Kenneth Jacobsohn

Robotic-assisted Endoscopic Inguinal Lymphadenectomy

INTRODUCTION Open inguinal lymphadenectomy is a well-established therapeutic and diagnostic option for patients with invasive penile squamous cell carcinoma who are at risk of regional and distant metastases. We report the use of endoscopic robotic-assisted bilateral inguinal lymph node dissections in a patient with palpable inguinal nodes despite oral antibiotics. TECHNIQUE A 2-cm mid-thigh incision was made to develop a plane just deep to Campers (fatty) fascia. Once a sufficient working space was created to place 3 robotic ports and 1 assistant port, subcutaneous gas was instilled, and the robotic device was docked and used to perform the dissection. The surgical approach replicated the principles of open techniques such that the contents of the femoral canal were dissected to the inguinal ligament superiorly, the sartorius muscle laterally, and the adductor longus muscle medially to include both superficial and deep lymph nodes in the dissection template. CONCLUSIONS To our knowledge, this is the first report of an endoscopic robotic-assisted inguinal lymph node dissection. A minimally invasive approach circumventing the need for thick skin flaps, the improved flexibility afforded by robotic instruments, and the improved magnification could decrease the morbidity associated with inguinal lymphadenectomy while maintaining oncologic principles.

Oncological efficacy and safety of nephron-sparing surgery for selected patients with locally advanced renal cell carcinoma

Authors from the USA evaluated complication and survival rates in a large group of patients who had nephron‐sparing surgery or radical nephrectomy for locally advanced RCC. They found that in a highly selected group of patients with locally advanced disease, nephron‐sparing surgery is safe and has equivalent outcomes to radical nephrectomy.

Duloxetine for the treatment of post-prostatectomy stress urinary incontinence

OBJECTIVES Stress urinary incontinence (SUI) is a known complication following prostatectomy. Duloxetine, a combined serotonin/norepinephrine reuptake inhibitor, can decrease SUI by increasing urethral sphincter contractility. We examined the outcomes of patients with mild to moderate post-prostatectomy SUI treated with duloxetine. METHODS We conducted a retrospective review of men treated with duloxetine to manage mild to moderate post-prostatectomy SUI from 2006 to 2012. All patients received oral duloxetine 30 mg once a week, then 60 mg thereafter. Patients were seen one month later to determine drug efficacy and side effects. RESULTS In total, 94 men were included in the study. Daily pad usage decreased from 2.9 (range: 1-5) to 1.6 (range: 0-4) (p < 0.05). Incontinence Impact Questionnaire (IIQ-7) scores decreased from 13.0 (range: 6-18) to 7.9 (range: 2-16) (p < 0.05). Linear satisfaction scores improved from 0.8 (range: 0-2) to 2.0 (range: 1-3) (p < 0.05). Following a 1-month duloxetine trial, 33/94 (35%) men reported satisfactory SUI improvement and requested to continue the medication. The drug was discontinued in 61/94 (65%) patients due to poor efficacy in 32/94 (34%), intolerable side effects in 14/94 (15%) or both in 15/94 (16%). Reported side effects included fatigue, light-headedness, insomnia, nausea and dry mouth. CONCLUSIONS Duloxetine improved post-prostatectomy SUI in 47/94 (50%) men following a 1-month trial. However, only 33/94 (35%) patients were able to tolerate the drug. Duloxetine may be considered a treatment option for men with mild to moderate post-prostatectomy SUI.

V-Loc urethro-intestinal anastomosis during robotic cystectomy with orthotopic urinary diversion

INTRODUCTION Robotic-assisted radical cystectomy (RARC) is an emerging minimally invasive alternative for the treatment of invasive bladder cancer. The V-loc (Covidien, Mansfield, MA) suture is a unidirectional barbed suture that provides even distribution of tension. We determined the rate of urinary leak at the urethro-intestinal anastomosis following orthotopic neobladder construction performed with V-loc suture. METHODS We retrospectively reviewed charts on all patients that underwent RARC with orthotopic neobladder urinary diversion performed with a V-loc suture from February 2010 to February 2012. The urethro-intestinal anastomosis was evaluated for urinary leak by cystogram at 3 to 4 weeks, postoperatively. RESULTS In total, 11 patients were available for analysis. The mean patient age was 57.2 years (range: 47-71). The average clinical follow-up was 8 months (range: 4-15). On surgical pathology, 8 (73%) patients had pT2 or less disease, 3 (27%) had pT3/T4 disease, and 1 (9%) had N+ disease. The mean intraoperative blood loss was 315 mL (range: 150-600) and the average operative time was 496 minutes (range: 485-519). No patient (0%) demonstrated a urinary leak at the urethro-intestinal anastomosis on postoperative cystogram. Eight patients (73%) were continent by 4 months, postoperatively. CONCLUSIONS Orthotopic neobladder urethro-intestinal anastomosis can be performed effectively and safely with V-loc suture with an acceptably low urinary leak rate.

Thermoacoustic contrast of prostate cancer due to heating by very high frequency irradiation.

Prostate cancer may be a good application for thermoacoustic imaging induced by very high frequency (VHF) radiation for several reasons. Mechanical properties of healthy and cancerous prostate tissue are well matched, so the assumption of constant sound speed is accurate. Signal production by VHF irradiation is proportional to ionic content, and ionic content of prostatic fluids produced by healthy tissue in the peripheral zone are approximately three times higher than in blood and plasma whereas cancer suppress ionic content of prostatic fluid. Signal strength is expected to decrease with extent of cancerous involvement. To test the utility of VHF-induced thermoacoustics to prostate cancer imaging we imaged fresh human prostate specimens ex vivo and compared to the gold standard, histology. Specimens were scanned immediately after radical prostatectomy performed as part of normal care.

Specific heat capacity of freshly excised prostate specimens

The specific heat capacity of tissue is a critical parameter for thermal therapies that act over a long period of time. It is also critical for thermoacoustic signal generation. We present ex vivo measurements of specific heat capacity performed by a dual-pin probe with tight temperature control of the specimen. One 30 mm × 1.28 mm probe heats steadily for 30 s, while another measurement probe measures temperatures 6 mm away from the center of the heater probe. Specific heat values ranging from 2.9 to 4 J cm(-3) °C(-1) were measured on 20 lobes from ten fresh prostate specimens with varying degrees of cancerous involvement as confirmed by histology.

Optimized b -value selection for the discrimination of prostate cancer grades, including the cribriform pattern, using diffusion weighted imaging

Abstract. Multiparametric magnetic resonance imaging (MP-MRI), including diffusion-weighted imaging, is commonly used to diagnose prostate cancer. This radiology–pathology study correlates prostate cancer grade and morphology with common b-value combinations for calculating apparent diffusion coefficient (ADC). Thirty-nine patients undergoing radical prostatectomy were recruited for MP-MRI prior to surgery. Diffusion imaging was collected with seven b-values, and ADC was calculated. Excised prostates were sliced in the same orientation as the MRI using 3-D printed slicing jigs. Whole-mount slides were digitized and annotated by a pathologist. Annotated samples were aligned to the MRI, and ADC values were extracted from annotated peripheral zone (PZ) regions. A receiver operating characteristic (ROC) analysis was performed to determine accuracy of tissue type discrimination and optimal ADC b-value combination. ADC significantly discriminates Gleason (G) G4-5 cancer from G3 and other prostate tissue types. The optimal b-values for discriminating high from low-grade and noncancerous tissue in the PZ are 50 and 2000, followed closely by 100 to 2000 and 0 to 2000. Optimal ADC cut-offs are presented for dichotomized discrimination of tissue types according to each b-value combination. Selection of b-values affects the sensitivity and specificity of ADC for discrimination of prostate cancer.

STAT5A/B BLOCKADE SENSITIZES PROSTATE CANCER TO RADIATION THROUGH INHIBITION OF RAD51 AND DNA REPAIR

Purpose: The standard treatment for organ-confined prostate cancer is surgery or radiation, and locally advanced prostate cancer is typically treated with radiotherapy alone or in combination with androgen deprivation therapy. Here, we investigated whether Stat5a/b participates in regulation of double-strand DNA break repair in prostate cancer, and whether Stat5 inhibition may provide a novel strategy to sensitize prostate cancer to radiotherapy. Experimental Design: Stat5a/b regulation of DNA repair in prostate cancer was evaluated by comet and clonogenic survival assays, followed by assays specific to homologous recombination (HR) DNA repair and nonhomologous end joining (NHEJ) DNA repair. For HR DNA repair, Stat5a/b regulation of Rad51 and the mechanisms underlying the regulation were investigated in prostate cancer cells, xenograft tumors, and patient-derived prostate cancers ex vivo in 3D explant cultures. Stat5a/b induction of Rad51 and HR DNA repair and responsiveness to radiation were evaluated in vivo in mice bearing prostate cancer xenograft tumors. Results: Stat5a/b is critical for Rad51 expression in prostate cancer via Jak2-dependent mechanisms by inducing Rad51 mRNA levels. Consistent with this, genetic knockdown of Stat5a/b suppressed HR DNA repair while not affecting NHEJ DNA repair. Pharmacologic Stat5a/b inhibition potently sensitized prostate cancer cell lines and prostate cancer tumors to radiation, while not inducing radiation sensitivity in the neighboring tissues. Conclusions: This work introduces a novel concept of a pivotal role of Jak2–Stat5a/b signaling for Rad51 expression and HR DNA repair in prostate cancer. Inhibition of Jak2–Stat5a/b signaling sensitizes prostate cancer to radiation and, therefore, may provide an adjuvant therapy for radiation to reduce radiation-induced damage to the neighboring tissues. Clin Cancer Res; 24(8); 1917–31. ©2018 AACR.

Initial experience with ketamine-based analgesia in patients undergoing robotic radical cystectomy and diversion.

INTRODUCTION We instituted a ketamine-predominant analgesic regimen in the peri- and postoperative periods to limit the effects of narcotic analgesia on bowel function in patients undergoing radical cystectomy. The primary end points of interest were time to return of bowel function, time to discharge, and efficacy of the analgesic regimen. METHODS We performed a retrospective chart review of patients undergoing robotic-assisted laparoscopic cystectomy (RARC) with urinary diversion by a single surgeon at our institution from January 1, 2011 to June 30, 2012. Patients receiving the opioid-minimizing ketamine protocol were compared to a cohort of patients undergoing RARC with an opioid-predominant analgesic regimen. RESULTS In total, 15 patients (Group A) were included in the ketamine-predominant regimen and 25 patients (Group B) in the opioid-predominant control group. Three patients (19%) in Group A discontinued the protocol due to ketamine side effects. The mean time to bowel movement and length of stay in Group A versus Group B was 3 versus 6 days (p < 0.001), and 4 versus 8 days, respectively (p < 0.001). Group A patients received an average of 13.0 mg of morphine versus 97.5 mg in Group B (p < 0.001). CONCLUSIONS Patients who received our ketamine pain control regimen had a shorter time to return of bowel function and length of hospitalization after RARC. Our study has its limitations as a retrospective, single surgeon, single institution study and the non-randomization of patients. Notwithstanding these limitations, this study was not designed to show inferiority of one approach, but instead to show that our protocol is safe and efficacious, warranting further study in a prospective fashion.

Radio-pathomic Maps of Epithelium and Lumen Density Predict the Location of High-Grade Prostate Cancer

Purpose: This study aims to combine multiparametric magnetic resonance imaging (MRI) and digitized pathology with machine learning to generate predictive maps of histologic features for prostate cancer localization. Methods and Materials: Thirty-nine patients underwent MRI prior to prostatectomy. After surgery, tissue was sliced according to MRI orientation using patient-specific 3-dimensionally printed slicing jigs. Whole-mount sections were annotated by our pathologist and digitally contoured to differentiate the lumen and epithelium. Slides were co-registered to the T2-weighted MRI scan. A learning curve was generated to determine the number of patients required for a stable machine-learning model. Patients were randomly stratified into 2 training sets and 1 test set. Two partial least-squares regression models were trained, each capable of predicting lumen and epithelium density. Predicted density values were calculated for each patient in the test dataset, mapped into the MRI space, and compared between regions confirmed as high-grade prostate cancer. Results: The learning-curve analysis showed that a stable fit was achieved with data from 10 patients. Maps indicated that regions of increased epithelium and decreased lumen density, generated from each independent model, corresponded with pathologist-annotated regions of high-grade cancer. Conclusions: We present a radio-pathomic approach to mapping prostate cancer. We find that the maps are useful for highlighting high-grade tumors. This technique may be relevant for dose-painting strategies in prostate radiation therapy.