High Risk Of Residual Disease Research Articles

Abstract C161: Rare Invasive Plasmacytoid Urothelial Carcinoma Presenting as Post-Renal Acute Kidney Injury: A Case Report

Abstract Purpose: Plasmacytoid urothelial carcinoma stands out as a rare and highly aggressive histological subtype within the spectrum of bladder carcinomas, constituting only 1-3% of all variants. Summary: In this case report, we present the case of a 72-year-old patient who initially presented with significant obstructive uropathy and hydronephrosis secondary to invasive plasmacytoid urothelial carcinoma. Admission labs were concerning for a hemoglobin level of 3.8, requiring 3 units of red blood cells for correction, potassium level of 8.8, for which urgent hemodialysis was given, and a lactate level of 5.4. The patient subsequently developed delayed hematuria one month later. Follow-up CT imaging revealed an alarming increase in the size of the bladder mass, underscoring the rapid progression of the malignancy. Discussion: The aggressive nature of this malignant neoplasm can be attributed to its diffuse pattern of infiltration and high risk of residual disease following radical surgery. Clinical manifestations often include abdominal pain, but lack early-onset hematuria and other urinary symptoms typically seen with other subtypes, leading to diagnostic delays and late-stage identification. Conclusion: This case report highlights the uncommon clinical presentation of plasmacytoid urothelial carcinoma (PUC), manifesting as obstructive nephropathy. The inherent aggressiveness associated with PUC poses a challenge in treatment due to the advanced stage of the malignancy at the time of diagnosis. The scarcity of guidelines for the management of PUC underscores the need for extensive future studies to bridge this gap. Citation Format: Andressa Uzeda, Toral Shastri, Kamilia Moalem, Kendra Van Kirk. Rare Invasive Plasmacytoid Urothelial Carcinoma Presenting as Post-Renal Acute Kidney Injury: A Case Report [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C161.

Practical Guide to VI-RADS: MRI Protocols, Lesion Characterization, and Pitfalls.

Urothelial carcinoma is the most common type of bladder cancer (BC), accounting for approximately 90% of all cases. Evaluating the depth of tumor invasion in the bladder wall (tumor staging) is essential for determining the treatment and prognosis in patients with BC. Neoadjuvant therapy followed by radical cystectomy is the most common treatment of localized muscle-invasive BC (MIBC). Therefore, it is vital to differentiate non-MIBC from MIBC. Transurethral resection of bladder tumor (TURBT) is the reference standard to determine the extent of tumor invasion into the bladder wall through tissue sampling. However, this diagnostic and therapeutic method may not adequately sample the muscularis propria, leading to a higher risk of residual disease, early recurrence, and tumor understaging in approximately 50% of patients during the initial TURBT. Multiparametric MRI can overcome some of the limitations of TURBT when evaluating BC, particularly regarding tumor staging. In this context, the Vesical Imaging Reporting and Data System (VI-RADS) classification was developed to establish standards for bladder multiparametric MRI and interpretation. It uses a 5-point scale to assess the likelihood of detrusor muscle invasion. T2-weighted MR images are particularly useful as an initial guide, especially for categories 1-3, while the presence of muscular invasion is determined with diffusion-weighted and dynamic contrast-enhanced sequences. Diffusion-weighted imaging takes precedence as the dominant method when optimal image quality is achieved. The presence of a stalk or a thickened inner layer and no evidence of interruption of the signal intensity of the muscular layer are central for predicting a low likelihood of muscle invasion. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by Hoegger in this issue.

Circulating tumor-derived small extracellular vesicles micro RNAs plus CA-125 objectively tests residual tumor prior to debulking surgery in advanced ovarian cancer (525)

<b>Objectives:</b> No residual disease after debulking surgery (R0 resection) is the most critical independent prognostic factor for advanced ovarian cancer (AOC). There is an unmet clinical need for selecting primary or interval debulking surgery in AOC patients using existing prediction models, such as CA-125, CT, PET-CT, or laparoscopy. Therefore, it is of paramount importance to preoperatively estimate the likelihood of R0 resection for choosing the best therapeutic strategy. In this study, we sought to develop a novel, non-invasive, and objective detection method. <b>Methods:</b> Differentially expressed microRNAs (miRNA) in circulating small extracellular vesicles (sEVs) between any residual disease (R0) and no residual disease (non-R0) AOC patients were revealed using small RNA sequencing. miRNA expression of plasma samples was measured by TaqMan qRT-PCR. The prediction model of residual disease risk was established via LASSO and logistic regression analysis based on the discovery-validation set. Tissue sEVs were extracted from primary tumor tissue, metastatic tumor tissue, adjacent tissue, or non-tumor tissue by differential ultracentrifugation and size exclusion chromatography (SEC). Cell-type-specific markers (EpCAM, FAP, CD45, CD31) in tumor sEVs pool were evaluated by western blot analysis. Plasma sEVs were captured by the magnetic bead sorting system (MACS) using specific surface proteins as markers (EpCAM, CD45, CD235a). <b>Results:</b> A total of 270 subjects were recruited in this study from four clinical centers. According to the comprehensive plasma sEVs miRNAs profile in AOC patients, we identified and optimized a risk model consisting of plasma sEVs 5-miRNA and CA-125 for predicting residual disease (AUC:0.912; sensitivity:0.964; specificity:0.884; PPV:0.911; NPV:0.905;). Moreover, there were significant differences in model index scores between AOC patients and patients with benign ovarian tumors, early-stage ovarian cancer with FIGO I or II, and advanced colorectal cancer. Our data showed that EpCAM-positive sEVs accounted for the highest in tumor sEVs pool. Besides, these 5-miRNAs were a high concentration horizontal packaging in plasma EpCAM-sEVs. By further comparing the sEVs 5-miRNA expression in paired tumor and non-tumor tissue as well as plasma, we found that they were mainly originated from epithelial ovarian cancer cells and their tumor microenvironment. These results indicated that plasma sEVs 5-miRNA in AOC patients was associated with residual disease. <b>Conclusions:</b> Collectively, our study demonstrated a distinct profile of circulating sEVs miRNAs between R0 and non-R0 patients and obtained a robust model of circulating tumor-derived sEVs 5-miRNA combined with CA-125 to preoperatively anticipate a high risk of residual disease for optimizing clinical treatment and guiding differential diagnosis. This prediction panel, as a tool of non-invasive liquid biopsy, can be part of a standard monitoring strategy for screening high-risk patients who are allowed for neoadjuvant chemotherapy.

Residual melanoma in wide local excision specimens after 'complete' excision of primary cutaneous in situ and invasive melanomas.

Wide local excision (WLE) to achieve adequate clearance margins is the standard initial definitive treatment for patients with biopsy-proven primary cutaneous melanoma. Residual melanoma in WLE specimens after prior complete excision-biopsy (CEB) is reported in 0-6.3% of cases. However, studies evaluating the prevalence, clinicopathological features and relevance of persistent disease in WLE specimens are limited. This study sought to determine the frequency of and clinicopathological characteristics associated with residual melanoma in WLE specimens performed after a CEB of primary cutaneous or acral melanoma (in situ or invasive) with clinically and histologically tumour-free margins, and assess its relevance. A review of the research database and pathology archives of a large Australian tertiary referral melanoma treatment centre was performed. Eligible patients were those for whom a definitive WLE was performed after CEB of a primary melanoma (in situ or invasive) with negative clinical and histological margins, between May 2013 and May 2015. All partial biopsies were excluded. Of 640 eligible patients, 510 (79.7%) had invasive melanoma and 130 (20.3%) had melanoma in situ. Residual disease was identified in 20 cases (20/640, 3.1%), of which three (15%) were melanoma in situ on CEB and 17 (85%) were invasive melanoma. On univariate analysis, the presence of residual disease in WLE specimens was associated with lentigo maligna (LM)/LM melanoma (LMM) subtype [odds ratio (OR) 10.33; 95% confidence interval (CI) 2.84-37.54; p=0.004], nodular melanoma (NM) subtype (OR 4.92; 95% CI 1.53-15.85; p=0.0076) and, for invasive tumours, higher tumour mitotic rate (mean 7.7, SD 7.51 vs 3.4, SD 4.83; OR 1.11; 95% CI 1.04-1.18; p=0.0014). Breslow thickness >4 mm was associated with a higher risk of residual disease (OR 7.30; 95% CI 1.88, 28.26; p=0.004). Cases with residual disease had primary tumours with a significantly larger diameter (median 14 mm, range 4-25) than those without residual disease (median 9 mm, range 2-60), (OR 1.07; 95% CI 1.03-1.11; p≤0.001) and were also more likely to be amelanotic (38% vs 14%), (OR 3.69; 95% CI 1.17, 11.60; p=0.026). Residual disease was associated with assessment of >3 slides of tissue (OR 6.98; 95% CI 1.54-31.62; p=0.0118) and complete blocking of the scar (OR 31.69; 95% CI 3.98-252.21; p=0.0011). Residual melanoma in WLE specimens is an infrequent occurrence. Risk factors for residual disease are LM/LMM and NM melanoma subtypes, higher mitotic rate, larger lesion diameter and amelanosis. Tumours with these features warrant more extensive pathological sampling. WLE after CEB for melanoma remains an important procedure to reduce local recurrence; however, limited pathological sampling of the WLE scar is probably appropriate for cases lacking high risk features.

Clinical outcome of non-curative endoscopic submucosal dissection for early colorectal cancer

ObjectiveEndoscopic submucosal dissection (ESD) in a curative intent for submucosa-invasive early (T1) colorectal cancers (T1-CRCs) often leads to subsequent surgical resection in case of histologic parameters indicating higher risk of...

Adjuvant radiotherapy of endometrial cancer: role of 18F-FDG-PET/CT in treatment modulation

Objective: Residual disease after surgery is related to an unfavorable prognosis in patients with endometrial cancer (EC). An early diagnosis and treatment of this condition could improve patients’ outcome. Aim of this study was to define the role of postoperative 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (18F-FDG-PET/CT) in patients with high risk of residual disease after EC surgery. Methods: Patients operated for EC, with one or more risk factors, who underwent 18F-FDG-PET/CT before adjuvant treatment were included in this observational study. The primary endpoint was the rate of patients in whom 18F-FDG-PET/CT changed the treatment strategy and/or the radiotherapy (RT) planning. Results: Our analysis included 58 patients (median age: 67.5 years, range: 48.0–86.0) with the following risk factors: lymphadenectomy not performed (26 patients; 44.8%), inadequate lymphadenectomy (23 patients; 39.7%), and high risk of residual disease due to advanced stage (nine patients; 15.5%). Postoperative 18F-FDG-PET/CT imaging was positive in 18 patients (31%) in the following sites: pelvic extra-nodal disease (one patient), pelvic and/or paraaortic lymph nodes (12 patients), distant metastases (one patient), or combination of previous sites (four patients). Based on these results, the adjuvant therapeutic strategy was changed in five patients, three of whom were referred to chemotherapy alone due to distant metastases and two of whom were referred to nodal-directed treatment due to lymph node metastases (lymphadenectomy and pelvic chemoradiation plus boost, respectively). Furthermore, based on the 18F-FDG-PET/CT results, the RT plan was modified in 13 patients (addition of a boost on residual pelvic/abdominal disease in 12 and target modification in one, respectively). Therefore, based on postoperative 18F-FDG-PET/CT findings, the therapeutic strategy and the RT plan were changed in 5 patients (8.6%) and 13 patients (22.4%), respectively. Conclusion: In this analysis, the adjuvant treatment was modified after post-operative 18F-FDG-PET/CT in about one third of patients. Further studies are needed to better define the risk factors (or their combinations) correlated with higher probability of residual disease after radical hysterectomy-adnexectomy for EC.

A Phase II Single Arm Study of Nivolumab As Maintenance Therapy after Autologous Stem Cell Transplantation in Patients with Hodgkin Lymphoma at Risk of Relapse or Progression

Introduction: Autologous stem cell transplants (ASCT) are standard of care for patients with primary refractory or recurrent Hodgkin lymphoma (HL). While transplant results in cure for some patients, others relapse and succumb from their disease. Studies have found high expression of programmed death ligand 1 (PD-L1) in HL cells. The anti-PD-1 monoclonal antibody, nivolumab, has been safe and efficacious in the treatment of relapsed, refractory HL (Ansell et al. 2015). We evaluated the safety and efficacy of nivolumab maintenance therapy post-ASCT in high risk for relapse Hodgkin disease.Methods: Patients with HL with high risk of residual disease following ASCT ( high risk defined as refractory disease, relapse <12 months, or relapse ≥12 months with extranodal disease after frontline therapy) received nivolumab (240 mg IV every 2 weeks) starting 45-180 days post-transplant for a maximum of 6 months of treatment. Patients were followed for AEs through 100 days after the last dose of drug. PET-CT response assessments were performed 1-3 month, 6 month, and 12 month post-ASCT. The primary objective was to evaluate the safety and tolerability of nivolumab as maintenance therapy early after ASCT. The secondary objective was to evaluate progression-free survival (PFS) at 12 months post-transplant.Results: To date, 37 patients were enrolled; median age 36 years; 25 patients (68%) male. The median number of prior systemic regimens was 2 (range 2-4). 25 patients (68%) had relapsed disease, and 12 patients (32%) had primary refractory disease. 18 patients (49%) had extranodal disease at relapse, 6 patients (16%) had B-symptoms at relapse, and 11 patients (30%) had residual disease after salvage, including 10 patients (27%) of whom had 2-3 prior salvage therapies. 22 patients (60%) had received prior brentuximab, and 3 patients (8%) had received prior nivolumab or pembrolizumab. 36 patients received ASCT and 1 patient received tandem ASCT. At the time of data cutoff, 28 patients (76%) had discontinued nivolumab treatment, 22 patients (60%) because they had completed the 6-month treatment course, 4 patients (11%) due to an adverse event (AE) (1 patient each with pain, pneumonitis, rhabdomyolysis, or hypothyroidism), and 2 patients (5%) due to disease progression. The median duration of treatment was 22.1 weeks. 17 patients (46%) experienced a treatment-related AE (TRAE), of which 5 patients (14%) experienced a ≥Grade 3 TRAE. The most common (≥5%) TRAEs were diarrhea, fatigue, bone pain, neutrophil count decreased, pruritus, rash, and vomiting. 2 patients experienced a treatment-related serious AE (pneumonitis, rhabdomyolysis). There were no treatment-related deaths. With a median follow up of 9.2 months, the median PFS and overall survival (OS) have not been reached. The 6 month PFS is 92.1% and the 12-month OS is 100%. There were no differences in OS when stratified based on prior treatment.Conclusions: The use of nivolumab maintenance early after ASCT is safe and tolerable in this high risk patient population. Early efficacy data is promising, but data need to mature to determine the 12 month PFS. [Display omitted] DisclosuresBachier: CRISPR: Membership on an entity's Board of Directors or advisory committees; Autolus: Membership on an entity's Board of Directors or advisory committees; Nkarta: Membership on an entity's Board of Directors or advisory committees; Mana: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Shah: Umoja: Consultancy; Incyte: Consultancy; Legend: Consultancy; Kite: Consultancy; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Lily: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy.

Risk factors for residual disease at re-TUR in a large cohort of T1G3 patients

Introduction and objectivesThe goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging.Persistent disease after resection of bladder tumors is not uncommon and is the reason why the European Guidelines recommended a re-TUR for all T1 tumors. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival.We present here the patient and tumor factors that may influence the presence of residual disease at re-TUR. Material and methodsIn our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 74% had multifocal tumors, 20% of tumors were more than 3 cm in diameter and 26% had concomitant CIS.In this subgroup of patients who underwent re-TUR, there was no residual disease in 267 patients (29%) and residual disease in 667 patients (71%): Ta in 378 (40%) and T1 in 289 (31%) patients. Age, gender, tumor status (primary/recurrent), previous intravesical therapy, tumor size, tumor multi-focality, presence of concomitant CIS, and muscle in the specimen were analyzed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions. ResultsThe following were not risk factors for residual disease: age, gender, tumor status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumors, tumors > 3 cm, and presence of concomitant CIS. Due to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001. The presence of muscle in the specimen was no longer significant, while the presence of CIS only remained significant in the model with tumor size, p < 0.001. ConclusionsThe most significant factors for a higher risk of residual disease at re-TUR in T1G3 patients are multifocal tumors and tumors more than 3 cm. Patients with concomitant CIS and those without muscle in the specimen also have a higher risk of residual disease.

Factores de riesgo de enfermedad residual en la re-RTU en una gran cohorte de pacientes con enfermedad T1G3

Introduction and objectivesThe goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging.Persistent disease after resection of bladder tumors is not uncommon and is the reason why the European Guidelines recommended a re-TUR for all T1 tumors. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival.We present here the patient and tumor factors that may influence the presence of residual disease at re-TUR. Material and methodsIn our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 74% had multifocal tumors, 20% of tumors were more than 3 cm in diameter and 26% had concomitant CIS.In this subgroup of patients who underwent re-TUR, there was no residual disease in 267 patients (29%) and residual disease in 667 patients (71%): Ta in 378 (40%) and T1 in 289 (31%) patients. Age, gender, tumor status (primary/recurrent), previous intravesical therapy, tumor size, tumor multi-focality, presence of concomitant CIS, and muscle in the specimen were analyzed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions. ResultsThe following were not risk factors for residual disease: age, gender, tumor status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumors, tumors > 3 cm, and presence of concomitant CIS. Due to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001. The presence of muscle in the specimen was no longer significant, while the presence of CIS only remained significant in the model with tumor size, p < 0.001. ConclusionsThe most significant factors for a higher risk of residual disease at re-TUR in T1G3 patients are multifocal tumors and tumors more than 3 cm. Patients with concomitant CIS and those without muscle in the specimen also have a higher risk of residual disease.

Predictive Factors for Residual Disease After Conization in Cervical Cancer.

The aim of this study was to evaluate predictive factors for the presence of residual disease after conization followed by definitive surgery in cervical cancer, and suggest a margin distance threshold that could predict residual disease. We retrospectively analyzed a series of 42 patients with early-stage cervical cancer who underwent primary conization before definitive surgical treatment from March 2009 to May 2020. All conization specimens were reviewed for endocervical, ectocervical, and radial margins. Cases with residual disease in magnetic resonance imaging before definitive surgery were excluded. Thirty-three (78.6%) patients underwent hysterectomies and 9 (21.4%) trachelectomies ± lymph node staging. Twelve (28.6%) cases were stage IA1, 5 (11.8%) cases were stage IA2, 13 (31%) cases were stage IB1, 11 (26.2%) cases were stage IB2, and 1 (2.4%) case was stage IIIC1 [International Federation of Gynecology and Obstetrics (FIGO) 2019]. We found residual disease in 17 (40.4%) surgical specimens. Of the 20 patients with negative margins, there were still 3 (15%) cases with residual disease. Conversely, residual disease was identified in 14 (63.6%) of the 22 patients with positive cone margins (p = 0.001). Tumor size [odds ratio (OR) 1.71, 95% confidence interval (CI) 1.02-1.33] and positive endocervical margin status (OR 33.6, 95% CI 3.85-293.3) were related to a higher risk of residual disease in multivariate analysis. Notably, all patients with tumors larger than 2cm had residual disease, in contrast to 29.4% in lesions up to 2 cm (p = 0.002). We found that tumor size and positive margin were predictive factors for residual disease. We could not suggest a reliable minimum margin distance threshold that could predict residual disease.

Chest CT imaging features for prediction of treatment response in cryptogenic and connective tissue disease-related organizing pneumonia.

To investigate CT imaging features associated with poor clinical outcome after corticosteroid treatment in patients diagnosed with cryptogenic organizing pneumonia (COP) and connective tissue disease-related organizing pneumonia (CTD-OP) and to assess the difference in CT findings and treatment responses between COP and CTD-OP. Chest CT images from 166 patients (COP, 131; CTD-OP, 35) with pathologically proven organizing pneumonia were reviewed by two thoracic radiologists. The type, distribution pattern, and extent of parenchymal abnormalities, along with other associated imaging features, were assessed for each patient. Logistic regression analyses were used to identify features associated with poor clinical outcomes such as residual disease (RD) and disease relapse. The differences between COP and CTD-OP were also analyzed. Consolidation involving more than 10% of parenchyma (hazard ratio [HR], 2.27), detectable bronchiectasis (HR, 3.59), and diagnosis of CTD-OP (HR, 4.31) were associated with a higher risk of RD after adjustments for patient age and sex. More than 10% consolidation involvement (HR, 2.54) and diagnosis of CTD-OP (HR, 6.42) were also associated with a higher risk of disease relapse. Compared with COP, CTD-OP demonstrated a greater extent of parenchymal abnormalities, especially consolidation, and was less likely to show a peribronchovascular distribution pattern. Bronchiectasis and a greater extent of consolidation were associated with RD, with the latter also being associated with disease relapse. Compared with COP, CTD-OP was associated with worse treatment outcomes and demonstrated a greater extent of parenchymal abnormalities, which were also less likely to show a peribronchovascular pattern. • The presence of bronchiectasis and a high parenchymal involvement of consolidation on initial chest CT were associated with a worse response to corticosteroids in patients with organizing pneumonia. • Connective tissue disease-related organizing pneumonia (CTD-OP) was associated with worse treatment outcomes than its idiopathic counterpart cryptogenic organizing pneumonia (COP). • Compared with COP, CTD-OP generally demonstrated a greater extent of parenchymal abnormalities, especially consolidation, and was less likely to show a peribronchovascular distribution pattern.

Evaluation of bipolar transurethral en-bloc resection in patients with primary non-muscle invasive bladder cancer

Background Conventional TURBT includes tumour fragmentation; this impairs pathological examination and is associated with a high risk of residual disease, tumour understaging and early recurrence. En-bloc TURBT (eTURBT) is supposed to overcome these major drawbacks. It includes uprooting of the whole tumour in one piece, providing an intact specimen for accurate pathological evaluation with a low risk of scattering malignant cells. Aim This study aimed to evaluate the efficacy, safety and oncological outcomes of bipolar eTURBT in resection of a small primary bladder mass. Patients and methods This prospective study included 63 patients with a primary bladder mass suspected to be non-muscle invasive bladder cancer (NMIBC). All patients underwent bipolar eTURBT using a mushroom loop electrode. All operations were performed by one experienced uro-oncologist and all the procedures were successfully completed. The patients included were scheduled for follow-up cystoscopy at 3, 6 and 12 months. Results The mean (SD) operative time was 37.01 (±5.50) min, enucleation time was 23.11 (± 6.26) min and obturator nerve jerk occurred only in three cases (4.76%); the mean (SD) postoperative irrigation time was 1.21 (±3.32) h, haemoglobin drop was 0.3 (± 0.57) g/dl, with no need for blood transfusion at all, and the mean (SD) hospital stay was 2.30 (±0.53) days. There were no other perioperative complications. Conclusion Bipolar eTURBT is effective and safe for managing NMIBC as it preserves well-intact specimens, with negligible perioperative complications.

Menopausal status is associated with a high risk for residual disease after cervical conization with positive margins.

BackgroundWe aimed to determine demographic and clinicopathological predictors for residual disease in women with cervical intraepithelial neoplasia (CIN 2/3) with endocervical cone margin involvement.Methods and findingsA cross-sectional study was conducted. The eligible patients were women who underwent hysterectomy as a treatment option after having a positive endocervical margin for CIN 2/3 in cervix conization specimens from 2000 to 2015. The patients were divided into two groups based on the persistence of CIN 2/3 and absence of CIN 2/3 in hysterectomy specimens. Demographic, clinical and histology information were collected in both groups. A total of 80 patients were eligible for the study; 37 (46.3%) had no persistence of CIN 2/3 and 43 (53.7%) had persistence of CIN 2/3 in the hysterectomy specimens. Demographic, clinical, and cone specimen characteristics, and a visible squamocolumnar junction and type of conization were analyzed as possible risk factors for the presence of residual lesions at hysterectomy, and none of these variables were associated with residual disease. Menopausal status was strongly associated with a high risk of persistent residual disease 81.2% (OR 4.9, CI 1.27–18.9), P = 0.014. In the multivariate analysis, only a menopausal status (P = 0.04) was associated with a high risk of persistent lesions.ConclusionThis analysis found that menopausal status exhibited an important association with persistent residual disease. Menopausal women with endocervical margin involvement exhibit a greater than 80% risk of persistent lesions.

Staging pancreatic carcinoma by computed tomography

Pancreatic carcinoma is becoming more common in our environment; the mortality rate for this tumor has barely changed over the last 20 years.Early diagnosis and accurate staging are crucial to ensure an appropriate therapeutic approach, which should aim to improve survival in patients in whom complete resection is possible and to minimize surgical morbidity and mortality in those with a high risk of residual disease after the intervention.Various imaging techniques are used for tumor staging: multidetector computed tomography (CT), magnetic resonance imaging, positron emission tomography (PET)-CT, endoscopic ultrasound, and diagnostic laparoscopy. Currently, multidetector CT is the technique of choice for the study of pancreatic tumors; thus, this article aims to review the state of the art in staging adenocarcinoma of the pancreas, focusing mainly on the applications and limitations of this technique.

Estadificación mediante tomografía computarizada del carcinoma de páncreas

Pancreatic carcinoma is becoming more common in our environment; the mortality rate for this tumor has barely changed over the last 20 years.Early diagnosis and accurate staging are crucial to ensure an appropriate therapeutic approach, which should aim to improve survival in patients in whom complete resection is possible and to minimize surgical morbidity and mortality in those with a high risk of residual disease after the intervention.Various imaging techniques are used for tumor staging: multidetector computed tomography (CT), magnetic resonance imaging, positron emission tomography (PET)-CT, endoscopic ultrasound, and diagnostic laparoscopy. Currently, multidetector CT is the technique of choice for the study of pancreatic tumors; thus, this article aims to review the state of the art in staging adenocarcinoma of the pancreas, focusing mainly on the applications and limitations of this technique.

The results of local excision with or without postoperative adjuvant chemoradiotherapy for early rectal cancer among patients choosing to avoid radical surgery.

The study aimed to establish the oncological outcome of patients who opted for close surveillance with or without adjuvant chemoradiotherapy rather than radical surgery after local excision (LE) of early rectal cancer. The Royal Marsden Hospital Rectal Cancer database was used to identify rectal cancer patients treated by primary LE from 2006 to 2015. All patientswere entered in an intensive surveillance programme. Twenty-eight of 34 analysed patients had a high or very high risk of residual disease predicted by adverse histopathological features for which the recommendation had been radical surgery. Eighteen (52%) of the 34 had received radiotherapy following LE. Three-year disease-free survival for the 34 patients was 85% (95% CI 78.8%-91.2%) and overall survival was 100%. Twenty-two of 24 patients with a low tumour which would have required total rectal excision have so far avoided radical surgery and remain disease free at a median follow-up of 3.2years. The findings suggest that with modern MRI and clinical surveillance radical surgery can be avoided in patients following initial LE of a histopathologically defined high risk early rectal cancer. These findings are comparable with those obtained after major radical resection and warrant further prospective investigation as a treatment arm in larger prospective trials.

Close and Positive Lumpectomy Margins are Associated with Similar Rates of Residual Disease with Additional Surgery.

Current guidelines state that "no ink on tumor" constitutes adequate surgical margins for lumpectomy specimens. However, there remains uncertainty when tumor is close (<1mm) to multiple inked margins. All local excisions for invasive breast cancer during 3years at one center were reviewed. Tumor characteristics, margin status, patient age, reoperations, and pathology of reexcised specimen were recorded. Chi-square analysis and regression models were used to identify factors associated with residual disease upon reoperation. In 533 lumpectomies for invasive cancer, 60 (11%) had at least one positive margin, and 106 (20%) had one or more close margin. Multiple margins were either close or positive in 67 cases. Reoperation was performed in 125 of 533 cases (23%) for close or positive margins. Positive margins were significantly more likely to undergo reoperation compared with close margins (p<0.001). On reoperation, 73 of 125 (58%) demonstrated residual cancer, including 39 of 68 (57%) with close margins, and 34 of 57 (60%) with positive margins (p=0.52). When multiple margins were close or positive, residual cancer was found on reexcision in 45 of 59 (76%) cases as opposed to 34 of 79 (43%) cases with only one involved margin (p<0.001). When controlling for other factors, positive margins were no more associated with residual disease than close margins (p=0.32), whereas multiple close or positive margins were associated with significantly higher risk of residual disease (odds ratio 6.1; p=0.002; 95% confidence interval 2.6-14.45). The only significant predictor of residual tumor was multiple close or positive margins. It may be appropriate to recommend reexcision for patients with multiple close margins.

A culture of open reporting results in improved quality of bladder tumour resections: a closed loop audit

Objective: Bladder cancer is the commonest cancer of the urinary tract. Transurethral Resection of Bladder Tumour (TURBT) is the gold standard for diagnosis and treatment of non-muscle invasive bladder cancer. The absence of muscle in a TURBT specimen is associated with a significantly higher risk of residual disease, early recurrence and tumour under staging. Materials and methods: TURBT and bladder biopsy specimens were examined before and after the introduction of an open reporting system as a quality improvement exercise. All specimens from the 4th quarter (between 2010 and 2014) were examined to determine the effect of open reporting on our inadequate resection rates. Results: A total of 244 cases were performed under the care of 5 consultant urologists. Analysis revealed a significant improvement in quality of both T1 and Ta resections (p=0.04*; p=0.02*) after the introduction of open reporting. The total number of TURBT cases increased per year, however the percentage of inadequate resections has significantly decreased (p=0.02*). Conclusion: Individual reporting provided surgeons with direct, personal and timely feedback on their performance. It did not negatively impact on trainee participation, but led to improved training outcomes. We have demonstrated that our simple intervention has improved quality of patient care.

Long-term Results of Endoscopically Assisted Pediatric Cholesteatoma Surgery.

Routine endoscopic examination during primary surgery decreased the rate of residual cholesteatoma to 18% in our early experience. Based on this, we stopped performing routine second-look surgery in children who were endoscopically free of cholesteatoma at the end of primary surgery. We sought to investigate if second-look procedures after endoscopic-assisted surgery could safely be performed only in children at a high risk of residual disease (extensive inflammation, spontaneously ruptured or fragmented cholesteatoma, residual disease intentionally left). Case series with chart review. Tertiary pediatric otolaryngology practice. Children aged 1 to 16 years who were treated for cholesteatoma over 15-year period by a single surgeon. Extent of disease and endoscopic findings were compared with rates of residual disease. Time to diagnosis of residual disease and prognostic factors were analyzed. Forty-two children underwent endoscopically assisted middle ear surgery for cholesteatoma. Of 42 children, 7 (17%) had additional disease found by endoscopy that was missed by microscopy alone. Twelve children at high risk had second looks; 5 (42%) had residual disease. Of 30 children, 2 (7%) presented with macroscopically evident residual cholesteatoma after no planned second look on office follow-up and subsequently underwent reoperation and were cured. Selective second-look surgery in high-risk children did not adversely affect outcome as compared with the low-risk group. Cholesteatoma was identified endoscopically in 7 of 42 (17%) children thought to be microscopically free of disease at initial surgery. The endoscope may aid in visualization of difficult middle ear recesses when used to complement microscopy. Further investigation with multicenter data is needed.

Abstract 2273: Mechanistic and functional implications of FABP4 in ovarian cancer metastasis

Abstract Purpose:The purpose of this study was to identify molecular predictors of residual disease (RD) in high grade serous ovarian cancer (HGSC) and further understand their role in promoting cancer metastasis. Method:The current study analyzed Affymetrix gene expression data of 504 HGSC cases from The Cancer Genome Atlas (TCGA) data to identify differentially expressed genes in tumors from patients with no gross residual disease after surgery (NRD) or presence of RD following initial debulking surgery. It was followed by qRT-PCR analysis of tumor samples for validation purposes. RPPA data of 354 patients from TCGA were analyzed. Immunohistochemical analysis was performed on the patient samples to determine the expression at the protein level (cancer versus stromal cells). Gene array was carried out after overexpressing the selected gene in ovarian cancer cells and the data was analyzed by Ingenuity Pathway Analysis (IPA). In vitro (migration and invasion) and in vivo (orthotopic mouse models) assays were used to determine the biological roles of gene(s) identified from the above analyses. Results: In TCGA data set, 97/107 (90.6%) of the patients with high expression of FABP4 gene had residual disease. In the validation cohort, among the 35 patients predicted to be at high risk for residual disease, 30 (86%) did have residual disease. In contrast, only 54 of the 104 patients with FABP4 values below the decision threshold (52%) had incomplete resection (p = 0.0002). RPPA analysis indicated that expression of FABP4 was positively correlated (Spearman correlation analysis) with expression of several other proteins known to increase tumor cell infiltration and metastasis such as JNK2 (p = 0.194), transglutaminase (p = 0.199), c-kit (p = 0.173), fibronectin (p = 0.364), PKC-A (p = 0.178), collagen-6 (p = 0.197) and paxillin (p = 0.239). It was negatively correlated with E-cadherin (p = -0.246) and claudin-7 (p = -0.201) expression. Immunohistochemical analysis confirmed that apart from endothelial cells and adipocytes, cancer cells also express significant amount of FABP4. In vitro assays showed significant reduction in invasion and migration after silencing FABP4 in HGSC cell lines (p&amp;lt;0.0001). On the other hand, overexpression of FABP4 led to increased invasion and migration (p&amp;lt;0.01). In vivo stable overexpression of FABP4 increased the tumor weight by 3.5 fold (p&amp;lt;0.05). It also increased the number of nodules by 2.5 fold (p&amp;lt;0.05). Overexpression also led to increase in metastasis sites including liver, spleen, diaphragm and omentum, while the tumor in the control group was confined to ovary and peritoneal cavity. Histological analysis of tumor tissues showed infiltrative phenotype after overexpression of FABP4. Conclusion:These findings provide a new understanding of ovarian cancer metastasis and identify a potentially important target for therapeutic intervention. Citation Format: Kshipra M. Gharpure, Susan L. Tucker, Shelley M. Herbrich, Anna K. Unruh, Alpa M. Nick, Erin K. Crane, Robert L. Coleman, Jamie Guenthoer, Heather J. Dalton, Sherry Y. Wu, Rajesha Rupaimoole, Gabriel Lopez-Berestein, Bulent Ozpolat, Cristina Ivan, Wei Hu, Keith Baggerly, Anil Sood. Mechanistic and functional implications of FABP4 in ovarian cancer metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2273. doi:10.1158/1538-7445.AM2015-2273