. The procedure was carried out under topical spray in eight patients and under general anaesthesia in one patient. The patients were followed up for a period ranging between 13 and 60 months. In eight of the nine patients, satisfactory positioning of the stent was achieved at the first instance, with immediate relief of dyspnoea. One patient with innominate artery aneurysm died 16 days after the procedure because of renal failure. At 1 month of follow up, six out of eight (75%) of our live patients were without any respiratory embarrassment. This dyspnoea‐free result reached almost 90% by the end of 1 year especially so in the fibrous strictures. Four out of the eight live patients (50%) had cough for 2 months and two (25%) had mild blood‐tinged sputum treated by inhalation and mucolytic agents. Secondary intervention was required in one patient at 1 month because of recurrent symptoms. The patient with tracheo‐oesophageal fistula required surgical intervention because of fracture of the stent. Fluoroscopically guided balloon dilatation and stenting of the tracheal stenosis is an effective non‐surgical therapy resulting in cure of fibrous strictures and palliation in cases of malignancy.     

MicroRNA‐204‐5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma

Xp11.2 translocation renal cell carcinoma (Xp11 tRCC) is a rare sporadic pediatric kidney cancer caused by constitutively active TFE3 fusion proteins. Tumors in patients with Xp11 tRCC tend to recur and undergo frequent metastasis, in part due to lack of methods available to detect early‐stage disease. Here we generated transgenic (Tg) mice overexpressing the human PRCC‐TFE3 fusion gene in renal tubular epithelial cells, as an Xp11 tRCC mouse model. At 20 weeks of age, mice showed no histological abnormalities in kidney but by 40 weeks showed Xp11 tRCC development and related morphological and histological changes. MicroRNA (miR)‐204‐5p levels in urinary exosomes of 40‐week‐old Tg mice showing tRCC were significantly elevated compared with levels in control mice. MicroRNA‐204‐5p expression also significantly increased in primary renal cell carcinoma cell lines established both from Tg mouse tumors and from tumor tissue from 2 Xp11 tRCC patients. All of these lines secreted miR‐204‐5p‐containing exosomes. Notably, we also observed increased miR‐204‐5p levels in urinary exosomes in 20‐week‐old renal PRCC‐TFE3 Tg mice prior to tRCC development, and those levels were equivalent to those in 40‐week‐old Tg mice, suggesting that miR‐204‐5p increases follow expression of constitutively active TFE3 fusion proteins in renal tubular epithelial cells prior to overt tRCC development. Finally, we confirmed that miR‐204‐5p expression significantly increases in noncancerous human kidney cells after overexpression of a PRCC‐TFE3 fusion gene. These findings suggest that miR‐204‐5p in urinary exosomes could be a useful biomarker for early diagnosis of patients with Xp11 tRCC.     

Endovascular treatment of a hepatic artery pseudoaneurysm using a novel pericardium covered stent

Visceral and renal artery aneurysms (VRAAs) and pseudoaneurysms are rare. Their increasing incidence is largely thought to be due to advances in medical imaging. Twenty percent of VRAAs occur in hepatic arteries, with approximately fifty percent of these represented by pseudoaneurysms, which are prone to spontaneous rupture. Many treatments for VRAAs exist, with the endovascular approach being favoured. Treatment aims to preserve visceral perfusion and exclude the aneurysm; however, complex aneurysms may require parent artery or end‐organ sacrifice. Covered stents allow rapid aneurysm exclusion while preserving parent artery patency, a favourable outcome when parent artery or end‐organ sacrifice is undesirable. The AneuGraft pericardium covered stent (PCS) combines the benefits of a low‐profile covered stent with those of a low immunogenic material. We describe the endovascular treatment of a patient with a hepatic artery pseudoaneurysm, where parent artery sacrifice was considered unacceptable. The AneuGraft PCS was used to provide immediate and complete exclusion, with dual antiplatelet therapy for 1 week, followed by single antiplatelet use. The procedure was a technical success, with preservation of the hepatic arteries and complete exclusion of the pseudoaneurysm. There were no complications immediately following the procedure or on post‐procedural follow‐up. The pseudoaneurysm remained excluded at 6‐week CT angiogram (CTA) follow‐up. This case describes a safe and effective method for completely excluding a complex pseudoaneurysm, utilising the AneuGraft PCS, allowing for the potential management of a wider range of aneurysms with unfavourable morphology.     

Updated long‐term outcomes after carbon‐ion radiotherapy for primary renal cell carcinoma

Long‐term oncological outcomes for primary renal cell carcinoma (RCC) treated with carbon‐ion radiotherapy (CIRT) are poorly understood. Patients with primary RCC were treated with 12 or 16‐fraction CIRT at The Hospital of the National Institute of Radiological Sciences outside of clinical trials. Outcome data were pooled and retrospectively analyzed for toxicity, local control, and disease‐free, cancer‐specific, and overall survival. From 1997 to 2014, 19 RCC patients (11 with T1aN0M0, 4 with T1bN0M0, and 4 with inoperable advanced stage [T4N0M0, T3aN1M0, and T1aN0M1]) were treated with CIRT and followed up for a median of 6.6 (range, 0.7‐16.5) years; 9 of these patients were inoperable because of comorbidities or advanced‐stage disease. Diagnoses were confirmed by imaging in 11 patients and by biopsy in the remaining 8. In 4 of 5 patients with definitive renal comorbidities, including diabetic nephropathy, sclerotic kidney or solitary kidney pre‐CIRT progressed to grade 4 chronic kidney disease (CKD). In contrast, the remaining 14 patients without definitive renal comorbidities did not progress to grade 3 or higher CKD. Furthermore, although 1 case of grade 4 dermatitis was observed, there were no other grade 3 or higher non‐renal adverse events. Local control rate, and disease‐free, cancer‐specific, and overall survival rates at 5 years of all 19 patients were 94.1%, 68.9%, 100%, and 89.2%, respectively. This updated retrospective analysis based on long‐term follow‐up data suggests that CIRT is a safe treatment for primary RCC patients without definitive renal comorbidities pre‐CIRT, and yield favorable treatment outcomes, even in inoperable cases.     

Large‐scale genome‐wide screening of circulating microRNAs in clear cell renal cell carcinoma reveals specific signatures in late‐stage disease

Circulating miRNAs have shown great promises as noninvasive diagnostic and predictive biomarkers in several solid tumors. While the miRNA profiles of renal tumors have been extensively explored, knowledge of their circulating counterparts is limited. Our study aimed to provide a large‐scale genome‐wide profiling of plasma circulating miRNA in clear‐cell renal cell carcinoma (ccRCC). Plasma samples from 94 ccRCC cases and 100 controls were screened for 754 circulating micro‐RNAs (miRNA) by TaqMan arrays. Analyses including known risk factors for renal cancer—namely, age, sex, hypertension, obesity, diabetes, tobacco smoking and alcohol consumption—highlighted that circulating miRNA profiles were tightly correlated with the stage of the disease. Advanced tumors, characterized as stage III and IV, were associated with specific miRNA signatures that significantly differ from both controls and earlier stage ccRCC cases. Molecular pathway enrichment analyses of their gene targets showed high similarities with alterations observed in renal tumors. Plasma circulating levels of miR‐150 were significantly associated with RCC‐specific survival and could marginally improve the predictive accuracy of clinical parameters in our series, including age at diagnosis, sex and conventional staging. In summary, our results suggest that circulating miRNAs may provide insights into renal cell carcinoma progression.     

Sarcomatoid renal cell carcinoma: Rapid dissemination detected on FDG PET‐CT

We present the FDG PET‐CT findings in a patient with persistent pain 7 weeks after a nephrectomy and lymph node dissection for a sarcomatoid renal cell carcinoma. Although conventional imaging was unable to detect evidence of metastatic spread outside the para‐aortic nodes, a PET‐CT scan showed unexpected extensive dissemination. Currently, there are no reports in the literature of the PET‐CT findings in sarcomatoid renal cell carcinomas.     

Contrast-enhanced Doppler ultrasound for renal artery stenosis

The use of renal artery Doppler ultrasound for the diagnosis of renal artery stenosis is a well-established technique in selected populations, but the technical failure rate of the examination leading to incomplete studies is a major drawback. The results of ultrasound contrast-enhanced renal artery Doppler for renal artery stenosis, using the echo-enhancing agent, Levovist, are reported here. Sixteen patients (22 arteries) were examined with Levovist. The technical success rate of these examinations was 91%, and all four renal artery stenoses were correctly identified. It is concluded that the use of ultrasound contrast (Levovist) increases the technical success rate of renal artery Doppler ultrasound in this setting, with similar accuracy to unenhanced Doppler examinations.     

Identification and validation of an eight‐gene expression signature for predicting high Fuhrman grade renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is a malignancy with heterogeneous outcomes. Currently, renal mass biopsies are commonly employed to extract disease characteristics and aid prognosis. Although the pathological diagnosis of malignant disease is accurate in contemporary reports, the classification of Fuhrman grade using biopsy specimens remains far from promising. To generate a gene signature to distinguish high‐grade ccRCC, we used the cancer genome atlas (TCGA) database to develop a gene expression signature for distinguishing high‐grade (G3/4) from low‐grade (G1/2) disease. The expression profile was further validated for performance and clinical use in 283 frozen renal cancer samples and 127 ex vivo renal mass biopsy samples, respectively. The area under curve (AUC) was used to quantify discriminative ability and was compared using the De‐long test. Using the discovery dataset, we identified a 24‐gene signature for high‐grade disease with an AUC of 0.884. After applied to the development dataset, an eight‐gene profile was defined and achieved an AUC of 0.823. Accuracy of eight‐gene panel was maintained in the renal mass biopsies (RMB) samples (AUC = 0.821). In summary, using three‐stage design, we validated an eight‐gene expression signature for predicting high Fuhrman grade of ccRCC. This tool may help to reveal the characteristics of ccRCC biopsy specimens.     

宫颈癌全段腹主动脉旁淋巴结转移的解剖分布和CTV边界

目的 明确宫颈癌全段腹主动脉旁淋巴结转移的解剖学分布,探讨临床靶区（CTV）的勾画边界。方法 回顾分析86例宫颈癌转移至腹主动脉旁淋巴结的患者。应用CT增强影像、淋巴结与周围结构的三维重建图像,明确腹主动脉旁转移淋巴结的解剖学边界。结果 86例左肾静脉以下腹主动脉旁转移淋巴结,位于腹主动脉分叉处至左肾静脉上缘之间,沿腹主动脉和下腔静脉周围分布,在十二指肠出现后,下腔静脉右前方未发现肿大淋巴结。所有转移淋巴结均位于双侧卵巢血管和输尿管内侧,肠系膜下静脉紧邻其左前方;自上而下位于肾静脉、十二指肠、肠系膜血管后方;位于腰椎体和腰大肌前方。27例左肾静脉以上腹主动脉旁转移淋巴结,位于双侧膈脚后方,在腹主动脉后方沿奇静脉、半奇静脉上行,25/27例位于食管贲门交界水平（平第11胸椎）之下,5/27例伴有下腔静脉后内侧和右侧膈脚之间转移淋巴结,上界至腹腔干水平。结论 推荐全段腹主动脉旁淋巴结CTV勾画边界：上界,平第11胸椎（食管贲门交界水平）;左肾静脉以下侧界,肠系膜下静脉、卵巢血管和输尿管的内侧缘;左肾静脉以上侧界,双侧膈脚;前界,肾静脉以上腹主动脉的侧后壁、肾静脉、十二指肠、肠系膜血管的后缘;后界,腰椎体和腰大肌的前缘。     

Combination immunotherapy with interleukin‐2 surface‐modified tumor cell vaccine and programmed death receptor‐1 blockade against renal cell carcinoma

Immunotherapy may be an effective way to prevent postoperative recurrence of renal cell carcinoma. Streptavidin‐interleukin‐2 (SA‐IL‐2) surface‐modified tumor cell vaccine developed through our protein‐anchor technology could induce specific antitumor T‐cell responses, but this immunotherapy cannot completely eradicate the tumor. These effector T cells highly expressed programmed death receptor‐1 (PD‐1), and the expression of programmed death ligand‐1 (PD‐L1) in the tumor environment also was upregulated after SA‐IL‐2‐modified vaccine therapy. PD‐1/PD‐L1 interaction promotes tumor immune evasion. Adding PD‐1 blockade to SA‐IL‐2‐modified vaccine therapy increased the number of CD4⁺, CD8⁺ and CD8⁺interferon‐γ⁺ but not CD4⁺Foxp3⁺ T cells. PD‐1 blockade could rescue the activity of tumor‐specific T lymphocytes induced by the SA‐IL‐2‐modified vaccine. Combination therapy delayed tumor growth and protected mice against a second Renca cells but not melanoma cells challenge. Taken together, PD‐1 blockade could reverse immune evasion in the treatment with SA‐IL‐2‐modified vaccine, and eventually induce a stronger specific antitumor immune response against renal cell carcinoma.