Developed Tumor Recurrence Research Articles

Abstract 3643: Utility of peritoneal and pleural lavages for detection of somatic alterations: A proof-of-concept study

Abstract Background: Surgical resection remains the best treatment option for early-stage endometrial (CE), colorectal (CRC) and lung cancer (LC) patients. However, a proportion of patients (p) develop tumor recurrence, even after curative resection. Peritoneal or pleural lavages may be performed during surgery but little data is available about their potential as liquid biopsies with predictive value for recurrence. This proof-of concept study aimed to determine if somatic mutations can be detected in these lavages. Methods: We analyzed mutations in paired surgical biopsies, blood and peritoneal or pleural lavages supernatants in an early-stage cohort of 25 EC, 12 CRC and 19 LC p. Molecular characterization of surgical biopsies was performed using the GeneReader NGS platform (Qiagen) and the Actionable Insight Tumor Panel, which includes 12 genes (KRAS, NRAS, KIT, BRAF, PDGFRA, ALK, EGFR, ERBB2, PIK3CA, ERBB3, ESR1, and RAF1). cfDNA was purified from blood and lavages using an automatic extractor and the hotspot mutations identified in tumor tissue were tested using a sensitive Taqman assay for codons 12, 13, and 61 in KRAS, codons 542, 545 and 1047 in PIK3CA and codon 600 in BRAF. Results: NGS of tumor biopsies revealed hotspot KRAS, PIK3CA or BRAF mutations in a total of 11/25 (44%) early-stage EC p, 7/12 (58%) early-stage CRC p and 6/19 (32%) early-stage LC p. In peritoneal lavages, hotspot mutations were found in 6/11 (55%) EC p and 2/7 (29%) CRC p and, in pleural lavages, hotspot mutations appeared in 2/6 (33%) LC p. Furthermore, 2/11 (18%) blood samples from EC p, 1/7 (14%) blood samples from CRC p and 1/6 (17%) blood samples from LC p were positive. Conclusions: Our study reveals that mutational analysis in peritoneal or pleural lavages from early stage tumors is feasible and that mutations are more frequently detected in lavages than in blood. Further research will determine if positivity in blood or lavages is associated with early relapse. Citation Format: Núria Jordana Ariza, Mónica Garzón Ibañez, Alejandro Martinez-Bueno, Sonia Gatius Caldero, Clara Mayo de las casas, Ana Velasco, Maria Ruiz, Berta Roman Canal, Jordi Bertran Alamillo, Sonia Rodríguez Muñoz, Raquel Campos Fuentes, Beatriz García, Ariadna Balada Bel, Sergi Villatoro, Miguel Ángel Molina-Vila, Xavier Matias-Guiu. Utility of peritoneal and pleural lavages for detection of somatic alterations: A proof-of-concept study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3643.

Intracranial Mesenchymal Chondrosarcoma: Report of 16 Cases

Limited data regarding intracranial mesenchymal chondrosarcoma (MCS) are available. The goal of this study was to report the clinical characteristics, challenges in management, and poor outcomes of intracranial MCS. Clinical data for 16 patients with MCS were reviewed retrospectively to evaluate their clinical characteristics, management, and outcomes. This study included 11 male and 5 female patients with a mean age of 22.9 ± 14.4 years. The most common presentations were headache (n= 10; 62.5%), followed by cranial deficits (n= 7; 43.6%). The radiologic spectrum for MCS was broad, and only 18.8% (3/16) of MCSs were correctly diagnosed preoperatively. Aggressive resection (including subtotal resection and gross total resection) and partial resection was performed in 62.5% (10/16) and 37.50% (6/16) of patients. With a median follow-up of 34 months (range, 10-78 months), 5 patients (31.3%) died and 8 patients (50%) developed tumor recurrence. The 1-, 3-, and 5-year rates of progression-free survival and overall survival were 86%, 53%, and 42% and 93%, 70%, and 56%, respectively. Although the differences were not significantly different, aggressive resection and the use of radiotherapy tended to improve the prognosis of the patients. Clinical characteristics of MCS are variable. The current management of intracranial MCS referring to conventional chondrosarcoma could not yield satisfactory outcomes. Further study is needed to identify the optimal treatments.

Prognostic factors and prognostic models for renal cell carcinoma: a literature review.

Following curative treatment for localised renal cell carcinoma (RCC), up to 30% of patients develop tumour recurrence. Prognostic scores are essential to guide individualised surveillance protocols, patient counselling and potentially in the future to guide adjuvant therapy. In metastatic RCC, prognostic scores are routinely used for treatment selection in clinical practice as well as in all major trials. We performed a literature review on the current evidence based on prognostic factors and models for localised and metastatic RCC. A number of prognostic factors have been identified, of which tumour node metastasis classification remains the most important. Multiple prognostic models and nomograms have been developed for localised disease, based on a combination of tumour stage, grade, subtype, clinical features, and performance status. However, there is poor level of evidence for their routine use. Prognostic scores for patients with metastatic RCC receiving targeted treatments are used routinely, but have limited accuracy. Molecular markers can improve the accuracy of established prognostic models, but frequently lack external, independent validation. Several factors and models predict prognosis of localised and metastatic RCC. They represent valuable tools to provide estimates of clinically important endpoints, but their accuracy should be improved further. Validation of molecular markers is a future research priority.

A single-center experience of liver transplantation for alcoholic liver disease

Objective To study liver transplantation in the treatment of alcoholic liver disease (ALD). Methods A retrospective study was conducted on 40 patients with ALD who underwent liver transplantation in the Changzheng Hospital of the Second Military Medical University from April 2005 to June 2017. The data were expressed as mean±standard deviation (±s) in populations with a normal distribution, and as median (min~max) in populations with an abnormal distribution. The survival rate was analyzed by life tables, and the Cox regression analysis was used for multivariate analysis. Results All patients were followed up until August 31, 2017. The follow-up time was 2~4 518 days, with a median of 997 days. Among the 40 patients, 8 had already died (3 died of multiple organ failure, 2 of biliary complications, 1 of liver failure, 1 of sepsis and 1 of recurrence of hepatocellular carcinoma (HCC). The 1-year survival rate was 81.0%, and the 5-year survival rate was 77.0%. Four of 40 patients developed tumor recurrence. The initial recurrence time was 189~337 days (median 236.5). The recurrence sites included the liver, colon combined with lungs, lungs, and lumbar vertebrae. Six of 40 (15.0%) patients had relapse in alcoholism. Multivariate analysis showed that age was a prognostic factor (RR=1.109, P 0.05). Conclusions ALD patients were mostly 40~60 years old. Age was an independent factor affecting survival. The younger the patient, the better the prognosis. Other factors were of no prognostic significance. Key words: Alcoholic liver disease(ALD); Liver transplantation(LT); Survival analysis; Alcoholism

Characterization and Management of Borderline Ovarian Tumors – Results of a Retrospective, Single-center Study of Patients Treated at the Department of Gynecology and Obstetrics of the University Medicine Greifswald

Borderline ovarian tumors (BOT) are malignant epithelial ovarian tumors with a very low incidence, therefore lacking sufficient clinical experience in diagnostics and treatment. This study characterized the histology, clinical features, diagnostics and therapy of BOT including patients treated at the Department of Gynecology and Obstetrics of the University Medicine Greifswald. In this retrospective, single-center study, patients with BOT treated between 1990 and 2010 were analyzed according to their histological and clinical reports. A total of 54 patients were enrolled. The median age was 54.6 (range=23-83) years. Distribution of histological subtypes was: serous in 31 patients (57.4 %) and mucinous in 23 patients (42.6%). All patients underwent surgery. Eight patients (14.8%) were treated according to actual therapy recommendations during the initial surgery. Eight patients (14.8%) received adjuvant chemotherapy contrary to treatment recommendations. In the case of 36 patients (66.7%), a frozen section was taken intraoperatively, which matched the definitive histological result in 88.9%. During average follow-up of 70.3 months (range=0-231 months), two patients (3.7%) developed tumor recurrence after 9 and 29 months, respectively, two patients (3.7%) died of causes other than BOT. Our study critically demonstrated that until a few years ago, BOTs were not usually treated according to international therapy recommendations. Nevertheless, the rate of tumor recurrence was very low.

Citral induced apoptosis in MDA-MB-231 spheroid cells

BackgroundBreast cancer remains a leading cause of death in women worldwide. Although breast cancer therapies have greatly advanced in recent years, many patients still develop tumour recurrence and metastasis, and eventually succumb to the disease due to chemoresistance. Citral has been reported to show cytotoxic effect on various cancer cell lines. However, the potential of citral to specifically target the drug resistant breast cancer cells has not yet been tested, which was the focus of our current study.MethodsThe cytotoxic activity of citral was first tested on MDA-MB-231 cells in vitro by MTT assay. Subsequently, spheroids of MDA-MB-231 breast cancer cells were developed and treated with citral at different concentrations. Doxorubicin, cisplatin and tamoxifen were used as positive controls to evaluate the drug resistance phenotype of MDA-MB-231 spheroids. In addition, apoptosis study was performed using AnnexinV/7AAD flowcytometry. Aldefluor assay was also carried out to examine whether citral could inhibit the ALDH-positive population, while the potential mechanism of the effect of citral was carried out by using quantitative real time- PCR followed by western blotting analysis.ResultsCitral was able to inhibit the growth of the MDA-MB-231 spheroids when compared to a monolayer culture of MDA-MB-231 cells at a lower IC50 value. To confirm the inhibition of spheroid self-renewal capacity, the primary spheroids were then cultured to additional passages in the absence of citral. A significant reduction in the number of secondary spheroids were formed, suggesting the reduction of self-renewal capacity of these aldehyde dehydrogenase positive (ALDH+) drug resistant spheroids. Moreover, the AnnexinV/7AAD results demonstrated that citral induced both early and late apoptotic changes in a dose-dependent manner compared to the vehicle control. Furthermore, citral treated spheroids showed lower cell renewal capacity compared to the vehicle control spheroids in the mammosphere formation assay. Gene expression studies using quantitative real time PCR and Western blotting assays showed that citral was able to suppress the self-renewal capacity of spheroids and downregulate the Wnt/β-catenin pathway.ConclusionThe results suggest that citral could be a potential new agent which can eliminate drug-resistant breast cancer cells in a spheroid model via inducing apoptosis.

'Very-low-risk' bladder tumours - a new entity?

To evaluate the homogeneity of the 'low-risk' bladder cancer group in an attempt to optimise follow-up protocols. Between June 1998 and December 2008, 211 patients (mean [sd] age of 66.7 [12.8]years) underwent transurethral resection of low-risk bladder cancer. Postoperative follow-up included cystoscopy at 3 and 12months after surgery, then annually for a total of 5years, and then annual ultrasonography indefinitely. After a median follow-up of 10years, 65 patients (30.7%) developed tumour recurrence and three (1.4%) stage progressions. In all, 84 patients (40%) had tumours of ≤1cm; these patients were significantly younger than patients with 1.1-3cm tumours (64.6 vs 68.3years, P = 0.03). Their 5-year recurrence-free survival rate was significantly higher (92% vs 70% in patients with larger tumours, P < 0.001). The median time to recurrence was 5.7years in patients with smaller tumours and 3.6years in patients with larger tumours (P = 0.03). Only 43.7% of the recurrences in patients with small tumours occurred within 5years, compared to 75.5% in patients with larger tumours. Patients with low-risk bladder cancer make an inhomogeneous group. They can be stratified according to tumour size. Patients with tumours of ≤1cm are younger, have lower risk of tumour recurrence, and most of their recurrences arise beyond the recommended 5-year surveillance period. It seems that these patients can be classified separately to a 'very-low-risk' group. Follow-up in these cases can be based on prolonged non-invasive evaluations.

Posterior decompression and occipitocervical fixation followed by intraoperative vertebroplasty for metastatic involvement of the axis

BackgroundMetastases to the upper cervical spine were rarely reported in the literature. However, metastases to this area may cause spinal instability and cord compression, which in turn can result in respiratory failure and neurological dysfunction. The present study investigated the efficacy and safety of posterior decompression and occipitocervical fixation followed by intraoperative vertebroplasty for this disease.MethodsThis was a retrospective study that included 10 patients with metastatic involvement of the axis from March 2002 to May 2014. All cases presented with occipitocervical pain: 5 patients with compressive myelopathy and 6 patients with radiculopathy. Japanese Orthopedic Association (JOA) scores and Visual Analogue Scale (VAS) were used to evaluate the improvement of neurological function and pain intensity, respectively.ResultsAll patients underwent posterior decompression and occipitocervical fixation followed by intraoperative vertebroplasty. The VAS scores and JOA scores both improved postoperatively, from 8.2 ± 0.4 to 2.3 ± 0.2 and from 10.1 ± 2.2 to 14.2 ± 2.9, respectively. Additionally, the improvement rate of JOA was 52.4 ± 1.8%. The mean overall survival was 12.8 months. The median survival time was 7 months. The 6-month and 12-month survival rates were 70% and 40%, respectively. The mean duration of operation was 182 min and blood loss was 450 mL. The mean volume of bone cement injected was 4.0 mL. The cement extravasation was observed in only 1 patient without clinical symptoms. One patient developed tumour recurrence and died 1 month later.ConclusionsPosterior decompression and occipitocervical fixation followed by intraoperative vertebroplasty was a safe and valuable palliative method with relatively less invasion to treat metastatic involvement of the axis.

Surgical results and outcome of sphenoid wing en plaque meningioma

Background Sphenoid wing en plaque meningioma is a subgroup of meningiomas defined by its particular sheet-like dural involvement and its disproportionately large bone hyperostosis. Sphenoid wing en plaque meningiomas are also called spheno-orbital meningiomas and pterioneal meningiomas en plaque. It represents 2–9% of all meningiomas and they are mainly located in the sphenoid wing. Objective The aim of this study was to analyze the outcome, surgical results, and recurrence rate in a series of 20 patents. Patients and methods This respective descriptive analytical study includes 20 patients with sphenoid wing en plaque meningiomas, who were surgically treated between 2010 and 2014. Results There were 14 women and 6 men, the mean age was 45 years (range: 20 and 70 years), six patients presented by extension of the dural component into the orbit, seven patients with cavernous sinus infiltration, adjuvant radiation therapy was performed for five patients after the surgery. After follow-up at 4 years, seven patients developed tumor recurrence, three patients submitted to surgical treatment, and four patients to radiation therapy. Patients without tumor extension to the orbit or cavernous sinus had the best prognosis, while patients with tumor extension, the recurrent rate was high. Conclusion Postoperative radiation therapy is indicated in cases with residual tumor in cavernous sinus and superior orbital fissure involvement is frequent and should be considered within surgical limits.

Extra-glissonian Approach for Total Laparoscopic Left Hepatectomy: A Prospective Cohort Study.

Laparoscopic liver resection under hemihepatic vascular inflow control has advantages over Pringle's maneuver, especially in patients with cirrhosis. From January 2016 to August 2016, 7 patients who underwent total laparoscopic left hepatectomy under hemihepatic vascular inflow occlusion using the extra-glissonian approach were included in this study. All were hepatitis B carriers and 4 had cirrhosis. The mean operation time was 247 minutes. The mean transection time was 110 minutes. No patient needed additional Pringle's maneuver. The mean intraoperative blood loss was 74 ml and no patient required blood transfusion. No open conversion happened. Postoperatively, no patient developed complications and there was no perioperative mortality. The mean resection margin was 2 cm. The mean hospital stay was 6 days. Upon a mean follow-up of 9 months, no patient developed tumor recurrence. The technique of total laparoscopic left hepatectomy using extra-glissonian approach was safe and feasible. The early surgical outcomes were good.

Intensified preoperative chemoradiation by adding oxaliplatin in locally advanced, primary operable (cT3NxM0) rectal cancer

PurposeThe major goals of preoperative treatment for locally advanced rectal cancers (LARCs) are improvement of local tumor control, tumor downsizing, and downstaging. Modifications with respect to standardized chemoradiation protocol, e. g., integrating oxaliplatin, are realized with the aim of improving primary tumor response and patient outcome.Patients and methodsIn this phase II multicenter study, patients with LARC of the mid- or lower rectum, cT3cNxcM0 as staged by MRI, were included and treated preoperatively with a combination of capecitabine and oxaliplatin following a standardized protocol during radiation. The focus of this long-term analysis was overall (OS) and disease-free survival (DFS).ResultsA total of 60 patients (19 women, 41 men, median age 60.5 years) were initially enrolled, 1 patient was excluded (violation of study protocol), and 1 was patient lost of follow-up, leading to a total of 58 patients for long-term analysis. The 3‑year OS was 85.5%; 3‑year DFS 71.2%. Over time, 15 patients (25.9%) developed tumor recurrence (1 locoregional, 6.7%; 11 distant, 73.3%; 3 locoregional+distant, 20%). Recurrence-specific therapy was planned in the majority of patients, in 9 of 15 patients (60%) with a radical surgical approach. Of these, 4 patients (44.4%) are again tumor-free at the end of investigation. While tumor downsizing (T level) or pathologically complete response did not influence patient survival, lymph node negativity (LNneg) after preoperative chemoradiation showed significant influence.ConclusionLNneg after preoperative treatment for LARC significantly influences patient survival. A radical surgical approach for recurrent LARC (locoregional, distant) should be contemplated when possible as we were able to clearly demonstrate its importance and efficacy.

Frequency and clinical impact of preoperative circulating tumor cells in resectable non-metastatic lung adenocarcinomas

ObjectivesDespite successful surgery, 30–50% of patients with resectable non-small cell lung cancer develop tumor recurrence within 5 years of surgery. Materials and methodsIn this prospective study, we performed CTC enumerations in 40 patients with non-metastatic lung adenocarcinoma (NMLA) using a size-based microfilter. Additionally, cfDNA isolated from plasma was analyzed in 35 out of 40 patients. ResultsCTCs were identified in 15 out of 40 patients (37.5%) with a range of 1–44 cells, whereas mutated cfDNA was only detected in 3 out of 35 patients (8.6%). Disease-free survival (DFS) was significantly associated with CTC positivity (log-rank p=0.025), grading (log-rank p=0.019), tumor stage (log-rank p=0.025) and lymph node status (log-rank p=0.029). Multivariate analysis, including tumor stage and grading, showed that CTC positivity (p=0.006), grading (0.039) and tumor stage (p=0.022) were independently associated with DFS. ConclusionOur study found that microfilter-based CTC enumeration in NMLA patients is an independent predictor of worse DFS. The used NGS-based cfDNA characterization had limited sensitivity to be clinically informative in our study cohort. CTC assessment before surgery can thus identify NMLA patients at high risk of disease recurrence.

Fluorescence in situ hybridization as prognostic predictor of tumor recurrence during treatment with Bacillus Calmette\u2013Gu\xe9rin therapy for intermediate- and high-risk non-muscle-invasive bladder cancer

A significant number of patients with intermediate- or high-risk bladder cancer treated with intravesical Bacillus Calmette–Guérin (BCG) immunotherapy are non-responders to this treatment. Since we cannot predict in which patients BCG therapy will fail, markers for responders are needed. UroVysion® is a multitarget fluorescence in situ hybridization (FISH) test for bladder cancer detection. The aim of this study was to evaluate whether FISH can be used to early identify recurrence during treatment with BCG. In a multicenter, prospective study, three bladder washouts at different time points during treatment (t0 = week 0, pre-BCG, t1 = 6 weeks following TURB, t2 = 3 months following TURB) were collected for FISH from patients with bladder cancer treated with BCG between 2008 and 2013. Data on bladder cancer recurrence and duration of BCG maintenance therapy were recorded. Thirty-six (31.6%) out of 114 patients developed a recurrence after a median of 6 months (range 2–32). No significant association was found between a positive FISH test at t0 or t1 and risk of recurrence (p = 0.79 and p = 0.29). A positive t2 FISH test was associated with a higher risk of recurrence (p = 0.001). Patients with a positive FISH test 3 months following TURB had a 4.0–4.6 times greater risk of developing a recurrence compared to patients with a negative FISH. Patients with a positive FISH test 3 months following TURB and induction BCG therapy have a higher risk of developing tumor recurrence. FISH can therefore be a useful additional tool for physicians when determining a treatment strategy.

Folate receptor overexpression can be visualized in real time during pituitary adenoma endoscopic transsphenoidal surgery with near-infrared imaging.

OBJECTIVE Pituitary adenomas account for approximately 10% of intracranial tumors and have an estimated prevalence of 15%-20% in the general US population. Resection is the primary treatment for pituitary adenomas, and the transsphenoidal approach remains the most common. The greatest challenge with pituitary adenomas is that 20% of patients develop tumor recurrence. Current approaches to reduce recurrence, such as intraoperative MRI, are costly, associated with high false-positive rates, and not recommended. Pituitary adenomas are known to overexpress folate receptor alpha (FRα), and it was hypothesized that OTL38, a folate analog conjugated to a near-infrared (NIR) fluorescent dye, could provide real-time intraoperative visual contrast of the tumor versus the surrounding nonneoplastic tissues. The preliminary results of this novel clinical trial are presented. METHODS Nineteen adult patients who presented with pituitary adenoma were enrolled. Patients were infused with OTL38 2-4 hours prior to surgery. A 4-mm endoscope with both visible and NIR light capabilities was used to visualize the pituitary adenoma and its margins in real time during surgery. The signal-to-background ratio (SBR) was recorded for each tumor and surrounding tissues at various endoscope-to-sella distances. Immunohistochemical analysis was performed to assess the FRα expression levels in all specimens and classify patients as having either high or low FRα expression. RESULTS Data from 15 patients (4 with null cell adenomas, 1 clinically silent gonadotroph, 1 totally silent somatotroph, 5 with a corticotroph, 3 with somatotrophs, and 1 somatocorticotroph) were analyzed in this preliminary analysis. Four patients were excluded for technical considerations. Intraoperative NIR imaging delineated the main tumors in all 15 patients with an average SBR of 1.9 ± 0.70. The FRα expression level of the adenomas and endoscope-to-sella distance had statistically significant impacts on the fluorescent SBRs. Additional considerations included adenoma functional status and time from OTL38 injection. SBRs were 3.0 ± 0.29 for tumors with high FRα expression (n = 3) and 1.6 ± 0.43 for tumors with low FRα expression (n = 12; p < 0.05). In 3 patients with immunohistochemistry-confirmed FRα overexpression (2 patients with null cell adenoma and 1 patient with clinically silent gonadotroph), intraoperative NIR imaging demonstrated perfect classification of the tumor margins with 100% sensitivity and 100% specificity. In addition, for these 3 patients, intraoperative residual fluorescence predicted postoperative MRI results with perfect concordance. CONCLUSIONS Pituitary adenomas and their margins can be intraoperatively visualized with the preoperative injection of OTL38, a folate analog conjugated to NIR dye. Tumor-to-background contrast is most pronounced in adenomas that overexpress FRα. Intraoperative SBR at the appropriate endoscope-to-sella distance can predict adenoma FRα expression status in real time. This work suggests that for adenomas with high FRα expression, it may be possible to identify margins and to predict postoperative MRI findings.

Expression of Fibrogenic Markers in Tumor and Tumor-Surrounding Tissue at Time of Transplantation Correlates with Recurrence of Hepatocellular Carcinoma in Patients Undergoing Liver Transplantation.

BACKGROUND Liver transplantation (LT) remains the only curative treatment option for patients with defined stages of hepatocellular carcinoma (HCC). Up to 25% of patients show a tumor recurrence following transplantation. The correlation of fibrogenic markers prior to LT with HCC recurrence has not been characterized. We explored the expression of fibrogenic markers in tumor tissue and tumor-surrounding liver tissue of patients undergoing LT and correlated these findings with tumor recurrence. MATERIAL AND METHODS Fibrogenic marker expression in explanted livers was assessed using tumor and tumor-surrounding liver tissue from patients who recently underwent liver transplantation at our center with a follow-up period of at least 3 years. Tissue was analyzed for the expression of fibrogenic proteins and genes, as well as collagen deposition into the extracellular matrix. Results were correlated with HCC recurrence. RESULTS Patients with recurrent HCC following LT exhibited increased levels of fibrogenic markers on both protein and RNA level within the non-tumorous liver tissue in comparison to the tumor tissue itself. Patients who did not develop tumor recurrence up to 4 years after LT showed a reversed expression pattern of fibrogenic markers with decreased levels of β-PDGFR, Collagen 1, and α-SMA in their non-tumorous liver tissue versus the tumor tissue at time of LT as assessed in protein and mRNA expression analysis. These findings correlated with analysis of collagen deposition in the liver. CONCLUSIONS Fibrogenic markers exhibit a differential expression pattern in HCC versus non-tumorous tissue in explanted livers of patients undergoing LT, showing a correlation with HCC recurrence.

Abstract 5721: Genome-wide discovery and identification of a novel microrna signature for recurrence prediction in colorectal cancer

Abstract Purpose: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. In 2016, there were estimated 95,270 newly diagnosed CRC cases, and 49,190 deaths from this disease in the United States. Survival of patients is closely associated with the tumor stage at the time of diagnosis as 5-year relative survival rates range from 65% for all stages, 90% for localized primary tumor, 71% for regional metastasis and 13% for distant metastasis. Post-surgery, adjuvant therapy is only recommended to those with high risk stage II, as well as stage III and IV tumors. However, approximately 40-50% of the patients undergo curative surgery only and 20-30% that are treated with adjuvant chemotherapy, eventually relapse and experience a metastatic disease and eventual death. The current gold standard TNM (Tumor, Node, Metastasis) staging for determining the prognosis of CRC patients remains inadequate at identification of high-risk stage II and III patients that have a high potential of developing tumor recurrence. MicroRNAs (miRNAs) play an important role in CRC development and are emerging as important disease biomarkers. Therefore, in this study we sought to determine the prognostic potential of the miRNAs using a systematic, genome-wide biomarker discovery approach, followed by validation of biomarkers in multiple patient cohorts Experimental design: Three independent publicly available genome-wide miRNA expression datasets were used for miRNA biomarker discovery (n=158) and validation (n=109 and n=40) of this miRNA signature for recurrence prediction in stage II and III CRC using multivariate Cox regression analysis. The eight gene miRNA signature discovered from the genome-wide analysis was analytically validated in two independent patient cohorts (n=127 and n=96) using Taqman-based RT-PCR assays. Results: The genome-wide comprehensive analysis led to the identification of an eight gene miRNA classifier that significantly predicted recurrence free survival (RFS) in training (log-rank p=0.003) and two independent validation cohorts (log-rank p&amp;lt;0.0001 and p=0.002). The RT-PCR based training and validation of the eight gene classifier in two independent clinical cohorts significantly associated with poor prognosis in stage II and III CRC patients (log-rank p&amp;lt;0.004 and p&amp;lt;0.0001). Multivariate analyses performed in these two patient cohorts revealed that the eight gene miRNA classifier served as an independent predictor of poor prognosis in stage II and III CRC patients. Conclusions: In conclusion, we have identified a novel miRNA-based classifier, which is robustly predictive of poor prognosis in patents with stage II/III CRC, and might facilitate identification and stratification of high-risk patients that are candidates for adjuvant chemotherapy and clinical surveillance. Citation Format: Raju Kandimalla, Feng Gao, Naoki Takahashi, Yasuhide Yamada, Takatoshi Matsuyama, Toshiyaki Ishikawa, Xin Wang, Ajay Goel. Genome-wide discovery and identification of a novel microrna signature for recurrence prediction in colorectal cancer [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 5721. doi:10.1158/1538-7445.AM2017-5721

Solid Renal Masses in Transplanted Allograft Kidneys: A Closer Look at the Epidemiology and Management.

The objective of this review is to explore the available literature on solid renal masses (SRMs) in transplant allograft kidneys to better understand the epidemiology and management of these tumors. A literature review using PubMed was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology. Fifty-six relevant studies were identified from 1988 to 2015. A total of 174 SRMs in 163 patients were identified, with a mean tumor size of 2.75 cm (range 0.5-9.0 cm). Tumor histology was available for 164 (94.3%) tumors: clear cell renal cell carcinoma (RCC; 45.7%), papillary RCC (42.1%), chromophobe RCC (3%), and others (9.1%). Tumors were managed by partial nephrectomy (67.5%), radical nephrectomy (19.4%), percutaneous radiofrequency ablation (10.4%), and percutaneous cryoablation (2.4%). Of the 131 patients (80.3%) who underwent nephron-sparing interventions, 10 (7.6%) returned to dialysis and eight (6.1%) developed tumor recurrence over a mean follow-up of 2.85 years. Of the 110 patients (67.5%) who underwent partial nephrectomy, 3.6% developed a local recurrence during a mean follow-up of 3.12 years. The current management of SRMs in allograft kidneys mirrors management in the nontransplant population, with notable findings including an increased rate of papillary RCC and similar recurrence rates after partial nephrectomy in the transplant population despite complex surgical anatomy.

Efficacy of microsurgical treatment of medulla hemangioblastoma

Objective To explore the microsurgical outcome of medulla hemangioblastomas. Methods A total of 88 cases of medulla hemangioblastoma underwent microsurgical treatment assisted with intraoperative neurophysiological monitoring at Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University between June 2011 and June 2016, whose clinical data and surgical outcomes were retrospectively analyzed. Results Among the 88 patients of medulla hemangioblastoma, 38 cases were cyst and solid and the remaining ones were purely solid. Moreover, there were 70 cases with a single lesion and 18 cases with multiple lesions. The Von Hippel-Lindau syndrome was present in 18 (20.5%) patients. All dorsal medullary tumors underwent gross total resection (GTR). Three (3.4%) deaths occurred postoperatively due to pulmonary infection. Temporary pulmonary embolism occurred in one patient. Other complications were also documented including stress-related gastrointestinal bleeding in 3 cases, pneumonia in 24(27.3%) cases, hematoma in 5 cases, deep venous thrombosis (DVT) in 7 cases, cerebrospinal fluid (CSF) leakage in 4 cases and infection of central nervous system in 6 cases. Eighty-one patients were followed up for about 3-60 months. Dizziness, headache, nausea and vomiting were reported in 56 instances, all of which were improved to varying degrees within 6 months. Out of 17 cases with decreased muscle strength prior to operations, 11 recovered and the others remained the same. Among 15 cases who presented with the lower cranial nerve-related symptoms, 9 were improved but the other 6 were not. Tumor recurrence developed in 15(17.0%) patients postoperatively including 2 cases with local recurrence that occurred 4 years and 10 years post GTR, respectively, and underwent the second operation. There were 13 cases developing tumor recurrence in other regions and 10 out of them underwent the second operation. Three (3.4%) patients died during the follow-up. Conclusion Satisfactory clinical outcomes could be achieved through microsurgery assisted with intraoperative neurophysiological monitoring. Key words: Hemangioblastoma; Medulla oblongata; Microsurgery

PD49-08 THE IMPACT OF ROUTINE FROZEN SECTION ANALYSIS DURING PENECTOMY ON SURGICAL MARGIN STATUS AND LONG-TERM ONCOLOGIC OUTCOMES

You have accessJournal of UrologySexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I1 Apr 2017PD49-08 THE IMPACT OF ROUTINE FROZEN SECTION ANALYSIS DURING PENECTOMY ON SURGICAL MARGIN STATUS AND LONG-TERM ONCOLOGIC OUTCOMES Alexandra Danakas, Caroline Bsirini, and Hiroshi Miyamoto Alexandra DanakasAlexandra Danakas More articles by this author , Caroline BsiriniCaroline Bsirini More articles by this author , and Hiroshi MiyamotoHiroshi Miyamoto More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2232AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Intraoperative frozen section analysis (FSA) of biopsy or resection specimens often provides critical information for appropriate surgical management. However, to the best of our knowledge, there are no recent studies focusing on assessing the role of FSA in the status of surgical margins (SMs) relating to the outcomes of penectomy cases. Instead, a few review articles discourage its use in the intraoperative assessment of SMs during penectomy, mainly because lesions often show well differentiated squamous proliferation that can mimic non-neoplastic conditions. The current study aims to investigate the utility of routine FSA of the SMs in men undergoing penectomy for squamous cell carcinoma. METHODS A retrospective review identified consecutive patients (n=38) who underwent partial (n=26) or total (n=12) penectomy for squamous cell carcinoma at our institution from 2004 to 2015. FSA findings were correlated with the diagnosis of the frozen section control, the status of final SM, and patient outcomes. RESULTS FSA of the SMs was performed in 20 (77%) partial penectomies and 9 (75%) total penectomies, while no FSA was done for SMs in other cases. FSAs were reported as positive (n=3, 10%), negative (n=24, 83%), and atypical (n=2, 7%). All of the positive or negative FSA diagnoses, including those in 7 cases of well differentiated carcinoma, were confirmed accurate on the frozen section controls, whereas the 2 cases with atypical FSA had non-malignant and carcinoma cells, respectively, on the controls. Final SMs were positive in 5 (13%) penectomies (2 partial and 3 total), including 3 (10%) FSA cases versus 2 (22%) non-FSA cases (P=0.574). Furthermore, 2 initially FSA-positive/atypical cases achieved negative conversion by excision of additional tissue sent for FSA. In contrast, 2 FSA-negative cases showed carcinoma at the final SM where FSA was not submitted. During follow-up (mean: 41.2; median: 42; range: 1-136 months), 3 patients (non-FSA/final SM-negative, non-FSA/final SM-positive, FSA-negative/final SM-negative) developed tumor recurrence, and one of them (non-FSA/SM-positive) died of cancer. Kaplan-Meier analysis revealed that the number or diagnosis of FSA was not significantly associated with disease progression. CONCLUSIONS Overall, performing FSA during penectomy does not appear to have any significant impact on final SM status nor long-term oncologic outcomes. However, as seen in at least 2 cases, select patients may benefit from the routine FSA. Meanwhile, diagnostic accuracy of FSA of the SMs was found to be quite high. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e977 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Alexandra Danakas More articles by this author Caroline Bsirini More articles by this author Hiroshi Miyamoto More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Analysis of Recurrence after Frontolateral Laryngectomy.

This study aimed to evaluate the recurrence and survival of patients treated with frontolateral laryngectomy for T1 and T2 glottic laryngeal carcinoma. Patients who underwent frontolateral laryngectomy for glottic laryngeal carcinoma at a tertiary hospital between March 2009 and June 2014 were included. Patient demographics, tumor stage, treatment and histopathological examination data, and adjuvant therapy details were evaluated. Thirty patients with T1aN0, T1bN0, and T2N0 vocal fold carcinoma were examined. The mean follow-up duration was 40 months. Of the 30 patients, nine (30%) were stage T1 and 21 (70%) were in stage T2. Twenty-nine patients were males and one was female, and the mean age was 59 (range, 42-81) years. During follow-up, local recurrence was observed in four patients following frontolateral laryngectomy. Six patients continued smoking after frontolateral laryngectomy, of which three developed tumor recurrence. The local control rate was poor in patients with anterior commissure involvement (66.6%) compared with those with no involvement (95.2%). Two of four patients with local recurrence were treated with salvage total laryngectomy and adjuvant postoperative radiotherapy; the remaining two were treated with only radiotherapy. One patient who was treated with only radiotherapy developed lung metastasis during follow-up and died because of distant metastasis. Frontolateral laryngectomy is an efficient choice of treatment for selected cases of T1 and T2 glottic laryngeal carcinoma.