Rebecca A. Nelson

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.

Identification of a 4-microRNA signature for clear cell renal cell carcinoma metastasis and prognosis.

Renal cell carcinoma (RCC) metastasis portends a poor prognosis and cannot be reliably predicted. Early determination of the metastatic potential of RCC may help guide proper treatment. We analyzed microRNA (miRNA) expression in clear cell RCC (ccRCC) for the purpose of developing a miRNA expression signature to determine the risk of metastasis and prognosis. We used the microarray technology to profile miRNA expression of 78 benign kidney and ccRCC samples. Using 28 localized and metastatic ccRCC specimens as the training cohort and the univariate logistic regression and risk score methods, we developed a miRNA signature model in which the expression levels of miR-10b, miR-139-5p, miR-130b and miR-199b-5p were used to determine the status of ccRCC metastasis. We validated the signature in an independent 40-sample testing cohort of different stages of primary ccRCCs using the microarray data. Within the testing cohort patients who had at least 5 years follow-up if no metastasis developed, the signature showed a high sensitivity and specificity. The risk status was proven to be associated with the cancer-specific survival. Using the most stably expressed miRNA among benign and tumorous kidney tissue as the internal reference for normalization, we successfully converted his signature to be a quantitative PCR (qPCR)-based assay, which showed the same high sensitivity and specificity. The 4-miRNA is associated with ccRCC metastasis and prognosis. The signature is ready for and will benefit from further large clinical cohort validation and has the potential for clinical application.

Human Islet Oxygen Consumption Rate and DNA Measurements Predict Diabetes Reversal in Nude Mice

There is a need for simple, quantitative and prospective assays for islet quality assessment that are predictive of islet transplantation outcome. The current state‐of‐the‐art athymic nude mouse bioassay is costly, technically challenging and retrospective. In this study, we report on the ability of 2 parameters characterizing human islet quality: (1) oxygen consumption rate (OCR), a measure of viable volume; and (2) OCR/DNA, a measure of fractional viability, to predict diabetes reversal in nude mice. Results demonstrate that the probability for diabetes reversal increases as the grafts OCR/DNA and total OCR increase. For a given transplanted OCR dose, diabetes reversal is strongly dependent on OCR/DNA. The OCR and OCR/DNA (the ‘OCR test’) data exhibit 89% sensitivity and 77% specificity in predicting diabetes reversal in nude mice (n = 86). We conclude that the prospective OCR test can effectively replace the retrospective athymic nude mouse bioassay in assessing human islet quality prior to islet transplantation.

Five-year lung cancer survival: which advanced stage nonsmall cell lung cancer patients attain long-term survival?

The core strategy of American College of Chest Physicians lung cancer guidelines is identification of the earliest symptoms of lung cancer and the immediate initiation of diagnosis and treatment. In the absence of screening, most symptomatic lung cancer is discovered at advanced stages, with the goal of long‐term survival entirely dependent on effective treatment of stage III and IV lung cancer.

Cardiac function during steep Trendelenburg position and CO2 pneumoperitoneum for robotic-assisted prostatectomy: a trans-oesophageal Doppler probe study.

Haemodynamic changes associated with pneumoperitoneum and steep Trendelenburg position were investigated in non‐obese, ASA I–II males, using general anaesthesia (sevoflurane in air/O2, 40%) undergoing robotic‐assisted laparoscopic prostatectomy.

Changing Patterns of Anal Canal Carcinoma in the United States

PURPOSE Persistent human papillomavirus infection is associated with squamous cell carcinoma of the anal canal (SCCA). With changing sexual behaviors, SCCA incidence and patient demographics may also have changed in recent years. METHODS The Surveillance, Epidemiology, and End Results public-use data set from 1973 to 2009 was analyzed to determine incidence trends for and demographic factors characterizing SCCA. Joinpoint analyses identified time points when incidence rates changed. For comparison, similar analyses were conducted for anal adenocarcinoma. RESULTS Joinpoint analyses identified 1997 as the single inflection point among 11,231 patients with SCCA, at which the slope of incidence rates statistically increased (1997 to 2009 v 1973 to 1996: risk ratio [RR], 2.2; 95% CI, 2.1 to 2.3). Annual percent change (APC) increased for all SCCA stages and was the greatest for anal carcinoma in situ (CIS; APC, 14.2; 95% CI, 10.2 to 18.4). Demographic changes characterizing later versus earlier time period included younger age at diagnosis and rising incidence rates in all stage, sex, and racial groups. During 1997 to 2009, women were less likely to present with CIS (RR, 0.3; 95% CI, 0.3 to 0.3) but more likely to present with localized (RR, 1.2; 95% CI, 1.1 to 1.3) and regional SCCA (RR, 1.5; 95% CI, 1.4 to 1.7). In contrast, adenocarcinoma APCs among 1,791 patients remained stable during this time period. CONCLUSION CIS and SCCA incidence increased dramatically after 1997 for men and women, although men were more likely to be diagnosed with CIS. These changes likely resulted from available screening in men and argue for efforts to identify high-risk individuals who may benefit from screening.

Reproductive Factors and Risk of Intermediate- or High-Grade B-Cell Non-Hodgkin’s Lymphoma in Women

PURPOSE The incidence rates of non-Hodgkins lymphoma (NHL) unrelated to human immunodeficiency virus infection are lower for women than for men; yet, few factors have been identified that may account for this difference in risk. NHL is difficult to study epidemiologically because this disorder represents a group of malignancies that differ in terms of morphologic presentation, immunologic features, genetic characteristics, prognosis, and etiology. PATIENTS AND METHODS We conducted a population-based case-control study in women to determine whether reproductive factors or hormonal exposures might be related to the risk of high- or intermediate-grade B-cell NHL. We interviewed 177 female residents of Los Angeles County who were diagnosed with high- or intermediate-grade B-cell NHL between 1989 and 1992; each case patient was individually matched on age and race to a control subject who lived in her neighborhood. RESULTS Women who had used oral contraceptives had significantly lower risk of intermediate- or high-grade NHL (multivariate odds ratio [OR] = 0.47; 95% confidence interval [CI], 0.26 to 0.86) than women who had never used these compounds. Among parous women, those who had used lactation suppressants (which contain high levels of estrogen) had significantly lower risk of NHL (multivariate OR = 0.50; 95% CI, 0.29 to 0.85) than unexposed women. Postmenopausal women had a somewhat greater risk of NHL than premenopausal women, whereas those postmenopausal women who had used hormone replacement therapy (HRT) (primarily estrogen) had somewhat lower risk than those who had not used HRT. CONCLUSION Exogenous estrogens seem to have a protective effect on the risk of high- and intermediate-grade B-cell NHL. Although the mechanisms for such protection are not known, alterations in immune reactivity, cytokine expression, or B-cell modulation may play a role.

Oncologic Outcomes for Complete Robot-Assisted Laparoscopic Management of Upper-Tract Transitional Cell Carcinoma

BACKGROUND AND PURPOSE The gold standard for treatment of upper-tract transitional cell carcinoma (TCC) is nephroureterectomy. For distal ureteral TCC, distal ureterectomy with ureteral reimplantation represents a treatment option. Multiple minimally invasive techniques have been introduced with the goal of replicating these open procedures. Currently, there is a paucity of literature for the use of robot-assisted laparoscopic (RAL) management of upper-tract TCC. We evaluated our experience with RAL management of upper-tract TCC. PATIENTS AND METHODS A retrospective chart review was performed on all patients who underwent complete RAL nephroureterectomy or distal ureterectomy with ureteral reimplantation at our institution. RESULTS Eleven patients with a mean age of 67.4 years underwent RAL nephroureterectomy. Mean operative time was 326 minutes (range 243-470 minutes), estimated blood loss 200 mL (range 100-400 mL), and mean length of hospital stay was 4.7 days. With a mean follow-up of 15.2 months (range 2-31 months), four patients experienced recurrence, and two ultimately died from metastatic disease. Four patients with a mean age of 73.5 years underwent RAL distal ureterectomy with ureteral reimplantation for distal ureteral TCC. Mean operative time was 311 minutes (range 225-446 minutes), estimated blood loss 200 mL (range 100-350 mL), and mean length of hospital stay was 4.7 days. With a mean follow-up of 30.5 months (range 12-48 months), only one patient, whose pathology exhibited carcinoma in situ within periureteral tissue, required adjuvant treatment for recurrent disease. CONCLUSIONS RAL nephroureterectomy and distal ureterectomy with ureteral reimplantation are feasible options for patients with upper-tract TCC with promising short-term oncologic outcomes.

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.

Ribonucleotide Reductase Small Subunit M2B Prognoses Better Survival in Colorectal Cancer

Ribonucleotide reductase subunit RRM2B (p53R2) has been reported to suppress invasion and metastasis in colorectal cancer (CRC). Here, we report that high levels of RRM2B expression are correlated with markedly better survival in CRC patients. In a fluorescence-labeled orthotopic mouse xenograft model, we confirmed that overexpression of RRM2B in nonmetastatic CRC cells prevented lung and/or liver metastasis, relative to control cells that did metastasize. Clinical outcome studies were conducted on a training set with 103 CRCs and a validation set with 220 CRCs. All participants underwent surgery with periodic follow-up to determine survivability. A newly developed specific RRM2B antibody was employed to carry out immunohistochemistry for determining RRM2B expression levels on tissue arrays. In the training set, the Kaplan-Meier and multivariate Cox analysis revealed that RRM2B is associated with better survival of CRCs, especially in stage IV patients (HR = 0.40; 95% CI = 0.18-0.86, P = 0.016). In the validation set, RRM2B was negatively related to tumor invasion (OR = 0.45, 95% CI = 0.19-0.99, P = 0.040) and lymph node involvement (OR = 0.48, 95% CI = 0.25-0.92, P = 0.026). Furthermore, elevated expression of RRM2B was associated with better prognosis in this set as determined by multivariate analyses (HR = 0.48, 95% CI = 0.26-0.91, P = 0.030). Further investigations revealed that RRM2B was correlated with better survival of CRCs with advanced stage III and IV tumors rather than earlier stage I and II tumors. Taken together, our findings establish that RRM2B suppresses invasiveness of cancer cells and that its expression is associated with a better survival prognosis for CRC patients.