Hyung L. Kim

Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease

Surveillance after surgery for RCC is important because approximately 50% of these patients will develop a disease recurrence, two thirds of who will recur within the first year. Although the prognosis is generally poor in these patients, some may respond favorably to immunotherapy. The small subset of patients who develop solitary metastases has the greatest chance to achieve long-term survival. Aggressive surgical resection is an integral part of this success. Proposed surveillance protocols using a stage-based approach or an integrated approach combining stage with other important prognostic factors attempt to provide a rational approach to identifying treatable recurrences while minimizing unnecessary examinations and patient anxiety. However, strict adherence to follow-up guidelines may not be appropriate for all patients. Factors including patient comorbidities and patient willingness to pursue aggressive management in the event of recurrence may alter the follow-up for each individual.

Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study.

PURPOSEnTo evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an international multicenter study.nnnPATIENTS AND METHODSn4,202 patients from eight international academic centers were classified according to the UISS, which combines TNM stage, Fuhrman grade, and Eastern Cooperative Oncology Group performance status. Distribution of the UISS categories was assessed in the overall population and in each center.nnnRESULTSnThe UISS stratified both localized and metastatic RCC into three different risk groups (P <.001). For localized RCC, the 5-year survival rates were 92%, 67%, and 44% for low-, intermediate-, and high-risk groups, respectively. A trend toward a higher risk of death was observed in all centers for increasing UISS risk category. For metastatic RCC, the 3-year survival rates were 37%, 23%, and 12% for low-, intermediate-, and high-risk groups, respectively; in 6 of 8 centers, a trend toward a higher risk of death was observed for increasing UISS risk category. A greater variability in survival rates among centers was observed for high-risk patients.nnnCONCLUSIONnThis study defines the general applicability of the UISS for predicting survival in patients with RCC. The UISS is an accurate predictor of survival for patients with localized RCC applicable to external databases. Although the UISS may be useful for patients with metastatic RCC, it may be less accurate in this subset of patients due to the heterogeneity of patients and treatments.

A Molecular Classification of Papillary Renal Cell Carcinoma

Despite the moderate incidence of papillary renal cell carcinoma (PRCC), there is a disproportionately limited understanding of its underlying genetic programs. There is no effective therapy for metastatic PRCC, and patients are often excluded from kidney cancer trials. A morphologic classification of PRCC into type 1 and 2 tumors has been recently proposed, but its biological relevance remains uncertain. We studied the gene expression profiles of 34 cases of PRCC using Affymetrix HGU133 Plus 2.0 arrays (54,675 probe sets) using both unsupervised and supervised analyses. Comparative genomic microarray analysis was used to infer cytogenetic aberrations, and pathways were ranked with a curated database. Expression of selected genes was validated by immunohistochemistry in 34 samples with 15 independent tumors. We identified two highly distinct molecular PRCC subclasses with morphologic correlation. The first class, with excellent survival, corresponded to three histologic subtypes: type 1, low-grade type 2, and mixed type 1/low-grade type 2 tumors. The second class, with poor survival, corresponded to high-grade type 2 tumors (n = 11). Dysregulation of G1-S and G2-M checkpoint genes were found in class 1 and 2 tumors, respectively, alongside characteristic chromosomal aberrations. We identified a seven-transcript predictor that classified samples on cross-validation with 97% accuracy. Immunohistochemistry confirmed high expression of cytokeratin 7 in class 1 tumors and of topoisomerase IIalpha in class 2 tumors. We report two molecular subclasses of PRCC, which are biologically and clinically distinct and may be readily distinguished in a clinical setting.

Cystic renal cell carcinoma: biology and clinical behavior.

The purpose of the study was to evaluate unilocular and multilocular cystic renal cell carcinoma (cRCC). These tumors are a rare entity, comprising approximately 1 to 2% of all renal tumors, and their true biologic behavior is not well-known. Initial review of renal cell carcinoma (RCC) cases treated at our institution between 1989 and 2001 identified 39 cases of cRCC. However, histopathologic review of these cases by 2 pathologists revealed that only 18 cases met the criteria that all tumors have a cystic component that constitutes at least 75% of the total lesion without evidence of necrosis. These cases were compared to 614 conventional clear cell RCC cases with regards to clinical outcomes. All 18 patients presented with localized (N0M0) disease. Thirteen (72%) of the tumors were Fuhrman Grade 1, while the remaining 5 (28%) were Fuhrman Grade 2. By comparison, only 60% of the clear cell RCC tumors were Grade 1 or 2. Similarly, 83% of cRCC were pT1 tumors compared to only 35% of conventional clear cell tumors. Mean tumor size for the cRCC tumors was 4.9 cm compared to 7.4 cm for conventional clear cell tumors. Cystic RCC patients had an 82% four-year disease-specific survival (DSS). Unilocular and multilocular cRCC is a distinct subtype of clear cell RCC. Its biology appears to be more favorable with regards to important prognostic factors such as metastatic presentation, Fuhrman grade, 1997 T stage, and tumor size. These findings suggest that cRCC patients may benefit from nephron sparing surgery.

Staging of renal cell carcinoma: current concepts

become particularly important in the context of the increased popularity of nephronsparing surgery. The more widespread and now mainstream use of partial nephrectomy for small T1 tumours has made the T1 threshold not only important in terms of prognostic value but also in relation to eligibility for nephron-sparing surgery. Hafez et al. [7] attempted to better delineate the optimal size threshold for tumours amenable to partial nephrectomy, ands in so doing showed significantly better survival for patients undergoing nephron-sparing surgery for T1 tumours of £ 4 cm. As a result, they recommended that the TNM T1 category be amended to T1a and T1b, based on a 4 cm threshold [7].

Immune gene therapy for kidney cancer: the search for a magic trigger

It is estimated that approximately 30,000 new cases of renal cell carcinoma (RCC) will be diagnosed in 20021. Approximately 20–30% of patients with RCC present with metastatic disease and their overall median survival is 6–8 months2. One of the most intriguing features of RCC is the dramatically favorable course of the disease in a small subset of patients3. Oliver et al. observed 73 patients with metastatic renal cell carcinoma without treatment4. In this series, 4% had complete and spontaneous regression of disease and 3% had partial regression of disease. Furthermore, 5% had stable disease with no evidence of progression for more than 12 months. There are also numerous cases of patients who recur with metastatic RCC over 10 years after undergoing a nephrectomy for apparently localized disease. It is presumed that microscopic foci of metastatic disease present at the time of nephrectomy had been held in check by the immune system.

Poster 253 Efficacy and Safety of a Lifestyle Balance Program for Antipsychotic Medication Associated Obesity

block after being evaluated by 2 independent pain physicians. The patient experienced an excellent result immediately on the procedure table. We will discuss 3 other case scenarios. We will review the medical literature to identify the pain generators after a spinal wedge fracture and evaluate the validity of the entire medical literature about vertebroplasty as a tool for pain management. Discussion: We believe that there has never been mention in the medical literature of thoracic medial branch block compared with the thoracic vertebroplasty for pain management. However, we will provide information about the pain generators in the spinal wedge fracture, and we will explain why we believe that possibly medial branch block would play a tremendous role for pain management in this group of patients.

Poster 241: Using the Siebens Domain Management Model (SDMM) for Rehabilitation Documentation

visual scanning and eye-hand coordination exercises using real and virtual reality equipment. Setting: Acute inpatient rehabilitation. Results: The patients had decreased ataxia, myoclonus, and opsoclonus. As these impairments improved, both patients made excellent progress with mobility and ADLs. Admission and discharge mobility FIM scores increased (Patient M.W.: from 9 to 23, Patient J.H.: from 9 to 35) as did ADL FIM scores (M.W.: from 19 to 47, J.H.: from 45 to 59). Communication/Cognitive FIM scores for both patients were high and relatively unchanged. Discussion: Rituximab with rehabilitation may be a clinically useful treatment for motor dysfunction caused by opsoclonus myoclonus. Mobility and ADL function improved dramatically; however, cognition did not. Interestingly, children with opsoclonus myoclonus have severe cognitive deficits, unlike our adult patients, who had limited cognitive dysfunction. The lack of cognitive improvement we observed may be a ceiling effect. Conclusions: Rituximab is a novel treatment option for opsoclonus-myoclonus in adults and should be considered in conjunction with a focused intensive rehabilitation program.

Poster 109: An Innovative Comprehensive Musculoskeletal Medicine Curriculum for First Year Medical Students

paraspinal and extremity muscle hypertonicity, which caused him to stand with a hyperextended posture and use a gait with a wide base of support. The examination identified increased tone in his paraspinal muscles, maintaining increased cervical spine extension, having proximal right upper extremity strength at 2/5 distally normal, decreased deep tendon reflexes compared to left upper extremity, intact sensation, and positive Hoffman’s sign bilaterally. Magnetic resonance imaging revealed a large posterior osteophyte formation within the disk material from C3-C6 causing marked canal stenosis. Abnormal cord signals indicating a chronic cord compression as well as degenerative bone marrow were detected at those levels. Setting: Tertiary care hospital. Results: The patient’s motor deficit and pain were attributed to an acute chronic cord compression due to canal stenosis caused by degenerative changes to the cervical spine. These changes are attributed to the cervical extension caused by an increased tone in paraspinal muscles in an otherwise well-functioning adult CP patient. The patient was treated conservatively with steroids, a rehabilitation program was instituted, and he started regaining some strength and function. Ultimately, plans were made for a surgical decompression once the acute stage resolved. Discussion: This challenging CP complication adversely affects patients who chronically maintain a high paraspinal extensor muscle tone. Conclusions: Rehabilitation physicians caring for these patients should understand the possible consequences of chronically altered spine biomechanics resulting in degenerative changes.

Renal Cancer Vaccines

It is estimated that approx 30,000 new cases of renal cell carcinoma (RCC) were diagnosed in 2002 (1). Approximately 20–30% of patients with RCC present with metastatic disease and their overall median survival is 6–8 mo (2). Although, metastatic RCC carries a poor prognosis, in a small subset of patients the disease has a variable course (3). Oliver et al. observed 73 patients with metastatic RCC without treatment (4). In this series, 4% had complete and spontaneous regression of disease and 3% had partial regression of disease. Furthermore, 5% had stable disease with no evidence of progression for more than 12 mo. There are also numerous cases of patients who recur with metastatic RCC over 10 yr after undergoing a nephrectomy for apparently localized disease. It is presumed from these observations that the immune system plays a key role in cases of spontaneous regression and durable remissions of RCC.