Pathological Complete Response to Pembrolizumab plus Axitinib Combination following Serious Immune-Related Adverse Events in an Advanced Renal Cell Carcinoma Patient with a History of Rheumatoid Arthritis.

Immune checkpoint inhibitors (ICIs)-based combinations have improved survival outcomes of advanced renal cell carcinoma (RCC) patients and are currently recommended as first-line treatment options. Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD) of unknown etiology characterized by a chronic inflammatory process involving joints and extra-articular organs. Patients with AD are usually excluded from large randomized clinical trials investigating immunotherapeutic drugs. Therefore, little is known about clinical outcomes of patients with a history of RA treated with ICIs in real-world practice. In the present study, we report the clinical outcome of an advanced RCC patient with a history of RA treated with pembrolizumab in combination with axitinib. The patient experienced serious immune-related adverse events (irAEs) and achieved pathological complete response following only one ICI administration. Our case report shows that ICI-based combinations can be administered efficaciously in advanced RCC patients with a history of AD. However, a close monitoring of these patients is required, given the risk of irAEs and clinical exacerbations of symptoms associated with the preexisting AD. Moreover, prospective clinical data are needed to assess the hypothesis of a correlation between the onset of irAEs and AD flares and responses and survival outcomes to ICIs.

Renal Function Impairment Below Safety Limits Correlates With Cancer-specific Mortality in Localized Renal Cell Carcinoma: Results From a Single-center Study.

BACKGROUND: A recent multi-center study showed how estimated glomerular filtration rate (eGFR) and cancer-specific mortality (CSM) are linearly and inversely related in organ-confined renal cell carcinoma (RCC) whenever the eGFR decreases below specific thresholds. We addressed our previous work limitations related to heterogeneity and missing data, and explored the relationship between eGFR and CSM also in locally advanced RCC. MATERIALS AND METHODS: All patients with RCC treated with either partial or radical nephrectomy from 1990 to 2018 at a single institution and with complete data on renal function were included. eGFR was managed as a time-dependent variable. The relationship between eGFR and CSM was analyzed using a Fine and Gray multivariable competing risks framework. Subdistribution hazard ratios (SHRs) were calculated accounting for deaths from other causes. RESULTS: Multivariable competing risks analysis showed a "piecewise" relationship between eGFR and CSM, with an inverse linear correlation for eGFR values below 85 mL/min. Below this breakpoint, a significant relationship existed between eGFR and CSM in both clinical (SHR, 1.27; P < .001) and pathologic (SHR, 1.27; P = .001) models in stage I to II RCC subgroup. Conversely, no significance was recorded in this subgroup when considering eGFR values above 85 mL/min. In the stage III to IV subgroup, no significant relationships were recorded, regardless of eGFR values. The retrospective design with inherent biases in data collection represents a limitation. CONCLUSIONS: In patients undergoing surgery for stage I to II RCC, preservation of renal function over "safety limits" is protective from CSM.

Long-term Prognostic Impact of Chromosome Abnormalities in Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIM: Clear cell renal cell carcinoma (ccRCC) shows variable chromosomal abnormalities. The aim of this study was to assess the prognostic role of ccRCC chromosomal abnormalities in a single-center cohort with an extended follow-up. MATERIALS AND METHODS: A systematic cytogenetic analysis was performed in 283 consecutive surgically-treated patients for renal masses between 1997 and 2002. Kaplan-Meier and multivariable Cox regression (MCR) models were used to calculate cancer specific survival (CSS). RESULTS: Among 174 ccRCC patients, the most common abnormality was deletion in chromosome 3 (54.6%). At a median follow-up of 119 months, 38 patients (21.8%) died from RCC. At MCR models, worse CSS was independently predicted by deletions in chromosomes 2, 19, 20 or 22 and insertions in chromosome 18. CONCLUSION: Specific ccRCC chromosomal abnormalities are independently associated with worse CSS. Cytogenetic evaluation may direct further genetic analysis for personalized prognostic stratification.

Positive Surgical Margins Predict Progression-free Survival After Nephron-sparing Surgery for Renal Cell Carcinoma: Results From a Single Center Cohort of 459 Cases With a Minimum Follow-up of 5 Years.

BACKGROUND: The role of positive surgical margins (PSMs) on the recurrence of renal cell carcinoma (RCC) after partial nephrectomy (PN) is debated, and available evidence lacks long-term data. The aim of this study was to evaluate the predictive role of PSMs on progression-free survival (PFS) in a large cohort followed for at least 5 years. METHODS: This study was a retrospective analysis of a prospectively compiled single-institution database collecting complete information on more than 2700 patients who had undergone surgery for renal tumor. The data of all the patients submitted to PN for RCC and with least 5 years follow-up were extracted. Surgical specimens were examined at the time of surgery only by 2 expert uro-pathologists. A PSM was defined as the presence of cancer cells at the inked surface of the specimen. The role of PSMs on survival was estimated by Cox regression models adjusted for influent covariates. RESULTS: A total of 459 patients fulfilled the inclusion criteria and were evaluated. PSMs were observed in 27 (5.9%) cases. No differences in preoperative and pathologic data were found comparing patients with and without PSMs. At a median follow-up of 96 months (interquartile range, 74-131 months), a clinically evident relapse of RCC was diagnosed in 36 (7.8%) patients at a median interval of 36 months from PN. Among these, 6 had a PSM for an incidence of relapse of 22.2% in the PSM group, whereas 30 had negative margins, for an incidence of 6.9% (P = .013). The sites of relapse were distant organs in 18 cases, and the kidney underwent PN in 21. The patients with PSMs showed a borderline significantly higher incidence of distant metastasis (11.1% vs. 3.5%; P = .071) and a significantly higher incidence of renal relapses (14.8% vs. 3.9%; P = .029). Multivariable Cox models confirmed that the presence of PSMs was an independent predictor of PFS (odds ratio, 3.127; P = .013). CONCLUSIONS: PSMs are an independent predictor of PFS in patients who underwent PN for RCC, owing to a higher incidence of distant and local relapses. Surveillance in presence of PSMs should be intensified and extended for a long time.

Features of Ipsilateral Renal Recurrences After Partial Nephrectomy: A Proposal of a Pathogenetic Classification.

BACKGROUND: Poor data are reported on the pathogenesis of ipsilateral relapse (IR) after partial nephrectomy (PN). The objective of this study was to investigate features of IR after PN with the intention to propose a pathogenetic classification. MATERIALS AND METHODS: Retrospective consultation of an institutional database that stores the data of 683 patients submitted to PN since 1993. The clinical, radiological, and follow-up data of the cases submitted to salvage nephrectomy due to an IR were analyzed. The slides of the sections from the tumor-parenchyma interface of PN and the bed of resection from the specimen of nephrectomy were reviewed. RESULTS: Eighteen patients were submitted to salvage nephrectomy for an IR. In 12 cases the IR harbored into the site of PN and a mixture of cancer cells and granulomatous reaction was found at the resection bed (IR type A). In the remaining 6, in microscopy of the resection bed was found only fibrosis: 3 of these cases had a clear-cell renal cell carcinoma (RCC) with diffuse microvascular embolization and the relapse in the same portion of the kidney of the primary tumor (IR type B); the other 3 had a non-clear-cell RCC and the primary and relapsing tumors were located in distinct portions of the kidney (IR type C). Six patients (4 IR type A, 2 type B) had a further progression and 5 of them died due to RCC. CONCLUSION: More frequently an IR is due to the incomplete resection of the primary tumor (IR type A), in a minority of the cases to the local spread of the tumor by microvascular embolization (IR type B), or true multifocality (IR type C). The prognosis of IR not due to multifocality (type A and B) is poor, despite salvage nephrectomy.

Features, risk factors and clinical outcome of "very late" recurrences after surgery for localized renal carcinoma: A retrospective evaluation of a cohort with a minimum of 10 years of follow up.

OBJECTIVE: To evaluate the features and the predictors of "very late" recurrences after surgery for localized renal cell carcinoma. METHODS: Since 1983, an institutional database with data of more than 2300 consecutive patients treated for renal cancer has been prospectively maintained. Patients N0 /Nx M0 followed for a minimum of 10 years without recurrences were retrieved. The site, time and treatment of recurrences observed afterwards were recorded, and the predictors were investigated by Cox regression analysis. RESULTS: A total of 554 patients (231 women, 323 men; age 59.3 ± 11.6 years) followed for a mean/median time of 15.1/13.6 years (range 10.0-34.1 years) were analyzed. A recurrence was observed in 26 patients (4.6%) after a mean/median interval of 13.3/12.3 years (range 10.5-30.2 years). The pathological stage 2/3 was the only independent predictor of recurrence (P = 0.003), and it was related also to the latency of recurrence (mean/median latency 15.4/14.0, 11.4/10.8 and 12.5/12.0 years, respectively, for stage 1, 2 and 3; P < 0.005 for stage 1 vs stage 2 or 3). The contralateral kidney was the most frequent site of relapse in patients with stage pT1, whereas multiple sites were more frequent for stage pT2 and pT3. CONCLUSIONS: The risk of a "very late" recurrence of renal cancer is approximately 5%, and it depends on the pathological stage. For stage pT1, the kidney/s should be surveilled for indefinite time, preferably by ultrasound to reduce the X-ray exposition; for stage pT2 and pT3, the abdomen and the lungs should be monitored, by computed tomography scan during the first years, and then by abdominal ultrasound and chest X-ray.

Venous tumor thrombus consistency is not predictive of survival in patients with renal cell carcinoma: A retrospective study of 147 patients.

OBJECTIVES: To evaluate the prognostic role of venous tumor thrombus consistency in patients with renal cell carcinoma. METHODS: A retrospective evaluation of the data of patients with renal cell carcinoma and a tumor thrombosis submitted to surgery from 2000 to 2013 was carried out. Histological slides were revised by two uropathologists, blinded of the clinical outcome, to assess venous tumor thrombus consistency classified as solid venous tumor thrombus consistency or friable venous tumor thrombus consistency. The statistical correlation between venous tumor thrombus consistency and other adverse features was assessed. Then the predictive ability of an integrated prognostic model, generated by Cox regression and random survival forest, was evaluated, with and without the inclusion of venous tumor thrombus consistency, by integrated Brier score, dynamic receiver operating characteristic curves, integrated discrimination improvement index and category-less net reclassification index. RESULTS: The data of 147 patients were analyzed, 79 with a solid venous tumor thrombus consistency and 68 with a friable venous tumor thrombus consistency, followed for a median period of 40.5 months. Venous tumor thrombus consistency was assessed with a high interobserver agreement (145/147 cases). The presence of a friable venous tumor thrombus consistency was associated with some adverse prognostic factors (symptoms, lymphnodal and distant metastasis, larger tumor diameter, higher cephalad thrombosis level, necrosis, microvascular invasion) and to a worse cancer-specific and overall survival at univariate analysis. However, venous tumor thrombus consistency was not predictive of survival, and did not improve the performance of a multivariable model that included a set of informative predictors. CONCLUSION: Venous tumor thrombus consistency does not seem to have an independent prognostic role in patients with renal cell carcinoma.

Renal mass with caval thrombus as atypical presentation of xantogranulomatous pyelonephritis. A case report and literature review.

INTRODUCTION: Xantogranulomatous pyelonephritis is a rare, severe, chronic renal infection typically resulting in diffuse renal destruction. Enlarged kidney is typical radiological finding. In this work we describe an extremely rare case in which a clinically classified cT3b Tumor (level II IVC thrombus) was detected; at specimen analysis to be xantogranulomatous pyelonephritis with IVC extension. MATERIAL AND METHOD: U.V., female, 86 years old, we diagnosed with right renal mass, with extension to IVC. By pathological analysis, it was found that renal mass and the thrombus was not due to RCC, but by xantogranulomatous pyelonephritis. DISCUSSION: Xantogranulomatous pyelonephritis with IVC thrombus is exceptional and has been described in 4 cases. Such a diagnosis could have anesthesiologic importance, in particular related to antimicrobial treatment. Xantogranulomatous pyelonephritis has its own classification, based on extension and organ involvement, but this case fall out of current classification. CONCLUSION: This possibility could be suspected and updating of disease's classification could be suggested.

Pre-existing type-2 diabetes is not an adverse prognostic factor in patients with renal cell carcinoma: a single-center retrospective study.

OBJECTIVES: Type-2 diabetes mellitus (DM) is a metabolic disease affecting several million people all over the world. The correlation between DM and malignancies is well established due to the findings of several large population-based studies. However, for endometrial, breast, colorectal, and liver cancers it has also been reported that DM could exert a negative impact on prognosis, causing a significant reduction in cancer-specific survival. A significant correlation with DM has also been demonstrated in renal cell carcinoma (RCC), but the possible prognostic role of DM in this setting has been poorly investigated and remains controversial. This study provides a retrospective analysis of a single-center surgical series with the aim of assessing the features and prognosis of RCC in DM patients. MATERIALS AND METHODS: Since 1987 a prospectively compiled database at our institute has collected the data of 1,761 patients who underwent surgery for RCC. All the patients are followed in a specially dedicated out-patient ambulatory. For this study, patients who were taking insulin or oral anti-hyperglycemic drugs before surgery for RCC were considered as DM cases. Their clinical and pathologic features were compared with those of patients without DM. Then, limiting the analysis to non-metastatic patients, the Kaplan-Meier method was used to calculate survival functions and univariable and multivariable Cox regression models addressed time to RCC-related and non RCC-related mortality. RESULTS: The data of 1,604 patients without DM and 157 with DM (prevalence 8.9%) have been analyzed; the latter were more frequently males, older, and with higher co-morbidity and with more asymptomatic, smaller, and low stage neoplasms, though with a higher grading. After a median follow-up time of 53.4 months (IQR 20-97 months), the factors that influenced RCC-related mortality were the presence of symptoms at diagnosis, tumor size, TMN staging, and grading, while those that influenced non-RCC-related mortality were age, gender, and co-morbidities, whereas the presence of DM showed no influence at all. Moreover, in patients without and with DM, progression rate (19.8% vs. 15.1%, P = 0.195) and RCC-related mortality rate (9.6% vs. 5.3%, P = 0.102) were also statistically equivalent. CONCLUSION: In our experience, the prevalence of DM in RCC patients is close to 10%. Such a condition does not determine any significant influence on prognosis of RCC.

Surgical treatment of atypical metastasis from renal cell carcinoma (RCC).

UNLABELLED: What's known on the subject? and What does the study add? The interest in metastatic renal cell carcinoma has increased in the last few years, mainly due to the advent of targeted therapies, but metastasectomy remains the sole therapy that can lead to a complete and durable regression, even if only in a minority of patients. The literature reports quite large series of metastasectomies for the most common sites of metastasis, e.g. lung, liver, bone, adrenal and brain, whereas little is known about the management of metastasis in 'atypical' sites. The prognosis of patients submitted to metastasectomy for a metastasis in an atypical site is equivalent to patients with lung metastasis. The characteristics of the primary tumour in these patients are not indicative, but atypical metastasis (AM) are often located in superficial sites and frequently associated with other metastases. So, physical examination should be included in all follow-up regimens and a complete re-staging should be performed after the diagnosis of an AM. OBJECTIVE: • To review the clinical characteristics and oncological results in patients submitted to surgical removal of metastasis from renal cell carcinoma (RCC) in atypical sites (atypical metastasis [AM], i.e. metastasis in sites other than the chest, liver, bone, adrenal, brain, kidney, and lymph nodes), compared with patients submitted to metastasectomy due to a lung metastasis (LM). PATIENTS AND METHODS: • From an institutional database of ≈1800 patients surgically treated for a RCC, we retrospectively identified 37 cases that had undergone metastasectomy for AM and 57 operated for LM. • Clinicopathological features of the primary RCC and metastasis, and cancer-specific survival (CSS) computed from the time of metastasectomy of patients with AM and LM, were compared. • A univariate and multivariable analysis applying a Cox regression model was used to evaluate CSS. RESULTS: • The patients with AM and LM were followed for an average of 40.8 and 50.7 months from metastasectomy, respectively (P= 0.372). • There were no significant differences in the characteristics of the primary tumour between patients with AM and LM. • In the cases with AM and LM the diagnosis was simultaneous with that of the primary tumour in 32.4% and 24.6%, (P= 0.40) respectively, and, when metachronous, occurred at an average delay of 53.4 and 44.3 months (P= 0.370). • More frequently in the cases with AM other metastases had been diagnosed in the previous medical history (35.2 vs 8.8%, P= 0.001) or simultaneously (48.6 vs 8.8%, P= 0.001). • CSS from metastasectomy was affected by the synchronicity in diagnosis between metastasis and primary tumour, and by the simultaneous presence of other metastases, while the type of metastasis (AM vs LM) did not affect CSS. In fact, metastasectomy in AM was as effective as in LM. CONCLUSION: • AM are an exceptional presentation of metastatic RCC, but the role of surgery is similar to that of pulmonary metastasis. In these cases, metastasectomy is accepted as possible care, and in AM the CSS after metastasectomy is similar.

Clinical features and prognosis of patients with renal cancer and a second malignancy.

OBJECTIVE: To evaluate the epidemiologic aspects, the clinical features, and the prognosis of patients with renal cancer affected by a second malignancy. MATERIALS AND METHODS: Since 1983, at our institution, a database concerning all the patients who underwent surgery for renal neoplasia has been prospectively compiled. In the present study, we compared patients with renal cancer and a second primary malignancy, diagnosed before, at the same time, or after the renal cancer, to those affected only by a renal malignancy. RESULTS: Out of 1,673 patients with renal cancer, 285 (17%) were diagnosed with a second malignancy. The follow-up lasted on average 71 months after the treatment of renal neoplasia. The second neoplasia was antecedent in 115 patients (average latency period 8.5 years), synchronous in 97 patients, and subsequent in 103 patients (average latency period 4.4 years). The sites of associated neoplasia were, in descending order of frequency, prostate, bladder, and bowel for men and breast, gynecologic organs, thyroid, and bladder for women. Compared with the patients not affected by a second neoplasm, those with multiple malignancies generally were older and had a smaller, low-grade, low-stage, and asymptomatic renal tumor. Comparing patients with associated neoplasia with a group without associated neoplasia matched for gender, mode of diagnosis, dimension, grade, stage, and histologic subtype of renal cancer, at survival analysis, no significant differences were noticed in renal cancer-related survival. However, among patients with multiple malignancies, the contemporaneous diagnosis of renal and associated cancer had an independent negative impact on survival. CONCLUSIONS: The association between renal cancer and other malignancies is a frequent event with an unremarkable impact on prognosis, and it shall not limit surgical indication to treat renal cancer, even if the negative prognostic impact of synchronous occurrence of multiple neoplasias should be regarded, especially in older or unhealthy patients, since ablative therapies or active surveillance could be considered as viable alternative options.

[T&G: an elementary integrated prognostic system for renal carcinoma N0 M0]. / T&G: un sistema prognostico integrato elementare per il carcinoma renale N0 M0.

INTRODUCTION: 25-30% of patients with renal cell carcinoma (RCC) develop metastatic progression during follow up. For this reason many prognostic systems have been developed to try to predict the possibility of recurrence. Unfortunately these systems are often complex in daily use. PATIENT AND METHODS: 1089 were selected from a total of 1985 patients undergoing surgery for renal cell cancer. We have excluded patients with a benign diagnosis, lymph node or distant metastases at diagnosis, with no radical surgery (R1) and those with follow up judged insufficient (<24 months). For each patient a score was defined after evaluating the histological examination of surgical specimens. This score was called T&G and it was equal to the sum of the T pathological (1 for T1, 2 for T2, 3 for T3a, b, c, 4 for T4) and the G according to Fuhrman (1 for G1, 2 for G2, etc.). The range is between 2 and 8. It was then evaluated the disease-free survival according to T & G score to stratify patients into risk classes. RESULTS: During follow-up we had recurrent disease in 246 cases (22.6%; 167 metastases in a single location, 34 local recurrences, 45 metastases) after surgery at a mean distance of 35.6 months (2-205). After comparing each one of the disease free survival curves, we have identified three classes of risk: low risk (T & G 2 and 3), intermediate risk (T & G 4-5), high risk (T & G 6-7-8). We have obtained statistically significant differences between the three classes of risk. The rate of progression was 8.9% for the class of low risk to 48% of the high risk class. The average time (in months) of disease progression decrease from 47 for LR class to 37 for IR up to 29 for a HR Class. DISCUSSION: The T & G score is an extremely basic prognostic system but at the same time it allows an accurate prognostic discrimination in patients with N0 M0 RCC, as demonstrated by the significant differences in the rates and time of progression and disease-free survival.

[Results of targeted therapies for m1 renal cell carcinoma: our experience]. / Risultati della target therapy nel carcinoma renale a cellule chiare m1: la nostra esperienza.

INTRODUCTION: Since a few years ago no effective medical therapies were available to cure metastatic renal cell carcinoma (RCC). Nowadays, encouraging preliminary results support some new therapeutic agents, collectively named as targeted therapies (TT). This paper reviews our experience with the use of TT in the setting of RCC with metastasis at the diagnosis. MATERIAL AND METHODS: Retrospective evaluation of the data of 24 patients (7 females, 17 males, median age: 59aa) affected by clear cell RCC with distant metastatis at diagnosis, treated with TT from 2005 to 2012.20 of the 24 patients (83,3%) underwent preliminary cytoreductive nephrectomy, whereas for the others a percutaneous biopsy of the renal tumor was obtained. 5 (20.8%) patients received an immunotherapy with IL-2 or IFN and then a TT due to a progression. Schedules were applied following heterogeneous regimens along the period of data collection (randomized clinical trial, expanded access, standard indication). Response has been evaluated by RECIST criteria. RESULTS: As first-line therapy of TT 18 patients received Sunitinib, 4 Sorafenib, 2 Temsirolimus; 11 received a second-line (8 Sorafenib, 2 Sunitinib, 1 Everolimus); 6 received also a third-line (5 Everolimus, 1 Tensirolimus). At last available control, after a mean follow up time of 13,7 months (1-29) a progressive disease was present in 12 cases (50%), a stable disease in 6 (25%), a reduction of the disease in 4 (16.5%); 7 patients (29.5%) died; overall mean survival of the entire group was 14,7 months. Even if the study suffers from the limitations related to the small number of cases and the retrospective design, seems that no factors played a role in determining the response to theraphy. CONCLUSIONS: The results of TT in clinical practice resemble the ones from randomised clinical trials. It's extremely hard to predict the response to treatment.

[Did the staging of renal neoplasm improve with time? Retrospective study on a cohort of 2000 patients]. / La stadiazione della neoplasia renale è migliorata nel tempo? Studio retrospettivo su una coorte contemporanea di 2000 pazienti.

OBJECTIVES: During the last 3 decades ultrasonographic and cross-sectional imaging techniques have been widely adopted in the pre-operative staging of renal masses with a progressive technological refinement. The aim of this study is to evaluate if, according to such a change, the accuracy of pre-operative staging is getting better. MATERIALS AND METHODS: A retrospective analysis of 1935 patients, surgically treated at our Institute since 1983 for a renal neoplasm, has been carried out. Dividing the experience in 2 periods, before and after the year 2000, the diagnostic tools adopted during pre-operative staging and their accuracy have been evaluated by a comparison with the post-operative data (accuracy=true positive+true negative/total number of cases), also taking into account each single aspect of staging (dimension of tumor, local extension, venous invasion, lymphnodal and distant metastasis). RESULTS AND DISCUSSION: 994 patients have been treated before 2000, and 941 afterwards. During time, a progressive reduction in the use of urography and, on the other hand, a diffusion of chest CT have been observed, whereas NMR maintained a similar and limited field of application in both periods. During time, the overall accuracy of staging has not significantly improved (69.5% vs 72.3%, p=0.18), but a slightly better staging of distant (93.9% vs 96.7%, p=0.01) and lymphnodal metastasis (90.9% vs 94.8%, p=0.01) can be found. CONCLUSIONS: The pre-operative staging of renal cancer has not really improved during the last 3 decades, in spite of the availability of more precise radiological tools. Anyway, due to the diffusion of CT scan, a slightly better definition of lymphnodal and distant metastasis can be observed. This fact could play a role in indicating a targeted therapy for advanced disease, especially in the light of a neo-adjuvant setting.

Prognostic value of cytogenetic analysis in clear cell renal carcinoma: a study on 131 patients with long-term follow-up.

BACKGROUND AND AIMS: Cytogenetic analysis has a role in diagnosis of conventional renal cell carcinoma, but its role in prognosis is still matter of debate. This study reviews the Authors' experience in cytogenetic analysis of clear cell renal carcinoma. PATIENTS AND METHODS: Data from 131 patients with clear cell renal carcinoma who underwent cytogenetic analysis of the tumour karyotype at the host institute between 1997 and 2002 were prospectively collected. In all cases, the cytogenetic analysis was carried out by a single experienced geneticist and the morphological features of the neoplasia were evaluated by a single experienced uropathologist. RESULTS: Patients were followed up for an average period of 67.3 months, median of 73 months, range 12-136 months. The statistical association among chromosome alterations, clinico-pathological features and disease-free survival were investigated. At univariate analysis, symptoms at diagnosis, tumour diameter, Fuhrman's grading, TNM stage and sarcomatoid differentiation were all significantly correlated with survival, whereas among chromosomal abnormalities, deletion of chromosomes 19, 20 and 22 showed a significant impact on survival. At multivariate analysis of these factors, TNM stage and deletion of chromosome 19 maintained an independent and statistically significant association with disease-free survival. CONCLUSION: Although these results may be considered as preliminary, it is possible to conclude that the alterations of the tumour karyotype may contribute to determining prognosis of patients with clear cell renal carcinoma.

Cytogenetic features, clinical significance and prognostic impact of type 1 and type 2 papillary renal cell carcinoma.

The purpose of this paper is to evaluate the clinical, pathologic, and cytogenetic features, as well as the disease-free survival in patients with papillary renal cell carcinoma (PRCC) subdivided into types 1 and 2, according to the definition given by Delahunt and Eble. The clinical, surgical, and follow-up data for the PRCC cases treated since 1995 were taken from an institutional database. The samples were revised by an experienced pathologist, who subdivided them into types 1 and 2. The data from the cases in which the tumor karyotype was available were analyzed. Out of 1,150 patients surgically treated for renal cancer, 132 cases of PRCC were detected (prevalence 11.5%), 57 with type 1 and 75 with type 2, followed for a mean period of 50 months. Tumor diameter, peri-renal tissues, as well as venous invasion, lymphnodal, and distant metastasis were highlighted to be distributed with a significant difference between the two groups, which indicated higher aggressiveness in type 2 cases. Survival analysis has showed a significantly higher-progression risk and a shorter disease-free survival in type 2 cases. An evaluable tumoral karyotype was obtained in 26 cases. An overlapping distribution was detected in chromosomes 7, 17, 12, 16, and 20, while some alterations in chromosomes 10, 5, 6, 11, 15, 18, 22, and 8 appeared as typical of type 2 cases. In conclusion, types 1 and 2 PRCC have different pathologic and cytogenetic features and a radically different biologic behavior - indolent in type 1 and aggressive in type 2.

Second surgery for renal relapse after nephron sparing surgery: review of seven cases.

OBJECTIVE: Anatomo-pathologic review of the cases which underwent a second surgery operation for a renal neoplasm relapsed after conservative surgery, in order to find possible relations with the surgical technique. PATIENTS AND METHODS: At our institution nephron sparing surgery (NSS) is currently indicated for neoplasms smaller than 4 centimetres in diameter. The technique involves the removal of the neoplasm with a margin of healthy parenchyma and with the perilesional fat. Patients are firstly monitored by a CT check after 4 months and then with ultrasound/CT checks every 6 months in the first 2 years and then once a year In this study we analyze in the 1994-2005 period the records of cases undergoing a second operation for a renal tumour relapsed in the operated kidney after NSS. All specimens were reviewed by an individual experienced uro-pathologist who determined the size of surgical margins and relations between the site of the recidivism and the site of the preceding NSS procedure. RESULTS: Seven cases with renal relapse have been found out of 267 undergoing conservative surgery in the same period (incidence 2.6%). The diagnosis has always been made in the lack of other localizations of disease at a complete re-staging and the average latency of the relapse was 19.4 months (8-46 months). In 5 cases the second tumour has been found in the site of the previous NSS: for these cases the minimum margin of the enucleo-resection was lower then 3 millimetres (median minimum margin 1.6 mm). Differently, in the remaining 2 cases, both with a wider surgical margin (median minimum margin 12.0 mm), the site of thefirst and that of the second neoplasm were distant. In particular, in one case a multifocal recidivism with a spread microvascular embolisation has been found, while in the other the primary neoplasms and the relapse presented a different histotype. CONCLUSIONS: In the 5 cases with a narrow resection margin and relapsing tumour in the site of the enucleo-resection one can hypothise the persistence of a peritumoral microscopic neoplastic disease. In the other 2 cases with a wider surgical margin the relapse can be attributed to the widespread microscopic multifocality in one case and to the development of a second de novo neoplasm in the other one. The extension of the surgical margin seems then to have played a role in determining a relapse in the site of enucleo-resection.

Nephron-sparing surgery versus radical nephrectomy in the treatment of intracapsular renal cell carcinoma up to 7cm.

OBJECTIVE: To compare the oncologic outcomes of nephron-sparing surgery versus radical nephrectomy in intracapsular renal cell carcinoma (RCC) up to 7 cm by reviewing surgical experience retrospectively. METHODS: Data from 1290 consecutive patients who had surgery for RCC have been stored in a dedicated database since 1983. We selected and reviewed those related to disease-free patients who had been treated for unilateral pT1a/pT1b pN0/Nx M0 carcinomas up to 7 cm and later followed for a minimum of 12 mo. RESULTS: A total of 642 patients with mean follow-up of 72.9 mo were selected; 313 had been treated for tumours <4 cm in diameter (176 nephron-sparing surgery, 137 nephrectomy), whereas 329 had been treated for tumours measuring > or =4 cm (52 nephron-sparing surgery, 277 nephrectomy). The comparison between tumours <4 cm or > or =4 cm in diameter showed worse progression and disease-free survival rates for the latter, but the type of surgery (nephron-sparing or radical) seemed to have no significant impact. CONCLUSIONS: Conservative management can be cautiously suggested for RCC up to 7 cm because the worsening of prognosis as diameter increases shows no statistical differences for either nephron-sparing or radical surgery. The agreement of our results with those of similar studies available in the literature may suggest designing a prospective study to compare conservative and more radical surgery in the management of RCC up to 7 cm.

The follow-up management of non-metastatic renal cell carcinoma: definition of a surveillance protocol.

OBJECTIVE: To define a follow-up protocol based on the University of California Los Angeles Integrated Staging System (UISS) for patients undergoing surgery for N0M0 renal cell carcinoma (RCC). PATIENTS AND METHODS: The clinical records of patients treated with radical surgery for N0/NXM0 RCC and monitored through periodic follow-up studies (> or =24 months in disease-free patients) were reviewed retrospectively from 1399 patients surgically treated for renal neoplasms between 1983 and 2005. Each case was assigned a UISS risk category; recurrence features, time and site were recorded. In particular, recurrence sites were categorized into local, renal (ipsilateral or contralateral) and distant (single-site or disseminated). RESULTS: The records were reviewed of 814 patients with a mean follow-up of 75.6 months. UISS risk categories were distributed as follows: high-risk (HR) 17.2%, intermediate-risk (IR) 51.6% and low-risk (LR) 31.2%. Disease-free survival rates at 5 years were 63.9%, 88.3% and 96.5% (log-rank test P < 0.001), respectively. The disease recurred in 193 patients (23.7%), at distant sites (73.0% of recurrences), locally (11.9%), in the contralateral kidney (10.9%) and in the ipsilateral kidney (4.1%). There was a significant correlation between UISS category and risk of distant or local (both P < 0.001) recurrences, whereas there was no correlation of recurrences in the operated kidney (P = 0.372) or contralateral kidney (P = 0.898). CONCLUSIONS: The prognostic accuracy and applicability of the UISS for distant and local recurrences is confirmed, whereas renal relapses have an independent course. A follow-up scheme tailored to the recurrence patterns observed in each UISS risk group is recommended.

Surgical treatment of adrenal metastasis from renal cell carcinoma: a single-centre experience of 45 patients.

OBJECTIVE: To report, in a retrospective study, the diagnostic problems and oncological results of surgery in patients with either synchronous or metachronous adrenal metastasis, which are uncommon in renal cancer, at 2-10% of patients. PATIENTS AND METHODS: Of 1179 patients treated for renal cancer between 1987 and 2003, 914 had renal surgery with concomitant ipsilateral adrenalectomy (routinely in 875 and for abnormal findings on computed tomography, CT, in 39) and 15 contralateral adrenalectomy (all after suspicious findings on CT). During the follow-up after renal surgery, another 14 patients had adrenalectomy for CT evidence of an abnormal adrenal gland, contralateral to the previous renal tumour in 12 and bilaterally in two. RESULTS: Of 914 ipsilateral adrenal glands removed during renal surgery, 854 (93.5%) were normal on pathological examination, 28 (3%) had a benign pathology, six (0.8%) were directly infiltrated by the tumour and 26 (2.7%) were metastatic. For both benign and metastatic ipsilateral adrenal pathology, CT had sensitivity, specificity and positive/negative predictive values of 47%, 99%, 73% and 96%, respectively. Of 29 contralateral glands removed because of suspicious CT findings (15 at diagnosis of renal cancer, 14 during the follow-up) there was no abnormality in one (3.4%), a benign pathology in seven (24%) and a metastasis in 21 (72%). Thus there were 32 synchronous (incidence 2.7%; ipsilateral to the renal tumour in 24, contralateral in six and bilateral in two), and 13 metachronous adrenal metastases (incidence 1.0%; contralateral in 11 and bilateral in two). The metachronous metastases were diagnosed at a mean (range) interval of 30.6 (8-73) months after renal surgery. No ipsilateral adrenal metastases were discovered at diagnosis or during the follow-up in the 382 patients with an organ-confined renal tumour of <4 cm in diameter. Twenty-seven patients with an isolated adrenal metastasis (synchronous in 14, metachronous in 13) had statistically significantly (P < 0.001) better survival than the 18 (all synchronous) with multiple sites of metastatic disease. In particular, there was long-term survival (mean 83 months) in 10 patients with an isolated adrenal metastasis. CONCLUSION: Sparing the ipsilateral adrenal is advisable only for organ-confined renal tumours of <4 cm in diameter; clinical local staging of renal cancer is the best predictor of the risk of adrenal metastasis. Conversely, CT had good diagnostic ability for the contralateral adrenal gland, especially during the follow-up. Some patients with isolated adrenal metastasis could be treated by metastasectomy, with long-term survival free of disease and confirming that, even if in a few and unselectable patients, removing all the neoplastic bulk can be curative. Nevertheless, the high rate of relapse underlines the need for an effective systemic therapy, and more so for widespread metastatic disease that currently cannot be cured.