Urachal Adenocarcinoma Research Articles

Survival of Patients With UrAC and Primary BAC and Urothelial Carcinoma With Glandular Differentiation.

PurposeTo investigate the significance of demographic and pathological characteristics on the survival outcomes of urachal adenocarcinoma (UrAC), primary bladder adenocarcinoma (BAC) and urothelial carcinoma with glandular differentiation (UCGD) in China.Materials and MethodsWe retrospectively analyzed cases with non-distant metastases (≤ T4M0). Of 106 patients, 30 (28.3%), 40 (37.7%), and 36 (34.0%) met the criteria for UrAC, primary BAC, and UCGD, respectively. Data on patient demographics, tumor pathology, and survival outcomes were collected. The median follow-up was 36 months. Survival was analyzed using multivariate Cox regression.ResultsPatients with UrAC were younger (51.87 ± 15.25 years) than those with primary BAC (60.50 ± 12.56 years) and UCGD (63.83 ± 11.60 years) (P<0.001). Patients with UrAC were the most likely to be stage T3–4 (70.0% vs. 40.0% vs. 44.4%; P<0.001), while the primary BAC group had a higher rate of poor differentiation than the UrAC and UCGD groups (57.4% vs. 18.5% vs. 24.1%; P<0.001). The Kaplan–Meier curves showed that the overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) of the primary BAC group were poorer than those of both the UrAC and UCGD groups (P=0.0046,P<0.0001,P=0.0077 respectively). Regarding BAC, patients with mucinous adenocarcinoma tended to have better OS and PFS than those with other histological types (P<0.005,P=0.0245). Multivariate Cox regression analysis revealed that tumor type (P=0.002), T stage (P=0.034), and the age-adjusted Charlson Comorbidity Index (aCCI) scores (P=0.005) predicted the postoperative OS and DSS of the patients. For PFS, the tumor type (P=0.011), grade (P=0.000), and aCCI (P=0.002) scores were predictive.ConclusionAmong UrAC, primary BAC, and UCGD patients, the prognosis was poorest for those with primary BAC. Attempts should be made to diagnose these aggressive tumors early, since patients in whom tumors are detected early appear to survive longer.

Concurrent urachal abscess and florid cystitis glandularis masquerading as malignancy: a case report and literature review

BackgroundThe urachus is the embryological remnant of the cloaca and allantois. Failure of its regression can cause diseases any time after birth. It is difficult to differentiate an abscess from urachal adenocarcinoma based on the clinical presentation and image findings. Cystitis glandularis reflects chronic irritation of the bladder urothelium, and tumor-like florid cystitis glandularis can be misdiagnosed as malignancy. We report a patient with concurrent urachal abscess and florid cystitis glandularis which increased the resemblance of malignancy.Case presentationA 57-year-old female was incidentally found to have a heterogeneous pelvic mass abutting the urinary bladder. A cystoscopy examination revealed protruding tumors located in the bladder dome. Her blood test results were all normal, and urinalysis showed microscopic hematuria. Urachal cancer was diagnosed and en bloc excision of the umbilicus, tumor, and the involved bladder dome was performed. Pathology revealed urachal abscess with concurrent cystitis glandularis within the urinary bladder. No malignancy was identified in the resected specimen.ConclusionsIt is challenging to distinguish urachal abscess from a malignant tumor based on the clinical presentation and imaging studies. As in our case, the coexistence of urachal abscess and tumor-like florid cystitis glandularis increased the resemblance to a malignancy. This is the first reported case of the concurrence of these two disease entities, and emphasizes that the detection of bladder tumors on cystoscopy is not sufficient to make the diagnosis of urachal cancer with bladder involvement.

Urachal adenocarcinoma and its unusual metastatic behaviour - A case report

Introduction: Urachal adenocarcinoma is one of the rare bladder malignancies. The pathogenesis and behaviour of the disease is not fully known except for its aggressive nature especially with positive margins, advanced stage and regional lymph node involvement. Case report: Here we report a case of 50-year-old male patient who o our hospital with chief complaints of swelling below the umbilicus with active haematuria and on physical examination, a hard mass measuring 5x 3 cm was felt below the umbilicus. Contrast enhanced computed tomography (CECT) scan revealed a heterogeneously enhancing lesion occupying the dome of bladder with loss of fat planes involving the anterior abdominal wall muscles and at one location in the mesentery. Laparotomy revealed a fleshy mass arising from the dome of bladder with blood clots. En bloc removal of umbilicus with soft tissue underneath and partial cystectomy was done. Intraoperatively a mass measuring 8x6 cm was seen extending from the umbilical skin till bladder dome. In addition, multiple peritoneal as well as mesenteric deposits were noted. Histopathology confirmed the diagnosis of adenocarcinoma with positive margins along with mesenteric and peritoneal metastasis. The tumour was staged as Sheldon/ Mayo stage/ Tumour, Node, Metastasis (TNM) IV and started under palliative chemotherapy which included cisplatin and gemcitabine. After 2 cycles of chemotherapy, lung metastasis was detected and the patient succumbed to his illness. Conclusion: This case of urachal adenocarcinoma has been put up primarily to highlight the way of locoregional and distant metastatic spread, thereby adding contribution to the already existing sparse literature. The patient had peritoneal spread along with less frequently detected mesenteric involvement at the time of presentation and rapidly developed pulmonary metastasis. As many of its behaviours remain hidden, case series and case reports with shared experiences of surgeons, urologists and pathologists are essential to unravel its hidden behaviours.

798 A Rare Complication and Unexpected Pathology Following an Anterior Exenteration – A Case Report

Abstract We present a case report of an unexpected pathology in addition to a rare complication in a 62-year-old female following an anterior exenteration and an abdominal wall reconstruction. Initial biopsies characterised the malignancy as a potential urachal adenocarcinoma, but the final pathology revealed a solitary endometrial adenocarcinoma metastasis from endometrial cancer 6 years previously. Due to the nature of the tumour, an abdominal wall resection was required, and reconstruction involved a pedicled thigh flap. Post-operatively the small bowel herniated under the flap and this resulted in true mechanical small bowel obstruction. The loop of herniated bowel is visible on CT imaging in the area of the proximal thigh. The patient returned to theatre for an emergency laparotomy and the abdominal wall defect was closed instead with a surgical implant derived from animal tissue. The patient made an excellent recovery, was discharged home, and continues to do well. This patient is an example of excelling in adversity.

Urachal adenocarcinoma following renal transplantation

Urachal adenocarcinoma following renal transplantation

A new technological approach in diagnostic pathology: mass spectrometry imaging-based metabolomics for biomarker detection in urachal cancer

Urachal adenocarcinomas (UrC) are rare but aggressive. Despite being of profound therapeutic relevance, UrC cannot be differentiated by histomorphology alone from other adenocarcinomas of differential diagnostic importance. As no reliable tissue-based diagnostic biomarkers are available, we aimed to detect such by integrating mass-spectrometry imaging-based metabolomics and digital pathology, thus allowing for a multimodal approach on the basis of spatial information. To achieve this, a cohort of UrC (n = 19) and colorectal adenocarcinomas (CRC, n = 27) as the differential diagnosis of highest therapeutic relevance was created, tissue micro-arrays (TMAs) were constructed, and pathological data was recorded. Hematoxylin and eosin (H&E) stained tissue sections were scanned and annotated, enabling an automized discrimination of tumor and non-tumor areas after training of an adequate algorithm. Spectral information within tumor regions, obtained via matrix-assisted laser desorption/ionization (MALDI)-Orbitrap-mass spectrometry imaging (MSI), were subsequently extracted in an automated workflow. On this basis, metabolic differences between UrC and CRC were revealed using machine learning algorithms. As a result, the study demonstrated the feasibility of MALDI-MSI for the evaluation of FFPE tissue in UrC and CRC with the potential to combine spatial metabolomics data with annotated histopathological data from digitalized H&E slides. The detected Area under the curve (AUC) of 0.94 in general and 0.77 for the analyte taurine alone (diagnostic accuracy for taurine: 74%) makes the technology a promising tool in this differential diagnostic dilemma situation. Although the data has to be considered as a proof-of-concept study, it presents a new adoption of this technology that has not been used in this scenario in which reliable diagnostic biomarkers (such as immunohistochemical markers) are currently not available.New diagnostic strategies are needed to distinguish rarely arising urachal adenocarcinomas (UrC) from other types of adenocarcinomas, as therapy regimes differ. In situ metabolic differences between UrC and colorectal adenocarcinomas were revealed using mass spectrometry imaging combined with digital pathology. A classification accuracy of 87% was achieved, exceeding currently available approaches.

V13-10 ROBOTIC PARTIAL CYSTECTOMY FOR A URACHAL MASS

You have accessJournal of UrologyBladder & Upper Tract Urothelial Oncology (V13)1 Sep 2021V13-10 ROBOTIC PARTIAL CYSTECTOMY FOR A URACHAL MASS Joshua Palka, Kenneth Sands, Nicholas Pickersgill, and Ramakrishna Venkatesh Joshua PalkaJoshua Palka More articles by this author , Kenneth SandsKenneth Sands More articles by this author , Nicholas PickersgillNicholas Pickersgill More articles by this author , and Ramakrishna VenkateshRamakrishna Venkatesh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002100.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urachal masses are rare entities with urachal adenocarcinoma comprising approximately 0.2% of bladder tumors. Due to its rarity, the optimal approach to these tumors is unknown. Previous series describe a retrograde approach for urachal mass excision. We present an antegrade robotic approach to en bloc urachal mass excision. METHODS: After IRB approval was granted, retrospective review was carried on all urachal masses at our institution. All robotic-assisted laparoscopic urachal mass excisions with partial cystectomy were included. Patient demographics as well as intra- and post-operative findings were evaluated. We then selected the most recent urachal mass en bloc excision to highlight our approach these rare entities. All procedures were performed with the da Vinci® Xi or Si platforms (Intuitive Surgical Inc., Sunnyvale, CA). RESULTS: A total of 12 patients (5 females and 7 males) were identified with mean age of 52.8 years (SD±13.2). Mean BMI was 28.3 (SD±6.6) kg/m2. The majority of masses were discovered on incidental imaging (58.3%) with umbilical drainage (25%) or gross hematuria (16.7%). There were a total of three patients (25%) diagnosed with urachal adenocarcinoma in the specimen. Mean operative time was 147 minutes (SD±52 minutes) with mean estimated blood loss of 19.2 mL (SD±19.7 mL). Mean mass size was found to be 5.4 cm (SD±2.7cm) and average length of stay was 1.1 days (SD±0.3 days). All patients underwent an antegrade approach to en bloc removal of the urachal mass. CONCLUSIONS: This video demonstrates an antegrade approach to en bloc urachal mass excision and partial cystectomy with bilateral pelvic lymph node dissection that is familiar to most Urologists. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1081-e1081 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joshua Palka More articles by this author Kenneth Sands More articles by this author Nicholas Pickersgill More articles by this author Ramakrishna Venkatesh More articles by this author Expand All Advertisement Loading ...

Anterior wall adenocarcinoma of bladder with similar clinicopathological and prognostic characteristics as common bladder carcinomas should not be treated as or classified into urachal adenocarcinomas

PurposeTo discuss whether the dome or anterior wall of bladder adenocarcinoma (BAC) should be classified into urachal carcinoma (UrC) and the relationship of primary tumor location (PTL) as well as treatment with survival.MethodsSurveillance, Epidemiology, and End Results 18 database was examined for eligible patients from 1975 to 2016. Patients were classified into adenocarcinoma originating from the urachus (UAC), the dome (D‐BAC), the anterior wall (A‐BAC), and the other sites adenocarcinoma of the bladder (O‐BAC). The clinicopathological features, treatment, and survival were compared among the groups.ResultsComparable clinicopathologic features were obtained between UAC and D‐BAC, which were different from those of A‐BAC and O‐BAC; otherwise, the latter two had similar clinicopathologic features. Univariable and multivariable Cox regression analyses indicated that PTL was an independent predictor for survival. O‐BAC conferred the worst prognosis then followed by A‐BAC, D‐BAC, and UAC. For non‐metastatic UAC or D‐BAC, partial cystectomy (with an en bloc resection of the urachus and umbilicus) is optimal for survival. However, the worse survival of non‐metastatic D‐BAC (compared with UAC) suggested different modalities, maybe more intensive surgery approaches, should be considered for D‐BAC.ConclusionThis study illustrates that PTL of UAC and BAC was an independent predictor for survival. A‐BAC had comparable characters and prognosis with O‐BAC and should not be classified into and treated as UrC. For non‐metastatic disease, non‐metastatic D‐BAC may need more intensive modality.

Aggressive Recurrent Urachal Adenocarcinoma : A Case Report And Review Of The Literature

Recurrent urachal adenocarcinomas are rare. It is commonly associated with poor prognosis. A 51-year-old woman underwent a partial cystectomy for urachal cancer in 2014. She was well throughout follow-up with annual cystoscopies. She presented with a 1-month history of rapidly progressive suprapubic mass and hematuria. A contrasted computed tomography scan of the thorax, abdomen and pelvis showed a large mixed solid cystic tumour at the right lumbar region, suprapubic area and also at the pouch of Douglas. She refused surgical extirpation and now on chemotherapy. Urachal adenocarcinoma is rare, and resection is commonly advocated; usually, no standard adjuvant therapy is advocated. Recurrent cancers represent a management dilemma, and no standard follow-up protocols exist.&#x0D; Bangladesh Journal of Medical Science Vol.20(4) 2021 p.911-913

Digital Ischemia and Necrosis from Oxaliplatin

Oxaliplatin is a chemotherapeutic agent used in a variety of malignancies such as colorectal cancer and pancreatic cancer. It is a platinum derivative that results in direct cell cytotoxicity with resultant cell death. The most common side effects often noted are neurotoxicity, nausea, vomiting, diarrhea, hepatotoxicity and myelosuppression. Oxaliplatin induced digital ischemia and necrosis is a rare side effect that was observed in our patient. In general, digital ischemia is a rare vascular disorder that is often associated with autoimmune disease [1]. Here, we intend to present a patient with digital ischemia due to Oxaliplatin, which was a chemotherapy agent used in the treatment of his urachal adenocarcinoma.

Primary urachal carcinoma: A systematic review.

e16502 Background: Primary urachal carcinoma (PUC) is a rare cancer of unknown definite cause, and various treatment approaches given its very low incidence and the scarcity of prospective studies. This review aimed to assess the clinicopathologic findings, treatment, and outcomes of PUC cases reported in the literature. Methods: We performed PubMed, Medline, ScienceDirect, and Scopus literature search for "urachus cancer" in adults (19+ years) from data inception through 2020, pooled with six cases from our institution. Results: We included 152 patients with a male: female ratio of 1.61:1 and mean age at diagnosis (±SD, range) of 50.0 (±13.5, 20–86) years. Most common presenting symptoms were hematuria, irritative voiding, abdominal pain, mucinuria, and a palpable mass in 49.5%, 17.3%, 10.2%, 8.7%, and 6.6% of patients, respectively, with a median duration of symptoms of 3 (range 0.25-240) months. Most common locations were the urinary bladder dome (83.6%), supero-anterior (7.03%), and the anterior wall (3.9%), with a median size of 4.9 (range 0.5–96) cm. Subgroups, according to tumor size, were divided into &lt; 4 cm (n = 54, 35.5%) vs ≥4 cm (n = 98, 64.5%) with a significant survival differences according to a log-rank test (p-value &lt; 0.0001). Histologically, the most common diagnoses were urachal adenocarcinoma (43.4%), followed by mucinous adenocarcinoma (24.1%), adenocarcinoma of enteric type (8.9%), and adenocarcinoma with signet ring cell (6.9%). 17.5% and 72.2% of patients were diagnosed at an early stage (stage I and II) while 82.5% and 27.8% were diagnosed at an advanced stage ( III and IV) using Sheldon staging system and Mayo staging system, respectively. Only 9.9% of patients lived for more than five years after their diagnosis. Early Sheldon stage is associated with a high survival probability based on a log-rank test (p-value: 0.003). Overall, most common treatment modalities included surgery alone (71.0%), followed by surgery with chemotherapy (18.6%), and surgery with chemoradiation (4.1%). Patients underwent partial cystectomy (65.4%), en bloc radical resection/exenteration (25.7%), local resection (8.8%), pelvic lymphadenectomy (38.2%), and umbilectomy (16.9%). Almost 79% of patients were alive with an average duration of follow-up of 12 (range 0.9-240) months, and 20.9% were deceased with an average time to death of 23.9 (range 5-139) months. Conclusions: Early Sheldon stage and smaller tumor size were notable predictors of higher survival probability in PUC patients. Hence, early and correct diagnosis is crucial in improving outcomes. This review serves as real-world evidence to promote our understanding of this rare entity and shed light on future clinical trial design.

Robot-assisted laparoscopic intracorporeal urachal mass resection and partial cystectomy for a huge urachal adenocarcinoma: a case report and review of literature

Urachal adenocarcinoma is rare, accounting for only 10% of adenocarcinomas of the bladder and the prognosis of urachal adenocarcinomas is poor since most cases are detected late. Since urachal adenocarcinoma is a rare disease, no effective standard treatment has yet been established. However, in recent studies, resection of carcinoma is considered the only treatment considered for non-metastatic cases. Although for large sized urachal adenocarcinoma, open surgery or laparoscopic surgery is usually considered, we have recently experienced huge urachal carcinoma by robotic surgery. We used cystoscopy and the robot to assess the cancer margins and safely perform the operation. A 71-year-old man with a medical history of hypertension and arrhythmia visited our urology department with urachal cancer detected by computed tomography (CT). CT showed a lobulated low-density mass, most likely urachal carcinoma, abutting the anterior dome of the bladder and anterior abdominal wall. We performed preoperative cystoscopy to assess the extent of the protrusion of the urachal cancer into the bladder wall and the area requiring resection during surgery. We confirmed the size and extent of the mass protruding into the anterior wall of the urinary bladder and Robot-assisted laparoscopic intracorporeal urachal mass resection and partial cystectomy using cystoscopy together was performed. After one month, the patient has no complications and no complaining symptoms complaints without any abnormal finding of follow up imaging test. Although more procedures must be performed to ensure the safety of robotic surgery as a treatment strategy for large urachal carcinomas, we confirm that robotic surgery can replace open or laparoscopic surgery for such tumors.

Resección laparoscópica de adenocarcinoma de uraco

El adenocarcinoma de uraco es una enfermedad neoplásica rara, con una incidencia de 1 por 5 millones de habitantes. Clínicamente se manifiesta con hematuria (73%), dolor abdominal (14%), disuria (13%), mucosuria (10%), síntomas irritativos (40%), masa palpable en la parte baja del abdomen (17%), bacteriuria (8%), flujo mucoso umbilical (2%). Presentamos el caso de paciente de 45 años, con diagnóstico de adenocarcinoma de uraco, que recibió múltiples tratamientos sin respuesta, realizándose, cirugía radical con resección en bloque de ombligo, uraco, peritoneo, fascia posterior del musculo recto del abdomen y cistectomía parcial, por abordaje laparoscópico, con excelentes resultados oncológicos y estéticos, con recuperación rápida, y sin complicaciones. El papel de la quimioterapia y radioterapia y su beneficio para el paciente aún no está claro. Con este caso queremos aportar con un nuevo caso a la literatura, además de poder mostrar que el manejo con mínima invasión puede ser adecuada en manos expertas, con resultados iguales a la cirugía abierta, con el beneficio ya conocido del abordaje laparoscópico.

Clinical Utility of 18F-FDG PET/CT for Staging and Treatment Planning in Urachal Adenocarcinoma.

Our objective was to evaluate the impact of 18F-FDG PET CT on the management of urachal adenocarcinoma (UrC-ADC). Methods: A retrospective analysis of patients with UrC-ADC from 2001 to 2019 at Memorial Sloan Kettering was performed. Mayo stage before 18F-FDG PET/CT, rate of detection of the primary malignancy and metastases on 18F-FDG PET/CT, Mayo stage after 18F-FDG PET/CT, and change in patient management were determined. Results: Of 21 patients with UrC-ADC before 18F-FDG PET/CT, Mayo staging was I/II in 8, III in 3, and IV in 10. 18F-FDG PET/CT detected previously unidentified metastases in 8 (38%) of 21 patients, resulting in upstaging of disease in 3 (14%) patients and a change in treatment in 4 (19%) patients. Conclusion:18F-FDG PET/CT has clinical utility in patients with UrC-ADC by identifying metastatic disease not appreciated on anatomic imaging, leading to changes in staging and patient management.

Delayed 18F-FDG PET/CT Appearance of Urachal Adenocarcinomas.

Background Urachal carcinoma is a rare urological malignancy. Use of 18F-FDG PET/CT in urological oncology has developed slowly because of the urinary elimination of 18F-FDG. We investigated whether delayed postdiuretic 18F-FDG PET/CT could be used for diagnosing urachal carcinoma. Methods This retrospective study included 6 patients who underwent delayed postdiuretic 18F-FDG PET/CT for the evaluation of urachal carcinoma. The delayed postdiuretic PET/CT parameters and clinical characteristics of urachal carcinoma were investigated. Results There was no significant difference in the SUVmax between the primary tumors and the urine in the bladder before delayed diuresis (25.4 ± 19.5 vs. 42.9 ± 31.1, P=0.18). However, the SUVmax of the primary tumors was significantly higher than the SUVmax of urine after delayed diuresis (25.4 ± 19.5 vs. 3.5 ± 1.6, P=0.002). Diuretic 18F-FDG PET/CT was positive in all patients when compared with normal liver tissues or urine after delayed diuresis. The SUVmax, TLR, and TUR of the primary tumors were 25.4 (range: 7.2–58.9), 7.0 (range: 1.8–14.7), and 6.8 (range: 3.8–11.3), respectively. Delayed postdiuretic 18F-FDG PET/CT had a negative predictive value of 100% (5/5) for predicting lymph node metastasis. One patient received chemotherapy after radical resection of urachal carcinoma because 18F-FDG PET/CT found lung metastases, and one patient only received chemotherapy because PET/CT found peritoneal and skeletal metastases. Conclusions Delayed postdiuretic 18F-FDG PET/CT is a useful tool for the preoperative evaluation of urachal carcinoma. 18F-FDG PET/CT may improve clinical decision making and management of urachal carcinomas.

Robotic assisted laparoscopic partial cystectomy and En bloc resection of urachus and umbilicus for rare case of mucin producing Urachal adenocarcinoma: A Case Report

Background: Urachal carcinoma accounts for <1% of all bladder cancers, 90% are adenocarcinomas, accounting for 10% of the bladders’ adenocarcinomas. For its rarity, there is no consensus about the nomenclature, staging, diagnosis and treatment. Case report: We described a 42 years old male, who complained of post-voiding mucinous discharge for a long period (10 years). after extensive clinical evaluation and radiologic investigation and cystoscopy, the diagnosis of an early stage urachal adenocarcinoma had been confirmed. It had been completely excised with no metastasis. The surgical resection of the tumour done en-bloc through laparoscopy, robotic-assisted surgery. No chemotherapy nor radiotherapy had been indicated, the patient has been submitted to close follow-up, with our hoping look for recurrence of the disease. Excised specimen had been further submitted to histopathological and immunostaining examination. Histopathological grading had been done according to most recent staging systems (it confirmed the early staging mucinous adenocarcinoma of urachal origin). Conclusion: Here we described our experience with a rare case report of mucinous cystadenoma of urachal origin, robot-assisted laparoscopic surgery and early stage of cancer permits partial cystectomy, good outcome with no need for chemical or radiotherapy.

Ex vivo modelling of drug efficacy in a rare metastatic urachal carcinoma

BackgroundEx vivo drug screening refers to the out-of-body assessment of drug efficacy in patient derived vital tumor cells. The purpose of these methods is to enable functional testing of patient specific efficacy of anti-cancer therapeutics and personalized treatment strategies. Such approaches could prove powerful especially in context of rare cancers for which demonstration of novel therapies is difficult due to the low numbers of patients. Here, we report comparison of different ex vivo drug screening methods in a metastatic urachal adenocarcinoma, a rare and aggressive non-urothelial bladder malignancy that arises from the remnant embryologic urachus in adults.MethodsTo compare the feasibility and results obtained with alternative ex vivo drug screening techniques, we used three different approaches; enzymatic cell viability assay of 2D cell cultures and image-based cytometry of 2D and 3D cell cultures in parallel. Vital tumor cells isolated from a biopsy obtained in context of a surgical debulking procedure were used for screening of 1160 drugs with the aim to evaluate patterns of efficacy in the urachal cancer cells.ResultsDose response data from the enzymatic cell viability assay and the image-based assay of 2D cell cultures showed the best consistency. With 3D cell culture conditions, the proliferation rate of the tumor cells was slower and potency of several drugs was reduced even following growth rate normalization of the responses. MEK, mTOR, and MET inhibitors were identified as the most cytotoxic targeted drugs. Secondary validation analyses confirmed the efficacy of these drugs also with the new human urachal adenocarcinoma cell line (MISB18) established from the patient’s tumor.ConclusionsAll the tested ex vivo drug screening methods captured the patient’s tumor cells’ sensitivity to drugs that could be associated with the oncogenic KRASG12V mutation found in the patient’s tumor cells. Specific drug classes however resulted in differential dose response profiles dependent on the used cell culture method indicating that the choice of assay could bias results from ex vivo drug screening assays for selected drug classes.

Molecular Genetic Features of Primary Nonurachal Enteric-type Adenocarcinoma, Urachal Adenocarcinoma, Mucinous Adenocarcinoma, and Intestinal Metaplasia/Adenoma: Review of the Literature and Next-generation Sequencing Study

The diagnosis of primary adenocarcinoma of the urinary bladder may be challenging in routine practice. These tumors may morphologically and immunohistochemically overlap with urachal adenocarcinoma and colorectal adenocarcinoma. Further, their genetic background is poorly understood. We systematically searched the PubMed database for results of complex genetic evaluation of primary bladder adenocarcinoma subtypes. Subsequently, we designed our own series of bladder lesions. We evaluated 36 cases: 16 primary enteric-type adenocarcinomas, 7 urachal enteric adenocarcinomas, 3 primary mucinous/colloid adenocarcinomas, and 10 intestinal-type metaplasia/villous adenoma. Detailed clinical data were collected, and all cases were examined using targeted next-generation sequencing. On the basis of the literature, the first mutated gene in these tumors was reported to be KRAS in 11.3% of cases, followed by TERT promoter mutations in 28.5%. In addition to KRAS and TERT, other genes were also found to be frequently mutated in primary bladder adenocarcinoma, including TP53, PIK3CA, CTNNB1, APC, FBXW7, IDH2, and RB1. In our series, the most frequent gene mutations in primary enteric-type adenocarcinomas were as follows: TP53 (56%); BRCA2, KMT2B (both 33%); NOTCH2, KDR, ARID1B, POLE, PTEN, KRAS (all 28%); in urachal enteric adenocarcinoma they were as follows: TP53 (86%); PTEN, NOTCH (both 43%); in primary mucinous/colloid adenocarcinomas they were as follows: KRAS, GRIN2A, AURKB (all 67%); and, in intestinal-type metaplasia/villous adenoma, they were as follows: APC, PRKDC (both 60%); ROS1, ATM, KMT2D (all 50%). No specific mutational pattern was identified using cluster analysis for any of the groups. Herein, we describe the pathologic features and immunohistochemical staining patterns traditionally used in the differential diagnoses of glandular lesions of the bladder in routine surgical pathology. We outline the mutational landscape of these lesions as an aggregate of published data with additional data from our cohort. Although diagnostically not discriminatory, we document that the most common genetic alterations shared between these glandular neoplasms include TP53, APC (in the Wnt pathway), and KRAS (in the MAPK pathway) mutations.

U-shaped relationship of age at diagnosis and cancer-specific mortality in primary urachal adenocarcinoma: a cohort study.

BackgroundTo examine the association between age at diagnosis and cancer-specific mortality (CSM) in primary urachal adenocarcinoma.MethodsThe data was obtained from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program (SEER). A total of 393 patients were included in the study. Smooth curve fitting and two-piecewise Cox proportional hazards models were used to identify the nonlinearity between the age at initial diagnosis and cancer-specific survival rate. Survival time between different groups was compared using Kaplan-Meier survival curves and the log-rank test.ResultsUsing smooth curve fitting we found that the relationship between age at diagnosis and cancer-specific survival takes on a U-shaped curve. The inflection point that we identified for the age at initial diagnosis was 60 years. The log-likelihood ratio test (P<0.05) indicated that the two-piecewise Cox regression model was more appropriate for fitting the correlation of age at diagnosis and CSM. The two-piecewise Cox regression model showed that when the age was <60 years, reduced risk of CSM was significantly associated with increased age (HR: 0.95, P=0.0002). Conversely, when age was >60 years, increased risk of CSM was significantly associated with increased age (HR: 1.05, P=0.0499).ConclusionsIn summary, our study suggested that the relationship between age at diagnosis and cancer-specific survival is nonlinear, and takes on a U-shaped curve. Both younger and older age at initial diagnosis age were associated with increased CSM.

Ipilimumab challenge/re-challenge in metastatic urothelial carcinoma (mUC) and other genitourinary (GU) tumors treated with cabozantinib+nivolumab (CaboNivo) or cabozantinib+nivolumab+ipilimumab (CaboNivoIpi).

5039 Background: We investigated challenging/re-challenging pts with ipilimumab (ipi) after progression on CaboNivo or CaboNivoIpi. Methods: In a phase I expansion study, patients with mUC post-platinum chemotherapy and other GU tumors patients who progressed on Cabo 40 mg daily plus nivolumab, 3 mg/kg every 21 days (CaboNivo) alone or with ipi, 1 mg/kg every 21 days for 4 cycles (CaboNivoIpi)-and achieved a PR or SD≥6 mo, were challenged/re-challenged with ipi, 1 mg/kg every 21 days for up to 4 cycles. Restaging scans were done every 6 wks for the first 12 wks, then every 8 wks and evaluated by RECIST 1.1. Results: In total, 24 patients were evaluated: 18 pts (8 UC (5 bladder and 3 upper tract), 4 clear cell renal cell carcinoma (RCC), 3 urachal adenocarcinoma (adeno), 2 bladder adeno, and 1 sarcomatoid clear cell RCC) who progressed on CaboNivo were challenged with ipi. In the challenge group, median (m) follow-up was 21.2 months. One pt achieved a PR in the LNs, but was found to have brain metastases before the next restaging, 13 had SD and 4 had PD. Median duration of PR or SD was 3.6 months (95% CI: 1.4 – 7.8 months). The mOS from start of ipi challenge was 13.9 months (95% CI: 5.8 months- not estimable); mPFS was 4.6 months (95% CI: 1.9 – 8.7 months). Grade 1/2 treatment related adverse events (AEs) occurred in all 18 pts (100%) and ≥Grade 3 (G≥3) AEs occurred in 11 pts (61%). The most common G≥3 AEs were hypophosphatemia (22%), hypertension (6%), adrenal insufficiency (6%), increased AST (6%), and ALT (6%). Six patients (3 bladder UC, 1 penile squamous cell (SCC) carcinoma, 1 urethral SCC, and 1 clear cell RCC with sarcomatoid features) who progressed on CaboNivoIpi were re-challenged with Ipi. On re-challenge, mfollow-up was 20.9 months. There were no PRs, 3 SDs and 3 PDs. mOS from start of re-challenge was 4.0 months (95% CI: 2.2 – 23.3 months) and mPFS was 1.9 months (95% CI: 1.1 – 2.6 months). Grade 1/2 treatment related AEs occurred in all 6 pts (100%) and ≥Grade 3 (G≥3) AEs occurred in 2pts (33%). G≥3 AEs included 1 hypertension (17%) and 1 hyperphosphatemia (17%). Conclusions: Ipi challenge/re-challenge showed low response rates in pts previously treated with CaboNivo or CaboNivoIpi. However, pts treated with CaboNivo who were challenged with ipi had a better OS than patients who had progressed on CaboNivoIpi and were re-challenged with ipi. Larger trials are warranted testing the ipi challenge in pts progressing on CaboNivo. Clinical trial information: NCT02496208 .