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- PATIENTS AND METHODS
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Renal angiomyolipoma (AML) is a rare benign tumour composed of three components, i.e. adipose tissue, smooth muscle, and blood vessels, and that can develop spontaneously in the general population (0.2–0.3%) [1–3] or be part of the tuberous sclerosis complex (TSC), a dominant autosomal congenital disease characterized by seizures, mental retardation and hamartomatous lesions, including facial angiofibroma, subepididymal giant cell astrocytoma, cardiac rhabdomyoma and renal AML [4,5]. Renal AML in TSC is common and potentially serious, with a reported incidence of ≈ 70% in a recent population-based study . Renal AMLs have the propensity to grow and indeed, treatment has been suggested for asymptomatic lesions of >4 cm in greatest dimension to prevent associated complications such as rupture and haemorrhage, and for symptomatic AML of any size, while observation is the treatment of choice for small asymptomatic tumours, unless suspicious for malignancy [7–9]. As a generally benign lesion, although an uncommon subtype, the epithelioid AML can behave more aggressively, and whenever feasible AML must be managed conservatively.
Nephron-sparing surgery (NSS) currently represents the treatment of choice and, in the past 10 years, many refinements and advances have been made to improve this technique, its safety and the results, leading to a progressive decrease in the need for radical nephrectomy (RN) even for larger and centrally located lesions. We challenged the accepted wisdom and proposed simple enucleation as a safe and acceptable nephron-sparing treatment for RCCs, and have always adopted this technique also for treating renal AMLs, due to their peculiar exophytic growth and because it is possible to identify and follow the pseudocapsule during the procedure [10,11]. However, data on simple AML enucleation are sparse and generally are within series including NSS performed as enucleo-resection and partial nephrectomy [4,12].
The aim of the present study was to describe our surgical experience with simple enucleation for treating renal AMLs and to determine the role of this nephron-sparing technique in a series of 34 consecutive patients, treated in our department. To our knowledge this is the largest published series on the role of simple enucleation for treating renal AML.
PATIENTS AND METHODS
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- PATIENTS AND METHODS
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In a retrospective study, we reviewed all patients with a histopathological diagnosis of renal AML who had NSS by simple enucleation between January 1986 and December 2005. The preoperative evaluation consisted of a chest X-ray, routine laboratory studies (serum creatinine, urea, blood count, and electrolytes) and abdominal CT with and with no injection of contrast medium. When the latter was not indicated, MRI was requested and obtained.
The surgical technique was our standard protocol, as previously described [10,11]. Most patients (30/34, 88%) were treated by a lateral retroperitoneal approach. The patient is placed in an oblique position elevated to ≈ 75°; the incision is made above the 11th intercostal space towards the umbilicus. Due to scheduled bilateral surgical removal (two patients) or unilateral giant AML (two) an upper abdominal midline incision was used in four patients (15%).
Indications for intervention included either symptomatic AML or a tumour of >4 cm, regardless of the presence of symptoms or renal masses suspicious of malignancy.
Most patients were vigorously hydrated and mannitol was administered i.v. before arterial occlusion. When prolonged ischaemia times (>30 min) were expected, surface hypothermia with ice-slush was adopted to minimize ischaemic injury to the kidney. Once the tumour was enucleated the surgical margins were meticulously inspected and the renal surface examined to exclude possible residual tumour. Intraoperative ultrasonography and biopsies of the enucleation bed were rarely used.
Any visible bleeding vessels and incidental opening of the calyces were ligated using a running or single suture with 4/0 monofilament. Then either diathermy spray coagulation or argon-beam coagulation of the enucleation bed was used for both haemostatic and oncological reasons. The parenchymal defect was closed with horizontal interrupted sutures of polyglactin after either fibrin glue or cyanoacrylate glue apposition. The vascular clamp was then removed.
All tumours were treated by simple enucleation, using the natural cleavage plane between the pseudocapsule and normal parenchyma, by blunt dissection. In critical surgical steps where it seemed difficult to visualize the correct enucleation plane, a sharp dissection a few millimetres away from the tumour was used.
For the follow-up, if there were no complications, the two retroperitoneal drainage tubes were removed 3–4 and 4–5 days after surgery. Routine laboratory studies were obtained within 24–48 h of surgery, and usually patients were followed up with routine blood chemistry and renal ultrasonography at 3 and 6 months after surgery. CT was usually requested at 12 months after surgery, and if negative the patients were followed up every 6 months with ultrasonography and routine blood test for the next 2 years, and yearly thereafter. Occasionally, patients had further CT during the follow-up. The patients’ status was evaluated last in October 2006.
Statistical significance of differences was determined using the Wilcoxon signed-rank test, with P < 0.05 considered to indicate statistical significance. The tumour’s greatest dimension before surgery was taken as a continuous variable value and used to define a possible relationship between tumour size and the risk of intraoperative blood loss, prolonged ischaemic time and the time to discharge.
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Between January 1986 and December 2005, 37 patients had kidney surgery for pathologically confirmed AML, of whom 34 (92%) had simple enucleation while the remaining three (8%) had RN (11.5 : 1 enucleation/RN ratio). Demographic information, type of diagnosis, clinical presentation of the disease and mean (range) follow-up of the 34 patients (30 women and four men) who had elective NSS for AML are shown in Table 1.
Table 1. Demographic information, type of diagnosis, clinical presentation of the disease and mean (range) follow-up of 34 patients who had elective simple enucleation for renal AML
|Variable||Number (%) of patients||Mean (range) age, years||Men/women, n (%)||Right/ left, n (%)||Bilateral||Tumour size, cm||Follow-up, months|
|NSS: all patients||34||50 (26–75)||30 (88)/4 (12)||15 (44)/16 (47)||3 (9)||5.2 (1.5–15)||56 (10–120)|
|Bilaterally preserved kidney function||32 (94)||49 (26–75)||27 (81)/5 (19)||14 (41)/15 (44)||–||5.2 (1.5–15)||57 (10–120)|
|Solitary functioning kidney|| 2 (6)||51 and 69|| 2/0|| 1/1||–||2 and 4.5||34 and 53|
|TSC|| 5 (15)||51 (36–68)|| 4/1|| 1/1||3||9.1 (3–15)||39 (10–79)|
|Symptomatic <4 cm|| 8 (24)||51 (30–69)|| 8/0|| 4/4||0||3.1 (2–3.9)||71 (10–120)|
|Size ≥ 4 cm; asymptomatic|| 8 (24)||47 (28–65)|| 6/2|| 4/3||1||7.3 (4–15)||49 (18–79)|
|Size ≥ 4 cm; symptomatic|| 11 (32)||49 (26–75)|| 9/2|| 3/6||2||7.8 (4–15)||60 (12–120)|
|Suspicion of malignancy|| 7 (20)||53 (35–65)|| 7/0|| 4/3||0||2 (1.5–3.5)||39 (13–80)|
At diagnosis, 15 of the 34 tumours (44%) were detected incidentally; the mean (sd, median, range) tumour size on preoperative CT was 4.8 (3.3, 4, 0.8–15) cm. Men had larger tumours than women; the mean (sd, median, range) tumour size was 7.8 (4.9, 6, 4.2–15) and 4.4 (2.9, 4, 0.8–14) cm, respectively (P = 0.051). Overall, eight of the 37 patients were diagnosed as having TSC (22%); of these, three with multifocal unilateral AMLs were treated with RN while the remaining five (three multifocal synchronous bilateral lesions and two unilateral multifocal tumours) had simple enucleation. None of the patients unaffected by TSC had bilateral or multifocal lesions.
Simple enucleation was successful in all patients but in three (9%) a sharp dissection a few millimetres from the tumour was used during critical steps of the procedure where it seemed difficult to define the right plane of enucleation. In two of these three patients, the tumour was growing into the renal sinus. Warm ischaemia was used in 27 patients (79%); the mean (range) ischaemic time was 11.2 (9–21) min. Two patients (6%) required renal hypothermia, with a reported ischaemic time of 32 and 29 min, respectively. A simple parenchymal compression, avoiding clamping the renal pedicle, was used in five patients (15%). The mean (range) intraoperative blood loss was 170 (70–650) mL and the mean (range) time to discharge was 6 (5–11) days.
The tumour size before surgery was assessed to define a possible relationship between tumour dimension and the risk of intraoperative blood loss, prolonged ischaemia time and the time to discharge. As expected, increasing tumour size significantly correlated with higher intraoperative blood loss (P < 0.001), longer warm ischaemic time (P < 0.001) and duration of hospital stay (P = 0.034).
The mean (sd, median, range) pathological tumour size was 5.2 (3.4, 4.8, 1.5–15) cm. After surgery, none of the patients had bleeding requiring re-intervention, but one (3%) had two units of blood due to an early decline in serum haematocrit and haemoglobin level. There were no major complications, e.g. prolonged acute tubular necrosis/chronic renal insufficiency and urinary leakage/urinoma, requiring either open re-intervention or JJ stenting, but two patients had urosepsis not associated with perirenal fluid collection and that required targeted antibiotic therapy. One patient developed a wound infection, s.c. abscess and fever with associated positive culture for Citrobacter koseri; a drainage tube was placed in the abscess and an 8-day course of appropriate antibiotics was prescribed.
Overall, in patients with bilaterally preserved kidney function, the mean (sd, range) serum creatinine level increased from 0.95 (0.11, 0.6–1.2) mg/dL before to 0.99 (0.12, 0.6–1.3) mg/dL within 48 h after surgery (P = 0.063).
Two patients had a solitary functioning kidney (Table 1), due to either contralateral nephrectomy for RCC or to the presence of a contralateral silent kidney caused by PUJ obstruction. Their creatinine values before surgery were 1.6 and 1.2 mg/dL. These values increased slightly to 2.1 and 1.8 mg/dL immediately after surgery and returned to their preoperative values within a week after surgery.
The mean (median, range) follow-up was 56 (50.5, 10–120) months. None of the patients had local tumour recurrence during the follow-up. Two patients had a small AML (<4 cm in greatest dimension) elsewhere in the operated kidney, detected 18 and 36 months after surgery, giving a kidney recurrence incidence of 6%. These patients were followed and required no adjunctive treatments. Another patient had a contralateral NSS procedure performed as simple enucleation because scheduled kidney ultrasonography and further CT, at 6 years after the initial surgery and 14 months after pregnancy, showed a renal mass in the other kidney, suspected to be a malignancy. Histological examination of the renal tumour showed a nephrogenic adenoma.
Four of the five patients with multifocal disease had additional small residual AMLs after treatment; they were followed and none of them required adjunctive treatments.
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As a generally benign lesion, whenever feasible AML should be managed conservatively, and the two suitable treatments for this, with adequate data, are NSS and selective arterial embolization [3,13]. The latter is particularly well suited for treating acute haemorrhage, to stabilize the clinical condition, in patients needing prophylactic treatment when the tumour is exclusively fed by a distinct arterial branch, or when the patient is a poor operative candidate. However, this technique has a high tumour recurrence rate if used with curative intent in patients with TSC [3,13,14], but nevertheless it is considered by others as the most appropriate initial treatment for patients with symptomatic or large renal AMLs due to TSC .
NSS currently represents the treatment of choice and, in the past 10 years, many refinements and advances have been made to improve this technique, its safety and the results, leading to a progressive decrease in the need for RN even for larger and centrally located AMLs. Nevertheless, it remains an extreme curative option in patients with TSC or giant renal masses at risk of haemorrhage and in these clinical settings cannot be considered the ‘gold standard’ procedure.
Conservative surgery is the preferred treatment for AMLs, providing excellent oncological and functional results [4,12]; however, a review of previous reports showed only a few series reporting NSS for treating this benign tumour, with sporadic reports on the use of simple enucleation (Table 2) [7,4,8,12,16–24]. Together with its benign nature, AML shows a unique noninvasive exophytic growth pattern and maintains a distinct pseudocapsule that can be readily identified and that permits enucleation through a natural, avascular plane. The aim of the present study was therefore to investigate the role of simple enucleation in 34 patients with a histopathological diagnosis of AML, followed for a mean of nearly 5 years. To our knowledge, this represents the largest published series on the role of simple enucleation for treating histologically confirmed AMLs, and the first series where all patients were homogeneously treated with the same technique. Indeed, tumour enucleation was successful in all patients and only in three (9%) was a sharp dissection a few millimetres from the tumour used during critical steps of the procedure where it seemed difficult to define the right plane of enucleation. In two of these three patients, the tumour was growing into the renal sinus.
Table 2. A synopsis of published series on NSS for treating renal AMLs
|Reference||No. of patients||Tumour size, cm mean (range)||Creatinine level, mg/dL ||Complications, n (%)||Recurrence rate, %|
|Oesterling et al.|| 2||6 and 15||Normal||Stable||0||0|
|Malone et al.|| 2||2 and 10||Normal||Stable||0||0|
|Blute et al.|| 7||5.2 (0.8–19)||NA||Stable||0||0|
|Steiner et al.|| 2||>4.0||NA||NA||0||0|
|Kennelly et al.|| 6||4–8.5||NA||Δ < 0.1||NA||0|
|Koike et al.|| 10||5.4 (3–9)||NA||NA||1 nephrectomy||0|
|Kessler et al.|| 3||5.6 (3–8)||NA||0.7 (0.6–1.1)||0||0|
|Fazeli-Matin & Novick || 27||6.9 (2–26)||1.0 (0.7–1.9)||1.25 (0.8–4.6)||6 (22)||0|
|De Luca et al.|| 14||2.0 (0.3–10)||NA||NA||NA||0|
|Clark & Novick || 2||7.8 (6.3–9.4)||0.7 (case 1)||0.7 (case 1)||0||0|
|Heidenreich et al.|| 28||5.5 (2.5–17)||0.9 (0.7–1.3)||1.2 (0.7–1.5)||3 (10.7)||0|
|Marszalek et al.|| 7||NA||NA||NA||NA||0|
|Mullerad et al.|| 13||5.5 (2.5–13)||NA||Stable||1 adrenalectomy||0|
|Present|| 34||5.2 (1.5–15)||0.95 (0.6–1.2)||0.99 (0.6–1.3)||3 (8.8)||0|
On the contrary, Fazeli-Matin and Novick , although considering simple enucleation as a valid option in such cases, found it easier and safer to adopt sharp dissection in many cases in the presence of a not well-capsulated neoplasm.
Our good results in terms of complication rate and local recurrence rate are similar to those reported in previous large studies using NSS (Table 2), and show the absolute absence of tumour recurrence at the operative site with an incidence of recurrence (elsewhere in the kidney) of 6%, and a low complication rate for these conservative approaches, even in the presence of very large renal masses [22,25,26]. Fazeli-Matin and Novick  and Heidenreich et al. reported the two largest retrospective studies on AML treated by NSS in two very different populations of 27 and 28 patients, respectively. Interestingly, Fazeli-Matin and Novick  treated many patients presenting with TSC, giant AMLs, bilateral lesions, associated RCC and with solitary functioning or an impaired contralateral kidney; this last group allowed the authors a precise analysis of the ability of NSS to preserve renal function. In their series, the authors reported a significant decrease in renal function after NSS that was unrelated to tumour greatest dimension. Unfortunately, like Heidenreich et al., the authors did not report on the number of enucleations and/or consider postoperative creatinine values over a long period . On the contrary and as expected, the present series mainly constituted sporadic AMLs with a contralateral healthy kidney; we found no statistically significant difference in creatinine levels before and after surgery (P = 0.063). The enucleation technique allows for the maximum preservation of renal functioning tissue ; this is particularly useful in the presence of large masses where the resection of marginal normal tissue can be of more relevance for future renal impairment. Unfortunately, our analysis cannot provide valid data on this point; despite this, all patients had preserved renal function and in the two with a solitary functioning kidney, the creatinine level returned to that before surgery within a week after surgery.
We recently reported a mean warm ischaemia time of 16.3 min for the enucleation of pT1a RCC  and a mean warm ischaemia time of 15.7 min for treating RCC of 4–7 cm in greatest dimension . In the present study we report a lower mean warm ischaemic time of 11.2 min and a greater mean tumour size than in our two previous studies. A possible explanation for this finding could be related to the characteristic exophytic growth of AMLs, and therefore to the possibility of developing an avascular plane of enucleation before clamping the renal pedicle, and delaying this manoeuvre to the last step of the procedure at the point of tumour origin .
None of the present patients developed complications that required open re-intervention. The most frequent complication was urosepsis not associated with perirenal fluid collection (two patients, 6%) that required targeted antibiotic therapy. One patient (3%) had bleeding that required conservative treatment with transfusions. No patients developed urinary leakage/urinary fistula.
In conclusion, simple enucleation is a useful and acceptable technique for treating renal AMLs; it provides excellent long-term local control and can minimize the risk of urinary leakage/urinoma after surgery, allowing the maximum preservation of functioning kidney tissue.