Mark H. Kawachi

Perioperative Complications of Laparoscopic and Robotic Assisted Laparoscopic Radical Prostatectomy

PURPOSE While it remains controversial whether LRP or da Vinci RAP offers any advantages over radical retropubic prostatectomy, LRP and RAP are being used more frequently. We reviewed our experience with these minimally invasive techniques. MATERIALS AND METHODS We reviewed intraoperative and early postoperative complications of 358 LRPs performed from October 2000 to January 2003 with those of 322 RAPs performed from June 2003 to June 2004. The transperitoneal approach with bilateral pelvic lymph node dissection was performed using each technique. Data acquisition was done independently of the 3 surgeons. RESULTS The LRP and RAP groups had similar clinical characteristics in terms of patient race, body mass index, prostate specific antigen, risk group, and pathological tumor grade and stage. Median operative time and estimated blood loss for LRP and RAP were 4.1 and 3.1 hours, and 200 and 250 ml, respectively. No blood transfusions were given intraoperatively, although 8 patients with LRP (2.2%) and 5 with RAP (1.6%) were transfused postoperatively. Of the LRP and RAP patients 21 (5.9%) and 3 (0.3%), respectively, experienced intraoperative complications. Postoperatively 48 patients with LRP (13.4%) and 24 with RAP (6.8%) experienced urine leakage, while 19 with LRP (5.3%) and 9 with RAP (2.8%) had ileus. There were no deaths, myocardial infarctions, pulmonary emboli or cerebrovascular accidents. CONCLUSIONS In our series surgeon experience derived from LRP may contribute to the lower complication rate and operative time of RAP. Dissemination of surgical technique and management of complications may lead to improved perioperative LRP and RAP morbidity. However, the morbidity of these 2 approaches compares favorably with that of radical retropubic prostatectomy.

Insulin-Like Growth Factor (IGF) System Components in Human Prostatic Cancer Cell-Lines: LNCaP, DU145, and PC-3 Cells

Background: Evidence has been accumulating that in many tumors, insulin‐like growth factors (ICFs) promote cancer cell growth in an autocrine/paracrine manner via the IGF‐1 receptor. In an effort to understand the role of ICFs in prostate cancer cell growth, we characterized the IGF system components produced by human prostatic cancer cell‐lines, LNCaP, DU145, and PC‐3, grown in serum‐free medium.

NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection provide recommendations for prostate cancer screening in healthy men who have elected to participate in an early detection program. The NCCN Guidelines focus on minimizing unnecessary procedures and limiting the detection of indolent disease. These NCCN Guidelines Insights summarize the NCCN Prostate Cancer Early Detection Panels most significant discussions for the 2016 guideline update, which included issues surrounding screening in high-risk populations (ie, African Americans, BRCA1/2 mutation carriers), approaches to refine patient selection for initial and repeat biopsies, and approaches to improve biopsy specificity.

Expression of insulin-like growth factor (IGF)-II in human prostate, breast, bladder, and paraganglioma tumors.

Abstract Insulin-like growth factors (IGFs) are potent mitogens for a variety of cancer cells in vitro. A paracrine/autocrine role of IGF-II in the growth of breast and prostate cancer cells has been suggested. Information on cell-type-specific IGF-II expression in vivo in the breast and prostate is, however, limited. Thus, cell types expressing IGF-II mRNA and protein in tumors were identified by in situ hybridization and immunohistochemistry. Of 36 prostate, 17 breast, and 10 bladder cancers, and 9 paraganglioma tissues examined, IGF-II was expressed in more than 50% of prostate, breast, and bladder tumors, and in 100% of paraganglioma tumors. Expression levels of IGF-II were highest in the paraganglioma and bladder followed by prostate and breast tumors. In all the tumors expressing IGF-II, both mRNA and protein were localized to malignant cells, expression in the stroma being minimal. Since previous studies had indicated that an incompletely processed form of 15-kDa IGF-II exhibited higher mitogenic potency than the completely processed 7.5-kDa IGF-II form, the quantity and size of IGF-II proteins expressed in these tumors were analyzed by Western immunoblotting. Greater expression of 15-kDa IGF-II relative to the 7.5-kDa IGF-II form was clearly demonstrated in all six prostate cancers and in half of the two breast and four bladder cancers examined. The results are consistent with the hypothesis that the 15-kDa form of IGF-II expressed in cancerous cells contributes to autocrine cancer cell growth in vivo.

Early and Late Complications of Robot-Assisted Radical Cystectomy: A Standardized Analysis by Urinary Diversion Type

PURPOSE Minimally invasive surgical treatment for bladder cancer has gained popularity but standardized data on complications are lacking. Urinary diversion type contributes to complications and to our knowledge diversion types after minimally invasive cystectomy have not yet been compared. We evaluated perioperative complications stratified by urinary diversion type in patients treated with robot-assisted radical cystectomy. MATERIALS AND METHODS We analyzed the records of 209 consecutive patients who underwent robot-assisted radical cystectomy at our institution from 2003 to 2012 with respect to perioperative complications, including severity, time period (early and late) and diversion type. All complications were reviewed by academic urologists. Urinary diversion was also done. As outcome measurements and statistical analysis, univariate and multivariate logistic regression models were used to determine predictors of various complications. RESULTS The American Society of Anesthesiologists(®) (ASA) score was 3 or greater in 80% of patients and continent diversion was performed in 68%. Median followup was 35 months. Within 90 days 77.5% of patients experienced any complication and 32% experienced a major complication. The 90-day mortality rate was 5.3%. Most complications were gastrointestinal, infectious and hematological. On multivariate analysis patients with ileal conduit diversion had a decreased likelihood of complications compared to patients with Indiana pouch and orthotopic bladder substitute diversion despite the selection of a more comorbid population for conduit diversion. Continent diversion was associated with a higher likelihood of urinary tract infection. Our results are comparable to those of previously reported open and minimally invasive cystectomy series. CONCLUSIONS Open or minimally invasive cystectomy is a complex, morbid procedure. Urinary diversion is a significant contributor to complications, as is patient comorbidity. Although patients with an ileal conduit had more comorbidities, they experienced fewer complications than those with an orthotopic bladder substitute or Indiana pouch diversion.

Robotic Assisted Laparoscopic Salvage Prostatectomy for Radiation Resistant Prostate Cancer

PURPOSE We report on outcomes of robotic assisted laparoscopic radical prostatectomy as salvage local therapy for radiation resistant prostate cancer. MATERIALS AND METHODS We retrospectively reviewed the charts of all patients who underwent robotic assisted laparoscopic radical prostatectomy for biopsy proven prostate cancer after primary radiation treatment. Patient characteristics, intraoperative and perioperative data, and oncological and functional outcomes were assessed. RESULTS A total of 18 patients were identified with a median followup of 18 months (range 4.5 to 40). Primary treatment was brachytherapy in 8 patients and external beam radiation in 8, while 2 underwent proton beam therapy. Median age at salvage robotic assisted laparoscopic radical prostatectomy was 67 years (range 53 to 76). Median preoperative prostate specific antigen was 6.8 ng/ml (range 1 to 28.9) and median time to surgery after primary treatment with radiation was 79 months (range 7 to 146). Median operative parameters for estimated blood loss, surgery length and hospital stay were 150 ml, 2.6 hours and 2 days, respectively. No patient required conversion to open surgery or a blood transfusion, or experienced a rectal injury. Perioperative complications occurred in 7 patients (39%) of which the most common was urine leak identified by postoperative cystogram. Five patients (28%) had a positive surgical margin. Although some patients had limited followup, 6 (33%) were continent and 67% were free of biochemical progression. CONCLUSIONS Robotic assisted laparoscopic radical prostatectomy can be performed safely as salvage local therapy after failed radiation therapy. Outcomes are comparable to those of large series of open salvage prostatectomy.

Performance of a Single Assay for Both Type III and Type VI TMPRSS2:ERG Fusions in Noninvasive Prediction of Prostate Biopsy Outcome

BACKGROUND TMPRSS2:ERG fusions are promising prostate cancer biomarkers. Because they can occur in multiple forms in a single cancer specimen, we developed a quantitative PCR test that detects both type III and type VI TMPRSS2:ERG fusions. The assay is quantified from a standard curve determined with a plasmid-cloned type III TMPRSS2:ERG fusion target. METHODS We collected expressed prostatic secretion (EPS) under an institutional review board-approved, blinded, prospective study from 74 patients undergoing transrectal ultrasound-guided biopsy for prostate cancer. We compared the characteristic performance of the test for type III and type VI TMPRSS2:ERG fusions in predicting biopsy outcome and distinguishing between high and low Gleason scores with similar tests for the expression of PCA3 and DNA methylation levels of the APC, RARB, RASSF1, and GSTP1 genes. We used logistic regression to analyze the effects of multiple biomarkers in linear combinations. RESULTS Each test provided a significant improvement in characteristic performance over baseline digital rectal examination (DRE) plus serum prostate-specific antigen (PSA); however, the test for type III and type VI TMPRSS2:ERG fusions yielded the best performance in predicting biopsy outcome [area under the curve (AUC) 0.823, 95% CI 0.728-0.919, P < 0.001] and Gleason grade >7 (AUC 0.844, 95% CI 0.740-0.948, P < 0.001). CONCLUSIONS Although each test appears to have diagnostic value, PSA plus DRE plus type III and type VI TMPRSS2:ERG provided the best diagnostic performance in EPS specimens.

Detection and Phenotyping of Circulating Tumor Cells in High-Risk Localized Prostate Cancer

BACKGROUND In this study, we aimed to determine the feasibility of identifying CTCs in patients with HRLPC, using a modified isolation procedure using the CellSearch (Veridex) platform, and to assess the expression of stem cell and epithelial-mesenchymal transition (EMT) markers on the CTCs. PATIENTS AND METHODS Thirty-five patients with HRLPC who had chosen prostatectomy for definitive management were prospectively identified. After obtaining consent, four 30-mL blood draws were performed, 2 before surgery and 2 after surgery. The CTC-containing fraction was Ficoll-purified and transferred to a CellSave (Veridex) tube containing dilution buffer before standard enumeration using the CellSearch system. Loss of E-cadherin expression, a marker of EMT, and CD133, a putative prostate cancer stem cell marker, were characterized using the open channel of the CellSearch platform. CTC fragments were also enumerated. RESULTS Using the modified methodology, CTCs were detectable in 49% of patients before surgery. Although no correlation between CTC count and biochemical recurrence (BR) was observed, the percentages of CD133 and E-cadherin-positive CTC fragments were associated with BR at 1 year. CONCLUSION Our results suggest that further research into the development of CTCs as prognostic biomarkers in HRLPC is warranted.

Complications and outcomes of salvage robot-assisted radical prostatectomy: a single-institution experience.

To determine the peri‐operative outcomes of men undergoing salvage robot‐assisted prostatectomy (RARP) and to examine the complications, functional consequences and need for additional treatments after salvage RARP.

Expressed Prostatic Secretion Biomarkers Improve Stratification of NCCN Active Surveillance Candidates: Performance of Secretion Capacity and TMPRSS2:ERG Models

PURPOSE Active surveillance is a viable patient option for prostate cancer provided that a clinical determination of low risk and presumably organ confined disease can be made. To standardize risk stratification schemes the NCCN (National Comprehensive Cancer Network®) provides guidelines for the active surveillance option. We determined the effectiveness of expressed prostatic secretion biomarkers for detecting occult risk factors in NCCN active surveillance candidates. MATERIALS AND METHODS Expressed prostatic secretion specimens were obtained before robot-assisted radical prostatectomy. Secretion capacity biomarkers, including total RNA and expressed prostatic secretion specimen volume, were measured by standard techniques. RNA expression biomarkers, including TXNRD1 mRNA, prostate specific antigen mRNA, TMPRSS2:ERG fusion mRNA and PCA3 mRNA, were measured by quantitative reverse-transcription polymerase chain reaction. RESULTS Of the 528 patients from whom expressed prostatic secretions were collected 216 were eligible for active surveillance under NCCN guidelines. Variable selection on logistic regression identified 2 models, including one featuring types III and VI TMPRSS2:ERG variants, and one featuring 2 secretion capacity biomarkers. Of the 2 high performing models the secretion capacity model was most effective for detecting cases in this group that were up-staged or up-staged plus upgraded. It decreased the risk of up-staging in patients with a negative test almost eightfold and decreased the risk of up-staging plus upgrading about fivefold while doubling the prevalence of up-staging in the positive test group. CONCLUSIONS Noninvasive expressed prostatic secretion testing may improve patient acceptance of active surveillance by dramatically reducing the presence of occult risk factors among those eligible for active surveillance under NCCN guidelines.