Carlo Terrone

Changes in Bone Mineral Density, Lean Body Mass and Fat Content as Measured by Dual Energy X-Ray Absorptiometry in Patients With Prostate Cancer Without Apparent Bone Metastases Given Androgen Deprivation Therapy

PURPOSE We characterize the consequences of androgen deprivation therapy on body composition in elderly men. MATERIALS AND METHODS Using a dual energy x-ray absorptiometry instrument, we determined the changes in bone mineral density, bone mineral content, fat body mass and lean body mass in 35 patients with prostate cancer without bone metastases who received luteinizing hormone releasing hormone analogue for 12 months. RESULTS At baseline conditions 46% of cases were classified as osteopenic and 14% as osteoporotic at the lumbar spine and 40% were osteopenic and 4% osteoporotic at the hip. Androgen deprivation significantly decreased bone mineral density either at the lumbar spine (mean gm./cm.2 [SD] 1.00 [0.194], 0.986 [0.172] and 0.977 [0.182] at baseline, and 6 and 12 months, respectively, p <0.002) or the hip (0.929 [0.136], 0.926 [0.144] and 0.923 [0.138], p <0.03). A more than 2% decrease in bone mineral density was found at the lumbar spine in 19 men (54.3%) and at the hip in 15 (42.9%). Bone mineral content paralleled the bone mineral density pattern. Lean body mass decreased (mean gm. [SD] 50,287 [6,656], 49,296 [6,554] and 49,327 [6,345], p <0.003), whereas fat body mass consistently increased (18,115 [6,209], 20,724 [6,029] and 21,604 [5,923] p <0.001). CONCLUSIONS Serial bone densitometry evaluation during androgen deprivation therapy may allow the detection of patients with prostate cancer at risk for osteoporotic fractures, that is those with osteopenia or osteoporosis at baseline and fast bone loss. The change in body composition may predispose patients to accidental falls, thus increasing the risk of bone fracture.

Prognostic Impact of the 2009 UICC/AJCC TNM Staging System for Renal Cell Carcinoma with Venous Extension

BACKGROUND The prognostic significance of venous involvement and tumour thrombus level in renal cell carcinoma (RCC) remains highly controversial. In 2010, the American Joint Committee on Cancer (AJCC) and the Union International Centre le Cancer (UICC) revised the RCC staging system (7th edition) based on tumour thrombus level, differentiating the T stage of tumours limited to renal-vein-only involvement. OBJECTIVE We aimed to evaluate the impact of tumour thrombus extension in a multi-institutional cohort of patients. DESIGN, SETTING, AND PARTICIPANTS An international consortium of 11 institutions was established to retrospectively review a combined cohort of 1215 patients undergoing radical nephrectomy and tumour thrombectomy for RCC, including 585 patients with inferior vena cava (IVC) involvement or higher. MEASUREMENTS Predictive factors of survival, including histology, tumour thrombus level, nodal status, Fuhrman grade, and tumour size, were analysed. RESULTS AND LIMITATIONS A total of 1122 patients with complete data were reviewed. The median follow-up for all patients was 24.7 mo, with a median survival of 33.8 mo. The 5-yr survival was 43.2% (renal vein involvement), 37% (IVC below the diaphragm), and 22% with caval involvement above the diaphragm. On multivariate analysis, tumour size (hazard ratio [HR]: 1.64 [range: 1.03-2.59]; p=0.036), Fuhrman grade (HR: 2.26 [range: 1.65-3.1]; p=0.000), nodal metastasis (HR: 1.32 [range: 1.09-1.67]; p=0.005), and tumour thrombus level (HR: 2.10 [range: 1.53-3.0]; p=0.00) correlated independently with survival. CONCLUSIONS Based on analysis of the largest known cohort of patients with RCC along with IVC and atrial thrombus involvement, tumour thrombus level is an independent predictor of survival. Our findings support the changes to the latest AJCC/UICC staging system.

The number of lymph nodes examined and staging accuracy in renal cell carcinoma.

To determine the number of lymph nodes that need to be examined to accurately stage the pN variable in patients undergoing radical nephrectomy (RN) for renal cell carcinoma (RCC).

Novel mutation in the ATP-binding site of the MET oncogene tyrosine kinase in a HPRCC family.

Germline mutations in the tyrosine‐kinase domain of the MET proto‐oncogene were found in patients suffering from the hereditary predisposition to develop multiple papillary renal‐cell carcinomas (hereditary PRCC, HPRCC). PRCCs are often multiple and bilateral even in patients without a family history. We analyzed the germline of patients carrying multiple or single papillary tumors with and without family history. One patient had a familial cancer and carried a novel (V1110I) germline MET mutation, located in MET gene exon 16. This mis‐sense mutation was found in affected members of this patients family. Interestingly, the V1110I mutation is located in the ATP‐binding site of the MET kinase and is homologous to the V157I mutation that triggers the sarcomagenic potential of the v‐erbB oncogene. The V1110I mutated MET receptor is an active kinase and transforms NIH‐3T3 fibroblasts in the in vitro assays. Patients without familiality did not show germline mutations in the MET kinase domain, showing that multiple and bilateral papillary kidney tumors develop in the absence of these mutations. In conclusion, we describe a new mutation in the MET oncogene kinase domain, associated to HPRCC, affecting an amino‐acid residue critical for kinase activation in different oncogenes. Int. J. Cancer 82:640–643, 1999.

Assessment of surgical margins in renal cell carcinoma after nephron sparing: a comparative study: laparoscopy vs open surgery.

PURPOSE We compared the status of the peritumoral parenchyma after open and laparoscopic nephron sparing surgery for renal cell carcinoma. MATERIALS AND METHODS The records of 64 consecutive patients who underwent nephron sparing surgery for renal cell carcinoma of 4 cm or less were reviewed retrospectively. Patients in group 1 underwent open retroperitoneal surgery (1998 to 2000) and patients in group 2 underwent laparoscopic (transperitoneal or retro peritoneal) surgery (2001 to March 2004). A single pathologist was employed to analyze the specimens, and comparative analysis included examination of tumor size, weight, histological cell type, intraoperative histological biopsies and margin status. RESULTS The 2 groups were comparable in terms of clinical data, and mean lesion size was 31.4 mm in group 1 and 32 mm in group 2. Positive margins were found in 1 of 30 patients in group 1 and in 1 of 34 in group 2 (p = 0.9). An analysis of margins was performed by taking measurements at the minimum and maximum points of the section. The minimum mean measurement was 2 mm in group 1 and 2.08 mm in group 2 (p = 0.75). The maximum mean measurement was 4.56 mm in group 1 and 5.2 mm in group 2 (p = 0.09). The difference between minimum and maximum margin thickness was 2.56 mm in group 1 and 3.16 mm in group 2 (p = 0.04). Mean followup for group 1 was 50 months (range 30 to 72) and 16 months (range 2 to 35) for group 2. One local recurrence was recorded in group 1 and treated with radical nephrectomy, while no recurrence was recorded in group 2. CONCLUSIONS In this study we further confirmed the efficiency of resectioning lesions using laparoscopy. In our experience there is no difference between the 2 procedures in terms of efficient surgical margins. However, despite these encouraging results it is necessary to obtain more extensive followup data, which will allow us to be more specific in reporting on laparoscopic margin quality.

Chromophobe renal cell carcinoma (RCC): oncological outcomes and prognostic factors in a large multicentre series

Study Type – Outcomes (cohort)

Impact of Histologic Subtype on Cancer-specific Survival in Patients with Renal Cell Carcinoma and Tumor Thrombus

BACKGROUND Although different prognostic factors for patients with renal cell carcinoma (RCC) and vena cava tumor thrombus (TT) have been studied, the prognostic value of histologic subtype in these patients remains unclear. OBJECTIVE We analyzed the impact of histologic subtype on cancer-specific survival (CSS). DESIGN, SETTINGS, AND PARTICIPANTS We retrospectively analyzed the records of 1774 patients with RCC and TT who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 US and European centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariable ordered logistic and Cox regression models were used to quantify the impact of tumor histology on CSS. RESULTS AND LIMITATIONS Overall 5-yr CSS was 53.4% (confidence interval [CI], 50.5-56.2) in the entire group. TT level (according to the Mayo classification of macroscopic venous invasion in RCC) was I in 38.5% of patients, II in 30.6%, III in 17.3%, and IV in 13.5%. Histologic subtypes were clear cell renal cell carcinoma (cRCC) in 89.9% of patients, papillary renal cell carcinoma (pRCC) in 8.5%, and chromophobe RCC in 1.6%. In univariable analysis, pRCC was associated with a significantly worse CSS (p<0.001) compared with cRCC. In multivariable analysis, the presence of pRCC was independently associated with CSS (hazard ratio: 1.62; CI, 1.01-2.61; p<0.05). Higher TT level, positive lymph node status, distant metastasis, and fat invasion were also independently associated with CSS. CONCLUSIONS In our multi-institutional series, we found that patients with pRCC and vena cava TT who underwent radical nephrectomy and tumor thrombectomy had significantly worse cancer-specific outcomes when compared with patients with other histologic subtypes of RCC. We confirmed that higher TT level and fat invasion were independently associated with reduced CSS.

Urological laparoendoscopic single site surgery: Multi-institutional analysis of risk factors for conversion and postoperative complications

PURPOSE We analyzed the incidence of and risk factors for complications and conversions in a large contemporary series of patients treated with urological laparoendoscopic single site surgery. MATERIALS AND METHODS The study cohort consisted of consecutive patients treated with laparoendoscopic single site surgery between August 2007 and December 2010 at a total of 21 institutions. A logistic regression model was used to analyze the risks of conversion, and of any grade and only high grade postoperative complications. RESULTS Included in analysis were 1,163 cases. Intraoperatively complications occurred in 3.3% of cases. The overall conversion rate was 19.6% with 14.6%, 4% and 1.1% of procedures converted to reduced port laparoscopy, conventional laparoscopic/robotic surgery and open surgery, respectively. On multivariable analysis the factors significantly associated with the risk of conversion were oncological surgical indication (p=0.02), pelvic surgery (p<0.001), robotic approach (p<0.001), high difficulty score (p=0.004), extended operative time (p=0.03) and an intraoperative complication (p=0.001). A total of 120 postoperative complications occurred in 109 patients (9.4%) with major complications in only 2.4% of the entire cohort. Reconstructive procedure (p=0.03), high difficulty score (p=0.002) and extended operative time (p=0.02) predicted high grade complications. CONCLUSIONS Urological laparoendoscopic single site surgery can be done with a low complication rate, resembling that in laparoscopic series. The conversion rate suggests that early adopters of the technique have adhered to the principles of careful patient selection and safety. Besides facilitating future comparisons across institutions, this analysis can be useful to counsel patients on the current risks of urological laparoendoscopic single site surgery.

Predictive factors for skeletal complications in hormone-refractory prostate cancer patients with metastatic bone disease

Factors predictive of skeletal-related events (SREs) in bone metastatic prostate cancer patients with hormone-refractory disease were investigated. We evaluated the frequency of SREs in 200 hormone-refractory patients consecutively observed at our Institution and followed until death or the last follow-up. Baseline parameters were evaluated in univariate and multivariate analysis as potential predictive factors of SREs. Skeletal-related events were observed in 86 patients (43.0%), 10 of which (5.0%) occurred before the onset of hormone-refractory disease. In univariate analysis, patient performance status (P=0.002), disease extent (DE) in bone (P=0.0001), bone pain (P=0.0001), serum alkaline phosphatase (P=0.0001) and urinary N-telopeptide of type one collagen (P=0.0001) directly correlated with a greater risk to develop SREs, whereas Gleason score at diagnosis, serum PSA, Hb, serum albumin, serum calcium, types of bone lesions and duration of androgen deprivation therapy did not. Both DE in bone (hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.07–1.25, P=0.000) and pain score (HR: 1.13, 95% CI: 1.06–1.20, P=0.000) were independent variables predicting for the onset of SREs in multivariate analysis. In patients with heavy tumour load in bone and great bone pain, the percentage of SREs was almost twice as high as (26 vs 52%, P<0.02) and occurred significantly earlier (P=0.000) than SREs in patients with limited DE in bone and low pain. Bone pain and DE in bone independently predict the occurrence of SREs in bone metastatic prostate cancer patients with hormone-refractory disease. These findings could help physicians in tailoring the skeletal follow-up most appropriate to individual patients and may prove useful for stratifying patients enrolled in bisphosphonate clinical trials.

Is laparoscopic bladder diverticulectomy after transurethral resection of the prostate safe and effective? Comparison with open surgery

PURPOSE In a retrospective nonrandomized study, we compared our experience with transurethral resection of the prostate (TURP) plus sequential laparoscopic bladder diverticulectomy with a series of combined open bladder diverticulectomies with transvesical prostatectomy. PATIENTS AND METHODS We considered 12 consecutive patients (group A) having 16 diverticula who underwent sequential TURP and transperitoneal laparoscopic bladder diverticulectomy and 13 consecutive patients (group B) having 13 diverticula who underwent open bladder diverticulectomy and transvesical prostatectomy. We evaluated the size and position of the diverticulum, adenoma volume, operative time, postoperative hemoglobin variations, analgesia requirement, complications, postoperative hospital stay, and uroflowmetry results. RESULTS No statistically significant differences existed between the groups in adenoma volume or diverticulum size or position. However, a significantly longer operative time was recorded in group A. The endolaparoscopic approach proved to be statistically superior to open surgery regarding blood loss, postoperative analgesia requirement, and hospital stay. No intraoperative complications were recorded. In addition, no statistically significant difference was found in uroflowmetry results. CONCLUSIONS In our experience, the endolaparoscopic approach has proved to be safe, effective, and minimally invasive and therefore superior to transvesical prostatectomy and open bladder diverticulectomy. Its only disadvantage is the longer operative time.