Evidence Of Lymphovascular Invasion Research Articles

Prognostic Factors and Outcomes of Cutaneous Malignant Melanoma: A 174-Patient Cohort Study in a Tertiary Hospital in Thailand.

Malignant melanoma is a common skin cancer among Asians. However, some features, such as tumor type and initial stages, are not comparable with those found in Western countries. We audited a large cohort of patients at a single tertiary referral hospital in Thailand to identify factors affecting the prognosis. A retrospective study was conducted of patients diagnosed with cutaneous malignant melanoma between 2005 and 2019. Details of demographic data, clinical characteristics, pathological reports, treatments, and outcomes were collected. Statistical analyses of overall survival and factors affecting survival were investigated. The study enrolled 174 patients (79 men and 95 women) with pathologically confirmed cutaneous malignant melanoma. Their mean age was 63 years. The most common clinical presentation was a pigmented lesion (40.8%), with the plantar area being the most common site (25.9%). The mean duration of onset and hospitalization was 17.5 months. The 3 most common types of melanoma were acral lentiginous (50.7%), nodular (28.9%), and superficial spreading (9.9%). Eighty-eight cases (50.6%) had concomitant ulceration. Pathological stage III was the most common (42.1%). The 5-year overall survival was 43%, and the median survival time was 3.91 years. Multivariate analysis showed that clinically palpable lymph nodes, distant metastasis, a Breslow thickness ≥ 2 mm, and evidence of lymphovascular invasion were poor prognostic factors for overall survival. In our study, most patients with cutaneous melanoma presented with a higher pathological stage. Independent factors affecting survival are palpable lymph nodes, distant metastases, Breslow thickness, and the presence of lymphovascular invasion. The overall 5-year survival rate was 43%.

S2602 Gastric Leiomyosarcoma: A Rare Case of Upper GI Bleeding

Introduction: Leiomyosarcoma (LMS) is a tumor arising from parts of the body containing smooth muscle cells such as the uterus, stomach and walls of blood vessels. Primary gastric leiomyosarcomas are extremely rare, accounting for 0.1%-3% of gastrointestinal malignancies. They can be differentiated from Gastrointestinal Stromal Tumors (GIST) based on immunohistochemical staining that is positive for desmin and SMA and negative for staining of KIT (CD 117), CD 34, and DOG1.1. LMS is usually asymptomatic but can present with anorexia, weight loss, nausea, vomiting, or bleeding. Here we present a rare case of an aggressive LMS manifesting as hematemesis and melena. Case Description/Methods: A 76-year-old male with a past medical history of Hypertension, Bladder Cancer and Prostate Cancer presented with a chief complaint of three days of hematemesis and melena. Upper Esophagogastroduodenoscopy (EGD) done five months prior was notable for an esophageal ulcer and gastritis. Labs on admission were notable for Hg of 10.3. EGD was performed which showed a large polypoid mass at the gastroesophageal (GE) junction. Biopsies were notable for smooth muscle cells that tested positive for SMA and caldesmon but negative for desmin, CD34, CD117 and DOG-1 most consistent with leiomyosarcoma. Ultimately, the patient underwent surgical resection of a 8.5 × 7.2 × 3.3 cm tumor with negative surgical margins and no evidence of lymphovascular invasion. The patient did well post-operatively and has been following with oncology for further management (Figure 1). Discussion: Prior to 1998, gastrointestinal stromal tumors (GIST) were misdiagnosed as LMS due to lack of molecular markers. Since then there are only 10 reported cases of gastric leiomyosarcoma in the post-GIST era. On CT imaging LMS tends to show up as irregular central zones of low attenuation suggestive of extensive necrosis or hemorrhage. Endoscopically, LMS tends to appear mainly in the muscularis propria with increased vascularity and a heterogeneous appearance. For tumors greater than 2 cm surgical resection is the preferred method of treatment. For metastatic disease, however, there has been no clear benefit of adjuvant chemotherapy as there is a high risk of recurrence. Routine follow up for completely resected tumors consists of abdominal and pelvic imaging which should occur every three to six months for two to three years, and then annually. In conclusion, we highlight a rare case of an aggressive type of Leiomyosarcoma at the GE junction presenting as an upper GI bleed.Figure 1.: (1) Upper Endoscopy showing mass lesion at the gastroesophageal (GE) junction. (2) Axial computed tomography (CT) image showing mass lesion in the gastric cardia (3) Spindle cells with marked atypia, necrosis, rare mitosis and moderate pleomorphism (H and E, x20)

S2219 A Rare Subtype of Colorectal Cancer Presenting as a Contained Perforation

Introduction: Colonic perforation comprises 3-10% of the initial presentation of Colorectal Cancer (CRC). Signet Ring Cell Carcinoma and Mucinous Adenocarcinoma are 2 distinct subtypes which occur with a very low incidence of 10-20% and 0.9-4%, respectively. Both are usually diagnosed at an advanced stage and have an overall worse prognosis than other types of CRC. Here we present a rare case of colonic mucinous adenocarcinoma with signet ring cell features manifesting as a contained perforated intra-abdominal mass necessitating surgery. Case Description/Methods: A 60-year-old male presented with fatigue, shortness of breath and anemia with hemoglobin of 4.8 g/dL. A computed tomography (CT) scan of the abdomen and pelvis was obtained which showed an intraperitoneal mass with a central necrotic component and air, suggesting communication to the small bowel. Due to the initial concern of a possible contained perforation, colonoscopy was deferred despite the patient never having one previously. Ultimately, the patient underwent a diagnostic laparoscopy which showed a large intra-abdominal mass with a mucinous surface involving multiple parts of the small bowel and sigmoid colon. This mass was removed along with a small bowel and sigmoid colon resection. Pathology was notable for moderately differentiated mucinous adenocarcinoma of the sigmoid colon with focal signet ring features with negative margins and no evidence of lymphovascular invasion. He was eventually discharged with instructions to follow up with Oncology for further treatment. (Figure) Discussion: Mucinous adenocarcinoma is characterized by the presence of abundant extracellular mucin which accounts for at least 50% of the tumor volume. Signet ring cells have copious amounts of mucin in the cytoplasm and nuclei located at the cell periphery. These lesions are usually located in the right colon and share similar characteristics on CT imaging including segments of concentric bowel wall thickening and ulcerations. Studies have shown that even a minor signet-ring cell component in CRC was associated with higher patient mortality. This becomes evident as these tumors diffusely infiltrate the submucosa with full thickness involvement of the bowel wall and have a high propensity for pelvic, peritoneal and ovarian metastasis. Treatment centers on surgical resection with adjuvant chemotherapy showing some benefit. Our case highlights an atypical presentation of a rare subtype of CRC for which gastroenterologists should maintain a high index of suspicion.Figure 1.: (Top) Signet Ring Cells in background of mucus (from sigmoid colon) (Bottom) Computed Tomography (CT) scan showing an intra-abdominal mass with a contained perforation.

Primary High-grade Serous Carcinoma of the Fallopian Tube as an Incidental Intraoperative Finding: A Case Report

: Primary carcinoma of the fallopian tube is a rare, but fatal gynecologic cancer. The preoperative diagnosis of this carcinoma is challenging due to the absence of specific symptoms and signs, and in most patients, it is an intraoperative finding. A 55-year-old patient (G3Ab1P2) was referred to the urogynecology clinic of our hospital with the chief complaints of heavy, prolonged menstrual bleeding and a persistently abnormal yellow discharge, which could not be distinguished by the patient from urinary leaks. After a complete diagnostic work-up, the patient was identified as a candidate for hysterectomy due to abnormal vaginal bleeding resistant to megestrol acetate, family history of malignancy, and abnormal vaginal discharge. Laparotomy revealed unusual left fallopian tube features (large, bulky, and vegetative), suggesting malignancy. The intraoperative frozen-section analysis of the left fallopian tube and the ovarian specimens indicated the mass as a high-grade serous carcinoma of the fallopian tube. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, and partial omentectomy were performed for the patient. The definitive histopathological diagnosis was high-grade serous carcinoma of the left fallopian tube (stage 2b) with omental involvement, without any evidence of lymphovascular invasion. High-grade serous carcinoma of the fallopian tube is likely to have non-specific symptoms, causing a significant delay in diagnosis and treatment, which negatively affects the prognosis and survival of these patients.

Adenoid cystic carcinoma, report of a case

Introduction: Adenoid cystic carcinoma (CAQ) is a typical tumor of the salivary glands and infrequent in the breast (less than 0.1%). It stands out for being triple negative with a favorable prognosis. Its infrequency and slow progression mean that today there is no consensus regarding its therapeutic management and follow-up. Objective: To provide a new case to learn more about the nature, management and evolution of this type of neoplasm. Material and methods: We analyzed the data collected in our case and compared it with what was published in the literature. Results: a typical triple negative case is presented, with a large size with respect to the breast (T2), so it was decided to perform a simple mastectomy as initial treatment with immediate reconstruction due to the absence of axillary involvement. Subsequently, it was decided not to apply adjuvant treatment since the tumor was not aggressive, the hormone receptors were negative, and the final lesion was less than 5cm with wide margins and no evidence of lymphovascular invasion. Conclusion: To date, breast CAQ continues to present uncertain management and follow-up given that we do not have enough data in the literature to know its evolution correctly, therefore more studies are needed with the intention of being able to standardize treatment and surveillance of this tumor.

International validation of a risk prediction algorithm for patients with malignant colorectal polyps.

The optimal management strategy for patients with endoscopically resected malignant colorectal polyps (MCP) has yet to be defined. The aim of this study was to validate a published decision-making tool, termed the Scottish Polyp Cancer Study (SPOCS) algorithm, on a large international population. The SPOCS algorithm allocates patients to risk groups based on just two variables: the polyp resection margin and the presence of lymphovascular invasion (LVI). The risk groups are termed low (clear margin, LVI absent), medium (clear margin, LVI present) or high (involved/non-assessable margin). The International Polyp Cancer Collaborative was formed to validate the algorithm on data from Australia, Denmark, UK and New Zealand. In total, 1423 patients were included in the final dataset. 680/1423 (47.8%) underwent surgical resection and 108/680 (15.9%) had residual disease (luminal disease 8.8%, lymph node metastases 8.8%). The SPOCS algorithm classified 602 patients as low risk (in which 1.5% had residual disease), 198 patients as medium risk (in which 7.1% had residual disease) and 484 as high risk (in which 14.5% had residual disease) (P<0.001, χ2 test). Receiver operating characteristic curve analysis demonstrated good accuracy of the algorithm in predicting residual disease (area under the curve 0.732, 95% CI 0.687-0.778, P<0.001). When patients were designated as low risk, the negative predictive value was 98.5%. The SPOCS algorithm can be used to predict the risk of residual disease in patients with endoscopically resected MCPs. Surgery can be safely avoided in patients who have a clear margin of excision and no evidence of LVI.

MON-448 Detection of Thyroid Cancer Recurrence in Patients with Positive Thyroglobulin Antibody Receiving Immunoglobulin Therapy

Introduction: Differentiated thyroid cancers such as papillary and follicular thyroid cancer make up more than 90% of all thyroid cancers. The presence of thyroglobulin autoantibodies makes interpretation of the thyroglobulin level unreliable, as it could be falsely low or falsely high. Studies have shown that rising thyroglobulin antibody levels, could be used to monitor for disease recurrence in patients with negative thyroglobulin and imaging studies. However, there are challenges in detecting recurrence in patients with normal thyroglobulin level and thyroid imaging studies, who are on lifelong immunoglobulin therapy and who have increasing thyroglobulin antibody levels.Clinical case: A 63 yr old female was found to have an incidental left thyroid nodule at age 48yrs from a carotid ultrasound. She underwent US guided FNA of the thyroid nodule and was found to have papillary thyroid cancer. She had total thyroidectomy a month later, with removal of a 1.4cm primary, with no evidence of extrathyroidal extension, clear margins and no evidence of lymphovascular invasion – Stage T1bN0M0. There was left level 6 neck dissection with no carcinoma identified in the 2 lymph nodes removed. She received 105.3 mCi radioactive iodine (RAI) and whole body thyroid scan done 7 days later revealed, increased uptake involving the thyroid bed likely residual thyroid tissue. Activity was noted inferolateral to the right thyroid bed which most likely represents a lymph node. There was no evidence of distant metastasis.She was commenced on levothyroxine post operatively. Her other past medical history is significant for idiopathic urticaria and angioedema, immune deficiency disorder with low IgG and IgM and asthma. She was commenced on monthly IV immunoglobulins 5yrs post RAI therapy, due to recurrent sinusitis, rhinitis and chronic diarrhea. She was later transitioned to weekly SQ immune globulin – Hizentra which she is on till date.Over the past 15 years, serial neck ultrasounds post radioiodine ablation have been negative for recurrence. Her TSH ranged 14.91 to 0.04 (ref 0.27-4.2 uiu/ml) and thyroglobulin (Tg) titer remains <0.1 (ref <0.1). Her thyroglobulin antibody titers have trended up from <0.2 (ref <2.0) 5yrs post RAI therapy to 49 (ref <4 iu/ml)) on her most recent test this year. She is currently undergoing further work up to rule out recurrence of her cancer. In our review of the literature we found one report that showed use of Liquid Chromatography–Mass Spectrometry (LC-MS) was able to differentiate thyroid cancer recurrence in an individual with positive antithyroglobulin antibody receiving immunoglobulin therapy.Conclusion: In patients with negative Tg levels, but elevated thyroglobulin antibody while receiving immune globulin therapy, thyroglobulin antibody levels may not be a reliable indicator of thyroid cancer recurrence. Measurement of Tg levels using a LC-MS may provide some clarity.

Comprehensive Histopathological Examination and Breast Cancer

Background: The histological patterns and other microscopic parameters play important role in the therapeutic management and assessment of the prognosis of the carcinoma breast. As this carcinoma shows heterogeneity, a careful gross examination followed by a more detailed examination of tissue sections is the backbone of the histopathological analysis. Methods: Total of 103 cases of breast carcinoma were included in the study. Histopathological reports along with detailed gross examination findings were re-assessed for various histological patterns and associated features. Data obtained was analysed. Result: Gross examination findings showed 9.4% multiplicentricity of the tumor. Histopathology revealed infiltrating ductal cell carcinoma not otherwise specified (IDC NOS) as most common histologic type (77.6%), I as common grade (45.8%) and IIA as common stage (28%) with other unique microscopic characteristics. Conclusion: Gross findings were more or less similar with results shown in the literatures except 9.4% multiple invasive pattern of the tumor. Different histopathological findings were papillary carcinoma as second common histogical pattern, histologic grade I as common grade, evidence of lymphovascular invasion less common than perineural invasion. In addition atypical ductal hyperplasia was seen associated with papillary carcinoma commonly and desmoplasia with N0 tumor.

Abstract P1-06-09: Correlation of breast cancer index (BCI) results to lymphovascular invasion in early stage HR+ breast cancer

Abstract Background: Positive lymphovascular invasion (LVI) is a negative prognostic factor for women with early-stage ER+ breast cancer. LVI, along with other clinicopathologic factors such as larger tumor size, higher grade and positive nodal status, increase a patient's risk of late (post-5y) recurrence. Breast Cancer Index (BCI) is a validated gene expression-based assay for patients with early-stage HR+ breast cancer that reports an individualized risk of late distant recurrence based on a combination of the HOXB13/I17BR ratio and the molecular grade index (MGI). The correlation of LVI and individualized risk stratification by genomic analysis is not well characterized. Therefore, this study evaluated risk stratification by BCI based on the presence or absence of LVI. Methods: A population of 2,613 patients with known LVI status were identified in the Breast Cancer Index Clinical Database for Correlative Studies, an IRB-approved de-identified database which contains clinicopathologic and molecular variables of more than 19,000 clinical cases submitted for BCI testing. LVI was recorded as either positive or negative based on pathology report review. BCI results based on LVI status from LN- (n=2035) and LN+ patients (n=578) were evaluated separately. Chi-squared tests were used to compare BCI results between LVI groups. Results: In analyses of 2,613 patients with LVI data available (median age 59.1 y; range 28-89y; 74% ≥50y), 18.3% of patients showed evidence of LVI (LVI-pos). In comparison to the LVI-neg tumors submitted for BCI testing, the LVI-pos tumors had a higher proportion of grade 3 tumors (33% vs 16%, p&amp;lt;0.0001), more LVI-pos tumors were 2.0 cm or greater (45% vs 23%, p&amp;lt;0.0001), a higher percentage LVI-pos patients had node-positive disease (51% vs 16%, p&amp;lt;0.0001), and a higher proportion of LVI-pos tumors showed high Ki67 (Ki67 ≥14%; 64% vs 51%, p=0.004). A correlation between LVI positivity and high BCI prognostic risk was observed, with a higher proportion of LVI-pos patients classified as high risk of late distant recurrence in both the LN- (68% vs 49%, p&amp;lt;0.0001) and LN+ subsets (84% vs 70%, p&amp;lt;0.0001) compared to LVI-neg patients. LVI-pos patients had a higher median molecular proliferative status (MGI) compared to LVI-neg patients regardless of nodal status (p&amp;lt;0.0001 for both). In contrast to the categorical LVI prognostic factor, the wide distribution of BCI individual risk scores provides additional resolution that identifies a substantial subset of LVI positive tumors (32%) that that have a low risk of late recurrence by genomic analysis. Conclusion: While BCI Prognostic stratification correlated with LVI status, BCI identified a subset of patients with LVI positivity as having a low risk of late distant recurrence that otherwise would have an unfavorable prognosis based on LVI and/or LN positivity. These findings help to characterize differential patient stratification based on an individualized assessment of tumor biology versus LVI for patients considering EET. Citation Format: Vulchi M, Sagalnik M, Schnabel CA, Abraham J. Correlation of breast cancer index (BCI) results to lymphovascular invasion in early stage HR+ breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-06-09.

The clinical outcomes and risk factors associated with incomplete endoscopic resection of rectal carcinoid tumor.

The risk of lymph node metastasis of a small rectal carcinoid tumor (<10mm) is known to be lower than that of tumors at other gastrointestinal sites. Although rectal carcinoid tumors can be treated by endoscopic resection, the resected specimen may be incomplete. The consequences of an incomplete resection are not well known. From December 2008 to November 2015, cases of rectal carcinoid tumors resected by endoscopic resection techniques such as endoscopic submucosal dissection (ESD), or endoscopic mucosal resection using band ligation device (EMR-L), or cap aspiration (EMR-C) were enrolled. The factors associated with incomplete endoscopic resection and clinical outcomes were retrospectively analyzed. During the study period, a total of 134 rectal carcinoid tumors were resected by endoscopic techniques; ESD (n = 53), EMR-C (n = 65), and EMR-L (n = 16). The mean tumor size was 5.5 ± 2.4mm. The mean follow-up period was 835 ± 501 days. The en bloc resection and complete resection rates were 100 and 85.8%, respectively. Procedure time was longer and the size of the resected tumor was larger in the ESD group than in the EMR-C or EMR-L (p < 0.001) group by the univariate analysis. A factor related to incomplete resection was central depression on the surface (OR 11.529, 95% CI 2.377-55.922, p = 0.002), as revealed by the multivariate analysis. Nineteen patients had an incomplete resection status and did not undergo additional resection treatment; none of these patients had recurrence during the study period. A rectal carcinoid tumor with a central depression on the surface was associated with a higher incomplete resection rate. After an incomplete resection of small rectal carcinoid tumors, without evidence of lymphovascular invasion, a periodic follow-up examination without additional resection may be recommended.

An evidence-based treatment algorithm for colorectal polyp cancers: results from the Scottish Screen-detected Polyp Cancer Study (SSPoCS)

ObjectivesColorectal polyp cancers present clinicians with a treatment dilemma. Decisions regarding whether to offer segmental resection or endoscopic surveillance are often taken without reference to good quality evidence. The aim...

Abstract PD1-04: Association of aspirin and clinical outcomes in patients with invasive breast cancer

Abstract Long-term low-dose aspirin use has been observed to reduce the risk of colorectal, breast and other cancers. The most prominent effect has been in colorectal cancer, in which large-scale meta-analyses have shown that there is an approximately 20% relative risk reduction in participants who took aspirin for four or more years. The role of long-term NSAID use in breast cancer risk is less clear although preliminary observational case-control studies suggest an association between aspirin use and reduced incidence of hormone receptor-positive breast cancers though no clear evidence exists to support a clear mortality benefit among patients with a history of prior NSAID use as opposed to those who do not. To investigate whether a history of aspirin use is associated with improved clinical outcome in breast cancer, we examined the pattern of aspirin use, cancer pathology and overall survival of over 1000 patients diagnosed with and treated for invasive breast cancer at our institution, for whom long-term follow up was available. A history of aspirin use for at least a period of 30 days prior to breast cancer diagnosis was reported in nearly 14% of individuals. Aspirin use was associated with being older than the age of 50 at diagnosis (79.8% vs 66.5%; Fisher's Exact Test (P &amp;lt; 3.2x10-3) and being of African American race (49.1% vs 28.7%; P &amp;lt; 3.4x10-2), when compared to those who have not used aspirin. Aspirin use correlated with prognostic factors that are known to be associated with poor outcomes. They include axilla node positive disease (44.5% vs 27.0%, p&amp;lt; 0.032), evidence of lymphovascular invasion (24.7% vs 15.4%, p&amp;lt; 0.049), Her2-neu positive disease (&amp;lt;0.0083). In contrast to prior retrospective case-control studies, no significant association between aspirin use and hormone receptor positive disease was noted for either ER (p=0.19) or PR(+) receptor status (p=0.12). Finally, we examined if aspirin use prior to breast cancer diagnosis has any impact on disease outcome. Over a median follow up of 60.0 months, univariate analysis using cox proportional hazard modeling demonstrated that the use of low-dose aspirin prior to the diagnosis of breast cancer was associated with an increased all-cause mortality when compared to patients without aspirin use prior to cancer diagnosis (HR=3.084, 95% CI=1.961 to 4.848). On multivariate analysis, we found that recent history of aspirin use was significantly associated with a worse overall survival (HR 2.65; 95%CI 1.37 -5.12, P &amp;lt; 3.77 x 10-3), when controlled for other prognostic factors including receptor status, tumor size, tumor grade, number of positive regional lymph nodes, positive margins, as well as race and age at diagnosis. This is the first study to report on the association of aspirin use with breast cancer outcomes in a large patient cohort treated at a single institution. Although aspirin in breast and cancers has been associated with reduced cancer incidence, a history of aspirin use prior to breast cancer diagnosis does not appear to be protective or associated with improve clinical outcomes or survival among breast cancer patients. Ongoing efforts are examining the mechanism underlying this association. Citation Format: Li YR, Steel L, Carrigan E, Tchou J. Association of aspirin and clinical outcomes in patients with invasive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD1-04.

Predictors of Lymph Node Metastasis in Western Early Gastric Cancer

BackgroundThe application of endoscopic and local resection for early gastric cancer (EGC) is limited by the risk of regional lymph node (LN) metastasis. We sought to determine the incidence and predictors of LN metastasis in a contemporary cohort of Western patients with early gastric cancer. MethodsSixty-seven patients with pT1 gastric adenocarcinoma underwent radical surgery without neoadjuvant therapy at our institution between 1995 and 2011, and clinicopathologic factors predicting LN metastasis were analyzed. ResultsLN metastases were present in 15/67 (22 %) pT1 tumors, including 1/23 (4 %) T1a tumors and 14/44 (32 %) T1b tumors. Tumor size, site, degree of differentiation, macroscopic tumor sub-classification, perineural invasion status, and depth of submucosal tumor penetration did not predict LN metastasis. The presence of lymphovascular invasion (LVI) and positive nodal status by endoscopic ultrasound (EUS) were the only factors that predicted LN metastasis on multivariate analysis. T1a tumors without LVI had a 0 % rate of positive LN, whereas T1b tumors with LVI had a 64.3 % rate of positive LN. ConclusionsEGC limited to the mucosa, without evidence of LVI, and N0 on EUS, may be considered for limited resection. However, any EGC with submucosal invasion, LVI, or positive nodes on EUS should undergo radical resection with lymphadenectomy.

Feasibility of obtaining biomarker profiles from endoscopic biopsy specimens in upper tract urothelial carcinoma: Preliminary results

ObjectiveTo prospectively evaluate the feasibility of obtaining a reliable histochemical assessment of cell cycle biomarkers from endoscopic biopsy specimens of patients with upper tract urothelial cancer. MethodsOverall, 17 patients were identified who had an available biopsy as well as those who underwent subsequent radical nephroureterectomy (RNU) or segmental ureterectomy (SU) for clinically localized high-grade upper tract urothelial cancer of the renal pelvis or ureter. Of those 17 patients, 15 (88%) had sufficient tissue to undergo immunohistochemical staining. Biopsies were obtained using various endoscopic techniques. Tumor characteristics were recorded and prospectively evaluated for immunohistochemical expression of 5 biomarkers: p21, p27, p53, cyclin E, and Ki67/pRb. Unfavorable prognostic score (PS) was defined as>2 altered markers. ResultsThe median age of the patients was 68 years (range: 53–82y) with 87% being males. Of the 15 specimens, 9 (60%) tumors were organ confined (T≤2 and N0), and all were high grade. Of the 15 patients, 4 (27%), 7 (46.6%), 3 (20%), and 1 (6.7%) individuals had 1, 2, 3, and 5 markers altered on biopsy marker profiling, respectively, with Ki67 being the most frequent alteration (13/15; 87.7%).An overall concordance rate of 60% (9/15) was seen between biopsy and RNU/SU PS. Those patients with favorable biopsy biomarker PS were less likely to display adverse pathological features, with organ-confined disease in 7/11 (63.6%) patients and 9/11 (81.8%) being free of carcinoma in situ in the final specimen. Additionally, 10/11 (91%) had no evidence of necrosis and 7/11 (64%) had no evidence of lymphovascular invasion on final pathologic evaluation. ConclusionsPreliminary results suggest that obtaining interpretable biomarker profile of ureteroscopic biopsy specimens is feasible. Tumor heterogeneity and limited biopsy material may account for the discordance between biopsy and RNU/SU specimens. Meaningful biopsy biomarker profiling could serve as a powerful tool for individualizing treatment regimens and augmenting current predictive variables. Further studies are needed to evaluate clinical applicability.

A Case of Early Onset of Ileal Adenocarcinoma in a Patient With Crohn’s Disease

Introduction: Colonic adenocarcinoma is a well-known complication of inflammatory bowel disease. However, small bowel adenocarcinoma (SBA) is a rare complication of Crohn’s disease (CD). In a large observational study, incidence rates of SBA were 0.235 per 1000 patient-years in small bowel CD and 0.464 per 1000 patient-years in small bowel CD for more than 8 years. We report another case of ileal adenocarcinoma in a 69-year-old male diagnosed with CD 8 years ago. Case Report: A 69-year-old white male diagnosed with ileal CD 8 years ago was transferred from an outside facility for a second opinion. The patient was on mesalamine 8 years ago, but discontinued it 6 years ago. He was doing well until 6 months ago, when he developed right lower quadrant abdominal pain and weight loss of 30 lbs. He was started on steroids for possible CD flare. However, due to lack of improvement, he was given a dose of infliximab 1 month prior to transfer. He was admitted due to persistent symptoms and had leukocytosis. C.diff was negative. Enterography showed areas of stricturing and active inflammation in the distal ileum with a small abscess. Colonoscopy revealed terminal ileal stricture and inflammation. Biopsy revealed poorly differentiated adenocarcinoma. He underwent resection of 25 cm of the terminal ileum and right colon. There was evidence of lymphovascular invasion. The patient was seen in clinic 5 months after surgery and is currently undergoing chemotherapy. He is scheduled for a PET scan. Conclusion: Small bowel malignancies are rare. Incidence ranges from 0.2 to 2.4 for males and from 0.2 to 1.8 for females worldwide. SBA, a rare complication of CD, occurs predominantly in the ileum and has a male preponderance. Age of onset is usually between 30 to 50 years and more common after 10 years of the disease onset. In a study, the cumulative risk of SBA was 0.2% and 2.2% after 10 and 25 years of ileal CD, respectively. Our patient was unique in that he developed adenocarcinoma within 8 years of diagnosis of CD. He is also in a higher age group than that reported in the studies. This case reiterates to always consider small bowel malignancies in the differentials for patients presenting with sudden worsening of disease activity.Figure 1: Ileal stricture.

Clinical and Histologic Determinants of Mortality for Patients With Barrett’s Esophagus–Related T1 Esophageal Adenocarcinoma

Superficial (T1) esophageal adenocarcinoma (EAC) commonly is treated by endoscopic resection, yet little is known about factors that predict outcomes of this approach. We assessed clinical and histologic variables associated with the overall survival times of patients with T1 EAC who received therapy. In a retrospective analysis, we collected data from patients who underwent endoscopic mucosal resection (EMR) for T1 EAC (194 patients with T1a and 75 patients with T1b) at the Mayo Clinic, from 1995 through 2011. EMR specimens were reviewed systematically for depth of invasion, presence of lymphovascular invasion, grade of differentiation, and status of resection margins. Kaplan-Meier curves and proportional hazards regression models were used in statistical analyses. Demographic characteristics were similar between patients with T1a and T1b EAC. Overall survival at 5 years after EMR was 74.4% for patients with T1a (95% confidence interval [CI], 67.6%-81.8%) and 53.2% for patients with T1b EAC (95% CI, 40.3%-70.1%). Of surviving patients with T1a EAC, 94.1% remained free of cancer (95% CI, 89.8%-98.5%), and 94.7% of surviving patients with T1b EAC remained free of cancer (95% CI, 85.2%-100%). A multivariable model associated older age (per 10-year increment), evidence of lymphovascular invasion, and deep margin involvement with reduced overall survival in patients with T1 EAC. Systematic assessment of EMR specimens can help predict mortality and potentially guide treatment options for patients with T1 EAC.

MP77-10 PROGNOSTIC RELEVANCE OF PLATELET COUNT KINETICS IN PATIENTS WITH UPPER TRACT UROTHELIAL CARCINOMA AFTER RADICAL NEPHROURETERECTOMY

7/11 (63.6%) patients and 9/11 (81.8%) free of CIS in the final specimen. Additionally, 10/11 (91%) had no evidence of necrosis and 7/11 (64%) had no evidence of lymphovascular invasion on final pathological evaluation. CONCLUSIONS: Preliminary results suggest that obtaining interpretable biomarker profile of ureteroscopic biopsy specimens is feasible. Tumor heterogeneity and limited biopsy material may account for the discordance between biopsy and RNU/SU specimens. Meaningful biopsy biomarker profiling could serve as a powerful tool for individualizing treatment regimens and augmenting current predictive variables. Further studies are needed to evaluate clinical applicability. Figure 1: Correlation of Individual Markers between Biopsy and RNU/SU

MP77-09 FEASIBILITY OF OBTAINING BIOMARKER PROFILES FROM ENDOSCOPIC BIOPSY SPECIMENS IN UPPER TRACT UROTHELIAL CARCINOMA: PRELIMINARY RESULTS

Objective: To prospectively evaluate the feasibility of obtaining a reliable histochemical assessment of cell cycle biomarkers from endoscopic biopsy specimens of patients with upper tract urothelial cancer. Methods: Overall, 17 patients were identified who had an available biopsy as well as those who underwent subsequent radical nephroureterectomy (RNU) or segmental ureterectomy (SU) for clinically localized high-grade upper tract urothelial cancer of the renal pelvis or ureter. Of those 17 patients, 15 (88%) had sufficient tissue to undergo immunohistochemical staining. Biopsies were obtained using various endoscopic techniques. Tumor characteristics were recorded and prospectively evaluated for immunohistochemical expression of 5 biomarkers: p21, p27, p53, cyclin E, and Ki67/pRb. Unfavorable prognostic score (PS) was defined as 42 altered markers. Results: The median age of the patients was 68 years (range: 53–82 y) with 87% being males. Of the 15 specimens, 9 (60%) tumors were organ confined (T r 2 and N0), and all were high grade. Of the 15 patients, 4 (27%), 7 (46.6%), 3 (20%), and 1 (6.7%) individuals had 1, 2, 3, and 5 markers altered on biopsy marker profiling, respectively, with Ki67 being the most frequent alteration (13/15; 87.7%). An overall concordance rate of 60% (9/15) was seen between biopsy and RNU/SU PS. Those patients with favorable biopsy biomarker PS were less likely to display adverse pathological features, with organ-confined disease in 7/11 (63.6%) patients and 9/11 (81.8%) being free of carcinoma in situ in the final specimen. Additionally, 10/11 (91%) had no evidence of necrosis and 7/11 (64%) had no evidence of lymphovascular invasion on final pathologic evaluation. Conclusions: Preliminary results suggest that obtaining interpretable biomarker profile of ureteroscopic biopsy specimens is feasible. Tumor heterogeneity and limited biopsy material may account for the discordance between biopsy and RNU/SU specimens. Meaningful biopsy biomarker profiling could serve as a powerful tool for individualizing treatment regimens and augmenting current predictive variables. Further studies are needed to evaluate clinical applicability. r 2014 Elsevier Inc. All rights reserved.

Endoscopic assessment and management of early esophageal adenocarcinoma.

Esophageal carcinoma affects more than 450000 people worldwide and the incidence is rapidly increasing. In the United States and Europe, esophageal adenocarcinoma has superseded esophageal squamous cell carcinoma in its incidence. Esophageal cancer has a high mortality rates secondary to the late presentation of most patients at advanced stages. Endoscopic screening is recommended for patients with multiple risk factors for cancer in Barrett's esophagus. These risk factors include chronic gastroesophageal reflux disease, hiatal hernia, advanced age, male sex, white race, cigarette smoking, and obesity. The annual risk of esophageal cancer is approximately 0.25% for patients without dysplasia and 6% for patients with high-grade dysplasia. Twenty percent of all esophageal adenocarcinoma in the United States is early stage with disease confined to the mucosa or submucosa. The significant morbidity and mortality of esophagectomy make endoscopic treatment an attractive option. The American Gastroenterological Association recommends endoscopic eradication therapy for patients with high-grade dysplasia. Endoscopic modalities for treatment of early esophageal adenocarcinoma include endoscopic resection techniques and endoscopic ablative techniques such as radiofrequency ablation, photodynamic therapy and cryoablation. Endoscopic therapy should be precluded to patients with no evidence of lymphovascular invasion. Local tumor recurrence is low after endoscopic therapy and is predicted by poor differentiation of tumor, positive lymph node and submucosal invasion. Surgical resection should be offered to patients with deep submucosal invasion.

Long-term follow up of endoscopic resection for type 3 gastric NET

To clarify the short and long-term results and to prove the usefulness of endoscopic resection in type 3 gastric neuroendocrine tumors (NETs). Of the 119 type 3 gastric NETs diagnosed from January 1996 to September 2011, 50 patients treated with endoscopic resection were enrolled in this study. For endoscopic resection, endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) was used. Therapeutic efficacy, complications, and follow-up results were evaluated retrospectively. EMR was performed in 41 cases and ESD in 9 cases. Pathologically complete resection was performed in 40 cases (80.0%) and incomplete resection specimens were observed in 10 cases (7 vs 3 patients in the EMR vs ESD group, P = 0.249). Upon analysis of the incomplete resection group, lateral or vertical margin invasion was found in six cases (14.6%) in the EMR group and in one case in the ESD group (11.1%). Lymphovascular invasions were observed in two cases (22.2%) in the ESD group and in one case (2.4%) in the EMR group (P = 0.080). During the follow-up period (43.73; 13-60 mo), there was no evidence of tumor recurrence in either the pathologically complete resection group or the incomplete resection group. No recurrence was reported during follow-up. In addition, no mortality was reported in either the complete resection group or the incomplete resection group for the duration of the follow-up period. Less than 2 cm sized confined submucosal layer type 3 gastric NET with no evidence of lymphovascular invasion, endoscopic treatment could be considered at initial treatment.