Mean Number Of Tumors Research Articles

Retrospective analysis of 1470-/980-nm dual-wavelength laser en bloc resection versus transurethral resection of bladder tumor for primary non-muscle-invasive bladder cancer.

To compare the safety and efficacy of en bloc resection of non-muscle-invasive bladder cancer (NMIBC) using a 1470-/980-nm dual-wavelength laser (DwLRBT) compared to the gold standard, transurethral resection (TURBT). The study group included 251 patients with a confirmed diagnosis of NMIBC, 97 in the DwLRBT group and 154 in the TURBT group. Clinical characteristics, complications, and recurrence-free survival were compared between the two groups. There were no differences between the two groups with regard to age, sex, mean tumor size, mean tumor number, tumor location, risk, fever, and reoperation. Compared to TURBT, DwLRBT was associated with a shorter hospitalization time (mean±standard deviation: 5.81±1.48 days vs. 4.96±1.32, respectively, p=0.001), shorter catheterization time (4.98±1.47 vs. 4.20±1.48 days, respectively; p=0.035), and smaller volume of intraoperative bleeding (8.43±6.21 ml vs. 6.15±5.08, respectively; p=0.003). Recurrence-free survival (RFS) was better for DwLRBT than TURBT in the overall cohort (hazard ratio [HR], 0.4323; 95% confidence interval [CI], 0.2852-0.6554; p=0.0004) and for the following subgroups and tumor types: intermediate-risk (HR, 0.2654; 95%CI, 0.1020-0.6904; p=0.0245) and high-risk (HR, 0.4461; 95% CI, 0.2778-0.7162; p=0.0027) groups; and for pedunculate bladder tumors (HR, 0.4158; 95%CI, 0.2401-0.7202; p=0.0063), single bladder tumors (HR, 0.4136; 95%CI, 0.2376-0.7293; p=0.0072), and multiple bladder tumors (HR, 0.2727; 95%CI, 0.1408-0.5282; p=0.0014). DwLRBT is associated with better operative and postoperative outcomes, including, importantly, a longer RFS, compared to TURBT.

Feasibility and safety of percutaneous computed tomography guided radiofrequency ablation of lymph nodes in oligometastatic patients: a single center's experience.

To retrospectively evaluate feasibility and safety of CT-guided percutaneous radiofrequency ablation (RFA) of metastatic lymph nodes (LN) in terms of achieving local tumor control. Institutional database research identified 16 patients with 24 metastatic LNs who underwent percutaneous CT-guided radiofrequency ablation. Mean patient age was 66.6 ± 15.70 years (range 40-87) and male/female ratio was 8/8. Contrast-enhanced CT or MRI was used for post-ablation follow-up. Patient and tumor characteristics and RFA technique were evaluated. Technical and clinical success on per tumor and per patient basis as well as complication rates were recorded. Mean size of the treated nodes was 1.78 ± 0.83 cm. The mean number of tumors per patient was 1.5 ± 0.63. The mean procedure time was 56.29 ± 24.27 min including local anesthesia, electrode(s) placement, ablation and post-procedural CT evaluation. Median length of hospital stay was 1.13 ± 0.34 days. On a per lesion basis, the overall complete response post-ablation according to the mRECIST criteria applied was 75% (18/24) of evaluable tumors. Repeat treatment of an index tumor was performed on two patients (three lesions) with complete response achieved in 87.5% (21/24) of evaluable tumors following a second RFA. On a per patient basis, disease progression was noted in 10/16 patients at a mean of 13.9 ± 6.03 months post the ablation procedure. CT-guided percutaneous RFA for oligometastatic LNs is a safe and feasible therapy. With this percutaneous therapeutic option, metastatic LNs can be eradicated with a very low complication rate.

Laparoscopic hand-assisted liver resection for tumours in the left lateral section.

Context:The role of the laparoscopic left lateral sectionectomy (LLLS) is debatable, and Level-1 data are lacking.Aims:The aim of the study is to evaluate the feasibility and safety of this approach.Settings and Design:This was a retrospective study.Subjects and Methods:From 2007 to 2014, patients undergoing LLLS were identified from two institutions.Statistical Analysis Used:Continuous variables were compared between groups with Student's t-test or Mann–Whitney test, as appropriate by type of distribution. Categorical variables were compared with Chi-square or Fisher's exact test, depending on the number of observations.Results:Thirty-eight patients were included in the study. The mean age was 63.5 + 13 years (range, 31–89), and the mean number of tumours was 1.7 + 1.5. Eleven (29%) patients underwent LLS combined with an additional liver resection (combined resections group). The mean duration of the operation and the mean estimated blood loss were significantly decreased in the LLS group compared to the combined resection group (101 + 71 min vs. 208 + 98 min and 216 + 217 ml vs. 450 + 223 ml; P < 0.05 for both, respectively). The major complications rate was 8% and no mortality occurred.Conclusions:In a subset of carefully selected cases, LLLS may provide the benefits of laparoscopy. This does not appear to compromise perioperative morbidity rates. We believe that this approach may serve as a training platform for surgical trainees.

Safety of central compartment neck dissection for transoral endoscopic thyroid surgery in papillary thyroid carcinoma.

Remote access and endoscopic thyroid surgery has been gaining popularity because it allows patients to avoid a visible scar in the neck. There is limited data on transoral endoscopic thyroidectomy when it relates to patients with papillary thyroid carcinoma. We aim to evaluate the safety of ipsilateral central compartment dissection for patients who undergo transoral thyroidectomy (thyroidectomy vestibular approach-compartment lymph node dissection). A total of 80 patients who underwent thyroidectomy vestibular approach-compartment lymph node dissection for papillary thyroid carcinoma from June 2015 to September 2016 were identified. Over the same period, a matched cohort of 80 patients who underwent open thyroidectomy with routine ipsilateral central compartment dissection was also identified (Open-compartment lymph node dissection). The two groups were analyzed in terms of patient characteristics, perioperative clinical results and post-operative outcomes. All patients were female with a mean age of 32-year. There was no difference in mean maximum tumor size and number of lymph nodes dissected. Moreover, there was no difference in average positive lymph nodes between thyroidectomy vestibular approach-compartment lymph node dissection and Open-compartment lymph node dissection (1.48 vs 1.08, P=0.647). Operative time was longer in the thyroidectomy vestibular approach-compartment lymph node dissection group (193 vs 102 min, P<0.001). Thyroidectomy specific complications were similar with rates of temporary recurrent laryngeal nerve palsy of 6.3 vs 8.8% and temporary hypocalcemia rates of 2.5 vs 5% in the thyroidectomy vestibular approach-compartment lymph node dissection and Open-compartment lymph node dissection groups, respectively. Thyroidectomy vestibular approach-compartment lymph node dissection is a feasible and safe option for select patients with papillary thyroid carcinoma who require central node dissection compared with Open-compartment lymph node dissection, and can be a viable alternative for patients wishing to avoid a visible scar.

2835 Robot-Assisted Laparoendoscopic Single-Site (Ra-Less) Myomectomy Using Lapsingle Port

Study Objective To report our experience with robot-assisted laparoendoscopic single-site (RA-LESS) myomectomy using Lapsingle access, including outcomes & feasibility of this procedure. Design A Retrospective cohort study, from April 2018 to March 2019. Setting Single surgeon, Single medical center, University hospital. Patients or Participants Twenty-five patients with symptomatic subserosal or intramural myomas Interventions RA-LESS myomectomy was performed with the da Vinci Xi Surgical System (Intuitive Surgical, Inc, Sunnyvale, CA, USA) employing 8 mm endoscope and single-site 5 mm instrumentation through a laparoendoscopic single-site (LESS) port (Lapsingle, Sejong Medical, KOREA). Measurements and Main Results The mean age (±SD) and mean BMI were 40.2 ± 7.2 years and and 22.5 ± 2.7 kg/m2. Mean diameter of the largest tumor was 6.8 ± 1.5 cm (median 6.1 cm, range 3.1-9.7 cm), while mean number of tumors removed was 2.2 ± 1.8, ranging from 1 to 5 per surgery. The mean operating time, hemoglobin change, return of bowel activity, and length of hospital stay were 95.2±43.2 min, 1.5±0.7 g/dL, 36.8±9.1 h, and 3.8±0.7 days, respectively. All procedures were successfully performed without conversion to conventional LESS surgery, multi-port laparoscopy or laparotomy. There were no surgical or wound complications in any patient, and the histopathological result was leiomyoma in all the cases Conclusion RA-LESS myomectomy is a safe and feasible surgery with excellent cosmetic and postoperative outcomes in selected patients. Further investigation is needed to define the patient groups that will most benefit from it.

Diverse Roles of the Plasminogen Receptor, Plg‐RKT, in Mammary Tumor Development and Metastasis

ObjectivesPlg‐RKT is a unique transmembrane plasminogen receptor, highly expressed on tumor cells and macrophages. We investigated the role of Plg‐RKT in mammary tumor incidence, development, growth and metastasis in a PyMT transgenic mouse mammary tumor model.MethodsPlg‐RKT deficiency was bred into PyMT mice to compare mammary tumor development in PyMT/Plg‐RKT+/+ and PyMT/Plg‐RKT−/− female littermates.ResultsMultifocal mammary tumor development was observed in all animals with no difference between genotypes in time of first appearance of palpable tumors. Mice in both groups developed mammary tumors in 3 – 10 mammary glands per animal. However, the mean number of tumors in PyMT/Plg‐RKT−/− mice was significantly less than in PyMT/Plg‐RKT+/+ mice. Tumors in PyMT/Plg‐RKT−/− mice grew more slowly than tumors in PyMT/Plg‐RKT+/+ mice. At 20 weeks of age, cumulative mammary tumor volumes and tumor weights were significantly less for PyMT/Plg‐RKT−/− mice. Histological examination revealed abundant fibrin deposition in mammary tumors in PyMT/Plg‐RKT−/− mice but not in PyMT/Plg‐RKT+/+ mice, suggesting dysregulated fibrin surveillance and markedly dysregulated plasminogen activation due to the absence of Plg‐RKT. Early mammary tumors also differed markedly in their morphology: mammary foci in PyMT/Plg‐RKT−/− mice were primarily adenomas and were surrounded by a pronounced collagen‐rich extracellular matrix; whereas PyMT/Plg‐RKT+/+ mice had large, hyperproliferative tumor nodules that were not completely surrounded by extracellular matrix.We compared lung metastasis in PyMT/Plg‐RKT−/− and PyMT/Plg‐RKT+/+ mice, expecting fewer metastases in PyMT/Plg‐RKT−/− mice due to their decreased mammary tumor burden. Surprisingly, at 20 weeks of age PyMT/Plg‐RKT−/− mice had more metastatic lung tumors and a higher metastatic burden when tumor cells in the lungs were quantified by PCR for PyMT transcript expression. To evaluate the influence of mammary tumor burden on metastasis, we analyzed metastasis in a small cohort (n=8) of PyMT/Plg‐RKT−/− mice that at 22 weeks of age, had developed a mammary tumor burden similar to PyMT/Plg‐RKT+/+ mice at 20 weeks. When comparing metastasis in these mice with comparable tumor size, the larger metastatic burden in PyMT/Plg‐RKT−/− mice was even more striking. Staining of lung tissues for the pan‐macrophage marker (F4/80) revealed marked infiltration of macrophages both in the lung parenchyma and peritumoral to lung foci in PyMT/Plg‐RKT+/+ but not PyMT/Plg‐RKT−/− mice.ConclusionsTogether these results show that Plg‐RKT supports mammary tumor development and growth, and suggest that Plg‐RKT alters the ECM to promote tumorigenesis. Conversely, Plg‐RKT inhibits tumor metastasis, possibly because Plg‐RKT on non‐tumor cells, i.e., monocytes/macrophages, contributes to an anti‐metastatic environment in the target organ.Support or Funding InformationHL 081046, CA166473, Merit Rev. #5I01BX002026This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

What makes ultrasonography limited? Causes of missed hepatocellular carcinomas in surveillance ultrasonography for very high risk patients

Introduction Early detection of hepatocellular carcinoma (HCC) is very important because the prognosis largely relies on the tumor stage. Unfortunately, less than 30% of patients are diagnosed early enough for curative treatment. Ultrasonography is the standard surveillance tool for HCC. However, previous meta-analyses have highlighted the low per-patient sensitivity of US for the detecting early stage HCCs. We analyzed the causes of missed HCCs in surveillance ultrasonography in patients with very high risk of HCCs. Methods This is a preliminary analysis of prospective clinical trial comparing the performance of non-contrast liver MRI and ultrasonography as surveillance tools for detecting HCCs in patients with very high risk of HCC (MAGNUS-HCC, NCT02551250). In our institute, we enrolled 73 patients with estimated annual risk of HCC higher than 5%. During three-year follow up period, HCCs developed in 15 patients. Among them, six patients was only found in non-contrast MRI. We analyzed the causes of these missed HCCs on ultrasonography. Results Seven HCCs were found in six patients in whom ultrasonography missed HCCs (The mean tumor number=1.17). The mean diameter of HCCs was 2.0cm (range: 1.1 – 4.4 cm). Three HCCs were located in left hemiliver and another three HCCs were in right hemiliver. One HCC was in caudate lobe and this was the largest tumor (4.4 cm). We tried radiofrequency ablation for three HCCs and all of them were visible on guiding ultrasonography for radiofrequency ablation. Conclusion Ultrasonography for HCC detection is not a perfect tool for HCC surveillance. Ultrasonography can miss HCCs in any part of the liver and even large tumors might not be detected. For patients with very high risk of HCC, alternative surveillance tool should be considered because of the limitation of ultrasonography.

Reduced Recurrence of Low-grade Papillary Bladder Tumors Associated With Asymptomatic Bacteriuria

ObjectiveTo determine tumor recurrence rate of low-grade, papillary, and non–muscle-invasive (TaLG) bladder tumors in patients who have asymptomatic bacteriuria (ABU). Microbes in the urine trigger immune responses like intravesical Bacillus Calmette-Guerin, suggesting that common bacteria may also exert an antitumor effect. MethodsWe investigated recurrence rates in 387 patients with low-grade, papillary noninvasive bladder tumors TaLG, with or without ABU. They were followed every 6 months for 36 months, and did not receive antibiotics or intravesical chemotherapy. Recurrent tumors were treated generally by outpatient fulguration. Before cystoscopy, patients submitted a voided urine sample for culture, stratified as no growth, <104, >104, or >105 CFU/mL single organism. Any degree of bacteria on culture was classified as ABU. We also measured absolute neutrophil counts (ANC) and the presence of pyuria, as surrogate indicators of local immune response. ResultsOf the 387 cases, 200 (52%) had ABU, including 102 (27%) with >104 CFU/mL bacteriuria. With absolute 3-year follow-up, 75% of patients with ABU survived tumor-free compared to 40% of 187 uninfected patients (P = .001). Sixty percent of patients with negative cultures recurred vs 25%, 14%, and 29% of patients with <104, >104, or >105 CFU/mL. (P = .001). Mean number of recurrent tumors in colonized patients was 4.2 vs 8.4 in uninfected patients (P = .009). ANC averaged 6.3 K/mcL in bacteriuric vs 4.1 K/mcL in uninfected patients (P = .01). ConclusionPatients with papillary TaLG tumors and chronic ABU had fewer recurrences, fewer numbers of recurrent tumors, and longer tumor-free survival times than similarly staged uninfected patients. Bladder-resident bacteria may reduce bladder tumor recurrences through local immune mechanisms.

Microbiota modification by probiotic supplementation reduces colitis associated colon cancer in mice.

AIMTo investigate the effect of probiotic supplementation during the development of an experimental model of colitis associated colon cancer (CAC).METHODSC57BL/6 mice received an intraperitoneal injection of azoxymethane (10 mg/kg), followed by three cycles of sodium dextran sulphate diluted in water (5% w/v). Probiotic group received daily a mixture of Lactobacillus acidophilus, Lactobacillus rhamnosus and Bifidobacterium bifidum. Microbiota composition was assessed by 16S rRNA Illumina HiSeq sequencing. Colon samples were collected for histological analysis. Tumor cytokines was assessed by Real Time-PCR (Polymerase Chain Reaction); and serum cytokines by Multiplex assay. All tests were two-sided. The level of significance was set at P < 0.05. Graphs were generated and statistical analysis performed using the software GraphPad Prism 5.0. The project was approved by the institutional review board committee.RESULTSAt day 60 after azoxymethane injection, the mean number of tumours in the probiotic group was 40% lower than that in the control group, and the probiotic group exhibited tumours of smaller size (< 2 mm) (P < 0.05). There was no difference in richness and diversity between groups. However, there was a significant difference in beta diversity in the multidimensional scaling analysis. The abundance of the genera Lactobacillus, Bifidobacterium, Allobaculum, Clostridium XI and Clostridium XVIII increased in the probiotic group (P < 0.05). The microbial change was accompanied by reduced colitis, demonstrated by a 46% reduction in the colon inflammatory index; reduced expression of the serum chemokines RANTES and Eotaxin; decreased p-IKK and TNF-α and increased IL-10 expression in the colon.CONCLUSIONOur results suggest a potential chemopreventive effect of probiotic on CAC. Probiotic supplementation changes microbiota structure and regulates the inflammatory response, reducing colitis and preventing CAC.

MP83-06 THULIUM FIBER LASER EN BLOC RESECTION OF BLADDER CANCER.

You have accessJournal of UrologyBladder Cancer: Non-invasive II1 Apr 2018MP83-06 THULIUM FIBER LASER EN BLOC RESECTION OF BLADDER CANCER. Alim Dymov, Leonid Rapoport, Andrey Vinarov, Dmitry Enikeev, Nikolay Sorokin, Roman Sukhanov, Dmitry Kislyakov, Alexandra Proskura, Akhmed Damiev, and Gregory Gololobov Alim DymovAlim Dymov More articles by this author , Leonid RapoportLeonid Rapoport More articles by this author , Andrey VinarovAndrey Vinarov More articles by this author , Dmitry EnikeevDmitry Enikeev More articles by this author , Nikolay SorokinNikolay Sorokin More articles by this author , Roman SukhanovRoman Sukhanov More articles by this author , Dmitry KislyakovDmitry Kislyakov More articles by this author , Alexandra ProskuraAlexandra Proskura More articles by this author , Akhmed DamievAkhmed Damiev More articles by this author , and Gregory GololobovGregory Gololobov More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2754AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To date en bloc resection of non-muscle-invasive bladder cancer (NMIBC) is regarded by urologists as a promising surgical option. Previous studies have shown that en bloc resection of bladder tumors (ERBT) provides a high quality specimen with a muscle layer in 96-100% of cases, while conventional transurethral resection of bladder tumors (cTURB) in only 50-86% of cases. Different energy sources can be used for ERBT (electrocautery, laser, cyber-knife). Laser energy seems to be preferable due to absence of obturator nerve reflex and very precise resection. This study aims to evaluate the feasibility, safety and efficacy of thulium fiber laser en bloc resection of NMIBC. METHODS 71 laser en bloc resections for NMIBC with thulium fiber laser (Urolase, IRE Polus, Russia) were performed from 2015 to 2016. The mean tumor size was 2.28±0.15 cm. The mean tumor number was 1,72±0.18. Tumors location: lateral bladder wall – 43%; close to ureteral orifice – 25.4%; bladder neck – 4.2%; posterior bladder wall – 19,7%; anterior bladder wall – 4.2%; bladder triangle – 3.5%. The laser settings were as follows: 1J, 10Hz, 10W. Rigid 24Ch/26Ch resectoscope and flexible cystoscope with 600 and 400 μm laser fibers were used. Operating time, specimen quality, intra- and postoperative complications (obturator nerve reflex, bladder wall perforation, bleeding), recurrence rate at 6, 12,18 months postop were evaluated. RESULTS The average operating time was 38,7±1.87 min (10 – 80 min). Detrusor muscle was present in 91.55% of specimens. However, detrusor tissue was absent only in the specimens after a couple of first procedures. No obturator nerve reflex, bladder wall perforation or significant bleeding were observed. Early mitomycin C instillation in all cases was done. Recurrence rates at 6, 12, 18 months postoperatively were 9.86%, 11.27% and 2.81%, respectively. CONCLUSIONS Thulium laser en bloc resection of bladder cancer is a safe and effective procedure for NMIBC treatment. Apparently, it gives acceptable recurrence and low complication rates providing high quality specimen for proper staging and decision-making on further management strategy. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1117-e1118 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Alim Dymov More articles by this author Leonid Rapoport More articles by this author Andrey Vinarov More articles by this author Dmitry Enikeev More articles by this author Nikolay Sorokin More articles by this author Roman Sukhanov More articles by this author Dmitry Kislyakov More articles by this author Alexandra Proskura More articles by this author Akhmed Damiev More articles by this author Gregory Gololobov More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Use of electromagnetic navigational bronchoscopy in robotic pulmonary resection.

Robotic resection of pulmonary lesions has become a more common approach in the field of thoracic surgery. The greatest drawback of robotic resection is the lack of tactile feedback as compared to open approaches, making identification of intrapulmonary lesion difficult. Electromagnetic navigational bronchoscopy (navibronch) enables pre-incisional marking of pulmonary lesions for intraoperative identification. We sought to determine how effective navibronch was in our institution's robotic cases. Thirty-one patients underwent robotically assisted resection of 35 lesions with the assistance of navibronch from 7/2014 to 9/2015. Retrospective demographic and operative data were collected on these patients, and statistical analysis was conducted using ANOVA means testing, Chi-square, and non-parametric tests. The average age in this patient population was 63.7±13.5years. Eight patients (25.8%) were male. Twenty-five (80.6%) of the patients had pathology involving one lobe, with six (19.4%) in two lobes. 34 of the resections (97.1%) resulted in dye being localized to the first specimen; 34 (97.1%) were found to have the target pathology in the initial specimen. Further resection was carried out in 22 (62.9%) cases, with the final resection resulting in a segment in 2 (5.7%) and a lobe in 14 (40.0%). The mean number of lung specimens collected was 1.94±0.13. The mean number of tumors in each target resection was 1.46±0.66 in final pathology. Malignancy was found in 19 (54.3%) of final specimens. There were no complications related to navibronch. Navibronch is an effective technique in the identification and localization of pulmonary lesions in robotically assisted lung resections.

Chemopreventive effect of a novel nutrient mixture on lung tumorigenesis induced by urethane in male A/J mice.

Lung cancer, a leading cause of cancer death, is associated with exposure to inhalation carcinogens, most commonly those found in tobacco smoke. We investigated the in vivo effect of dietary supplementation with a nutrient mixture containing lysine, proline, arginine, ascorbic acid, green tea extract, N-acetyl cysteine, selenium, copper and manganese on the development of urethane-induced lung tumors in male A/J mice. After one week of isolation, seven-week-old male A/J mice (n = 25) weighing 17-19 g were randomly divided into three groups: group A (n = 5), group B (n = 10), and group C (n = 10). Mice in groups B and C were each given a single intraperitoneal injection of urethane (1 mg/g body weight) in saline, whereas group A mice received an injection of saline alone. Groups A and B were fed a regular diet, whereas group C was fed the same diet supplemented with 0.5% nutrient mixture. After 20 weeks, mice were sacrificed, lungs were excised and weighed, and tumors were counted and processed for histology. Urethane-challenged mice developed tumors. However, the mean number of tumors and the mean lung weights in the mice on the supplemented diet were significantly reduced, by 49% (P < 0.0001) and 18% (P = 0.0025), respectively, compared to mice on the control diet. We observed neither significant differences in body weight gains nor in diet consumption among the mice. Pulmonary lesions were morphologically similar for both the groups (adenomas), but lesions were smaller in the test group. The results suggest that nutrient mixture has inhibitory potential on the development of mouse lung tumors induced by urethane.

Combination of AKT inhibitor ARQ 092 and sorafenib potentiates inhibition of tumor progression in cirrhotic rat model of hepatocellular carcinoma.

The prognosis of patients with advanced hepatocellular carcinoma (HCC) is very poor. The AKT pathway is activated in almost half of HCC cases and in addition, long term exposure to conventional drug treatment of HCC, sorafenib, often results in over-activation of AKT, leading to HCC resistance. Therefore, it is important to assess the safety and the efficacy of selective allosteric AKT inhibitor ARQ 092 (Miransertib) in combination with sorafenib.Here, we demonstrated in vitro that the combination of ARQ 092 with sorafenib synergistically suppressed proliferation, promoted apoptosis, and reduced migration. To test the effect of the combination in vivo, rats with diethylnitrosamine-induced cirrhosis and fully developed HCC were randomized and treated with vehicle, sorafenib, ARQ 092 or the combination of ARQ 092 with sorafenib; (n=7/group) for 6 weeks. Tumor progression, size of tumors and the mean tumor number were significantly reduced by the combination treatment compared to the control or single treatments. This effect was associated with a significant increase in apoptotic response and reduction in proliferation and angiogenesis. Sirius red staining showed a decrease in liver fibrosis. Moreover, treatments improved immune response in blood and in tumor microenvironment.Thus, the combination of ARQ 092 with sorafenib potentiates inhibition of tumor progression and gives the possibility of therapeutic improvement for patients with advanced HCC.

LFM-A13, a potent inhibitor of polo-like kinase, inhibits breast carcinogenesis by suppressing proliferation activity and inducing apoptosis in breast tumors of mice.

The goals of the present study were to define the anticancer activity of LFM-A13 (α-cyano-β-hydroxy-β-methyl-N-(2,5-dibromophenyl)-propenamide), a potent inhibitor of Polo-like kinase (PLK), in a mouse mammary cancer model induced by 7,12-dimethylbenz(a)anthracene (DMBA) in vivo and explore its anticancer mechanism(s). We also examined whether the inhibition of PLK by LFM-A13 would improve the efficiency of paclitaxel in breast cancer growth in vivo. To do this, female BALB/c mice received 1mg of DMBA once a week for 6weeks with oral gavage. LFM-A13 (50mg/kg body weight) was administered intraperitoneally with DMBA administration and continued for 25weeks. We found that LFM-A13, paclitaxel, and their combination have a significant effect on the DMBA-induced breast tumor incidence, mean tumor numbers, average tumor weight, and size. At the molecular level, the administration of LFM-A13 hindered mammary gland carcinoma development by regulating the expression of PLK1, cell cycle-regulating proteins cyclin D1, cyclin dependent kinase-4 (CDK-4), and the CDK inhibitor, p21. Moreover, LFM-A13 treatment upregulated the levels of IκB, the pro-apoptotic proteins Bax, and caspase-3, and down-regulated p53 and the antiapoptotic protein Bcl-2 in mammary tumors. The combination of LFM-A13 with paclitaxel was found to be more effective compared with either agent alone. Collectively, these results suggest that LFM-A13 has an anti-proliferative activity against breast cancer in vivo and that LFM-A13 and paclitaxel combination could be a strategy for the treatment of breast cancer.

Abstract 5124: GNS561 a new quinoline derivative inhibits the growth of hepatocellular carcinoma in a cirrhotic rat and human PDX orthotopic mouse models

Abstract Background: Hepatocellular carcinoma (HCC) remains a major health problem, often diagnosed at late stages with limited number of therapeutic options. New drugs with original mechanisms of action are urgently aimed to improve current armamentarium in HCC patients. Quinoline derivatives are novel class of oral small molecules inducing multiple cellular effects such as inhibition of autophagy, induction of apoptosis, and cell cycle modulation. The aim of these studies was to assess tolerance and efficacy of a new quinolone derivative GNS561. Material and methods: In vitro experiments were realized with viability, apoptosis and migration in tumor cells in HCC cell lines and primary tumor. Drug tolerance and plasma and liver pharmacokinetic were evaluated after single and repeated dosing in mice and rat. GNS561 and sorafenib efficacy in vivo were evaluated in a PDX orthotopic BALB/c-nu mouse model and in a diethylnitrosamine (DEN)-induced HCC cirrhotic rat model. AFP, cell proliferation and tumor weight and size were assessed in mice. In rat tumor progression was followed by MRI, pathological analysis (tumor size and number), immunohistochemistry and PCR analysis after 6weeks of treatment. Results: GNS 561 shows potent anti-proliferative activity when assayed against a panel of human tumor cell lines and notably against a panel of HCC patient primry tumors even in those with sorafenib resistance (Mean EC50 3µM vs 11µM for sorafenib). GNS561 is highly selectively trapped in the liver. Plasma and liver PK in mice and rats after single and repeated doses confirm this selectivity with good tolerance and oral bioavailability. In PDX mouse model, tumor growth was significantly reduced by GNS561 with a dose-response manner, this tumor regression was associated with AFP level decreases by 72% with GNS561 (p=0.002) and 54% with sorafenib (p=0.046) compared to control. In rat model, mean number of tumors was significantly lower in GNS561 at 15mg/kg group (n=50.6), in sorafanib at 10mg/kg (n=65.1) and in combination group (n=40.6), when compared to control (n=100.4; p=0.0024, p= 0.029 and p=0.0002). Tumor decrease measured by MRI was associated with a significantly reduced proliferation of tumor cells particularly in GNS561 group (70%) and combination (84%) compared to control, whereas the effect of sorafenib alone on proliferation was modest (30%). Conclusions: GNS561 is a liver selective drug with good tolerance and promising efficacy in different HCC animal models. GNS 561 was more efficient than sorafenib to control tumor growth in preclinical models. Based on its safe toxicity profile and potent activity in rodent models, GNS 561 is now aimed to further reach clinical development in patients with HCC in 2017. Citation Format: Firas BASSISSI, Zuzana Macek Jilkova, Sonia Brun, Jerome Courcambeck, Jennifer Tracz, Keerthi Kurma, Gaël S. Roth, Cindy Khaldi, Corinne Chaimbault, Benoit Quentin, Emilie Asseraf, Antoine Beret, Eric Raymond, Philippe Halfon, Thomas Decaens. GNS561 a new quinoline derivative inhibits the growth of hepatocellular carcinoma in a cirrhotic rat and human PDX orthotopic mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5124. doi:10.1158/1538-7445.AM2017-5124

Basal Cell Carcinoma Multiplicity – a Retrospective Analysis of 899 Biopsy-proven Patients from a Single Institute

An interesting clinical feature of basal cell carcinoma (BCC) of the skin is a marked interpatient variation in tumor number, lesion accrual and anatomic distribution. We analyzed a proportion of patients with multiple BCCs in the cohort of pathology report-confirmed cases of BCC and investigated clinicopathological differences between individuals suffering from multiple tumor lesions and patients with a single tumor. All consecutive patients with primary cutaneous BCCs, who were histologically diagnosed at our Department of Pathology during a 10-year period were enrolled into the study. A cohort of 899 participants with a total of 1,239 histologically proven primary BCCs were assessed. Of them, 728 (81%) had single BCC and 171 (19%) had multiple BCCs. Multiple lesions occurred more frequently in men than women. Mean number of tumors per patient was 1.5 in males and 1.2 in females. Among participants with multiple BCC manifestation, there was a steady increase of the male-to-female ratio with rising tumor number per individual. In the multiple BCC subgroup, the tumors were found more commonly in the trunk and upper limbs, and less frequently in the face. Histologically, these BCCs much more commonly included superficial subtype. There was a positive correlation between the non-aggressive histologic phenotype of BCC and multiple tumor presentations on the one hand, and the aggressive histologic phenotype of BCC and a single tumor occurrence on the other. Our analysis shows that clinicopathological features associated with multiple BCC manifestations include male gender, tumor location in the trunk and upper extremities, and superficial histological subtype. Focus on this risk profile may be beneficial for clinical screening and may help clinicians in the selection of individuals, who should be followed-up more closely.Key words: basal cell carcinoma - single and multiple manifestations - clinicopathological differences.

Practical Considerations of Real Life of Hepatocellular Carcinoma in a Tertiary Center of Brazil

Background. Hepatocellular carcinoma (HCC) is the most common malignancy that develops in cirrhotic livers. Its clinical and epi-demiological characteristics and mortality rates vary according to geographical region. The objective of this study was to evaluate the clinical profile, epidemiological characteristics, laboratory parameters, treatment and survival of patients with HCC.Material and methods. Patients with HCC seen between 2000 and 2012 were studied. The Kaplan-Meier method was used for survival analysis according to variables in question.Results. The study included 247 patients with a mean age of 60 ± 10 years. There was a predominance of males (74%). The main etiologies of HCC were HCV infection (55%), excessive alcohol consumption (12%), and HBV infection (8%). Liver cirrhosis was present in 92% of cases. The mean tumor number and diameter were 2 and 5 cm, respectively. Patients meeting the Milan criteria corresponded to 43% of the sample. Liver transplantation was performed in 22.4% of patients of the Milan subset and in 10% of the whole sample. The overall mean survival was 60 months, with a 1-, 3- and 5-year survival probability of 74%, 40% and 29%, respectively. Lower survival was observed among patients with alcoholic etiology. Survival was higher among patients submitted to liver transplantation (P < 0.001), TACE (P < 0.001), or any kind of treatment (P < 0.001). However, no difference was found for surgical resection (P = 0.1) or sorafenib (P = 0.1).Conclusion. Patients with HCC were mainly older men diagnosed at an advanced stage. Treatment was associated with better overall survival, but few patients survived to be treated.

Embolization for Bleeding after Hepatic Radiofrequency Ablation

PurposeTo evaluate safety and clinical efficacy of embolization for management of bleeding after hepatic radiofrequency (RF) ablation. Materials and MethodsFrom January 2000 to December 2014, 5,196 patients with 9,743 tumors underwent 8,303 RF ablation sessions. Of these patients, 62 experienced bleeding after hepatic RF ablation; 15 patients (12 men and 3 women; mean age 62 y; range, 49–76 y) underwent embolization and composed the final study cohort. Tumors were hepatocellular carcinomas in 13 (87%) patients and metastatic adenocarcinomas from colorectal cancer in 2 (13%) patients. Mean number of tumors was 1.5 (22 nodules; range, 1–3). Tumor locations were segment I (n = 1), segment II (n = 2), segment III (n = 1), segment IV (n = 1), segment V (n = 3), segment VI (n = 5), segment VII (n = 1), and segment VIII (n = 9). Mean tumor size was 2.3 cm (range, 0.9–5 cm). ResultsMedian time interval between presentation and angiography was 22 hours (mean 38.4 h; range, 3–168 h). On angiography, contrast extravasation with or without pseudoaneurysm was seen in all 15 patients; 14 patients underwent transarterial embolization, and 1 patient underwent percutaneous transhepatic portal vein embolization. Successful hemostasis was achieved in all patients. There was no rebleeding within 30 days after embolization. No embolization-related major complications were observed. ConclusionsEmbolization is safe and effective for controlling bleeding related to hepatic RF ablation without the need for surgery.

Renal functional outcomes after robotic multiplex partial nephrectomy: the National Cancer Institute experience with robotic partial nephrectomy for 3 or more tumors in a single kidney.

To identify renal function outcomes after robotic multiplex partial nephrectomy (RMxPNx), we reviewed our institutional database at the National Institutes of Health, National Cancer Institute. To our knowledge, we present the largest series of RMxPNx renal function outcomes to date. Robotic partial nephrectomy has been employed for oncologic control and to prevent dialysis dependence in hereditary multifocal renal cell carcinoma conditions. We have termed robotic surgery on a single kidney with three or more lesions a RMxPNx. We evaluated patients from a prospectively maintained database at a single institution (NIH/NCI) that underwent RMxPNx from 2007 to 2013. Demographic and operative data were compiled with statistical analysis with T test performed to determine renal function outcomes. A total of 54 patients underwent RMxPNx. Mean number of tumors removed was 8.63 (range 3-52). Mean preoperative creatinine and eGFR were 1.02±0.26mg/dL and 85.4±21.5mL/min, respectively. Postoperatively, creatinine increased from baseline by 0.45mg/dL (p<0.001). Similarly, a mean decrease in eGFR by 24.6mL/min was observed (p<0.001). At 3-month follow-up, the creatinine increase from baseline was 0.05mg/dL (p=0.10) and mean decrease in eGFR was 3.01mL/min (p=0.21). When stratifying based on preoperative CKD stages I-III, similar results were observed. Robotic multiplex partial nephrectomy is a safe and feasible approach to patients with multifocal renal masses. These complex surgeries have a demonstrated learning curve, but this minimally invasive approach for nephron-sparing surgery allows patients to preserve renal function where they would otherwise require open surgery or a radical nephrectomy.

Radiofrequency ablation vs. hepatic resection for resectable colorectal liver metastases.

The treatments of resectable colorectal liver metastases (CRLM) are controversial. This study aimed to evaluate the relative efficacy and safety of hepatic resection (HR) and radiofrequency ablation (RFA) for treating resectable CRLM. Between January 2004 and May 2010, the enrolled patients were given hepatic resection (HR group; n=32) or percutaneous RFA (RFA group; n=21) as a first-line treatment for CRLM. All the tumors had a maximum diameter of 3.5 cm and all patients had five or less tumors. The patient background, tumor characteristics, cumulative survival rate and recurrence-free survival rate were assessed in both groups. There were significantly more patients with comorbidities in the RFA group than those in the HR group (17 in RFA group vs. 10 in HR group; P<0.000). The mean maximum tumor diameter in the HR group and RFA group was 2.25±0.68 and 1.89±0.62 cm (P=0.054), and the mean number of tumors was 2.28±1.05 and 2.38±1.12 (P=0.744), respectively. The 1-, 3- and 5-year cumulative survival rates in the HR group were 87.5%, 53.1% and 31.3%, respectively, and those in the RFA group were 85.7%, 38.1% and 14.2%, respectively with the differences being not significant between the two groups (P=0.062). The 1-, 3- and 5-year recurrence-free survival rates in the HR group were 90.6%, 56.3% and 28.1%, respectively, and those in the RFA group were 76.1%, 23.8% and 4.8%, respectively, with the differences being significant between the two groups (P=0.036). In conclusion, as HR has greater efficacy than RFA in the treatment of resectable CRLM, we recommend it as the first option for this malignancy.