Multifocal synchronous renal cell carcinoma in the functioning allograft is a rare disease; there is no consensus regarding its treatment, and few cases have been reported. In isolated masses, some authorities advocate graft nephrectomy, and some recommend partial nephrectomy. To our knowledge, we describe the first experience of nephron-sparing surgery in multifocal synchronous renal cell carcinoma in an allograft with its long-term outcome. A 42-year-old male patient with a history of living related-donor kidney transplant from his brother (18 years previously) presented with a history of gross hematuria over the past few months. Imaging studies revealed a 5.5-cm exophytic cystic mass lesion in lower pole and an 11-mm solid mass in the upper pole of the renal allograft. Both graft nephrectomy and nephron-sparing surgery were offered to him. After the patient provided written informed consent, zero-ischemia partial nephrectomy of lower pole and enucleation of upper pole mass were performed. Pathology reports for both lesions indicated clear cell carcinoma, and margins were free of tumor. Twelve months after surgery, the patient was free of tumor, and his creatinine level was 1.6 mg/dL. At 29 months after surgery, his creatinine level was 2.4 mg/dL, and imaging revealed a tumor-free allograft. Nephron-sparing surgery in multifocal renal cell carcinoma in the functioning renal allograft was feasible in our patient, and the long-term outcome was satisfactory. This surgical option provided dialysis-free and long-term tumor-free survival to the patient.
Key words : Hematuria, Kidney transplantation, Tumor
Malignancy after kidney transplant is a significant complication.1 In recipients of kidney allografts, about 3% of diagnosed malignancies are from the genitourinary tract, which is 4 to 5 times greater than its occurrence in those who do not receive transplant.2 Renal cell carcinoma (RCC) is the most common malignancy after skin disorders, lympho-proliferative disorders, and Kaposi sarcoma in renal transplant recipients.3 Only 10% of RCCs in renal transplant recipients occur in the allograft.3 Some authorities believe, and there appears to be a general consensus, that renal grafts with tumors should be removed urgently and that such patients should be treated with dialysis.4 If technically possible, it has been recommended that nephron-sparing surgery should be performed for renal allograft tumors.5 Renal function decreases by approximately 20% after partial nephrectomy of the operated kidney, due to ischemic injury or deprivation of nephron mass.6 Ischemic injury can be prevented by zero-ischemia partial nephrectomy.6 We describe a zero-ischemia partial nephrectomy for a multifocal synchronous RCC in a renal allograft with long-term outcome.
A 42-year-old man, who was a recipient of a renal allograft (from his brother, 18 years previously in our center for end-stage renal disease of unknown cause), presented with intermittent gross hematuria over the past 6 months. The patient was a cigarette smoker and addicted to opium and was being treated with cyclosporine and prednisolone, and his serum creatinine level was 1.6 mg/dL at presentation. Ultrasonography revealed a 52-by-45 mm cystic complex mass in the lower pole of the allograft. Abdominopelvic computed tomography scan revealed a complex exophytic cystic lesion of 41-by-40 mm in diameter in the lower pole (enhanced with contrast; see Figure 1). A magnetic resonance imaging study revealed a 40-mm cyst with a mural nodule in the lower pole and another 11-mm mass in the upper pole (Figure 2). Metastatic work-up was negative.
Different treatment options were discussed with the patient, and he desired to preserve his allograft with nephron-sparing surgery. The patient was treated with general anesthesia, and we incised and extended the previous incision with the extra-peritoneal approach. The allograft was dissected carefully, and the capsule was kept intact. Severe fibrosis was present; thus, we did not dissect the hilar vessels, as there was significant risk of injury to the main renal artery and vein.
With direct compression of renal allograft tissue, a partial nephrectomy of both masses was ac-complished successfully with acceptable blood loss. The lower pole mass was removed with a margin of 0.5 cm of normal parenchyma attached to the tumor. After an incision was made around the tumor with cautery and the incision was deepened toward the parenchyma, a resection was quickly completed using scissor and cautery. Bleeding from parenchyma was controlled with bipolar cautery and with direct compression of tissue.
After we removed the mass, deep bleed areas were ligated with 3-0 chromic suture. The capsule and the attached parenchyma were sutured with 2-0 polyglactin running sutures, and hemostasis was secured. After excision of the lower pole mass was completed, the well-encapsulated and demarcated upper pole mass was cleaved and enucleated from the attached parenchyma without cutting the normal tissues. The mass was removed quickly, and allograft repair was performed by the same technique as used for the lower pole mass, except that no normal parenchyma was resected in the upper pole. The intraoperatively frozen sections from the renal side of resection of both poles were free of tumor. After hemostasis was accomplished, a Hemovac drain was inserted. The incision was closed in anatomic layers. The operation time was 90 minutes, and blood loss was 360 mL.
The postoperative course was uneventful, and the patient was discharged on postoperative day 5, with creatinine level of 1.6 mg/dL. Pathology of the lower pole revealed one cystic mass that measured 5 × 3 × 1.5 cm, with the smooth external surface containing necrotic material; this material was diagnosed as clear cell carcinoma (Fuhrman grade 4). Pathology of the upper pole mass revealed 1 encap-sulated solid mass that measured 2.2 × 1.5 × 1 cm, and the cut surface was observed to be solid, homogenous, and tan-creamy in color; we diagnosed this as clear cell carcinoma (Fuhrman grade 2/4). The inked surgical margins of both lesions were free of tumor.
At postoperative month 12, the patient’s crea-tinine level was 1.6 mg/dL, and computed tomography revealed a tumor-free allograft. At 24 months after surgery, his creatinine level was 2.2 mg/dL, and magnetic resonance imaging revealed a tumor-free allograft. At 29 months after surgery, he remains tumor free as observed in ultrasonographic exam-ination.
Due to long-term immunosuppression and the effect of oncogenic viruses after solid-organ transplant, the incidence of neoplasm is high in renal transplant recipients. In younger patients (< 35 years old), as in our case, the risk of cancer is considerably higher than shown in the general population and has standardized incidence ratio of 3.68, although this risk gradually decreases with increasing age.4 Particularly high risks are observed for cancer of the kidney (standardized incidence ratio of 3.60).4 Obesity, cigarette smoking, and the occurrence of recurrent pyelonephritis are known risk factors for RCC in renal transplant recipients. The first case of RCC in an allograft was reported in 1988.7 In 2003, DeLong and associates published the first multifocal papillary renal carcinoma in an allograft, in which the patient was treated with transplantectomy.8 Penn reported 24 cases in 1995.9 Tillou and colleagues, in a multicenter study in France, published the most extensive series of 79 cases.10 The incidence of RCC in the allograft was 0.19% and 0.5% in the studies by Tillou and colleagues and Penn, respectively.9,10 In the study by Tillou and associates, 35 patients (44.3%) were treated with partial nephrectomy; all were unifocal tumors.10 Most of the tumors were inci-dental, small, papillary carcinomas and of low grade and low stage.
Indications for nephrectomy are low-functioning graft, tumor in the center, and tumors more than 4 cm in maximum diameter.10 Tillou and colleagues stated that the most critical conclusion from this largest series is that most tumors in these cases are low grade and of the papillary subtype.10 Papillary tumors have better prognosis than the clear cell type.10 Others believe that RCC in the allograft is more aggressive, with a higher potential for a poor outcome.5 Although some strongly advise routine biopsies for a mass in a renal allograft,11 we did not perform a biopsy before the partial nephrectomy. Melchior and colleagues argued that it is contro-versial that all patients with allograft mass should have needle biopsy, as there is a risk of tumor seeding in the needle tract in patients with suppressed immunity.12 In light of this report, we changed the immunosuppressive treatment of the patient to sirolimus. Sirolimus has been used in the post-transplant period while treating malignancies and has demonstrated antitumor activity.13 It has been said that a sirolimus immunosuppressive regimen has been associated with lower neoplasm in renal transplant recipients.4 In 83% of patients treated in the study by Tillou and colleagues, the immuno-suppressive drug was not changed.10
We performed enucleation for small upper tumor. Some authors believe that enucleation of RCCs can have excellent oncologic results. Minervini and associates, in a multicenter study that compared 982 partial nephrectomies with 537 simple enucleations, showed that enucleation of the tumor produced excellent results compared with partial nephrectomy, with multivariable analysis showing that either technique was not an independent predictor of cancer-free survival.14 It has been said that margin thickness around the tumor for long-term sur-veillance is not essential and that the important prognostic factor is simply that the margin be tumor free.9 To our knowledge, our study is the first report of nephron-sparing surgery in multifocal RCC in the functioning renal allograft with a long-term positive result.
Volume : 17
Issue : 1
Pages : 145 - 147
DOI : 10.6002/ect.MESOT2018.P13
From the Department of Urology and Kidney Transplantation, Shahid Labbafinejad
Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to disclose.
Corresponding author: Mohammad Nadjafi-Semnani, Department of Urology and Kidney Transplantation, Shahid Labbafinejad Medical Center; and the Shahid Beheshti University of Medical Sciences, Unit no. 4- 17th St., North Kargar St., Tehran, Iran 1438837316
Phone: +98 2122588016
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Figure 1. Computed Tomography Showing Tumor in the Lower Pole of Allograft, With Enhanced Contrast (Arrow)
Figure 2. Magnetic Resonance Imaging Study of Patient