Biomedical subjects

Ken-ryu Han

Publications and source records attributed to Ken-ryu Han.

9 recordsLinked to original sources

PubMed2004

Epithelial cell adhesion molecule (KSA) expression: pathobiology and its role as an independent predictor of survival in renal cell carcinoma.

PURPOSE: Epithelial cell adhesion molecule (EpCAM) is a widely expressed adhesion molecule in epithelial cancers. The purpose of this study is to determine the protein expression patterns of EpCAM in renal cell carcinoma (RCC) using tissue arrays linked to a clinicopathological database to evaluate both its predictive power in patient stratification and its suitability as a potential target for immunotherapeutic treatment strategies. EXPERIMENTAL DESIGN: The University of California, Los Angeles kidney cancer tissue microarray contains specimens from 417 patients treated with nephrectomy. EpCAM protein expression in tumors and matched morphologically normal renal tissues was evaluated using anti-EpCAM immunohistochemistry. The resultant expression reactivity was correlated with clinicopathological variables. RESULTS: EpCAM is consistently expressed in the distal nephron on normal renal epithelium. Clear cell RCCs show minimal and infrequent EpCAM expression, whereas chromophobe and collecting duct RCCs both demonstrate intense and frequent expression. Of 318 clear cell carcinomas used in the analysis, 10% were EpCAM positive in > or = 50% of cells, and 8% of patients would be considered candidates for EpCAM-based therapy, based on high expression [> or = moderate intensity and frequent (> or = 50%) expression] and the need for systemic treatment. EpCAM expression was an independent prognostic factor for improved disease-specific survival, with a multivariate hazard ratio of 0.63 (P = 0.017; 95% confidence interval, 0.43-0.92). CONCLUSIONS: EpCAM is a novel prognostic molecular marker in RCC patients, and its positive expression is an independent predictor associated with improved survival. However, high expression in morphologically normal renal tissues and minimal or absent expression in clear cell carcinomas will likely limit the utility of this epithelial marker in targeted treatments of this most common RCC type.

Adenocarcinoma, Clear Cell↗

PubMed2004

Use of American Society of Anesthesiologists physical status classification to assess perioperative risk in patients undergoing radical nephrectomy for renal cell carcinoma.

OBJECTIVES: To perform a retrospective analysis to determine the operative morbidity in patients with substantial comorbidities requiring renal surgery. Increasing numbers of patients requiring renal surgery are presenting with substantial comorbidities, such as diabetes mellitus, chronic obstructive pulmonary disease, and cardiovascular disease. METHODS: The American Society of Anesthesiologists (ASA) physical status classification was used to define perioperative risk. Of 1087 patients who underwent nephrectomy between 1989 and 2001, 237 patients were classified as ASA classification 1 or 2 (low risk), 297 were ASA classification 3 (intermediate risk), and 17 were ASA classification 4 (high risk). RESULTS: No statistically significant differences were found among the low-risk, intermediate-risk, or high-risk patients with regard to 1997 T stage distribution, mean tumor size, vascular and/or inferior vena cava involvement, percentage of partial nephrectomy, adjacent organ resection, or preoperative hemoglobin. Intermediate-risk patients did have a greater estimated blood loss (946 versus 739 mL, P = 0.05), leading to greater transfusion rates (42% versus 28%, P = 0.001). However, no increase occurred in intraoperative or postoperative morbidity. High-risk patients also had greater transfusion rates, as well as a greater rate of complications occurring more than 24 hours after surgery. CONCLUSIONS: Partial or radical nephrectomy can be offered to patients with comorbid conditions. ASA classification 3 patients are more likely to require transfusion. This may have been a result of a lower threshold to transfuse patients with preoperative morbidities. However, the perioperative and postoperative complication rates were similar to those of low-risk patients. Not surprisingly, high-risk patients had greater rates of transfusions and complications.

Aged↗

PubMed2004

Eastern Cooperative Oncology Group performance status predicts bone metastasis in patients presenting with renal cell carcinoma: implication for preoperative bone scans.

PURPOSE: We identified a subset of patients with renal cell carcinoma (RCC) who have a high likelihood of presenting with bone metastasis and would most benefit from a preoperative bone scan. MATERIALS AND METHODS: A database of 1,357 patients undergoing nephrectomy and/or immunotherapy for RCC at our institution was queried. Patients presenting with metastasis to the bones were identified and stratified according to T stage, Eastern Cooperative Oncology Group (ECOG) score, musculoskeletal symptoms and alkaline phosphatase. RESULTS: Of the patients 37% presented with metastasis. Bone metastasis was identified in 14% of patients. The incidence of bone metastasis was 5.4%, 13.8%, 15.4% and 28.2% in patients with T1 to T4 lesions, and 1.4%, 19% and 41% in those with an ECOG score of 0 to 2 and greater, respectively. T stage and ECOG score were then integrated. Bone metastasis was confirmed in 0.046%, 3.8%, 1.4% and 0% of patients with T1 to T4/ECOG 0 disease, and in 13.4%, 20%, 21.5% and 31% of those with T1 to T4/ECOG greater than 0 disease, respectively (p < 0.0001). Only 1.4% of patients with an ECOG score of 0 harbored bone metastasis, of whom 71% complained of musculoskeletal pain, 100% manifested extraosseous metastases and 25% had increased alkaline phosphatase at presentation. CONCLUSIONS: Performance status is an important predictor of bone metastasis in patients presenting with presumed RCC lesions. Bone scan should be performed in patients with an ECOG score of greater than 0 regardless of T stage but is unnecessary in those presenting with an ECOG score of 0, particularly when lacking symptoms and extraosseous metastasis.

Adult↗

PubMed2003

Scoring algorithm to predict survival after nephrectomy and immunotherapy in patients with metastatic renal cell carcinoma: a stratification tool for prospective clinical trials.

BACKGROUND: The objective of this study was to develop an algorithm capable of stratifying the survival of patients with metastatic renal cell carcinoma (RCC) after nephrectomy and immunotherapy. METHODS: The medical records of 173 patients who underwent radical nephrectomy for metastatic RCC and received recombinant interleukin-2 (IL-2)-based immunotherapy between 1989 and 2000 were evaluated. Survival was the primary endpoint and was assessed based on clinical, surgical, and pathologic parameters. The clinical parameters included age, gender, performance status, existing hypertension, thyroid-stimulating hormone (TSH) levels, location of metastases, and presenting symptomatology. The surgical features included the requirement for blood transfusion or adrenalectomy. The pathologic factors involved tumor stage, tumor size, nuclear grade, lymph node status, and histologic subtype. Disease-specific survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used to determine associations between clinical and pathologic features and survival. RESULTS: The median follow-up was 3.2 years (range, 0.2-9.3 years). Death due to RCC occurred in 123 patients (71%) at a median of 13 months (range, from 0.1 months to 8.4 years) after nephrectomy. Multivariate analysis revealed that the following features were associated with survival: lymph node status (P = 0.002), constitutional symptoms (P = 0.005), location of metastases (P < 0.001), sarcomatoid histology (P = 0.003), and TSH level (P = 0.038). A scoring system based on the features in the multivariate model was created to stratify patients into low-risk, intermediate-risk, and high-risk groups. Estimated survival rates at 1 years, 3 years, and 5 years were 92%, 61%, and 41%, respectively, for the low-risk group and 66%, 31%, and 19%, respectively, for the intermediate risk group. The high-risk group had 1% survival at 1 year and no survivors at 3 years. CONCLUSIONS: In patients with metastatic RCC who were treated with nephrectomy and IL-2 immunotherapy, regional lymph node status, constitutional symptoms, location of metastases, sarcomatoid histology, and TSH levels were associated with survival. The authors present a scoring algorithm based on these features that can be used to predict survival in patients who present with metastatic RCC and to stratify such patients for prospective clinical trials.

Adult↗

PubMed2003

Paraneoplastic signs and symptoms of renal cell carcinoma: implications for prognosis.

PURPOSE: Renal cell carcinoma (RCC) can present with a wide range of signs and symptoms. To our knowledge we report the first study to describe the frequency of paraneoplastic findings in a modern RCC series and assess the prognostic significance of each finding. MATERIALS AND METHODS: Using the kidney cancer database at our institution 1,046 patients undergoing nephrectomy for RCC between 1989 and 2001 were assessed. The prognostic significance of symptoms present at diagnosis and findings on preoperative laboratory evaluation were examined in a univariate analysis as well as on multivariate analysis controlling for TNM stage, Fuhrman grade and Eastern Cooperative Oncology Group performance status (ECOG-PS). RESULTS: Mean followup to date of death or last contact for all patients was 40.3 months. Median time to death was 19.3 months. Most paraneoplastic signs and symptoms correlated with poor survival, although on multivariate analysis hypoalbuminemia, weight loss, anorexia and malaise predicted shorter survival. The frequency of each of these findings was 19.9%, 22.9%, 10.6% and 19.1%, respectively. Cachexia, defined as the presence of at least 1 of these findings, was noted in 35.3% of patients. Cachexia did not predict a higher recurrence rate in patients with localized disease and only malaise correlated with a decreased likelihood of responding to immunotherapy. CONCLUSIONS: Cachexia, defined as hypoalbuminemia, weight loss, anorexia or malaise, predicts worse survival after controlling for well established indicators of prognosis (TNM stage, Fuhrman grade and ECOG-PS). Consideration should be given to expanding the ECOG-PS to include measures for cachexia when applied to patients with RCC.

Analysis of Variance↗

PubMed2003

Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy.

PURPOSE: Metastatic renal cell carcinoma (RCC) has a poor prognosis and an unpredictable course. To date, there are no molecular markers which can reliably predict RCC outcome. We investigated whether a novel kidney cancer marker, carbonic anhydrase IX (CAIX), is associated with progression and survival. EXPERIMENTAL DESIGN: Immunohistochemical analysis using a CAIX monoclonal antibody was performed on tissue microarrays constructed from paraffin-embedded specimens from patients (N = 321) treated by nephrectomy for clear cell RCC. CAIX staining was correlated with response to treatment, clinical factors, pathologic features, and survival. RESULTS: CAIX staining was present in 94% of clear cell RCCs. Survival tree analysis determined that a cutoff of 85% CAIX staining provided the most accurate prediction of survival. Low CAIX (</=85%) staining was an independent poor prognostic factor for survival for patients with metastatic RCC, with a hazard ratio of 3.10 (P < 0.001). CAIX significantly substratified patients with metastatic disease when analyzed by T stage, Fuhrman grade, nodal involvement, and performance status (P < 0.001, = 0.001, = 0.009, = 0.005, respectively). For patients with nonmetastatic RCC and at high risk for progression, low CAIX predicted a worse outcome similar to patients with metastatic disease (P = 0.058). Overall expression of CAIX decreased with development of metastasis; as demonstrated by the lower CAIX staining levels in metastatic lesions relative to matched primary tumor specimens (P = 0.036). CONCLUSIONS: On the basis of our data, CAIX is the most significant molecular marker described in kidney cancer to date. Decreased CAIX levels are independently associated with poor survival in advanced RCC. CAIX reflects significant changes in tumor biology, which should be used to predict clinical outcome and identify high-risk patients in need for adjuvant immunotherapy and CAIX-targeted therapies.

Adenocarcinoma, Clear Cell↗

PubMed2002

Tumor markers for the early detection of bladder cancer.

Several urine markers have been and are currently being investigated for the diagnosis and prognostication of bladder malignancies. While cystoscopy and urine cytology remain the gold standard in the detection of bladder cancer, cystoscopy is invasive and cytology yields low sensitivities in low-grade disease. The availability of a non-invasive, accurate, office-based test would be ideal. In this review, we discuss markers that are useful in the prevention and detection of transitional cell carcinoma of the bladder. In general, each of the markers has better sensitivities than cytology, but lower specificities. Furthermore, each of these markers must still be used in adjunct with cystoscopy.

Biomarkers, Tumor↗

PubMedDate not supplied

Emerging technologies in uroradiologic imaging.

Advances in imaging technologies have readily been incorporated into the practice of urology and have led to important advances in patient care and outcomes. In the area of oncology, advances in radiologic imaging are improving the ability of the urologist to diagnose and monitor urologic malignancies. Some of these technologies include positron emission tomography (PET), intraoperative ultrasound (IUS), 3-dimensional computerized tomography (3D-CT), and magnetic resonance spectroscopy (MRS). We provide an overview of these four emerging imaging modalities and their potential applications and limitations in the diagnosis and management of urologic malignancy.

Female↗

PubMedDate not supplied

Positron emission tomography in urologic oncology.

BACKGROUND: Positron emission tomography (PET) is an emerging imaging modality that is being investigated for use in urologic oncology. PET scanning using the radioactive glucose analog FDG has proven to be a highly accurate imaging test for diagnosing and staging a variety of non-urologic cancer types. This review was performed to determine the role of PET imaging in genitourinary malignancies. METHODS: A review of the literature focusing on PET and urologic oncology was performed. The role of PET imaging was reviewed in prostate, bladder, renal, and testicular cancer. RESULTS: In testicular cancer, PET has a higher diagnostic accuracy than computed tomography (CT) for both staging and re-staging and should be the test of choice for the assessment of a CT-visualized residual mass following chemotherapy. In prostate, renal, and bladder cancer, the current role of PET is still being defined, but it has a high positive predictive value and can be used for problem solving in patients with indeterminate findings on conventional imaging. Its role in the diagnosis and staging of prostate cancer is hampered by the generally low glycolytic rate of most prostate tumors and their metastases. It has shown promise for staging and re-staging patients with advanced-stage disease and aggressive tumors suspected by a high tumor grade and high prostate-specific antigen velocity. PET has also demonstrated success when applied to renal cell carcinoma in classifying indeterminate renal masses as well as residual renal fossa masses following nephrectomy, gauging response to therapy, and staging and re-staging patients with a known diagnosis of renal cell carcinoma. CONCLUSIONS: PET imaging has demonstrated great potential in certain applications, but further investigations are necessary to determine its eventual place as an imaging modality in genitourinary malignancies.

Humans↗