Adrenal Invasion Research Articles

Analysis of renal cell carcinoma with subdiaphragmatic macroscopic venous invasion (T3b)

To review our institutional experience of surgery for renal cell carcinoma (RCC) with subdiaphragmatic macroscopic venous invasion (T3b) and to assess variables associated with cancer-specific survival (CSS), as the stratification of RCC with venous involvement (T3b and T3c) is subject to debate. We retrospectively reviewed the hospital records of patients who underwent a radical nephrectomy with resection of subdiaphragmatic tumour thrombus (T T) between October 1990 and May 2006. The log-rank and Cox uni- and multivariate regression analysis were used to evaluate predictive factors for CSS. In all, 101 cases were identified. In the N0M0 group, univariate Cox regression analysis confirmed that ipsilateral adrenal gland invasion, Mayo Clinic level of T T, histological subtype and fat invasion were significantly associated with worse CSS. In multivariate Cox regression analysis, only Mayo Clinic level of T T was an independent predictor for CSS. In the subgroup with renal vein involvement only, the median CSS was not reached. In the subgroups with level I, II and III T T involvement, the median CSS was 69, 26 and 21 months, respectively. In the N+ and/or M+ group, only tumour size and type were independent predictors of CSS, while the level of T T was not. Radical nephrectomy yielded poor results with a median CSS of 13 months. The Mayo Clinic level of T T is an independent prognostic predictor for CSS in non-metastatic T3b RCC. We strongly support the need for re-classification of the currently applied 2002 Tumour-Node-Metastasis staging system, which in its present form does not discriminate between levels of subdiaphragmatic venous invasion.

Location of Extrarenal Tumor Extension Does Not Impact Survival of Patients With pT3a Renal Cell Carcinoma

The current TNM classification for pathological pT3a renal cell carcinoma includes patients with perinephric or sinus fat invasion, suggesting that the prognoses are similar for these pathological findings. However, sinus fat invasion was proposed by some investigators to be an independent predictor of inferior cancer specific outcome following surgical treatment. To assess and improve the predictive ability of the current pT3a primary tumor classification we evaluated the prognostic significance of location of extrarenal tumor extension on cancer specific survival following surgery. The database of 3,470 patients at our institution who were treated for renal cell carcinoma from 1990 to 2006 was searched for those with pT3a tumors managed by partial or radical nephrectomy. Patients with nonrenal cell carcinoma histology, direct adrenal invasion or a followup of less then 6 months were excluded from analyses. The prognostic importance of all clinical and pathological variables was investigated using Cox proportional hazards regression. A total of 365 patients with pT3a renal cell carcinoma and a mean followup of 33.5 months (range 6.1 to 158.6) met study inclusion criteria and they comprise the data set for this analysis. There was no difference in 5-year cancer specific survival between 166 patients (45.5%) with SF invasion and 199 (54.5%) with PF invasion only (50.8% and 54.1%, p = 0.782 respectively). On univariate analyses neither sinus fat invasion nor the location of extrarenal extension, assessed as perinephric fat vs sinus fat vs perinephric plus sinus fat, correlated with cancer specific survival following surgical treatment (HR 1.052, p = 0.783 and HR 1.072, p = 0.543, respectively). After adjusting for the effects of nodal and systemic metastases tumor grade and sarcomatoid differentiation remained independent predictors of renal cell carcinoma specific survival in our pT3a cohort of patients (HR 1.508, p = 0.003 and HR 1.810, p = 0.018, respectively). In contrast to previously reported observations, in our cohort of surgically treated patients with pT3a renal cell carcinoma the location of extrarenal extension was not an important prognosticator of cancer specific mortality. Based on our findings we confirm that perinephric and/or sinus fat should be similarly subclassified in the primary tumor staging system.

A New Staging System for Locally Advanced (pT3–4) Renal Cell Carcinoma: A Multicenter European Study Including 2,000 Patients

We provide an adequate prognostic stratification for locally advanced renal cell carcinoma and propose a new TNM classification. We analyzed clinical and pathological data on a large series of patients undergoing radical nephrectomy for pT3-4 renal cell carcinoma at 12 European centers. Cancer specific survivals were estimated using the Kaplan-Meier method. The log rank test was used for comparing survival curves and for univariate analysis. The Cox proportional hazards regression model was used for multivariate analysis. The analysis included 1,969 patients. Median survivor followup was 49 months. Five-year cancer specific survival was 60% for pT3a, 46.2% for pT3b, 10% for pT3c and 12% for pT4 tumors (p <0.0001). According to median survival we identified 3 prognostic groups, including 1--patients with renal vein thrombosis (117 months), fat invasion (98 months) or infradiaphragmatic vena caval thrombosis (67 months), 2--patients with adrenal invasion alone (24 months), renal vein thrombosis plus fat invasion (24 months) or infradiaphragmatic vena cava plus fat invasion (24 months) and 3--patients with renal or infradiaphragmatic caval thrombosis plus adrenal involvement (11 months), supradiaphragmatic vena caval thrombosis (12 months) or Gerota's fascia invasion (12 months). Five-year cancer specific survival rates in groups 1 to 3 were 61%, 35% and 12.9%, respectively (p <0.0001). On multivariate analysis the proposed classification had an independent prognostic value. Our results suggest the necessity of reclassifying locally advanced renal cell carcinoma according to the 3 described prognostic categories.

Proposal for Reclassification of the TNM Staging System in Patients with Locally Advanced (pT3–4) Renal Cell Carcinoma According to the Cancer-Related Outcome

ObjectivesThe optimal stratification of locally advanced renal cell carcinoma (RCC) is controversial, with the prognostic relevance of ipsilateral adrenal gland invasion and cranial extension of vena cava thrombosis being the most debatable issues. We evaluated the prognosis of patients with locally advanced RCC and identified a new model to stratify their outcome. Materials and methodsWe analyzed the data of 227 patients who had undergone partial or radical nephrectomy for pT3–4 RCC at two academic centers between 1986 and 2002. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analysis, respectively. ResultsAt a median follow-up of 29 mo, we censored 108 (47.6%) cancer-related deaths. On univariate analysis, the 2002 T stage was not statistically significant. According to cancer-related outcome, we identified three subgroups of patients with different prognoses: pT3a(n): tumors with perirenal fat invasion or renal vein thrombosis or thrombosis within the vena cava below the diaphragm; pT3b(n): tumors with renal vein thrombosis or thrombosis within the vena cava below the diaphragm and concomitant perirenal fat invasion; pT4(n): adrenal gland or Gerota fascia invasion or thrombosis within the vena cava above the diaphragm. The three subgroups had significantly different prognoses. The new reclassification was an independent predictive variable on multivariate analysis, as well as the pathologic lymph node stage. ConclusionsThe 2002 version of TNM of locally advanced RCC did not stratify patient outcome. The present study suggests the possibility of reclassifying pT3–4 RCC into three categories capable of predicting cancer-specific survival, regardless of all other prognostic factors.

Comparison of the Prognosis between pT3a Only Patients with Perirenal Fat Invasion and T1/T2 Patients, Respectively: Is It Necessary to Revise Stage T3a?

Purpose: As compared with pathologic stages T1 and T2, we aimed to investigate the difference of the prognosis for the patients with perirenal fat invasion (pT3a), and the patients were divided into two groups by the tumor size of 7cm. Materials and Methods: Of the 503 patients who underwent an operation for renal cell carcinoma between June 1995 and April 2004, we retro- spectively reviewed the records of 455 patients with T1, T2 and T3a stage renal cell carcinoma without adrenal invasion. We evaluated the cell type, the multifocality of the tumor, the nuclear grade, the presence of a sar- comatoid component and the coagulative histologic necrosis. We divided the patients with pT3a renal cell carcinoma into two groups according to the tumor size of 7cm (Group 1; †7cm pT3a, Group 2; ĥ7cm pT3a). The overall survival was estimated using the Kaplan-Meier method and the log-rank test. We used Students s t-test to compare each factors between groups 1 and 2 and the T1 and T2 groups, respectively. The prognostic factors that had an influence on survival were estimated using the Cox proportional hazard regression model in each group. Results: After the exclusion criteria (the presence of adrenal invasion in pT3a patients) were applied, 24 patients were in group 1, 23 patients were in group 2, 328 patients had pT1 disease and 80 patients had pT2 disease. The median follow-up was 45.4 months. When group 1 was compared to the pT1 group, there was no significantly difference of the estimated survival (p=0.21). There was a similar result when comparing the esti- mated survival between group 2 and the pT2 group (p=0.80). Conclusions: No significant difference exists for the disease specific survival when patients with pT3a disease (Groups 1 and 2) are compared to the patients with either pT1 or pT2 disease. These findings reveal that patients with pT3a disease without adrenal invasion have similar outcomes to patients with either with pT1 or pT2 disease. Therefore, our result sug- gests that pT3a tumor should be re-classified according to tumor size into

IS RENAL SINUS FAT INVASION THE SAME AS PERINEPHRIC FAT INVASION FOR pT3a RENAL CELL CARCINOMA?

Perinephric and renal sinus fat invasion are classified as pT3a renal cell carcinoma (RCC) according to the 2002 American Joint Committee on Cancer. We investigated the prognostic significance of each of these pathological features using a cohort of pT3a patients. Between 1970 and 2002, 205 patients without direct adrenal invasion underwent nephrectomy for pT3a clear cell RCC. The associations of fat invasion with death from RCC were evaluated using Cox proportional hazards regression models. Of the 162 patients with perinephric fat invasion and 43 patients with renal sinus fat invasion 95 (59%) and 31 (72%), respectively, died of RCC. Patients with renal sinus fat invasion were 63% more likely to die of RCC compared with those with perinephric fat invasion (RR 1.63, 95% CI 1.09-2.46, p=0.018). In addition, the risk of death persisted in multivariate analysis after adjusting for regional lymph nodes and distant metastases (RR 1.91, 95% CI 1.26-2.89, p=0.002) and after adjusting for the Mayo Clinic SSIGN (stage, size, grade and necrosis) score (RR 1.90, 95% CI 1.25-2.88, p=0.003). Our results indicate that clear cell tumors invading the renal sinus fat are more aggressive than tumors with perinephric fat involvement. We believe both of these features should be individually assessed during routine pathological examination. External validation is needed before suggesting a change to the TNM staging system.

Reclassification of patients with pT3 and pT4 renal cell carcinoma improves prognostic accuracy

The significance of adrenal invasion and tumor thrombus in renal cell carcinoma (RCC) has been debated recently. The authors evaluated the associations of direct adrenal invasion, perinephric fat invasion, and tumor thrombus level with outcome to determine whether reclassification would improve the prognostic accuracy of the current primary tumor classification. The authors studied 697 patients treated with nephrectomy for pT3 and pT4 RCC between 1970 and 2000. Associations with outcome were evaluated using Cox proportional hazards regression and prognostic accuracy was measured using the c index. Among patients with pT3 RCC, direct adrenal invasion was significantly associated with death from RCC (risk ratio, 2.11; P = 0.004). No significant difference in survival was found between patients with pT4 RCC and pT3 tumors with direct adrenal invasion (P = 0.490). Among patients with pT3b RCC, those with level I-III tumor thrombus were significantly more likely to die of RCC compared with patients harboring level 0 tumor thrombus (risk ratio, 1.62; P < 0.001). In addition, patients with fat invasion were more likely to die of RCC compared with pT3 patients without fat invasion (risk ratio, 1.87; P < 0.001). Therefore, patients with pT3 RCC were reclassified into 4 prognostic groups, and this reclassification significantly improved prediction of death from RCC compared with the current classification (c indices of 0.61 vs. 0.55, respectively). Direct adrenal invasion from RCC should be reclassified as pT4. In addition, the proposed reclassification for patients with pT3 RCC improved prognostic accuracy.

SHOULD DIRECT IPSILATERAL ADRENAL INVASION FROM RENAL CELL CARCINOMA BE CLASSIFIED AS pT3a?

The 2002 American Joint Committee on Cancer primary tumor classification for renal cell carcinoma (RCC) defines a tumor as pT3a if it invades the perinephric or renal sinus fat or directly invades the ipsilateral adrenal gland. In the current study we evaluated the association of direct ipsilateral adrenal invasion with outcome to determine if reclassification of these tumors as pT4 would improve the accuracy of the current tumor classification. We studied 424 patients who underwent nephrectomy and adrenalectomy for unilateral, sporadic, pT3 or pT4 RCC between 1970 and 2000 at the Mayo Clinic. Cancer specific survival was estimated using the Kaplan-Meier method. Cancer specific survival for the 22 patients with pT3a or pT3b tumors that directly invaded the ipsilateral adrenal gland was significantly worse compared with that of patients with pT3a (p <0.001) or pT3b (p = 0.011) disease that did not invade the adrenal gland. There was no significant difference in the 5-year cancer specific survival between the patients with pT3a or pT3b tumors that directly invaded the ipsilateral adrenal gland and patients with pT4 tumors (cancer specific survival rates of 20% and 14%, respectively, p = 0.490). Although rare, RCC with direct ipsilateral adrenal invasion behaves more aggressively than tumors involving perinephric or renal sinus fat. We believe that RCC tumors with direct adrenal invasion should be classified as pT4.

MULTI-INSTITUTIONAL VALIDATION OF A SYMPTOM BASED CLASSIFICATION FOR RENAL CELL CARCINOMA

We validate the prognostic value of a symptom based classification (S classification) in a multi-institutional study. A total of 2,242 patients from 5 European centers were included in this study. Based on symptoms at diagnosis, patients were stratified into 3 groups of S1-asymptomatic tumors, S2-tumors with local symptoms and S3-tumors with systemic symptoms. Variables such as age, gender, tumor size, TNM stage, Fuhrman grade, Eastern Cooperative Oncology Group (ECOG) performance status, perinephric fat, renal vein and adrenal invasion were also considered for prognostic value. The end point of the study was cancer specific survival. Survival assessment was made with univariate and multivariate analyses using the Kaplan-Meier method and Cox regression analysis. Of the patients 1,018 (45.4%) were classified as S1, 865 (38.6%) S2 and 339 (16.0%) S3. The S classification correlated to tumor stage, grade and ECOG (p <0.001). On univariate analysis ECOG performance status, S classification, tumor size, TNM stage, Fuhrman grade, and adrenal, perinephric fat or vein invasion were significant prognostic factors (p <0.001). The S classification provided a significant prognostic stratification in the aggregate as well at each of the 5 centers. On multivariate analysis the S classification, TNM stage, Fuhrman grade, and perinephric fat and renal vein invasion remained independent prognostic factors (p <0.001). This study confirms that it is possible to graduate symptoms for a prognostic purpose. The proposed symptom score should be evaluated for its integration in prognostic algorithms.

TNM T3a Renal Cell Carcinoma: Adrenal Gland Involvement is Not the Same as Renal Fat Invasion

Upper pole tumors with direct extension into the adrenal gland are currently staged as pT3a tumors in the 1997 TNM staging system. To determine whether the clinical behavior of pT3a adrenal tumors differs from that of tumors with perinephric fat invasion (also stage pT3a) a retrospective analysis was performed. Of 1,087 patients who underwent nephrectomy 27 were identified with direct adrenal involvement and 187 were identified with perinephric fat or renal sinus involvement. Variables and outcomes analyzed in each group included the percent of patients with metastatic disease at presentation, lymph node involvement, Eastern Cooperative Oncology Group score, response to immunotherapy, and median and overall survival using Kaplan-Meier curves. Median survival for patients with pT3a disease and perinephric or renal sinus fat involvement was 36 months with a 36% 5-year cancer specific survival rate. In contrast, patients with adrenal gland invasion had significantly worse survival at a median of 12.5 months and a 0% 5-year cancer specific survival rate (p <0.001), which was similar to median survival of those with stage pT4 disease (11 months). Upper pole tumors with direct extension into the adrenal gland predict significantly worse survival than similarly staged tumors with fat invasion and they have a prognosis similar to that of stage pT4 disease. While these data await external validation, consideration should be given to re-categorizing tumors with direct adrenal gland involvement as stage pT4 or in a subcategory such as pT4a.

Prognostic significance of the mode of detection in renal tumours.

To evaluate the mode of detection of 400 renal tumours as a prognostic factor compared with the usual clinical and pathological prognostic variables. The data were reviewed for 400 patients operated for a renal tumour at our institution between 1984 and 1999, analysing the prognostic value of age, sex, tumour size, stage, grade, vein invasion, adrenal gland invasion, lymph node invasion, metastasis, and mode of detection (incidental or not). The survival rates were assessed using the Kaplan-Meier method and log-rank test, and the data evaluated using multivariate analysis with the Cox proportional-hazard model. In all, 151 (38%) renal tumours were discovered incidentally. There was no significant difference in the percentage of renal cell carcinoma found between the groups of patients discovered incidentally or not (94.4% vs 93.9%). Tumours were smaller in the incidental group (5.7 cm vs 8.7 cm, P < 0.001). In the incidental group, 15.2% of the tumours were treated with partial nephrectomy, against 1.2% in the symptomatic group (P < 0.001). The specific survival was significantly better in patients with renal tumours discovered incidentally (log-rank test, P < 0.001). The multivariate analysis showed that the mode of detection, stage, grade, metastasis (all P < 0.001), and lymphatic extension (P = 0.005) were independent prognostic factors. The incidental discovery of renal tumours gives a supplementary benefit to patients in terms of survival, and should be considered as a prognostic factor in addition to stage and grade.

Radiologic Findings of Direct Splenic Invasion by Malignant Tumors of Adjacent Organs

Purpose: To evaluate the radiologic findings of direct invasion of the spleen by malignant tumors of adjacent organs. Materials and Methods: We retrospectively reviewed the CT(n=6) and MR(n=3) images of six patients with direct invasion of the spleen by malignant tumor of left lower lung, stomach, colon, pancreas, left kidney, and left adrenal gland. We evaluated the tumor margin, attenuation or intensity, perisplenic fat infiltration, regional lymphnode enlargement, and invaded site of the spleen. Results: Ill-defined masses were found in the spleen with central necrosis and infiltration into perisplenic fatty tissue in all six patients; left adrenal mass was present also in three patients. Regional lymphnode enlargement was found in four patients. The masses showed heterogenous low attenuation on CT. The invaded site was variable and corresponding to their anatomical connections to the spleen. Conclusion: Direct invasion of the spleen by malignant tumors of adjacent organs showed ill-defined masses with central necrosis and were commonly associated with infiltration to perisplenic fatty tissue and adrenal invasion. The pattern and invaded site can be helpful to assess the primary cancer.

IS ADRENALECTOMY A NECESSARY COMPONENT OF RADICAL NEPHRECTOMY? UCLA EXPERIENCE WITH 511 RADICAL NEPHRECTOMIES

We determine the incidence and characteristics of adrenal involvement in localized and advanced renal cell carcinoma, and evaluate the role of adrenalectomy as part of radical nephrectomy. The records of 511 patients undergoing radical nephrectomy with ipsilateral adrenalectomy for renal cell carcinoma at our medical center between 1986 and 1998 were reviewed. Mean patient age was 63.2 years (range 38 to 85), and 78% of the subjects were males and 22% were females. Patients were divided into subgroups of 164 with localized (stage T1-2 tumor, group 1) and 347 with advanced (stage T3-4N01M01, group 2) renal cell carcinoma. Staging of tumors was performed according to the 1997 TNM guidelines. A retrospective review of preoperative computerized tomography (CT) of the abdomen was performed. Radiographic findings were subsequently compared to postoperative histopathological findings to assess the predictive value of tumor characteristics and imaging in determining adrenal metastasis. Of the 511 patients 29 (5.7%) had adrenal involvement. Average size of the adrenal tumor was 3.86 cm. (standard deviation 1.89). Tumor stage correlated with probability of adrenal spread, with T4, T3 and T1-2 tumors accounting for 40%, 7.8% and 0.6% of cases, respectively. Upper pole intrarenal renal cell carcinoma most likely to spread was local extension to the adrenal glands, representing 58.6% of adrenal involvement. In contrast, multifocal, lower pole and mid region renal cell carcinoma tumors metastasized hematogenously, representing 32%, 7% and 4% of adrenal metastasis, respectively. The relationship between intrarenal tumor size (mean 8.9 cm., range 3 to 17) and adrenal involvement (independent of stage) was not statistically significant. Renal vein thrombus involvement was demonstrated in 8 of 12 cases (67%) with left and 2 of 9 (22%) with right adrenal involvement. Preoperative CT demonstrated 99.6% specificity, 99.4% negative predictive value, 89.6% sensitivity and 92.8% positive predictive value for adrenal involvement by renal cell carcinoma. With a low incidence of 0.6%, adrenal involvement is not likely in patients with localized, early stage renal cell carcinoma and adrenalectomy is unnecessary, particularly when CT is negative. In contrast, the 8.1% incidence of adrenal involvement with advanced renal cell carcinoma supports the need for adrenalectomy. Careful review of preoperative imaging is required to determine the need for adrenalectomy in patients at increased risk with high stage lesions, renal vein thrombus and upper pole or multifocal intrarenal tumors. With a negative predictive value of 99.4%, negative CT should decrease the need for adrenalectomy. In contrast, positive findings are less reliable given the relatively lower positive predictive value of this imaging modality. Although such positive findings may raise suspicion of adrenal involvement, they may not necessarily indicate adrenalectomy given the low incidence, unless renal cell carcinoma with risk factors, such as high stage, upper pole location, multifocality and renal vein thrombus, is present.

Micrometastatic adrenal invasion by renal carcinoma in patients undergoing nephrectomy.

To examine adrenal invasion by renal cell carcinoma (RCC), particularly by adrenal micrometastasis, to determine whether adrenalectomy should be performed during radical nephrectomy. From 1987 to 1994, 129 patients with RCC (90 men and 39 women, mean age 61.4 years, range 22-81) underwent radical nephrectomy with associated adrenalectomy because they had risk factors for adrenal invasion (tumour size > 5 cm. or tumour of the superior pole). Pathological examinations were carried out systematically and records of these examinations reviewed. The tumour size was recorded and the frequency of invasion calculated. There were 10 cases where the gland was invaded: one was a synchronous contralateral metastasis and nine (7%) were ipsilateral invasions of which two were tumours in the superior pole that invaded the gland by direct extension and the other seven invaded the gland by distant metastasis, six being micrometastatic (4.7%). A single micrometastasis was found in two cases (1.5%). There was no adrenal invasion by tumours of < 5 cm in diameter from the superior pole. When only tumours > 5 cm in diameter were considered, the ipsilateral invasion rate was 11% (9/80) and the micrometastatic rate was 7.5% (6/80). Adrenalectomy need not be performed routinely in small tumours which are detected early, but the possibility of adrenal micrometastasis from larger tumours (> 5 cm) should be considered.

Angiographic findings in adrenal masses.

The angiographic findings in 34 patients with adrenal lesions were reviewed, including 11 adrenal metastases, 9 adrenal pheochromocytomas, 4 adrenal cortical carcinomas, 4 adrenal cortical adenomas, 3 cases of adrenal hyperplasia and 3 cases of adrenal invasion from carcinoma of the upper pole of the kidney. The results indicate differential diagnostic difficulties in distinguishing among these various entities by angiography.

Adrenal Invasion From Renal Carcinoma with Emphasis on Selective Angiography

異常動脈と寄生動脈が腫瘍の位置と特徴を表わしている. これら動脈の分析から周囲への拡がりを推定できる. 腎腫瘍の副腎への直接浸潤は, 外科的アプローチや予後判定の上で重大な因子となりうる. 症例は57才の日本人女性で, 上記動脈分析の結果, 下副腎動脈, 腎被膜動脈, 腰動脈, 上副腎動脈 (下横隔膜動脈), と肝動脈右葉枝が寄生動脈として同定された. 肝動脈と腎動脈とは生理的吻合を持たないので, 病的吻合である. この吻合は副腎を介して形成されている. すなわち肝と副腎の間に血管性癒着が想定される. これは腫瘍性浸潤あるいは慢性炎症の波及によってできる. また腎被膜動脈と副腎動脈は. その支流範囲内に悪性像を持ち, 悪性血管塊に参加している. 静脈相では副腎も異常濃染を示した. 上腎被膜動脈が右腎上極で上に凸の走行を示すことから, 腫瘍の進展ベクトルが推定される. 手術によって上記所見が確かめられた. 腎腫瘍が副腎に直接浸潤を示した症例を検討する上に, 栄養血管の詳細な分析が重要である.