Retroperitoneal Node Metastases Research Articles

Magnetic resonance versus computed tomography for the detection of retroperitoneal lymph node metastasis due to testicular cancer: A systematic literature review

IntroductionIt is essential to see if MRI can be used as an alternative to CT for the detection of retroperitoneal lymphadenopathy in patients with testicular neoplasms. By doing so, the amount of radiation received by these young patients might be reduced. Material and methodsA systematic literature review was carried out in 5 databases between January 1984 until December 2020. The articles included were randomized and non-randomized clinical trials, cross-sectional studies, cohort, case and control, and retrospective studies that compare the accuracy of MRI against CT to detect retroperitoneal lymph nodes in patients with testicular neoplasms. ResultsThe search string initially retrieved 222 non duplicated papers from which a total of 3 studies of diagnostic accuracy were included for analysis. These articles evaluated a total of 127 patients with testicular neoplasm; the sample size per study ranged from 25 to 52 patients, with a mean age between 29–34 years. MRI presented a sensitivity ranging from 98−80% and specificity of 100 % when read by an experienced radiologist. However, when it was read by a radiologist with 1 year of experience, the sensitivity dropped to 78 % and specificity to 91%. ConclusionThis systematic literature review shows a knowledge gap since not much has been published regarding this topic; therefore, randomized clinical trials are mandatory. Research on when to use MRI over CT is necessary to reduce radiation exposure. The authors strongly suggest that readers start researching on this subject.

Mismatch Repair Gene Expression In Testicular Germ Cell Tumors And Retroperitoneal Lymph Node Metastasis

Abstract Introduction/Objective Testicular germ cell tumors (TCGT) with somatic mismatch repair pathway defects have shown to have worse prognosis and response to therapy. Immunohistochemical staining pattern of MMR panel was classified in a previous study as low (absent or minimal) and high staining (moderate or high staining), with the low staining pattern suggestive of poor prognosis and high risk of recurrence. Herein, we studied the MMR staining pattern in TGCT and lymph node metastasis. Methods 21 TGCT were included in the study: 10 primary testicular tumors and 11 unrelated retroperitoneal lymph node metastasis. All cases were analyzed for MMR protein expression by immunohistochemistry. Clinical, histopathological and follow-up was obtained in all cases. Retained MLH1, MSH2, MSH6, and PMS2 was defined as nuclear staining. Loss of expression was defined as absence of nuclear staining within tumor cells with retained expression in internal control cells, including benign testicular tissue, stromal cells, and infiltrating lymphocytes. Results All primary testicular tumors were mixed GCT: embryonal carcinomas was present in 5, yolk sac tumor in 3 and teratoma in 6 cases. One (10%) of the primary tumors showed focal loss of MLH1 and PMS2 expression in a focus of embryonal carcinoma. All lymph node metastases consisted of teratoma. Seven (64%) metastatic cases showed scattered areas of focal MLH1 loss, 5 (45%) of which showed also focal loss of PMS2. High staining for MSH2 and MSH6 was detected in all 21 cases. Conclusion In our small cohort, focal loss of MLH1 and PMS2 was detected in 10% of primary TGCT, compared to focal loss of MLH1 and PMS2 is 64% and 45%, respectively, of metastatic tumors, suggesting a possible relationship between heterogeneous MLH1 and PMS2 expression and retroperitoneal lymph node metastasis. The current cohort will be expanded to include additional cases.

Mapping Of Retroperitoneal Lymph Nodal Metastases After Surgery For Lower Thoracic Esophageal Cancer: A Recommendation For Clinical Target Volume

Our previous study showed that retroperitoneal lymph node (RetroLN) metastasis was common in patients with lower thoracic esophageal squamous cell cancer (LTESCC) treated after surgery, indicating a possible benefit of adjuvant radiotherapy in retroperitoneal region. However, little is known about the pattern of RetroLNs failure in LTESCC, which hinders further study. We herein document the site of RetroLNs failure in LTESCC treated after surgery, and propose a delineation for CTV boundaries. LTESCC patients having RetroLNs metastasis after R0 radical esophagectomy in our institution were reviewed. The epicenter of each RetroLN was represented by a circle of 5 mm diameter, and was registered onto corresponding axial CT images of a standard patient, with reference to the surrounding vascular and bony structures. After analyzing the node distribution features, a CTV boundary was proposed, based on which a post-operative RT plan was applied in three simulated cases for safety analysis. A number of 257 RetroLNs from 69 patients were recorded. Twelve patients had solitary RetroLNs metastasis, and 31 patients had RetroLNs failure with distant metastasis. The three most frequent metastasis sites were lateral aortic (48.3%), pre-aortic (22.0%) and intermediate lumber (20.5%). Longitudinally, one LN was higher than the middle level of vertebral T12, and 75.7% of the LNs were seen above the border of 2 cm inferior to the left renal artery, which often near the bottom of vertebral L2. Horizontally, 80% of LNs in celiac level were located within the region confined by the anterior surface of aorta, inferior vena cava (IVC), portal vein, splenic vein and celiac branches. In the superior mesenteric artery (SMA) level, all the LNs except 1 post-aortic LNs were behind the anterior edge of the SMA and anterior to the posterior edge of aorta, 85% were left to the left edge of IVC, and 95% were within 1.5 cm of the left side of the SMA. In the region beneath SMA, 92.7% of LNs appeared right to the lateral edge of the left psoas major (LPM), and all the LNs lied behind the anterior surface of the left renal vein or adjacent to the anterior surface of the aorta, left to the right border of the IVC, and anteriorly to the vertebral and the anterior edge of the LPM. The proposed CTV from the middle level of vertebral T12 to the 2cm below the left renal artery or the bottom of vertebral L2 (depending on which one is lower) with aforementioned boundaries can cover 74.52% of the LNs in the studied group. The post-operative RT treatment plan which included the commonly used T-shield field and the proposed CTV for RetroLNs in three simulated cases all met with satisfactory in the dosimetric analysis. The proposed CTV is the first that focus on the high-risk area of RetroLNs failure in LTESCC patients treated after surgery, and is also feasible in terms of dosimetric performance. The result can serve as a reference for future study to better improve the disease control in LTESCC.

Ureteroiliac artery fistula caused by full-length metallic ureteral stenting in a malignant ureteral obstruction: a case report

BackgroundThe metallic stent is a new device for relieving the urinary tract in patients with malignant ureteral obstruction with short life expectancy and has been used frequently worldwide for its efficacy and safety. A ureteroarterial fistula with indwelling ureteral stent is rare but highly fatal, and there are several reports of ureteroarterial fistula treated by conventional polymer stents, although there are no reports on metallic stents. To our knowledge, this paper describes the first case of a ureteroiliac artery fistula caused by a full-length metallic ureteral stent in malignant ureteral obstruction.Case presentationOur patient was a 57-year-old Asian woman with a history of locally advanced cervical cancer who underwent abdominal total hysterectomy and chemoradiotherapy. She was diagnosed with right hydronephrosis and hydroureter secondary to upper ureteral obstruction because of retroperitoneal lymph node metastasis. A urinary tract obstruction after placement of 12 months of polymer stent followed by 18 months of metallic stent was relieved, consequently resulting in intermittent gross hematuria with bladder tamponade and anemia. Contrast-enhanced computed tomography could not reveal a ureteroarterial fistula; however, retrograde pyelography emphasized the existence of a ureteroiliac artery fistula. The patient underwent successful endovascular heparin-bonded stent graft placement, and her gross hematuria disappeared thereafter.ConclusionThe metallic stent is a useful device for patients with malignant ureteral obstruction with a short life expectancy, although it may impose a higher pressure on the extraureteral tissue than conventional polymer stents due to its properties and may cause a ureteroarterial fistula. The narrowing of the external iliac artery diameter visualized by computed tomography may be helpful for predicting ureteroarterial fistulas.

S1630 Uncomfortably Numb: A Unique Case of Metastatic Neuroendocrine Cancer Found in the Colon

INTRODUCTION: High grade neuroendocrine neoplasms that arise from the gastrointestinal tract consist of well differentiated and poorly differentiated carcinomas. The latter is associated with rapid disease progression and widespread metastases, infrequently involving the central nervous system. We report the case of a young patient with mild neurologic symptoms discovered to have late stage metastatic neuroendocrine carcinoma originating in the colon. CASE DESCRIPTION/METHODS: A 38-year-old male with no medical history presented with complaints of intermittent right thumb numbness, headaches and mild visual changes. He saw an ophthalmologist who found no visual deficits on exam. Shortly after, the patient experienced a recurrent episode of facial numbness and decided to come into the hospital. Due to his neurologic symptoms, the patient underwent a CT and MRI of the brain which found metastatic lesions in the occipital and parietal lobes with surrounding edema. Subsequent malignancy workup with CT of the chest, abdomen and pelvis demonstrated a 4cm ascending colon mass, multiple liver and lung metastatic lesions with meso-colonic and retroperitoneal lymph node metastasis. Colonoscopy found a fungating, partially obstructing large mass in the cecum that could not be bypassed with the endoscope, with pathology showing a poorly differentiated neuroendocrine carcinoma. The patient was ultimately diagnosed with metastatic poorly differentiated neuroendocrine carcinoma of the colon with metastasis to the brain, liver, lung, and retroperitoneum. He successfully underwent a left-sided craniotomy for resection of the brain lesions with improvement in neurologic symptoms and was started on a chemotherapy regimen of Atezolizumab and Etoposide. DISCUSSION: Poorly differentiated gastroenteropancreatic neuroendocrine carcinomas are associated with early, widespread metastases and rarely originate in the cecum. Due to the aggressive nature of this carcinoma, most patients have metastatic disease at diagnosis and may present with symptoms associated with tumor location or related to distant metastases. Brain metastases are extremely uncommon and general screening for them is not currently recommended. This may be due to the longer timeframe for development of brain metastases as compared to other organs. Given the overall poor survival of neuroendocrine tumors, further research is needed to determine the incidence of brain metastases and whether screening could be advisable regardless of neurological symptoms.Figure 1.: Colonoscopic Images of a Large Obstructive Cecal Mass Ultimately Diagnosed as a Neuroendocrine Carcinoma.

Management of Para-Aortic Lymph Node Metastasis in Rectal Squamous Carcinoma

Background: Squamous cell carcinoma (SCC) of the rectum is a rare malignancy, and retroperitoneal nodal metastasis (RNM) represent 1-2% of colorectal cancer metastasis (CRC), and radical retroperitoneal lymphadenectomy (RRL) in this setting remains controversial. However, there are no reports in the literature on how to treat SCC retroperitoneal lymph node metastasis. Case Presentation: The patient was a 47-years-old woman with SCC of the rectum. Concomitant chemoradiotherapy (CRT) followed by surgery was planned. After 8 weeks, CT of the abdomen for restaging showed a 6 cm para-aortic mass involving and obstructing the medium third of the left ureter. The patient was submitted to abdominoperineal rectal resection with left nephrectomy and en-bloc resection of para-aortic tumor (nodal bulking). Conclusion: After a thorough review of the literature regarding RNM for rectal SCC, we found no mention of how to treat RNM for rectal SCC. The purpose of this paper is to report a very rare case of RNM for rectal SCC and to discuss the surgical approach. Surgery seems to be the best option for local control and improvement in overall survival (OS).

MP79-16 LONG-TERM RESULTS OF CYTOREDUCTIVE RADICAL PROSTATECTOMY IN MEN WITH HORMONE-NAIVE, LOW VOLUME METASTATIC PROSTATE CANCER(MHNPCA)

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) IV (MP79)1 Apr 2020MP79-16 LONG-TERM RESULTS OF CYTOREDUCTIVE RADICAL PROSTATECTOMY IN MEN WITH HORMONE-NAIVE, LOW VOLUME METASTATIC PROSTATE CANCER(MHNPCA) Patricia John*, David Pfister, Axel Heidenreich, and Florian Hartmann Patricia John*Patricia John* More articles by this author , David PfisterDavid Pfister More articles by this author , Axel HeidenreichAxel Heidenreich More articles by this author , and Florian HartmannFlorian Hartmann More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000971.016AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Androgen deprivation combined with apalutamide, abiraterone or docetexal represents the treatment of choice in mhnPCA. Cytoreductive radical prostatectomy (cRP) has been proposed as part of a multimodality treatment in selected patients with oligometastatic prostate cancer. Recently, our group has demonstrated that the combination of 6 months neoadjuvant ADT followed by cRP exerted a significant benefit in terms of progression-free, local symptom-free survival and time to castration resistance. We report on the long-term outcome of this cohort of men with low volume mhnPCA. METHODS: 32 patients with hnmPCA were retrospectively analysed. All men had low volume skeletal metastases (≤3 lesions on a bone scan), absence of visceral and retroperitoneal lymph node metastases, and a PSA-decrease <1,0 ng/ml following 6 months of ADT. 38 case-matched patients with mhnPCA and ADT monotherapy served as a control group. Perioperative complications were assessed according to Clavien-Dindo, PSA-free, symptom-free, cancer specific and overall survival was analysed and assessed via descriptive statistics. RESULTS: Mean age of the patients was 61 (42–69) years. Mean PSA at time of diagnosis was 135.2 (3.5-150.4) ng/ml, the mean PSA at time of cRP was 0.42 (0.01-9.8) ng/ml. All patients demonstrated a mean of 2.1 (1-3) osseous metastases, intrapelvic lymph node metastases were identified preoperatively in 17.4% of patients. All men underwent cRP and extended pelvic lymphadenectomy. The median follow-up is 75,5 (7–135) months, 27/32 (84.4%) patients are still alive. 16/27 (59.2%) have developed mCRPC. Median overall survival is 78.9 months and the median time to CRPC is 40 (9–65) months. Overall survival, progression-free survival and time to CRPC was significantly superior in the cRP group as compared to ADT alone (p = 0.003). 10 (31.2%) patients developed perioperative complications of whom only 3/32 (9.4%) patients required interventions and were defined as Clavien-Dindo IIIa/b. 28/32 (87.5%) patients are continent (0-1 pads/day). None of the patients developed locally symptomatic relapses after cRP whereas this was the case in 12 (31.6%) pts in the ADT alone group. CONCLUSIONS: Even after long-term follow-up neoadjuvant ADT and cRP result in good oncological and functional outcome with a 6-year overall survival rate of more than 80%. As compared to about 25% symptomatic local relapses following radiation therapy and to 31% relapses following ADT alone, none of the patients developed symptomatic local relapses following cRP. Although data from prospective randomized trials are lacking, cRP should be considered as a valid treatment option in well selected patients with low volume metastatic disease and good response to neoadjuvant ADT. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1221-e1222 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Patricia John* More articles by this author David Pfister More articles by this author Axel Heidenreich More articles by this author Florian Hartmann More articles by this author Expand All Advertisement PDF downloadLoading ...

Port-site metastasis and atypical recurrences after robotic-assisted radical cystectomy (RARC): an updated comprehensive and systematic review of current evidences.

The objective of this systematic review is to evaluate the current evidence regarding atypical metastases in patients undergoing robotic-assisted radical cystectomy (RARC). A review of the current literature was conducted through the Medline and NCBI PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases in October 2019. From the literature search using the cited keys and after a careful evaluation of the full texts, we included 31 articles in the study. Fourteen studies (45.2%) reported at least an atypical recurrence during the follow-up period with a rate between 4 and 40% of all the recurrences. Overall, 105 (1.63%) of the 6720 patients who have been evaluated in the included studies developed an atypical recurrence. Sixty-three (60%) of these atypical metastases were peritoneal carcinomatosis, 16 (15.2%) extrapelvic lymph nodes metastases, 11 (10.5%) port-site metastases, 10 (9.5%) retroperitoneal nodal metastases, while 5 (3.8%) patients developed more than one type of atypical recurrence. In literature, there is a low but not negligible incidence of atypical recurrences after RARC. However, publication bias and retrospective design of most studies could influence the evidences. Further prospective randomized studies are needed to clarify the real risk of patients undergoing RARC to develop atypical metastases.

Abstract P3-01-09: Clonal heterogeneity and tumor evolution inform treatment resistance in a patient with HER2+ breast cancer

Abstract Resistance to therapy in metastatic breast cancer patients results from acquired mutations and selection of resistant clones. Understanding the mechanisms of resistance in the clinical setting is complicated by the lack of genomic characterization of tumor specimens. This case report describes a patient with ER+ and dynamic HER2+ status with exposure to a range of different therapies, suggesting that inference of tumor subclonal composition and evolution can be leveraged to study treatment resistance. A female patient was diagnosed with estrogen receptor positive (ER+) and human epidermal growth factor receptor positive (HER2+) stage I (T1N0) breast cancer. After receiving standard of care adjuvant chemotherapy (AC-TH) and Tamoxifen for two years, the patient developed metastatic disease to the liver. Upon metastatic disease, she received first line treatment with the trastuzumab emtansine antibody-drug conjugate (T-DM1). After fifteen months, enlargement of supraclavicular and retroperitoneal lymph nodes was observed, Letrozole was added to the treatment regimen until the patient progressed after eight months. Subsequent therapy with Fulvestrant and the CDK4/6 inhibitor Palbocicilb was administered for three months until the patient developed brain metastases. We analyzed biopsies taken at different time points of metastatic disease and, using whole exome sequencing (WES), reconstructed the subclonal architecture of each of the tumor specimens and inferred the evolutionary history of these clones. These results suggest potential mechanisms of resistance to the different therapies administered during disease progression. Biopsies obtained originated from a retroperitoneal lymph node at 3 years after diagnosis, a liver metastasis at 4 years after diagnosis and a brain metastasis after 4 years and 3 months after diagnosis. WES was performed on these tumor specimens and characterization of mutational events and copy number alterations was made using standard analytical pipelines. Inference of subclonal populations in the three tumor specimens analyzed revealed presence of a founding clone with mutations common to the three metastatic biopsies with alterations in TP53 p.K305* and PIK3CA p.E545K. A clone unique to the ER+/HER2- retroperitoneal lymph node metastasis shows no known driver mutations. In the liver metastasis (ER+/HER2-), we observed the presence of a dominant clone (cellular prevalence 93.5%) with mutation in ESR1 p.G442R and another subclone detected at low cellular prevalence (~5%) with an amplification in the ERBB2 gene. In the brain metastasis (ER+/HER2-), the latest tumor specimen obtained, we observed clonal selection of the ERBB2-amplified subpopulation (clonal prevalence 60%). The subclonal population dynamics and the different alterations in the clones present at different time points of tumor evolution provide a rationale to understand the therapeutic sensitivity and resistance observed in this patient. The ER+/HER2- retroperitoneal lymph node metastasis which appeared under T-DM1 treatment, suggests that this subclone is resistant to T-DM1, explained by the HER2 negative status, and was selected while the patient was on this regime. At the time of appearance of this clone, Letrozole was added to the treatment and a clone with an ESR1 p.G442R mutation appeared and dominated the tumor population, suggesting that this mutation provides resistance to the aromatase inhibitor. When treatment was switched to Fulvestrant and Palbociclib, a potentially dormant clone with ER+ and HER2+ features re-appeared in the tumor. Evolutionary analysis of this patient's tumor specimens underscores the importance of multiple therapies directed at all tumor vulnerabilities present, since targeting a single driver feature of the tumor will result in selection of other resistant subclones. Citation Format: Jorge E. Buendia-Buendia, Sonia Pernas, Ofir Cohen, Ping Ping Mao, Kailey Kowalski, Nancy Lin, Eric Winer, Nikhil Wagle. Clonal heterogeneity and tumor evolution inform treatment resistance in a patient with HER2+ breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-01-09.

Risk factors of acquired T790M mutation in patients with epidermal growth factor receptor-mutated advanced non-small cell lung cancer.

Background: It is still controversial to employ osimertinib as the first-line therapy for EGFR-mutated non-small cell lung cancer (NSCLC) patients in practice. The aim of the current study was to explore the risk factors of acquired T790M mutation during EGFR-TKIs therapy, and to identify the potential patients most likely to benefit from first-line osimertinib treatment.Methods: A total of 222 patients with EGFR-mutated (non-T790M) advanced NSCLC were analyzed. The progression-free survival (PFS), overall survival (OS), and cumulative incidence of acquired T790M mutation were calculated with the Kaplan-Meier method. The independent risk factors were investigated with the multivariate analysis.Results: A total of 70 patients acquired T790M mutation and were treated with osimertinib as a second-line treatment. These patients showed a significantly better OS (P=0.003) than those without T790M mutation. Multivariate analysis indicated that BMI ≤ 25 (P= 0.031), NSE > 17.9 ng/ml (P= 0.013) before treatment, and retroperitoneal lymph node (LN) metastasis (P= 0.002) were independent risk factors of acquired T790M mutation. At last, the actuarial risks of acquired T790M mutation at 1 year after EGFR-TKI treatment were 6.6% in patients with 0-1 risk factor and 31.5% in patients with 2-3 risk factors.Conclusions: Patients developing acquired T790M mutation during EGFR-TKI treatment had a better OS of osimertinib treatment. Lower BMI, higher NSE before treatment, and retroperitoneal LN metastasis are independent risk factors of acquired T790M mutation. Our study suggested that patients with 2-3 risk factors were highly recommended the first-line osimertinib treatment.

Feasibility and clinical value of computed tomography-guided125I brachytherapy for pain palliation in patients with retroperitoneal lymph node metastases.

The aim was to evaluate the feasibility and clinical value of computed tomography (CT)-guided125 I brachytherapy for pain palliation in patients with retroperitoneal lymph node metastases. A total of 23 patients with retroperitoneal lymph node metastases and those who had moderate-to-severe pain from January 2014 to December 2018 were enrolled in the study. The primary tumors included pancreatic (n = 12), gastric (n = 4), hepatocellular (n = 4), colorectal (n = 2), and esophageal carcinomas (n= 1). Patients were treated with CT-guided percutaneous125 I brachytherapy during the study. The Brief Pain Inventory-Short Form was used to record and compare pain intensity and interference by pain. Treatment-related complications were also evaluated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Criteria. Statistical analysis was performed using SPSS software version 22.0. The primary success rate of125 I seed implantation was 95.7% (22 of the 23 patients). As pain evolved, the patients achieved obvious pain palliation ratings for "worst pain" and "average pain" at 72 h and 4 weeks after brachytherapy, respectively, whereas "pain right now" at 12 weeks was significantly relieved after brachytherapy. No serious complications developed during the perioperative period. In the treatment of intractable carcinomatous pain in patients with retroperitoneal lymph node metastases, CT-guided125 I brachytherapy is a feasible and effective modality for pain palliation.

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of a case of a huge abdominal mass.

Testicular mixed germ cell tumor is characterized by high degree of malignancy and prone to metastasis, the common of which is retroperitoneal lymph node metastasis. At present, EUS has a very important diagnostic value for mediastinal, enterocoelia and retroperitoneal lymph node metastasis of malignant tumors. It also has a positive value for the space occupying of parenchyma or cavity organ and can be used for the puncture operation of multiple lesions under real-time ultrasound monitoring with high safety and small complications.

Radiomics allows for detection of benign and malignant histopathology in patients with metastatic testicular germ cell tumors prior to post-chemotherapy retroperitoneal lymph node dissection.

To evaluate whether a computed tomography (CT) radiomics-based machine learning classifier can predict histopathology of lymph nodes (LNs) after post-chemotherapy LN dissection (pcRPLND) in patients with metastatic non-seminomatous testicular germ cell tumors (NSTGCTs). Eighty patients with retroperitoneal LN metastases and contrast-enhanced CT were included into this retrospective study. Resected LNs were histopathologically classified into "benign" (necrosis/fibrosis) or "malignant" (viable tumor/teratoma). On CT imaging, 204 corresponding LNs were segmented and 97 radiomic features per LN were extracted after standardized image processing. The dataset was split into training, test, and validation sets. After stepwise feature reduction based on reproducibility, variable importance, and correlation analyses, a gradient-boosted tree was trained and tuned on the selected most important features using the training and test datasets. Model validation was performed on the independent validation dataset. The trained machine learning classifier achieved a classification accuracy of 0.81 in the validation dataset with a misclassification of 8 of 36 benign LNs as malignant and 4 of 25 malignant LNs as benign (sensitivity 88%, specificity 72%, negative predictive value 88%). In contrast, a model containing only the LN volume resulted in a classification accuracy of 0.68 with 64% sensitivity and 68% specificity. CT radiomics represents an exciting new tool for improved prediction of the presence of malignant histopathology in retroperitoneal LN metastases from NSTGCTs, aiming at reducing overtreatment in this group of young patients. Thus, the presented approach should be combined with established clinical biomarkers and further validated in larger, prospective clinical trials. • Patients with metastatic non-seminomatous testicular germ cell tumors undergoing post-chemotherapy retroperitoneal lymph node dissection of residual lesions show overtreatment in up to 50%. • We assessed whether a CT radiomics-based machine learning classifier can predict histopathology of lymph nodes after post-chemotherapy lymph node dissection. • The trained machine learning classifier achieved a classification accuracy of 0.81 in the validation dataset with a sensitivity of 88% and a specificity of 78%, thus allowing for prediction of the presence of viable tumor or teratoma in retroperitoneal lymph node metastases.

An Orthotopic Endometrial Cancer Model with Retroperitoneal Lymphadenopathy Made From In Vivo Propagated and Cultured VX2 Cells

Endometrial cancer is the most common gynecologic malignancy in North America and the incidence is rising worldwide. Treatment consists of surgery with or without adjuvant therapy depending on lymph node involvement as determined by lymphadenectomy. Lymphadenectomy is a morbid procedure, which has not been shown to have a therapeutic benefit in many patients, and thus a new method to diagnose lymph node metastases is required. To test novel imaging agents, a reliable model of endometrial cancer with retroperitoneal lymph node metastases is needed. The VX2 endometrial cancer model has been described frequently in the literature; however, significant variation exists with respect to the method of model establishment. Furthermore, no studies have reported on the use of cultured VX2 cells to create this model as only cells propagated in vivo have been previously used. Herein, we present a standardized surgical method and post-operative monitoring method for the establishment of the VX2 endometrial cancer model and report on the first use of cultured VX2 cells to create this model.

Retroperitoneal lymph node metastases as a prognosis factor in overall survival in metastatic colorectal cancer

Retroperitoneal lymph node metastases as a prognosis factor in overall survival in metastatic colorectal cancer

Adenocarcinoma of the Rete Testis: Clinicopathologic and Immunohistochemical Characterization of 6 Cases and Review of the Literature.

Adenocarcinoma of the rete testis is rare and its etiological and pathologic characteristics are not well studied. We therefore investigated the clinical, morphologic, and immunohistochemical features of 6 cases diagnosed at our institution and conducted a detailed review of the literature. The mean age was 64 years. All patients presented with testicular masses; 4 were right-sided. On gross examination, all tumors were centered in the hilum and had solid and cystic cut surfaces. Microscopically, all had intrarete and invasive growth and showed multiple patterns, with a variable proportion of papillary, solid and glandular morphology, the latter varying from slit-like lumens to well-formed glands and tubules. Less common patterns included corded/trabecular (n=3), cribriform (n=3), glomeruloid (n=3), nested (n=2), and micropapillary (n=2). Discrete nests of eosinophilic and clear cells were a distinctive feature in 3 cases. Geographic necrosis occurred in 3 cases. All showed at least moderate nuclear pleomorphism with ovoid nuclei. Transition from benign to malignant rete epithelium was seen in all cases. The stroma was hyalinized to partially fibrotic. On immunohistochemical study, the tumor cells were positive for CK7 (5/5), AE1/AE3 cytokeratin (5/5), EMA (5/5), vimentin (5/5), EpCAM (detected by BerEP4 anitbody) (4/5), CK5/6 (4/5), nuclear Wilms Tumor-1 (4/5), epithelial specific antigen (detected by MOC31 antibody) (3/4), PAX8 (3/5), and calretinin (2/5). OCT3/4, SALL4, CD30, NKX3.1, PSA, α-inhibin, CK20, and S100 protein were negative. Ki-67 proliferative index ranged from 5% to 60% (mean: 40, median: 43). At presentation, 5 patients had retroperitoneal lymph node metastasis and one of these also had pulmonary metastases. The sixth patient developed pulmonary metastasis within 15 months of diagnosis. Three died within 4 years of diagnosis. In summary, adenocarcinoma of the rete testis is a rare malignant tumor with poor survival and a high propensity for retroperitoneal lymph node metastasis that must be distinguished from other testicular neoplasms and metastasis to the testis. Hilar localization, transition from benign to malignant rete epithelium, and supportive immunostains aid its accurate diagnosis.

Predicting vital retroperitoneal residual tumors of metastatic testicular tumor patients after chemotherapy using radiomics.

527 Background: About 50% of patients undergoing post-chemotherapy retroperitoneal lymph node dissection (pcRPLND) are overtreated due to missing markers or valid prediction scores prior surgery. The potential of radiomics and machine learning applied on computed tomography (CT) imaging to predict the presence of viable tumor or teratoma in retroperitoneal lymph node metastases from germ cell tumor (GCT) patients prior to pcRPLND has not been explored. Therefore, we applied radiomics and machine learning to CT images of GCT patients prior to pcRPLND. Methods: Metastasized GCT patients who were treated with chemotherapy and received a contrast-enhanced CT prior to pcRPLND possessing complete clinical data were included in the study. Only lymph nodes which were identified in the CT images and correlated with the pathological findings (benign: necrosis / fibrosis vs. viable: viable tumor/ teratoma) were included. Lymph nodes identified in the CT images, were semiautomatically segmented and 93 radiographic features were analyzed. A linear support vector machine (SVM) algorithm was applied to analyze reproducible radiomics features. Additionally, a continuous reduction of the features analyzed was performed using Random Forest algorithms, as well as consecutive correlation and receiver operating curve analyzes. Results: Forty-two patients fulfilled the inclusion criteria and were included in the study. Total in these patients 96 lymph nodes were segmented on CT. Histologically, 41 lymph nodes were classified as viable tumors and 55 as benign. To train the SVM, 67 lymph nodes were randomly selected. Of the 93 radiomic features analyzed, 51 features were reproducible. Applying the trained algorithm to the remaining 29 lymph nodes resulted in a classification accuracy of 82% with a diagnostic sensitivity of 81% and a specificity of 83%. After multistep feature reduction, the three most important predictors for viable tumor achieved a sensitivity of 66% and a specificity of 78% when combined in a multivariate model. Conclusions: The applied radiomics model, solely based on CT images achieved a good sensitivity and specificity in predicting viable metastases.

Impact of increased aspartate aminotransferase to alanine aminotransferase (De Ritis) ratio in prognosis of testicular cancer.

PurposeImaging studies can show metastasis in testicular cancer (TCa); however, a test for risk of metastasis in TCa has not been described. The ratio of aspartate aminotransferase to alanine aminotransferase, also called the De Ritis ratio (DRR), is used for many other malignancies. We aimed to evaluate the association between preoperatively assessed DRR and prognosis in patients with TCa.Materials and MethodsOne hundred twenty-eight patients with TCa were enrolled in a retrospective study between March 2007 and January 2017. Clinical, biochemical, and pathological data were recorded. Univariate and multivariate logistic regression analyses were used. The prognostic value of DRR and the threshold value were assessed by use of receiver operating characteristic curves. Significance was defined as p<0.05.ResultsMean follow-up was 37±9.7 months. There were 45 and 73 TCa patients with and without lymph node metastasis, respectively. Lung metastases and other solid organ metastases occurred in 14 and 4 patients, respectively. The optimal DRR threshold was 1.30 for both retroperitoneal lymph node involvement and metastasis. DRR was determined as an independent prognostic factor for retroperitoneal lymph node involvement and organ metastasis in univariate and multivariate analyses (p<0.001, p=0.006 and p=0.002, p=0.047, respectively).ConclusionsA preoperative DRR greater than 1.30 may be an independent risk factor for retroperitoneal lymph node involvement and organ metastases in patients with TCa.

Benefits of Elective Para-Aortic Radiotherapy for pN1 Prostate Cancer Using Arc Therapy (Intensity-Modulated or Volumetric Modulated Arc Therapy): Protocol for a Nonrandomized Phase II Trial.

BackgroundIn patients with prostate cancer (PCa) with histopathologically proven pelvic lymph node (LN) metastasis (pN1) after extended pelvic lymph node dissection (ePLND), multimodality treatment consisting of treatment of the primary tumor and whole pelvic radiotherapy (WPRT) combined with androgen deprivation therapy (ADT) offers promising results, leading to better cause-specific survival rates compared with ADT alone. However, in case more than one pelvic LN is invaded by the tumor, approximately 40% of the patients relapse biochemically and clinically. Clinical relapse is present in the para-aortic LNs (M1a disease) in up to 77% of the relapsing cases.ObjectiveWe hypothesize that, based on the evidence that positive LNs represent the door to hematogenous dissemination, elective para-aortic irradiation will reduce the development of both retroperitoneal nodal (M1a) and distant metastasis (M1b or M1c disease), postpone the need for palliative ADT, and prolong the time to castration-refractory disease.MethodsTo test this hypothesis, we will conduct a prospective, nonrandomized phase II trial to study the efficacy of additional elective para-aortic radiotherapy (PART) in pN1 patients compared with those who were historically treated with adjuvant WPRT alone. We aim to include 137 patients with PCa and presence of pN1 disease after ePLND. With this number of patients, an improvement of 15% in the 5-year clinical relapse-free survival can be detected with a power of 80%.ResultsRecruitment of patients for this trial started in 2017 and will be completed approximately by March 2020.ConclusionsThis is the first phase II trial to investigate the benefits of an elective PART in patients with PCa. The results of this trial will potentially serve as a sound base for a later randomized phase III trial. All participants are given a PART information sheet and required to give written informed consent. Results are expected to be published in a peer-reviewed journal.Trial RegistrationClinicalTrials.gov NCT03079323; https://clinicaltrials.gov/ct2/show/NCT03079323 (Archived by WebCite at http://www.webcitation.org/73ELimv1d)International Registered Report Identifier (IRRID)PRR1-10.2196/11256

The Value of 99mTc-PSMA SPECT/CT-Guided Surgery for Identifying and Locating Lymph Node Metastasis in Prostate Cancer Patients.

This study evaluated the effect of technetium-99m (99mTc)-labeled prostate-specific membrane antigen (PSMA)-based image-guided surgery on the oncologic outcomes for patients with primary or recurrent prostate cancer (PCa). This study retrospectively analyzed 54 consecutive patients with PCa who underwent 99mTc-labeled PSMA-based image-guided surgery between January 2016 and September 2017. These patients received a radical prostatectomy (RP) with pelvic lymph node dissection (PLND) or salvage lymph node dissection (sLND). The resected specimens were compared with findings of postoperative histologic analysis. The responses to the treatment were recorded during the follow-up period. In 31 patients, PSMA single-photon emission computerized tomography (SPECT) and computed tomography (CT) could find 52 suspicious lymph node metastases (LNMs). With the help of PSMA SPECT/CT, 12 patients with recurrence received sLND, 19 primary PCa patients received RP with extended PLND, and 23 primary PCa patients received RP with standard PLND. The findings showed that PSMA SPECT/CT could detect LNMs with high sensitivity and specificity. In six patients, PSMA SPECT/CT could find more LNMs that were not found by MRI and help to modify the extent of lymphadenectomy. At the latest follow-up evaluation, 39 patients showed a biochemical response (BR), 9 patients showed a biochemical recurrence (BCR) after BR, and 6 patients never exhibited BR. The patients who received RP with standard PLND or extended PLND had a better prostate-specific antigen (PSA) response than the patients who received sLND. The patients with pelvic LNMs also had a better PSA response than the patients with retroperitoneal LNMs. This study showed that 99mTc-PSMA SPECT/CT-guided surgery can remove more LNMs than conventional imaging with high sensitivity and specificity and delay disease progression in PCa patients.