Selective Arterial Embolization for Large or Symptomatic Renal Angiomyolipoma: 10 Years of Follow-up.

OBJECTIVE: To assess long-term outcome after selective arterial embolization (SAE) as first-line treatment for large or symptomatic AML. DESIGN, SETTING, AND PARTICIPANTS: Data from a prospectively maintained database on 71 patients who underwent SAE for large or symptomatic AML were reviewed. Patients with sporadic and tuberous-sclerosis-complex (TSC) were included. OUTCOME MEASUREMENTS: The main endpoints were re-embolization rates, occurrence of clinical events related to AML, size of AML, and renal function. RESULTS: Thirteen (19.1%) patients reported at least 1 major clinical event. Major complications affected 2 patients (2.9%), both ending in complete loss of renal unit function. Four renal units (5.9%) were eventually treated surgically. The re-embolization rate was 41.1%, with an average time from the initial to a repeat SAE of 2.18 years (range 0.31-10.65 years). The size of the tumor prior to SAE and after 5 and 10 years of follow-up were 8.9 cm (7-12), 6.5 cm (4-7.5), 7 cm (4-7.8), respectively [median (IQR)]. These results are translated to a size reduction of 27% in 10 years follow-up. Patients with TSC had larger tumors on long-term follow-up (77.8 vs 41.3 mm, P = .045). The long-term follow-up estimated average glomerular filtration rate was 81.97 (range 26-196). No patient needed renal replacement therapy, and disease-specific survival was 100%. CONCLUSIONS: SAE is a safe treatment option for patients with symptomatic or large AML. It represents a minimally invasive intervention with good long-term outcome. SAE may be offered as first-line treatment in most cases, though, it is associated with high retreatment rates.

Hepatic angiomyolipoma: an international multicenter analysis on diagnosis, management and outcome.

BACKGROUND: Hepatic angiomyolipoma (HAML) may easily be misdiagnosed as a malignancy. The study aim was to assess diagnostic dilemmas, clinical management and outcome of this rare tumor. METHODS: This retrospective international multicenter study included all patients with pathologically proven HAML diagnosed between 1997 and 2017. Data on patient characteristics, diagnostic work-up, management and follow-up were analyzed. RESULTS: Thirty-eight patients were included, 32 female. Median age was 56yrs (i.q.r. 43-64) and median HAML-diameter was 57.5 mm (i.q.r. 38.5-95.3). Thirty patients had undergone CT and 27/38 MRI of the liver, diagnostic biopsy was performed in 19/38. Initial diagnosis was incorrect in 15/38 patients, of which 13 were thought to have malignancy. In 84% biopsy resulted in a correct preoperative diagnosis. Twenty-nine patients were managed with surgical resection, 4/38 with surveillance and 3/38 with liver transplantation. Recurrence after resection occurred in two cases. No HAML related deaths or progression to malignancy were documented. CONCLUSION: HAML diagnosis proved problematic even in hepatobiliary expertise centers. Biopsy is indicated and may provide valuable additional information when HAML diagnosis is considered on cross-sectional imaging, especially when surgical resection imposes a risk of complications. Conservative management with regular imaging follow-up might be justified when biopsy confirms (classic type) HAML.

Management of hepatic angiomyolipoma: A systematic review.

Hepatic Angiomyolipoma (HAML) is a rare mesenchymal liver tumour assumed to be predominantly benign, although incidental cases with malignant behaviour such as invasive growth, recurrence after resection and metastases have been reported. The aim of this systematic review was to assess the biological behaviour, estimate the risk of HAML related mortality and recommend on a justifiable management strategy. We performed a systematic literature search in Embase, Medline, Web-of-Science, Scopus, Pubmed Publisher, Cochrane and Google Scholar. We included all articles published from inception until March 2016 which reported on follow-up of various treatment strategies. We included 18 articles reporting on 292 patients. Male:female ratio was estimated at 1:3 with gender not reported in 31 cases. Of 292 patients 247 were treated with surgery, including one liver transplant, seven with chemotherapy or Sirolimus, three with embolization, and 35 conservatively. Recurrence after resection was described in 6/247 (2.4%) with pathologically proven HAML resulting in metastases and death in 2/247 (mortality rate 0.8%). Progression was described in 6/35 patients treated conservatively (21.4%). Two of 12 patients with malignant behaviour of HAML had an epithelioid-type HAML, of the remaining 10 histological subtype was undefined. With a risk estimate of 0.8% in surgically treated patients HAML related mortality is very low. Biopsy is indicated when imaging is inconclusive. In case of certain HAML diagnosis on imaging conservative management with annual imaging is justified. Resection should be considered in case of symptoms, inconclusive biopsy or growth in follow-up.

Renal angiomyolipomas: At least two diseases. A series of patients treated at two European institutions.

OBJECTIVE: The aim of this study is to analyze the outcome of renal angiomyolipomas (AML) at two European institutions. METHODS: The data were collected from patients with a primary AML who were treated at Gustave Roussy, Villejuif, France and Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy from 1998 to 2014. The specimens were classified as classic AML (C AML) or epithelioid AML (E AML) based on the percentage of epithelioid cells. RESULTS: There were 40 patients identified for the study (35 C AML, 5 E AML). One patient had an associated tuberous sclerosis complex. Six patients (15%) had bilateral AML. The imaging results were significantly different between C/E AML. E AML was associated with fewer bilateral lesions, more renal vein/vena cava extension, and more poor or non-fatty aspects. Surgery/active surveillance (AS)/chemo radiation were applied for 28/11/1 patients, respectively. The median tumor size was significantly smaller (3.75 cm) in patients receiving AS (median 15 cm when surgically resected). The median patient follow-up was 43 months. The three-year overall survival was significantly better for patients with C AML than E AML (100% versus 50%, p < 0.0001). The univariate analysis identified the OS prognostic factors were E AML histologic subtype (p < 0.001), poor/non fatty features (p = 0.002), and renal vein extension on imaging (p = 0.01). CONCLUSION: AML manifests as at least two different entities with significantly different outcomes. Epithelioid subtype, poor/non-fatty features, and renal vein involvement are all associated with worse survival.

Review of the Tuberous Sclerosis Renal Guidelines from the 2012 Consensus Conference: Current Data and Future Study.

Renal-related disease is the most common cause of tuberous sclerosis complex (TSC)-related death in adults, and renal angiomyolipomas can lead to complications that include chronic kidney disease (CKD) and hemorrhage. International TSC guidelines recommend mammalian target of rapamycin (mTOR) inhibitors as first-line therapy for management of asymptomatic, growing angiomyolipomas >3 cm in diameter. This review discusses data regarding patient outcomes that were used to develop current guidelines for embolization of renal angiomyolipomas and presents recent data on 2 available mTOR inhibitors - sirolimus and everolimus - in the treatment of angiomyolipoma. TSC-associated renal angiomyolipomas can recur after embolization. Both sirolimus and everolimus have shown effectiveness in reduction of angiomyolipoma volume, with an acceptable safety profile that includes preservation of renal function with long-term therapy. The authors propose a hypothesis for mTORC1 haploinsufficiency as an additional mechanism for CKD and propose that preventive therapy with mTOR inhibitors might have a role in reducing the number of angiomyolipoma-related deaths. Because mTOR inhibitors target the underlying pathophysiology of TSC, patients might benefit from treatment of multiple manifestations with one systemic therapy. Based on recent evidence, new guidelines should be considered that support the earlier initiation of mTOR inhibitor therapy for the management of renal angiomyolipomas to prevent future serious complications, rather than try to rescue patients after the complications have occurred.

Incremental Expression of 14-3-3 Protein Beta/Alpha in Urine Correlates with Advanced Stage and Poor Survival in Patients with Clear Cell Renal Cell Carcinoma.

We investigated the urinary levels of 14-3-3 protein beta/alpha to evaluate their diagnostic significance with regard to clear cell renal cell carcinoma (ccRCC) and angiomyolipoma (AML). Urine samples from 91 patients with ccRCC, 16 patients with AML and 24 healthy volunteers were assessed. We used an enzyme-linked immunosorbent assay (ELISA) to quantify 14-3-3 protein beta/alpha levels in urine. Values were higher in patients with ccRCC than in those with AML and in healthy volunteers. High levels were associated with pathologic stage, lymph node status, distant metastasis and poor survival. Urinary levels of 14-3-3 protein beta/alpha were significantly increased in patients with small-sized carcinoma, irrespective of being less than 4.0 cm and 2.0 cm, compared with levels in patients with AML. This study is the first to report that increased expression of 14-3- 3 protein beta/alpha in urine is associated with advanced stage and poor survival in patients with ccRCC. In addition, urinary 14-3-3 protein beta/alpha may differentiate AML from RCC, even when small sized. These results suggest that examination of urinary 14-3-3 protein beta/alpha could serve as a diagnostic and prognostic marker in patients with ccRCC.

Long-term Follow-up Assessing Renal Angiomyolipoma Treatment Patterns, Morbidity, and Mortality: An Observational Study in Tuberous Sclerosis Complex Patients in the Netherlands.

BACKGROUND: Long-term data from patients with tuberous sclerosis complex (TSC)-associated renal angiomyolipoma (angiomyolipoma) are limited. STUDY DESIGN: Retrospective observational study. SETTING & PARTICIPANTS: Adult patients with TSC treated at the University Medical Center Utrecht (the Netherlands) from January 1990 through April 2012. PREDICTORS: Patient age and angiomyolipoma stage, based on computed tomography lesion count, size, and impact on renal anatomy, with higher stage representing higher angiomyolipoma burden. Patients in stages 3 or higher were considered at high risk for hemorrhage and candidates for selective arterial embolization. OUTCOMES: Kidney-related outcomes included hypertension, anemia, decreased kidney function, dialysis, kidney transplantation, nephrectomy, kidney-related blood transfusions, and mortality. Observed mortality was compared to the Dutch National Bureau of Statistics using standardized mortality ratio. RESULTS: Median follow-up was 15.8 years, of which staging was available for 5.4 years. Of 351 patients with TSC, 244 (69.5%) had confirmed angiomyolipoma; 144 (59.0%) reached stage 3 or higher. Age and angiomyolipoma stage were positively correlated: median age in the none-detected stage was 36.8 years, increasing to 43.6 years for stage 6. Embolization was performed in 117 patients; 57 had 2 or more embolization procedures. Higher stage was associated with hypertension, anemia, decreased kidney function, and transfusion. Hypertension, anemia, and decreased kidney function were more common in patients who underwent selective arterial embolization. 7 patients required dialysis, 7 received a kidney transplant, and 16 underwent nephrectomy. 29 deaths were recorded, most commonly related to renal complications (n=9[31%]). Mortality was significantly higher in the study cohort versus the general population (standardized mortality ratio, 4.8; 95% CI, 3.4-6.9). LIMITATIONS: Duration of follow-up with staging was too short to observe stage progression in most patients. CONCLUSIONS: Despite the use of preventive selective arterial embolization, patients with TSC exhibit clinically significant kidney disease and excess mortality, largely because of kidney-related complications.

Twenty years experience in oncologic surgery for primary cardiac tumors.

INTRODUCTION: Primary cardiac tumors are uncommon in cardiac surgery. To investigate the clinical presentation, surgical results and long-term follow-up we retrospectively analyzed our experience in the treatment of primary cardiac tumors. PATIENTS AND METHODS: Ninety-one patients with primary cardiac tumors underwent surgery in our department in the last 20 years. Fifty-one patients were female, the mean age was 62,2 years. Sixty-three had myxomas, 22 had papillary fibroelastoma, 4 had malignant neoformations and 2 had other benign tumors. RESULTS: All myxomas, fibroelastomas and angiomyolipoma were radically removed. Only a palliative treatment was possible in malignant disease. In-hospital mortality was 1.2%. The mean follow-up time was 78.5 months. Three patients had recurrence of myxoma, all patients with malignant disease dead during the follow-up. DISCUSSION: Primary benign cardiac tumors can be treated with low morbidity and mortality. The follow-up demonstrates that radical surgery is curative in case of benign tumors. The prognosis of malignant tumors is still poor. Palliative procedures have small impact on survival in these patients.

Microwave ablation versus partial nephrectomy for small renal tumors: intermediate-term results.

BACKGROUND AND OBJECTIVES: Prospective randomized comparison of intermediate-term outcomes of patients with small renal tumors who were treated with partial nephrectomy (PN) or microwave ablation. METHODS: Of 102 selected patients with solitary small renal tumors who had prospectively completed at least 2 years of follow-up since December 2004, randomizedly, 54 had either open (19) or laparoscopic (35) PN and 48 had laparoscopic (28) or open (20) microwave ablation. Patient and tumor characteristics, surgical data, complications, histologic and oncologic data, and functional data of the two approaches were compared. RESULTS: Patients in microwave ablation group and PN group matched for age, sex, American Society of Anesthesiologists score, body mass index, and tumor size and were respectively followed for median 32 and 36 months. Surgical and hospitalization times were comparable in both groups. Estimated blood loss, complication rates, and decline of postoperative renal function were significantly less in the microwave ablation group (P = 0.0002, P = 0.0187, and P = 0.0092, respectively). The decrease in estimated glomerular filtration rate at the last available follow-up was similar in both groups (P = 1.0000). There were no disease-specific deaths. Kaplan-Meier estimates of overall local recurrence-free survival at 3 years were 91.3% for microwave ablation and 96.0% for PN (P = 0.5414); the respective numbers for renal cell carcinomas were 90.4 and 96.6% (P = 0.4650). CONCLUSIONS: Microwave ablation can be also safely and efficiently done for patients with small renal tumors. This intermediate analysis showed that microwave ablation provides favorable results compared to PN. However, longer term data are still needed.

Bilateral renal masses: pathologic concordance and impact of temporal presentation.

AIM: The aim of this paper was to evaluate the pathologic concordance of bilateral renal masses and the influence of synchronous or asynchronous occurrence on patient long term survival. METHODS: Thirty-one consecutive patients with bilateral synchronous (N.=17, 55.0%) or asynchronous (N.=14, 45.0%) renal masses were retrospectively reviewed from January 2000 to December 2010. We included all patients with confirmed diagnosis on pathologic examination of a specimen or a percutaneous biopsy and evidence of angiomyolipoma on CT. Survival was assessed using the Kaplan-Meier method. RESULTS. The first lesion was larger than the second (60 vs. 30 mm, P<0.001). Pathologic concordance rate between tumors was 87.1%. A clear cell carcinoma was associated with a papillary carcinoma in 3.2%, and an angiomyolipoma in 6.4%. Median time of occurrence of a metachronous lesion was 50 months (IQR: 24; 92). Disease-free survival at 5 and 10 years was 87.2% and 78.5%. No statistical difference in disease free survival was observed between synchronous and metachronous tumors. conclusion: Discordant pathology between bilateral renal masses is uncommon, with a slight probability of benign tumor. Occurrence of a metachronous tumor can exceed 10 years.

Diagnosis and treatment of hepatic angiomyolipoma.

BACKGROUND AND OBJECTIVE: Hepatic angiomyolipoma is more frequently encountered in clinical practice, its diagnosis is difficult, its treatment remains controversial. We review a single-center experience in the treatment of hepatic angiomyolipoma. METHOD: The clinical data of 79 patients with hepatic angiomyolipoma treated at the authors' institute between January 1992 and December 2006 were retrospectively reviewed. RESULTS: During a period of 15 years, a total of 79 patients with hepatic angiomyolipoma underwent liver resection at our hospital. There are 58 women and 21 men. The tumor size varied from 1 to 25 cm in diameter (6.1 ± 4.08). Fifty-four patients (68%) were asymptomatic. Accurate preoperative diagnosis was made in 41 patients (52%). Tumors less than 6 cm in size were more frequently misdiagnosed. Spontaneous rupture occurred in one patient. One patient had tumor recurrence 6 years after the surgery, and died of the disease 1 year later. Symptom relief was achieved in 92% of the symptomatic patients. Median survival was 90 months (90.12 ± 30.84). CONCLUSIONS: Hepatic angiomyolipoma poses a diagnostic challenge clinically and radiologically. Surgical resection is a safe and effective treatment option. It is important to realize the potential of malignant transformation and risk of rupture as life-threatening complications.

Diagnostic difficulties and treatment strategy of hepatic angiomyolipoma.

OBJECTIVE: Based on a large series of histopathologically confirmed hepatic angiomyolipomas, we retrospectively studied the typical diagnostic features of hepatic angiomyolipoma and proposed a treatment strategy for this disease. MATERIALS AND METHODS: From December 1997 to December 2007, 74 consecutive patients who received definitive treatment for hepatic angiomyolipoma, at a single tertiary center, were studied. RESULTS: There was a marked female predominance (54 females vs. 20 males) and the mean age was 42 years. Forty patients had no symptoms and the tumors were detected incidentally during a medical check-up. From this study, we proposed the typical diagnostic features of hepatic angiomyolipoma to be the absence of risk factors for malignancy, normal tumor marker levels, and typical imaging features on ultrasound (USG), abdominal contrast computed tomography (CT), or magnetic resonance imaging (MRI). Only 23% of patients could have been diagnosed before surgery using these features. One patient (1.4%) had a malignant angiomyolipoma, and died with distant metastases 14 months after surgery. After a median follow-up of 64 months, there was no recurrence in the other 73 patients. CONCLUSION: Patients with typical diagnostic features suggestive of hepatic angiomyolipoma could be observed with regular surveillance. Definitive treatment should be performed when the tumor has symptoms/complications, when the tumor is enlarging, or when a malignant lesion cannot be ruled out.

Renal epithelioid angiomyolipoma with atypia: a series of 40 cases with emphasis on clinicopathologic prognostic indicators of malignancy.

As epithelioid cellular morphology can be seen in clinically benign usual angiomyolipomas (AMLs), we divide epithelioid AMLs into those without and with atypia, the latter category associated in the literature with malignant potential. We herein report the histologic spectrum and biologic behavior of 40 consecutive cases of epithelioid AML with atypia and assess whether cases can be stratified prognostically based on clinical and pathologic features. Atypical epithelioid cells were defined as atypical polygonal cells with abundant cytoplasm, vesicular nuclei, prominent nucleoli, and nuclear size that exceeds x2 the size of adjacent nuclei. The degree of atypia was divided to moderate and severe. Cases with bland epithelioid cells with minimal variation in nuclear size were not included. Mean age was 50.5 years (range 17 to 81), and the female to male ratio was 1.6:1. Average tumor size was 7.2 cm (range 1.0 to 17.7). The percentage of epithelioid component ranged from 5%-100% (mean 68%). Of the epithelioid component, the percentage of cells exhibiting nuclear atypia ranged in individual cases from 5% to 100% (mean of 58.4% atypical cells); 26/40 (65%) cases showed severe nuclear atypia. Cells displaying severe nuclear atypia were typically of large size with abundant cytoplasm, compared with those with moderate atypia being of small to intermediate in size with scant to moderate amount of cytoplasm. Neoplastic multinucleated giant cells and necrosis was present in 22 cases (55%) and 15 cases (37.5%), respectively. Mitoses were identified in 72.5% (29/40) of cases and ranged from 1 to 6 per 10 hpf with 7 cases showing atypical mitotic figures. Lymphovascular invasion or renal vein invasion was present in 3 cases each. Hilar and perinephric fat involvement was present in 5 and 6 cases, respectively. Clinical follow-up was available in 34 out of the 40 cases. Of the 34 cases, 9 (26%) were malignant and showed local recurrence or distant metastases. Of the 9 patients with malignant tumors, 4 died of the disease at 6, 12, 15, and 34 months after the original diagnosis was rendered, and 4 were alive with disease (mean follow-up period of 52 mo, range 24 to 72 mo). Twenty-four patients showed no evidence of recurrence and/or metastases with a mean follow-up period of 34 months (range 1 to 156 mo). We compared the 21 cases of atypical epithelioid AMLs that exhibited a benign clinical course with a minimum follow-up period of 6 months postsurgery to the 9 cases with malignant behavior. All of these were more frequently observed in clinically malignant cases: older age, larger tumor size, higher percentage of epithelioid component, severe atypia, higher percentage of atypical cells, higher mitotic count, atypical mitotic figures, necrosis, lymphovascular invasion, and renal vein invasion. Using these features, we developed a predictive model of 4 atypical features that included: (1) > or =70% atypical epithelioid cells, (2) > or =2 mitotic figures per 10 hpf, (3) atypical mitotic figures, and (4) necrosis; the presence of 3 or all of the features was highly predictive of malignant behavior. This model accurately categorized 78% of clinically malignant and 100% of the clinically benign epithelioid AMLs with atypia.

Hepatic angiomyolipoma: a clinical experience in diagnosis and treatment.

BACKGROUND: Hepatic angiomyolipoma is a rare mesenchyme-derived neoplasm often misdiagnosed as hepatocellular carcinoma, and the treatment for it remains controversial. AIMS: To develop the optimal preoperative diagnoses means and treatment modalities of hepatic angiomyolipoma. METHODS: Retrospective analysis of the clinical features, treatment, and prognostic data of 17 hepatic AML patients admitted to Chinese People's Liberation Army Generation Hospital between 1996 and 2006. RESULTS: Most hepatic angiomyolipoma were solitary. The overall preoperative diagnostic rate was 18% and the most common misdiagnosis was hepatocellular carcinoma (10/17, 59%). In three patients, observation was performed for 2-3 years before being admitted. The tumors increased 1-9 cm in size in all patients. All of the 17 patients finally received various liver resection procedures, and postoperative mortality and morbidity was 0 and 12% (2/17). After a median follow-up period of 73 months, the tumor recurred only in one patient 9 years post-operatively. CONCLUSIONS: Hepatic angiomyolipoma should be suspected in liver tumor patients with normal α-fetoprotein levels and no concomitant hepatitis. Preoperative MRI combined with percutaneous fine-needle biopsy should be the diagnostic methods of choice. Small hepatic AML proved through pathologic examination (<5 cm) may be managed by observation with close follow-up, but surgery is indicated in patients suffering from large tumors or significantly larger tumors during follow-up.

Renal manifestations of tuberous sclerosis complex.

Patients with tuberous sclerosis complex (TSC) are at increased risk of renal disease, predominantly angiomyolipomas and renal cysts. We retrospectively reviewed clinical data of 71 patients diagnosed with TSC. Progression of renal lesions was noted. TSC patients with renal lesions were compared with TSC patients without renal disease. Fifteen of 38 patients had renal abnormalities by imaging at presentation. Six of 9 with initially normal kidneys subsequently developed new lesions. Although not of statistical significance, there was a trend toward increased retinal hamartomas, cardiac rhabdomyomas, and skin lesions in those patients who also had renal abnormalities. Renal disease should be considered and sought in all patients with TSC, both at initial presentation and subsequently, since renal disease is a very significant cause of morbidity and mortality.