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Keywords:

  • contrast-enhanced ultrasound;
  • recurrence;
  • renal cell carcinoma

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case reports
  5. Discussion
  6. Conclusion
  7. References

Abstract  We studied contrast-enhanced ultrasound (CEU) for recurrence of renal cell carcinoma (RCC) at the contralateral kidney during postoperative follow up of localized renal cell carcinoma. CEU successfully detected all recurring cases, despite the fact that 5/6 cases were observed using conventional ultrasound; the remaining one case was not detected using conventional ultrasound. CEU using Levovisto successfully revealed renal tumors as RCC. Lesions were diagnosed as cystic renal tumors by Bosniac classification, and pathological findings demonstrated RCC, in accordance with the prior tumor.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case reports
  5. Discussion
  6. Conclusion
  7. References

Though postoperative recurrence of renal cell carcinoma (RCC) is well known in the lungs, liver, bones, and lymph nodes, we experienced frequent recurrence in the contralateral kidney during long-term postoperative follow up. In cases of recurrence in the remaining kidney, the status of recurrence plays an important role in prognosis and quality of life (QOL) following surgery or treatment. Consequently, urological examination must be dedicated to detecting any recurrence in the remaining kidney before a malignancy metastasizes or influences QOL.

In recent years, progress in modern imaging techniques such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) has increased the incidental diagnosis of small renal cell carcinoma (RCC) and has improved the prognosis of these malignancies.1

In this context, we report the usefulness of contrast-enhanced ultrasound (CEU)2 for diagnosing recurrence of renal cell carcinoma in the contralateral kidney during postoperative follow up of localized renal cell carcinoma.

Among patients treated at our institution from January 1980 to April 2000 were 156 consecutive patients with RCC (mean age 59 years) who did not demonstrate either distant metastasis or lymph node metastasis. The disease-free survival rate at 5 and 10 years was 81.3% and 75.3%, respectively. Among these 156 cases, 27 demonstrated postoperative recurrence in the lung (8 cases), lymph node (4 cases), liver (3 cases), bone (3 cases), small intestine (3 cases) and the remaining kidney (6 cases). The background of the six kidney cases are shown in Table 1.

Table 1.  Characteristics of six patients
PatientsGender/ ageCell type initial/recurrenceGradeStageComparison of detectionPeriod of recurrenceTreatment
  1. BU, B mode ultrasound; CU, contrast-enhanced ultrasound; NSS, nephron-sparing surgery; TAE, transarterial catheter embolization.

1M/62clear/clearG1/G1pT1a/pT1aCT(–) BU(–) CU(+)24 monthsNSS
2M/80clear/?G1/?pT1a/T1bCT(+) BU(+) CU(+)193 monthsTAE
3M/41clear/clearG1/G1pT1a/pT1aCT(+) BU(+) CU(+)36 monthsNSS
4F/55clear/?G1/?pT2/T3bCT(+) BU(+) CU(+)86 months 
5F/48clear/clearG1/G1pT2/pT2CT(+) BU(+) CU(+)10 monthsNSS
6M/62clear/?G2/?pT2/T2CT(+) BU(+) CU(+)32 monthsTAE

Patients were examined in the supine and lateral decubitus positions using transverse, intercostal, and parasagittal scanning. The study was performed using a Yokogawa GE Medical System (Yokogawa Medical Systems, Tokyo, Japan), and a convex phased array 3.5-MHz probe was used. Each renal lesion was evaluated by conventional ultrasound (US), color Doppler imaging, with a spectral analysis of the peripheral and intratumor vessels.

The US contrast agent must be strong enough to withstand passage through the lungs and capillaries and at the same time should be injectable intravenously without significant side-effects such as nephrotoxicity.2 The US contrast agent used most often for the characterization of renal tumors was Levovisto (Schering, Berlin, Germany). Levovisto was injected intravenously as a bolus of 2.5 g, with an 8 mL normal saline flush for 8 s, using a 22-gauge peripheral intravenous cannula, and coded harmonic angio mode and TruAgent detection were performed at 20 s after the start of Levovisto injection and every 10–15 s during the arterial (20–60 s) and delayed (60–120 s) phases.

Case reports

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case reports
  5. Discussion
  6. Conclusion
  7. References

We present three clinically interesting cases as follows.

Case 1 was a 62 year-old man with a history of (right) nephrectomy for diagnosis of renal cell carcinoma in July, 2002. The pathological diagnosis was clear cell carcinoma, grade 1 > 2, INF-α, pT1b. In April 2003, CT revealed a cyst in upper pole of the remaining (left) kidney. As shown in Figure 1, conventional B-mode US (Fig. 1a) and power Doppler imaging failed to detect the solid tumor. We therefore performed contrasted US using Levovisto, which demonstrated an enhanced tumor with a thick, irregular peripheral pattern wall with an echoic mural nodule (Fig. 1b,c). We then diagnosed the lesion as a cystic renal tumor according to Bosniac classification.3 The renal tumors were enucleated in June 2003 using a microwave tissue coagulator (MTC) without renal pedicle clamping (Fig. 1d). The histopathological diagnosis of the tumors was clear cell carcinoma, grade 1, and the surgical margin of the tumors showed no evidence of malignancy.

image

Figure 1. Conventional B-mode (a) failed to detect renal tumor. Both coded harmonic angio mode (b) and TruAgent detection mode (c) detected cystic renal tumor in the upper pole of the remaining left kidney. Both modes demonstrated an enhanced tumor with a thick, irregular peripheral pattern wall with an echoic mural nodule. This tumor was diagnosed a cystic renal tumor according to Bosniac classification.4 The resected specimen demonstrated cystic renal tumor (d). Pathological diagnosis was clear cell carcinoma, grade 1.

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Case 2 was an 80 year-old male with history of nephrectomy for diagnosis of left renal cell carcinoma in May 1986. The pathological diagnosis was clear cell carcinoma, grade 1 > 2, INF-α, pT3a. Although plain CT in October 2002 revealed a right renal tumor of 5.0 cm diameter, renal function (blood urea nitrogen 32.4 mg/dL, creatinine 2.17 mg/dL) did not allow examination by enhanced CT. The patient therefore underwent CEU using Levovisto, which can detect the diffuse, heterogeneous contrast enhancement of an early arterial phase. The results of CEU were consistent with RCC, and the patient underwent transarterial catheter embolization using ethanol. Two years later, CT detected neither an enlargement of the tumor nor distant metastasis.

Case 3 was a 41 year-old male with history of left nephrectomy for diagnosis of multiple RCC with von Hippel Lindau disease (VHL) in 1998. The pathological finding for all tumors was clear cell carcinoma, grade 1. Three years later, an abdominal CT scan revealed multiple RCC in the remaining (right) kidney. An abdominal CT scan showed three individual tumors measuring 20 mm, 13 mm, and 9 mm in maximum diameter in the right kidney. The renal tumors were enucleated in July, 2001 using an MTC without renal pedicle clamping. The histopathological diagnosis of all tumors was clear cell carcinoma, grade 1, and the surgical margin of all tumors showed no evidence of malignancy.

In April, 2002, an abdominal CT scan showed an enhanced tumor in the remaining (right) kidney, with a maximum tumor diameter of 20 mm. Additionally MRI revealed an enhanced tumor in the same lesion of the kidney. This lesion was located in the middle portion of the kidney, where one of the prior tumors presented.

The pattern of enhanced color Doppler indicated characteristics similar to the prior right RCC, including blood flow and a basket-like appearance of the marginal blood vessels (Fig. 2a). In July, 2002, the patient underwent nephron-sparing surgery. During the operation, US detected a renal tumor which had been suggested preoperatively. We removed the renal lesion using an MTC without renal pedicle clamping. We failed to detect any other lesions in this organ. The postoperative course was uneventful, with no major complications such as postoperative hemorrhaging or persistent urine leakage. The pathological diagnosis cancer-free for the enucleated renal tissue. Postoperatively, both an abdominal CT scan and US detected no renal tumor in the right kidney. At 18 months after the above-described surgery, there is no evidence of renal tumor in the remaining (right) kidney (Fig. 2b).

image

Figure 2. (a) Conventional sonogram showed the presence of a 20 mm slightly hyperechoic renal mass (left arrow). Enhanced color Doppler demonstrated blood flow and a basket-like appearance of the marginal blood vessels (right arrow). This appearance was consistent with renal cell carcinoma. At 18 months after, although postoperatively an abdominal computed tomography scan showed deformity of the right kidney due to nephron-sparing surgery, there is no evidence of renal tumor in the remaining right kidney (b).

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Case numbers 4 through 6 are summarized in Table 1.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case reports
  5. Discussion
  6. Conclusion
  7. References

Although a radical surgical procedure is still considered the gold standard curative method for localized renal cell carcinoma (RCC),4 nephron-sparing surgery (NSS) for RCC has also become popular due to recent advances in renal imaging, surgical techniques of renal vascular surgery, and the growing number of incidentally discovered low-stage RCC.

The increased use of modern imaging modalities has led to a significant increase in the period of postoperative follow up for early clinical RCC. Even though we reported that one of the angiogenic factors (thymidine phosphorylase) might be a predictor of postoperative recurrence with localized RCC,5 we have to pay attention to detect the recurrence lesion using adequate imaging modalities.

We observed 6 renal recurrence cases among 156 cases undergoing a curative surgical procedure. This recurrence may influence not only the prognosis, but also postoperative QOL, and we stress the importance of detecting tumor recurrence and performing removal before metastasis. Siracusano6 showed that CEU can detect small solid renal tumors; additionally, Levovisto may differentiate solid RCC from angiomyolipoma.

As described above, in our experienced, CEU has a demonstrated problem, as shown in Case 3, where the results suggested that the influence of prior nephron-sparing surgery on the right kidney may have engendered a tumor-like appearance. In such cases, we recommend a strategy of expectant management until the kidney tumors reach a size of 3 cm,7 based on the findings that there could be up to 600 microscopic clear cell carcinoma and 1100 cysts in an average VHL kidney.7 Herring8 reported that no patient with metastatic disease who underwent NSS in this fashion was observed during 10 years.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case reports
  5. Discussion
  6. Conclusion
  7. References

Contrast-enhanced ultrasound using Levovisto appears to be a useful tool for detecting recurrent tumors not inferred by renal function during postoperative follow up of nephrectomy.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case reports
  5. Discussion
  6. Conclusion
  7. References