Papillary Type Research Articles

Ileocecal Valve Agenesis: A Rare Anatomical Variant

Intubation of the ileocecal valve (ICV) is an important portion of colonoscopy as it marks the transition from the cecum to the small bowel. Anatomical variation of the ICV is an unusual finding as very few cases have been reported. Furthermore, complete absence of the ICV can pose diagnostic challenges for the endoscopist. Herein, we describe a patient with complete absence of the ICV. A 71-year-old male with a past medical history of hypertension, bradycardia and stroke presented to the emergency department for dizziness, sweating and hematochezia. He reported episodes of bright red blood pre rectum for 2 weeks. He had a normal screening colonoscopy 3 years ago. Laboratories on admission were normal. Diagnostic colonoscopy was performed and a few medium-sized diverticula were found in the sigmoid, descending and ascending colon. The ICV was not identified and there was direct emptying of the ileum into the cecum with no noted intestinal atresia. The colonoscope was retroflexed in the cecum to confirm the absent ICV and assess the terminal ileum. Identification of cecal landmarks is fundamental to high quality colonoscopy. These landmarks are the ICV, the ICV orifice, the appendiceal orifice, and the cecal sling fold (also known as the strap fold). The “bow and arrow sign” within the cecum can assist in locating the ICV. However, variations of the ICV are based on its morphological appearance and includes labial, papillary, and lipomatous types. Specifically, the labial type has a slit like opening, the papillary type is dome shaped, and the lipomatous type contains a substantial fat deposit within its lips. While anatomical variations of the ICV are rare, endoscopists should be aware of the possibility of ICV agenesis. Complete absence of the ICV in our patient was an incidental finding. Further studies are needed to determine whether ICV reconstruction is needed in cases of valvular atresia, as well as to study any role in gastrointestinal tract physiology and pathology.1650_A Figure 1. TI Opening Into Cecum (No ICV)1650_B Figure 2. TI Opening Into Cecum (No ICV)1650_C Figure 3. TI Opening Into Cecum (No ICV)

Thyroid Cancer Profile: Experience of Liga Contra El Cancer Honduras 2014-2017

Background: In recent years we have observed increase in thyroid carcinoma TC incidence at cancer centers in Honduras. TC is linked to exposure to ionizing radiation. Other risks factors described in literature are obesity, diabetes, nitrites and nitrates in diet and alcohol. DNA rupture, activation of oncogenes, and secretion of inflammatory cytokines are initial events that derive in mutations and malignant transformation. Papillar, follicular and undifferentiated carcinoma are the histologic types. Little is known about TC in the population, and there are no efficient models for prevention and early detection to date. Aim: Describe the clinical and demographic profile of patients diagnosed with TC at La Liga Contra el Cancer Hospital LCC from 2014-2017, with intention to identify patterns that allow approaches to pathogenicity and prevention. Methods: We revised 103 medical records of all TC patients treated at LCC from Jan 2014-December 2017 to obtain information about geographical origin, age, gender, localization of tumor, identifiable risk factor, treatment and outcomes. A digital database was in Microsoft Office Excel and exported to SPSS. Patient information was deidentified before data extraction. Results: 91.3% patients were female. Median age 49.3 ± 15.6 years (95% CI, 46.05-52.2). Patients went from 11/18 departments (political division), 74% gathered in the northern zone of the country. Histology type: papillary 91.3%; follicular 4.9%, anaplasic 1.9%; medullary 1.0%. Papillary TC, 37% of patients were in fifth decade, 22.9% in patients 31-40 yo, 17.3% in patients 41-50 yo, 9.7% were under 30s. Clinical stage at diagnosis: I I (n = 24) 23.6%, II (n = 13), 12.6%. III (n = 18), 17.5%. IV (n = 14), 15.6%; not suitable for staging 5.8%, the rest had no precise information for staging. 12.6% of patients reported family history of cancer (any type), 33% of patients reported comorbidities. Conclusion: Thyroid carcinoma has increased in the last years, from our experience we can identify that women are mostly affected, with papillary type being the most common. Ages affected are between 41-60 years old. One third of patients had comorbidities as hypothyroidism, diabetes and arterial hypertension. 74% reside in the northern zone of Honduras, there is need to elucidate if it is a matter of geographical location of the LCC. No emerging risk factors were identified in this cohort. More research is needed to profile thyroid carcinoma in our region.

Malignant Transformation of Type I Biliary Cyst into Papillary Type Neoplasm

Malignant Transformation of Type I Biliary Cyst into Papillary Type Neoplasm

Cystic Appearance on Imaging Methods (Bosniak III-IV) in Histologically Confirmed Papillary Renal Cell Carcinoma is Mainly Characteristic of Papillary Renal Cell Carcinoma Type 1 and Might Predict a Relatively Indolent Behavior of Papillary Renal Cell Carcinoma

Aim: The aim of this study was to determine the proportion of cystic tumors according to preoperative CT (Bosniak III, IV) among surgically treated patients with histologically confirmed papillary renal cell carcinoma (pRCC) and to assess progression rates among patients with and without cystic appearance on imaging. Methods: A total of 138 patients with pRCC histology surgically treated in the period of January 2007–March 2017 were included. Clinical and radiological characteristics, type of surgery, histopathology results, and follow-up data were recorded and statistically evaluated. Results: Forty-one cases (29.7%) of cystic lesions (10× BIIF, 14× BIII, 17× BIV) were detected by CT. Patients with pRCC1 significantly more frequently presented with cystic appearance on CT (33/78; 42.3%) in comparison to other papillary types (8/60; 13.3%; p = 0.0002). During a median follow-up time of 49.4 months, only 2 patients with cystic lesions progressed after surgery. Conclusions: Cystic appearance on imaging methods is mainly a characteristic of pRCC1 (42.3%). Cystic morphology on imaging might predict a relatively indolent behavior of all pRCC types. Preoperative scoring systems including tumor growth patterns (cystic vs. solid) are needed for further classification.

Association between Repeated Praziquantel treatment and Papillary, and Intrahepatic Cholangiocarcinoma

Introduction and aim. The carcinogenesis of tubular and papillary cholangiocarcinoma (CCA) differ. The available epidemiologic studies about risk factors for CCA do not differentiate between the tubular and papillary type. The current study investigated the relationship between the number of repeated use of Praziquantel (PZQ) treatments and each type of CCA.Material and methods. This was a hospital-based, matched, case-control study of patients admitted to Srinagarind Hospital, Khon Kaen University. The patients were 210 pathologically-confirmed cases of CCA, while the controls were 840 subjects diagnosed with other diseases. The 4 controls were individually matched with each case by sex, age, and date of admission. The cases were classified according to location (intrahepatic vs. extrahepatic) and cell type (papillary vs. tubular). Multivariable conditional logistic regression was used for the analysis.Results. After adjusting for confounders, there were statistically significant associations between intrahepatic and papillary CCA and repeated use of PZQ treatment. The respective odds of developing intrahepatic CCA for those who used PZQ once, twice, or more was 1.54 (95%CI:0.92-2.55 ), 2.28 (95%CI:0.91-5.73), and 4.21 (95%CI:1.61-11.05). The respective odds of developing papillary CCA for those who used PZQ once, twice, or more was 1.45 (95%CI:0.80-2.63), 2.96 (95%CI:1.06-8.24), and 3.24 (95%CI:1.09-9.66). There was no association between number of uses of PZQ treatment and developing extrahepatic or tubular CCA.Conclusion. The current study found an association between papillary and intrahepatic CCA and repeated use of PZQ treatment. We suggest further study on the risk factors for papillary and tubular CCA should be performed separately.

Carcinoma of Unknown Primary Site (CUP) With Metastatic Renal-Cell Carcinoma (mRCC) Histologic and Immunohistochemical Characteristics (CUP-mRCC): Results From Consecutive Patients Treated With Targeted Therapy and Review of Literature.

Carcinoma of unknown primary site (CUP) is a heterogenous group of metastatic cancer with no detectable primary tumor site. Diagnostic assessment occasionally presents CUP with metastatic renal-cell carcinoma (mRCC) histologic and immunohistochemical characteristics (CUP-mRCC). Efficacy and toxicity data for vascular endothelial growth factor inhibitor therapies in CUP-mRCC patients are few. We retrospectively reviewed consecutive patients with CUP-mRCC at a single institution between 2007 and 2018. Treatment outcomes were assessed from initiation of renal-cell carcinoma-specific therapy, including response rate, progression-free survival, and overall survival. Ten patients with CUP-mRCC were identified. Median age was 64 years. Histologies were clear-cell (30%), papillary type II (20%), and unclassified renal-cell (50%) carcinoma. International Metastatic Renal Cell Carcinoma Database Consortium risk group were favorable, intermediate, and poor in 0, 40%, and 60%, respectively. One patient received empiric first-line chemotherapy. Targeted treatments were pazopanib (n= 7), sunitinib (n= 2), and sorafenib (n= 1). Objective response rate was 40%, progression-free survival was 2.5 months (95% confidence interval, 1.2-3.8), and overall survival was 5.7 months (95% confidence interval, 0-24.0). Stratified for International Metastatic Renal Cell Carcinoma Database Consortium risk, overall survival in intermediate versus poor risk group were 18.6 months and 2.3 months, respectively. Second-line therapy did not result in disease control. No new or unexpected toxicities were observed. CUP-mRCC treated with vascular endothelial growth factor-targeted therapy is valid, feasible, and safe even though these patients had several negative prognostic factors. CUP-mRCC patients should be identified among CUP patients for specific renal-cell carcinoma therapy.

Modulating ATP binding cassette transporters in papillary renal cell carcinoma type 2 enhances its response to targeted molecular therapy.

Papillary renal cell carcinoma (PRCC) is the most common nonclear cell RCCs and is known to comprise two histological subtypes. PRCC2 is more aggressive and is molecularly distinct from the other subtypes. Despite this, PRCCs are treated together as one entity, and they show poor response to the current therapies that do not target pathways implicated in their pathogenesis. We have previously detected ABCC2 (an ABC transporter), VEGF, and mTOR pathways to be enriched in PRCC2. In this study, we assess the therapeutic potential of targeting these pathways in PRCC2. Twenty RCC cell lines from the Cancer Cell Encyclopedia were compared to the Cancer Genome Atlas PRCC cohort (290), to identify representative PRCC2 cell lines. Cell lines were further validated in xenograft models. Selected cell lines were treated in vitro and in vivo (mice models) under five different conditions, untreated, anti‐VEGF (sunitinib), ABCC2 blocker (MK571), mTOR inhibitor (everolimus) and sunitinib + MK571. Sunitinib +ABCC2 blocker group showed a significant response to therapy compared to the other treatment groups both in vitro (P ≤ 0.0001) and in vivo (P = 0.0132). ABCC2 blockage resulted in higher sunitinib uptake, both in vitro (P = 0.0016) and in vivo (P = 0.0031). Everolimus group demonstrated the second best response in vivo. The double‐treatment group showed the highest apoptotic rate and lowest proliferation rate. There is an urgent need for individualized therapies of RCC subtypes that take into account their specific biology. Our results demonstrate that combined targeted therapy with sunitinib and ABCC2 blocker in PRCC2 has therapeutic potential. The results are likewise potentially significant for other ABCC2 high tumors. However, the results are preliminary and clinical trials are needed to confirm these effects in PRCC2 patients.

The prognostic significance of tall cells in papillary thyroid carcinoma: A case-control study.

The subtype of the papillary thyroid carcinoma tall-cell variant has a worse prognosis than does the conventional papillary type (papillary thyroid carcinoma). The new World Health Organization 2017 classification defines a tall-cell variant as a tumour consisting of over 30% of cells that are two or three times as tall as they are wide. However, thresholds have differed. Our aim was to study how tall cells affect the prognosis of papillary thyroid carcinoma patients and to determine, for such cells, a cut-off percentage. Our cohort included 65 papillary thyroid carcinoma patients who underwent surgery at Helsinki University Hospital between 1973 and 1996: originally, 36 otherwise-matched patient pairs, eventually comprising 34 patients with an adverse outcome plus 31 who had recovered. All samples were digitally scanned and scored by two investigators based on tall cell composition. The cohort was analysed with four tall cell thresholds: 10%, 30%, 50% and 70% with a median follow-up of 22 years. In survival analysis, only the 70% threshold showed a correlation with reduced overall survival, disease-specific survival and relapse-free survival. A correlation also emerged with death from papillary thyroid carcinoma. In multivariate analysis, a 70% cut-off and age at diagnosis significantly affected DSS. Increasing tall cell score correlated with increasing age and extrathyroidal extensions. A tall cell composition of 10%, 30% or 50% showed no correlation with adverse outcome and suggests that the choice of pathologists reporting tall-cell variant should be a 70% threshold.

Abstract 2185: Multiple region whole-genome sequencing reveals intratumor heterogeneity and branching clonal architecture of non-clear-cell renal cell carcinoma

Abstract Limited knowledge about the intratumor heterogeneity (ITH) of non-clear-cell renal cell carcinoma (nccRCC) hinders therapeutic efficacy. We performed multi-region whole-genome sequencing, genome-wide methylation profiling and deep targeted sequencing of both primary and paired metastatic tumors in 124 samples from 29 subjects with papillary renal cell carcinoma type 1, papillary renal cell carcinoma type 2 and collecting duct kidney tumors. Samples were taken from the tumors' center to the periphery at ~1.5cm from each other. We conducted integrative ITH analysis of single nucleotide variants, somatic copy number alterations, structural variants, transposon element insertions, telomere length and DNA methylation, and inferred their respective evolutionary history. We also analyzed the concordance between physical and lineage phylogenetic evolution, and inferred the regions from which the metastases likely originated. ITH varied significantly across tumors and histological subtypes. For example, the average number of structural variants per tumor was 1.2 in papillary RCC type 1 vs. 23.6 in papillary RCC type 2. In papillary tumors, ITH was lowest for copy number alterations (~5% subclonal changes across all tumor types), intermediate for single nucleotide variants (~32%), and highest for structural variants (~60%), suggesting a tumor molecular evolution along these steps. Lineage trees commonly showed branching evolutions with a dominant subclone. Focal deletion of the CDKN2A gene characterized the collecting duct tumors. Methylation ITH was highest in the enhancer regions. Metastatic and primary tumors shared similar mutation signatures. Telomere length was generally longer in normal vs. tumor samples and was similar in physically adjacent samples. In summary, our study characterized ITH of nccRCC with unprecedented details for multiple types of somatic alterations, and delineated the branching architecture of clonal evolution, including the metastatic phase. Citation Format: Bin Zhu*, Luana Poeta*, Manuela Costantini*, Tongwu Zhang*, Steno Sentinelli, Jianxin Shi, Kevin Brown, Xing Hua, Meredith Yeager, Mingyi Wang, Belynda Hicks, Stephen Chanock*, Michele Gallucci*, Vito Fazio*, Maria Teresa Landi*. Multiple region whole-genome sequencing reveals intratumor heterogeneity and branching clonal architecture of non-clear-cell renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2185.

Importance of Regular Ultrasound Imaging in Renal Allografts for Early Diagnosis of De Novo Renal Cell Carcinoma

Introduction Renal malignancy development after kidney transplantation (KT) in renal allograft is a rare and an essential long-term complication. Renal cancer occurs mostly in native, end-stage kidneys rather than renal allografts. Prolonged use of immunosuppressive therapy, acquired cystic kidney disease, autosomal dominant polycystic kidney disease are among the increasing factors of malignancy. Renal cell carcinoma (RCC) with a papillary type is the most encountered pathology in allograft kidneys, followed by clear cell type. Case Reports We report here two separate cases of de novo clear cell RCC in kidney allografts. The first case is a 36-year-old female, who was diagnosed end stage renal disease (ESRD) of unknown origin 9 years ago and was performed a living related KT from his father in the following year. Seven years after KT, coming to the clinic with no complaints, on her ultrasonography (US) examination a 2 cm-sized of hyperechoic, hypervascular solid mass was detected in the renal cortex of the allograft (Figure 1). Looking retrospectively to her reports, she was seen to skip her ultrasound follow-ups for the last 2 years. Nephron-sparing surgery was performed after an US-guided stereotactic procedure with a 14-gauge wire. Clear cell RCC of a T1a, N0, M0 tumor with negative margins was reported. The patient is free of recurrence and allograft dysfunction after two years now. Our second case is a 46-year-old male, who had an ESRD due to pyelonephritis and underwent living related KT from his brother 19 years ago. During annual US follow-ups, a very small hyperechoic nodule was visualised in the posterior cortex of the allograft and short-term US follow-up was suggested. The patient was re-examined in 3 months by a different radiologist and a 9L4 linear transducer was used for screening the graft in addition to the routine 6C1 curvilinear transducer. This revealed multiple foci of hyperechoic nodules in the allograft which could not be determined in the prior US evaluation (Figure 2). Fine needle aspiration was RCC and no evidence of metastasis was noted with imaging modalities. In order to preserve graft function, nephron-sparing surgery was planned. During surgery, multiple foci were removed, and one in deep location of reach was ablated US-guided with alcohol. After partial nephrectomy, the patient still had millimetric foci of tumors seen on the US, therefore graft nephrectomy was performed in the following months. The patient is in good health now after 1 year, with no evidence of metastasis. Conclusion RCC in renal allografts is a rare and increasing malignancy detected after KT. US follow-ups after transplantation regularly with sensitive transducers for a more detailed screening, improves the early diagnosis of this cancer leading to better long-term results and preserving the allograft.

Abstract 3113: Expression of autophagy- and mitophagy-related genes in clear cell renal cell carcinoma

Abstract Objectives: First objective of this study was to establish primary cell cultures from renal cell carcinoma (RCC). Second objective was to analyze mRNA and protein expression of PINK1, PARK2, PACRG and a-Synuclein, genes involved in cell survival, apoptosis and mitophagy. Methods: Tumor and non-neoplastic tissue from 15 patients undergoing surgery for clear cell renal cell carcinoma (ccRCC, n=9), papillary renal cell carcinoma (pRCC, n=3) as well as three retroperitoneal metastases (two clear cell, one papillary type) were obtained. After tissue digestion and filtration malignant and non-malignant cells were cultivated in two different media in order to establish an optimized cultivation procedure. DNA and RNA were extracted and immunohistochemical analyses (IHC) and qPCR from cultivated cells were performed for VHL and CAIX to verify tumor histotype. RNA was isolated from fresh-frozen primary ccRCC samples and corresponding non-malignant tissues from 50 patients (30 male, 20 female). Expression of PINK1, PARK2, PACRG and a-synuclein was measured by qPCR in the cultivated ccRCC cell lines as well as in the patient samples. Results: All tumor specimens were successfully cultivated to first confluence. Six out of nine ccRCC cell lines and all other tumor specimens could be passaged more than two times. Cultivated RCC cells showed protein expression matching to their tumor of origin in IHC analyses, confirming tumor identity. QPCR demonstrated VHL expression downregulated or lost in all ccRCC cell lines and CA9 highly upregulated in most cases, which is both typical for ccRCC. The mRNA expression of PINK1, PARK2 and PACRG was downregulated in ccRCC cultures as well as in the 50 patient tumors in comparison to normal tissue. A-synuclein expression was highly variable. Conclusions: We successfully established primary cell cultures from various renal tumor entities suitable for further investigation. Loss of PACRG and PARK2 are common events in ccRCC. PACRG and PARK2 might function as tumor suppressors in ccRCC and their loss may be involved in tumor progression as reported before for other tumor entities. Further investigation of PINK1, PARK2 and PACRG might allow new therapeutic approaches. Citation Format: Adrian G. Simon, Joerg Ellinger, Yuri Tolkach, Stefan C. Mueller, Glen Kristiansen, Marieta I. Toma. Expression of autophagy- and mitophagy-related genes in clear cell renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3113.

Abstract 3361: Are mismatch repair (MMR) defects and microsatellite instability (MSI) relevant in renal cell and prostate carcinomas? Their significance for future therapies

Abstract Background Few studies have investigated mismatch repair (MMR) defects in renal and prostatic cancers. Normally, MMR accurately detects and corrects mistakes made during replication of a DNA strand. But, a defective MMR system is very likely to miss copy-number errors, particularly in microsatellites (short tandem base repeats). Alterations in function of MMR genes can result in microsatellite instability (MSI), known to facilitate tumor progression and poor prognosis. MMR deficiency is observed frequently in colonic and endometrial carcinoma as part of Lynch's syndrome, as well as occasionally in other neoplasms. In our study, we assayed MMR expression in a series of kidney tumors representing the spectrum of renal malignancies and in a wide-ranging group of prostate cancers (for which clinical information and Gleason grade was obtained in all cases). Materials and methods Immunohistochemical (IHC) staining of FFPE sections from 45 kidney cancers and 30 prostatic tumors was performed. The main MMR proteins of interest are MSH2 and MLH1, plus their heterodimer partners MSH6 and PMS2; staining was directed at these 4 targets. Antibody sources were Abcam, Cambridge, MA 02139 (MLH1, MSH6, PMS2) and Agilent Technologies, Wilmington, DE 19808 (MSH2). Also, PD-L1 expression was evaluated using antibody from Cell Signaling, Danvers, MA 01923. Results Forty-five cases of renal cell carcinoma (RCC) comprised 12 cases of clear cell VHL (von Hippel Lindau) related cancer, 11 papillary type 1, 11 chromophobe, and 11 HLRCC (hereditary leiomyomatosis and renal cell carcinoma). Only one case of chromophobe RCC with sarcomatoid differentiation showed complete loss of MLH1 and PMS2 (2% of 45 renal tumors). Of prostate cancers, only one of 30 tumors (3%) was completely negative for both MLH1 and PMS2; that tumor was Gleason grade 8. The remaining 29 cases were positive for all MMR proteins. Discussion Our study suggests that neither kidney nor prostate cancers are likely to possess significant MMR defects. In our series, clear cell, papillary and HLRCC tumors did not lack MMR expression; one chromophobe case negative for MMR (and presumed liable to MSI) may have developed genomic changes as disease progressed to a more aggressive, sarcomatoid pattern. Prostate cancer with MMR defects also appears to be rare, and we found no correlation with grade and stage. MMR defects lead to highly unstable microsatellite sequences and altered gene expression, so while only a small proportion of these tumors exhibited loss of MMR proteins, it is possible that in these few cases the loss may be significant and that such patients may benefit from new modalities of treatment. IHC detection of MMR defects (as predictors of probable MSI) may prove a useful prognostic tool in identification of rare renal and prostatic cancers likely to exhibit greater genetic instability and neoplastic advance. Citation Format: Xu Naizhen, Marston Linehan, Peter A. Pinto, Maria J. Merino. Are mismatch repair (MMR) defects and microsatellite instability (MSI) relevant in renal cell and prostate carcinomas? Their significance for future therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3361.

The application of renal sinus anatomy based tension-free reconstruction technique for robot-assisted nephron-sparing surgery of hilar tumors: a single center report and follow-up of 286 cases

Objective To describe our renal sinus anatomy based tension-free reconstruction step by step and report perioperative data and long-term outcomes of patients undergoing robot-assisted nephron-sparing surgery for hilar tumors. Methods From June 2013 to December 2016, data of 286 consecutive patients with hilar tumor who underwent RAPN in single center were retrospectively reviewed.There were 202 males and 84 females, aged(56.2±9.2)years.The body mass index was(26.8±3.5)kg/m2.The median diameter of tumor was 2.6 cm(0.8-6.0 cm), and R. E.N.A.L.score was 8.2±1.8. The anatomy-based Garland specialized in protecting the large hilar vessels and minimizing the tension of trans/retroperitoneal defect suturing approach for anterior/posterior lip hilar tumor respectively. Patient′s perioperative complications and long-term follow-up including renal function and oncological outcomes were analyzed. Results Garland technique was successfully applied in 284 patients, the warm ischemia time (WIT) was (18.2±4.1) min. Median estimated blood loss (EBL) for RAPN was 100 ml (range: 10-600 ml). Median operative time was 120 min (range: 60-230 min). No patient was converted to open surgery. Postoperative hospital stay was 4.0 d (range: 2.0-9.0 d). Three patients (1.1%) had positive surgical margins. Of all the pathological results, 260 cases (91.5%)were clear renal cell carcinoma, 8 cases (2.8%)were chromophobe renal carcinoma, 7 cases (2.5%)were papillary type renal cell carcinoma, 5 cases(1.8%) were oncocytoma, 3 cases (1.1%)were angiomyolipoma, one case (0.3%)was mucinous tubular and spindle cell carcinoma. Two patients underwent blood transfusion. Three patients(1.0%) had local recurrence.284 patients were alive at a median follow-up of 36 months (range: 12-54 months). Conclusions Garland technique is safe and feasible for hilar tumor resection and reconstruction with less surgical complications. Large renal vessel injury was avoided and tension of wound closure was minimized. The trans/retroperitoneal approaches are capable for anterior/posterior hilar tumor. Patients with hilar tumor could benefit from robotic surgery with a well preserved renal function and good oncological outcomes. Key words: Kidney neoplasms, renal hilum; Robot; Nephron-sparing surgery; Renal sinus anatomy; Kidney reconstruction

Can multiphase CT scan distinguish between papillary renal cell carcinoma type 1 and type 2?

To investigate the utility of multiphase computed tomography (CT) and percutaneous renal mass biopsy (PRMB) in differentiating between papillary renal cell carcinoma (pRCC)-Type 1 and -Type 2, as emerging data have suggested differential enhancement patterns in different renal tumor histologies. Retrospective analysis of 51 patients (23 pRCC-Type 1/28 pRCC-Type 2) who underwent multiphase CT followed by surgery from July 2011 to April 2016 was performed. Data were analyzed between subgroups based on histology. Multiphase CT was analyzed for tumor size, and attenuation [Hounsfield Units (HU)]. Change in HU (ΔHU) was calculated between noncontrast (NC), corticomedullary (CM), nephrographic (N), and delayed (D) phases. Subset analysis was carried out on patients who underwent PRMB prior to surgery. There was no difference in median tumor size (pRCC-Type 1 2.8 vs. pRCC-Type 2 2.6 cm, p=0.832). In addition to tumor size being similar between groups, distribution of tumor stages between groups was also similar (p=0.651). Greater proportion of high-grade tumors (III/IV) was noted in pRCC-Type 2 (42.9% vs. 8.7%) (p=0.011). There was no difference in HU values for NC (p=0.961), CM (p=0.118), N (p=0.277), and D (p=0.256) phases, and in ΔHU between CM-NC (p=0.278), N-NC (p=0.316), and D-NC (p=0.103). Thirteen patients underwent percutaneous biopsy, 11 of whom had diagnostic samples. Examination of 10/11 (90.9%) samples accurately predicted correct histology, and of 6/11 (54.5%) samples correctly identified high-vs. low-grade histology. Our findings suggest substantial overlap of CT findings, despite pRCC-Type 2 having greater proportion of high-grade tumors. Utility of CT is limited in the differentiation between pRCC subtypes. Patients with suggested pRCC on CT imaging being considered for a non-extirpative strategy should undergo PRMB for risk stratification.

Carcinome papillaire thyroïdien variante solide/trabéculaire avec mutation DICER1 chez une enfant de 11 ans

We report the case of an 11-year-old patient diagnosed with a solid variant of papillary thyroid carcinoma. Papillary thyroid carcinoma (PTC) is the most common thyroid cancer, representing 80-90% of all newly diagnosed thyroid cancers. Among the many variants described, solid/trabecular variant of papillary thyroid carcinoma is a rare entity and account for 3% of thyroid cancers. It is more common in children and young adults, and it is seen in higher proportion in post radiation papillary thyroid carcinoma cases. Histologically, solid variant papillary carcinoma is characterized by a predominantly solid, trabecular or insular growth pattern, and the presence of cytological features typical of PTC. Its main differential diagnosis is poorly differentiated thyroid carcinoma. It has a less favorable prognosis than the classical papillary type, with a higher risk of distant metastasis, extrathyroidal extension and lympho-vascular invasion. It is associated with a slightly lower long-term survival in adult cases, but not in children. The management of solid variant PTC includes surgery, associated or not with postoperative radioiodine ablation, according to the aggressiveness criteria. Our patient had a DICER1 somatic mutation. Carriers of germline DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 syndrome, with a higher risk of numerous tumors and infrequently differentiated thyroid carcinomas.

Outcome predictors in the management of intramedullary classic ependymoma: An integrative survival analysis.

This is a retrospective study.The aim of this study was to illustrate the survival outcomes of patients with classic ependymoma (CE) and identify potential prognostic factors.CE is the most common category of spinal ependymomas, but few published studies have discussed predictors of the survival outcome.A Boolean search of the PubMed, Embase, and OVID databases was conducted by 2 investigators independently. The objects were intramedullary grade II ependymoma according to 2007 WHO classification. Univariate Kaplan–Meier analysis and Log-Rank tests were performed to identify variables associated with progression-free survival (PFS) or overall survival (OS). Multivariate Cox regression was performed to assess hazard ratios (HRs) with 95% confidence intervals (95% CIs). Statistical analysis was performed by SPSS version 23.0 (IBM Corp.) with statistical significance defined as P < .05.A total of 35 studies were identified, including 169 cases of CE. The mean follow-up time across cases was 64.2 ± 51.5 months. Univariate analysis showed that patients who had undergone total resection (TR) had better PFS and OS than those with subtotal resection (STR) and biopsy (P = .002, P = .004, respectively). Within either univariate or multivariate analysis (P = .000, P = .07, respectively), histological type was an independent prognostic factor for PFS of CE [papillary type: HR 0.002, 95% CI (0.000–0.073), P = .001, tanycytic type: HR 0.010, 95% CI (0.000–0.218), P = .003].It was the first integrative analysis of CE to elucidate the correlation between kinds of factors and prognostic outcomes. Definite histological type and safely TR were foundation of CE's management.Level of Evidence: 4

Mo1354 CURVED LINEAR ARRAY ENDOSCOPIC ULTRASOUND FINDING CAN SIGNIFICANTLY PREDICT "A DIFFICULT-TO-CANNULATE CASE" ON ERCP

To clarify the curved linear array endoscopic ultrasonography (CLAEUS) findings that would enable prediction of cases with difficult selective biliary cannulation during endoscopic retrograde cholangio-pancreatography (ERCP). In this single-institution retrospective observational study, patients who underwent CLAEUS prior to an initial ERCP were examined. Patients who fulfilled the definition of difficult selective biliary cannulation were placed into a refractory (R) group and patients where biliary cannulation was completed within 20 minutes were placed into a straightforward (S) group. Difficult selective biliary cannulation was defined as when more than 20 minutes were required from the time to view the papilla to successful biliary cannulation, when the bile duct could not be cannulated, when the precut technique was necessary, when a CLAEUS-guided intervention was necessary, or when a transhepatic approach was necessary. We retrospectively compared CLAEUS findings, side-viewing scope findings, and other factors between the R and S groups as following. Variables examined: patient characteristics: 1) age, 2) gender, 3) diagnosis, and 4) gallbladder presence or absence; papillary findings on a side-viewing scope: 1) papillary type, 2) papillary size, and 3) periampullary diverticulum presence or absence; CLAEUS findings: 1) bile duct collapse with probe on regular evaluation at 2nd portion of duodenum (D2), 2) coaxial depiction of the cholangio-pancreatic duct at D2, and 3) background pancreas. A p value of <0.05 was considered statistically significant. The subjects were selected from 986 patients who underwent ERCP in the 36 months from July 1, 2014, to June 30, 2017. From these, 98 patients were selected who underwent naïve ERCP after CLAEUS. Of these, 17 and 81 were placed in the R (10 men, mean age 73.0±13.2 years, median 74 years) and S (42 men, mean age 67.6±15.1 years, median 70 years) groups, respectively (p=0.15). A significant difference was observed for bile duct collapse (p=0.02) and coaxial depiction of the cholangio-pancreatic duct (p<0.0001) on univariate analysis. The sensitivity, specificity, positive predictive value, and negative predictive value were 0.71, 0.87, 0.54, and 0.93, respectively. A significant difference was observed between ROC curves to predict difficult biliary cannulation by using bile duct collapse (AUC=0.55), and the factor plus coaxial depiction of the cholangio-pancreatic duct (AUC=0.81; p<0.0001). A finding of coaxial depiction of the cholangio-pancreatic duct on CLAEUS can be used to predict difficult ERCP cannulation.

Histopathologic and Immunohistochemistry Findings in Feline Renal Cell Carcinoma.

The biological behavior and immunohistochemical features of feline renal cell carcinoma (RCC) have not been well characterized. In the present study, immunohistochemical examinations were performed in 12 feline cases of RCC. The RCC consisted of solid ( n = 2), solid-tubular ( n = 2), tubular ( n = 3), papillary ( n = 2), tubulopapillary ( n = 2), and sarcomatoid ( n = 1) type lesions. Of the cases with RCC, 1 developed metastatic disease and 6 cases had no evidence of recurrence at 80 to 2292 days after surgery. One papillary-type tumor had cuboidal cells with scant cytoplasm and monomorphic nuclei, and the other had pseudostratified columnar cells with abundant cytoplasm. Immunohistochemistry revealed that the tumor cells in most cases were positive for cytokeratin (CK)7, CK20, KIT, and CD10, with the exception of cases of the solid type with clear cytoplasm (solid anaplastic), papillary type with columnar cells, and sarcomatoid types. A small number of tumor cells in the solid anaplastic and in the sarcomatoid types were positive for aquaporin-1. Increased expression of N-cadherin and Twist along with nuclear accumulation of β-catenin were observed in the sarcomatoid type. These results indicated that CK, KIT, and CD10 are relatively strongly expressed in most feline RCC. The solid anaplastic RCC exhibited CD10 expression with the absence of distal tubule marker expression. Although immunohistochemistry profiles were relatively consistent with those described in human RCC, the histopathologic features were different from those seen in humans. Epithelial-mesenchymal transition (EMT) marker expression in the current cases may suggest the involvement of an EMT-like mechanism in the development of sarcomatoid RCC in cats.

Su1327 - Comparison of Flat type and Low Papillary type of Pancreatic Carcinoma in Situ

Su1327 - Comparison of Flat type and Low Papillary type of Pancreatic Carcinoma in Situ

SWI/SNF protein expression status in fumarate hydratase–deficient renal cell carcinoma: immunohistochemical analysis of 32 tumors from 28 patients

Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare, aggressive RCC type, originally described in the setting of hereditary leiomyomatosis and RCC syndrome, which is defined by germline FH gene inactivation. Inactivation of components of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex is involved in renal medullary carcinoma (SMARCB1/INI1 loss), clear cell RCC (PBRM1 loss), and subsets of dedifferentiated RCC of clear cell, chromophobe, and papillary types (loss of different SWI/SNF components). FH-RCC and SWI/SNF-deficient RCC share anaplastic nuclear features and highly aggressive course. We analyzed 32 FH-RCCs from 28 patients using 7 commercially available SWI/SNF antibodies (SMARCB1/INI1, SMARCA2, SMARCA4, SMARCC1, SMARCC2, PBRM1, and ARID1A). Variable loss of SMARCB1, ARID1A, and SMARCC1 was observed in 1 of 31, 2 of 31, and 1 of 29 evaluable cases, respectively; 3 of these 4 SWI/SNF-deficient tumors had confirmed FH mutations. No correlation of SWI/SNF loss with solid or sarcomatoid features was observed. Two tumors with SMARCB1 and ARID1A deficiency had available SWI/SNF molecular data; both lacked SMARCB1 and ARID1A mutations. The remaining 5 SWI/SNF components were intact in all cases. Especially PBRM1 seems not to be involved in the pathogenesis or progression of FH-RCC. Our data showed that a subset of FH-RCC (12%) have a variable loss of SWI/SNF complex subunits, likely as secondary genetic events. This should not be confused with SWI/SNF-deficient RCC of other types. Evaluation of FH and SWI/SNF together with comprehensive molecular genetic profiling is needed to explore possible prognostic implications of FH/SWI-SNF double deficiency and to better understand the somatic mutation landscape in high-grade RCC.