Ampullary Adenocarcinoma Research Articles

A population-based study on incidence, treatment, and survival in ampullary cancer in the Netherlands

IntroductionAmpullary cancer is rare and as a result epidemiological data are scarce. The aim of this population-based study was to determine the trends in incidence, treatment and overall survival (OS) in patients with ampullary adenocarcinoma in the Netherlands between 1989 and 2016. MethodsPatients diagnosed with ampullary adenocarcinoma were identified from the Netherlands Cancer Registry. Incidence rates were age-adjusted to the European standard population. Trends in treatment and OS were studied over (7 years) period of diagnosis, using Kaplan-Meier and Cox regression analyses for OS and stratified by the presence of metastatic disease. ResultsIn total, 3840 patients with ampullary adenocarcinoma were diagnosed of whom, 55.0% were male and 87.1% had non-metastatic disease. The incidence increased from 0.59 per 100,000 in 1989–1995 to 0.68 per 100,000in 2010–2016. In non-metastatic disease, the resection rate increased from 49.5% in 1989–1995 to 63.9% in 2010–2016 (p < 0.001). The rate of adjuvant therapy increased from 3.1% to 7.9%. In non-metastatic disease, five-year OS (95% CI) increased from 19.8% (16.9–22.8) in 1989–1995 to 29.1% (26.0–31.2) in 2010–2016 (logrank p < 0.001). In patients with metastatic disease, median OS did not significantly improve (from 4.4 months (3.6–5.0) to 5.9 months (4.7–7.1); logrank p = 0.06). Cancer treatment was an independent prognostic factor for OS among all patients. ConclusionBoth incidence and OS of ampullary cancer increased from 1989 to 2016 which is most likely related to the observed increased resection rates and use of adjuvant therapy.

Preoperative Predictors for 90-Day Mortality after Pancreaticoduodenectomy in Patients with Adenocarcinoma of the Ampulla of Vater: A Single-Centre Retrospective Cohort Study.

Background The standard treatment for ampullary adenocarcinoma is pancreaticoduodenectomy. Identification of preoperative risk factors might help the clinician to select patients fit for resection and potentially decrease morbidity and mortality after PD. We conducted a cohort study to determine the preoperative factors related to 90-day severe morbidity and mortality after PD. Methods We conducted a retrospective cohort study in patients with a diagnosis of ampullary adenocarcinoma who underwent an open PD between January 2010 and December 2019 at our tertiary centre. Results Independent preoperative predictors of mortality were the albumin-bilirubin (ALBI) grade 3 (OR: 21.7; CI 95: 2.1–226.9; p=0.01) and the estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 (OR: 17.7; CI 95: 1.8–172.6; p=0.013). The eGFR <90 mL/min/1.73 m2 (OR = 6.6; CI 95: 1.9–23.4; p=0.003) and prothrombin time (OR = 1.5; CI 95; 1.1–2.1; p=0.005) were independent predictors for severe morbidity. Conclusion These findings suggest that baseline renal function measured by the eGFR and liver function categorized with the ALBI grading are predictors of severe morbidity and mortality. Thus, they should be considered when selecting patients for PD or the use of neoadjuvant treatments. Further research is warranted.

Giant solitary liver metastasis from ampullary adenocarcinoma

Background: The liver is one of the most frequent place of recurrence for the ampulla of Vater adenocarcinoma. Lesions are usually solitaries but smalls. We present the case of a patient with ampullary adenocarcinoma developing a giant solitary liver metastasis.

Axial slicing versus bivalving in the pathological examination of pancreatoduodenectomy specimens (APOLLO): a multicentre randomized controlled trial

BackgroundIn pancreatoduodenectomy specimens, dissection method may affect the assessment of primary tumour origin (i.e. pancreatic, distal bile duct or ampullary adenocarcinoma), which is primarily determined macroscopically. This is the first study to prospectively compare the two commonly used techniques, i.e. axial slicing and bivalving. MethodsIn four centres, a randomized controlled trial was performed in specimens of patients with a suspected (pre)malignant tumour in the pancreatic head. Primary outcome measure was the level of certainty (scale 0–100) regarding tumour origin by four independent gastrointestinal pathologists based on macroscopic assessment. Secondary outcomes were inter-observer agreement and R1 rate. ResultsIn total, 128 pancreatoduodenectomy specimens were randomized. The level of certainty in determining the primary tumour origin did not differ between axial slicing and bivalving (mean score 72 [sd 13] vs. 68 [sd 16], p = 0.21), nor did inter-observer agreement, both being moderate (kappa 0.45 vs. 0.47). In pancreatic cancer specimens, R1 rate (60% vs. 55%, p = 0.71) and the number of harvested lymph nodes (median 16 vs. 17, p = 0.58) were similar. ConclusionThis study demonstrated no differences in determining the tumour origin between axial slicing and bivalving. Both techniques performed similarly regarding inter-observer agreement, R1 rate, and lymph node harvest.

Absence of the celiac trunk and anomalous very low origin of the common hepatic artery arising independently from the abdominal aorta just above aortic bifurcation in patient undergoing radical pancreaticoduodenectomy

PurposeKnowledge of anomalies of the celiac trunk is very important during various surgical procedures (such as pancreatic and gastric resections including Appleby operation, liver resections and liver transplantations) and as well as radiologic procedures (such as chemoembolization of pancreatic and hepatic tumors).MethodsA 77-years-old woman was admitted to our department for surgical treatment of ampullary adenocarcinoma G2 confirmed in endoscopic retrograde cholangiopancreatography (ERCP) with papillotomy and ampullary biopsy. In the contrast-enhanced computed tomography, the ampullary tumor was not visible, but the main pancreatic duct within pancreatic head and isthmus was dilated (indirect radiological tumor signs). An absence of the celiac trunk (CT) was established via computed tomography. Therefore, computed tomography-based angiography (angio-CT) of the abdominal aorta (AA) was performed before operation.ResultsAngio-CT confirmed an extremely rare vascular anomaly: an absence of CT. The left gastric (LGA), splenic (SA), and common hepatic (CHA) arteries connected above origin of the superior mesenteric artery (SMA) from the AA. Pylorus-preserving pancreaticoduodenectomy (PD) was performed. This anomaly was also confirmed intraoperatively. The postoperative course was uneventful and the patient was discharged on postoperative day 10. There were no signs of recurrence of the tumor during the 6 months follow-up.ConclusionThe proper preoperative identification of anomalies within major abdominal vessels and its relationship to the tumor is very important to avoid intraoperative vascular injury and major postoperative complications.

Novel method for evaluating the indication for endoscopic papillectomy in patients with ampullary adenocarcinoma

This study aimed to determine the clinicopathological features of the subtypes of ampullary carcinoma (AC) to explore the indications for endoscopic papillectomy (EP) in early AC. Fifty-seven patients with AC who underwent curative resection were retrospectively reviewed. The 0/IA stages were significantly more common in the intestinal type (I-type) than in the mixed and pancreatobiliary type (M&PB-type) (90.7% vs 35.7%, P < 0.001). Tis/T1a tumors limited to the ampulla [Tis/T1a(ampulla)] were significantly more likely to be I-type than M&PB-type (74.4% vs 14.3%, P = 0.002). The tub1 rate was significantly higher in the I-type than in the M&PB-type (81.4% vs 35.7%, P = 0.001). In the I-type, the tub1 rate was significantly higher for Tis/T1a(ampulla) than for T1a tumors limited to the sphincter of Oddi (100% vs 42.9%, P = 0.004). These observations suggest that I-type AC with tub1 is an indication for EP. The concordance rate of pathological subtypes between endoscopic biopsy and resected specimens was high (κ = 0.8053, P < 0.001). Tis/T1a(ampulla) showed no lymphovascular or perineural invasion. An endoscopic imaging finding of early AC with I-type and tub1 on biopsy could be an indication for EP. Identifying the pathological subtype of AC by endoscopic biopsy could be a novel preoperative approach for evaluating the indications for EP.

A Population-based Study on Incidence, Treatment and Survival in Ampullary Cancer in the Netherlands

Purpose: Ampullary cancer is rare and as result the epidemiological data are scarce. The aim of this population-based study was to determine the trends in incidence, treatment and overall survival (OS) in patients with ampullary adenocarcinoma in the Netherlands between 1989 and 2016. Methods: Patients diagnosed with ampullary adenocarcinoma were identified from the Netherlands Cancer Registry. Incidence rates were age-adjusted to the European standard population. Trends in treatment and OS were studied over 7 years period of diagnosis, using Kaplan-Meier and Cox regression analyses for OS and stratified by the presence of metastatic disease. Results: In total, 3840 patients with ampullary adenocarcinoma were diagnosed of whom, 55.0% were male and 87.1% had non-metastatic disease. The incidence increased from 0.59 per 100,000 in 1989-1995 to 0.68 per 100,000in 2010-2016. In non-metastatic disease, the resection rate increased from 49.5% in 1989-1995 to 63.9% in 2010-2016 (p<0.001). The rate of adjuvant therapy increased from 3.1% to 7.9%. In non-metastatic disease, five-year OS (95% CI) increased from 19.8% (16.9-22.8) in 1989-1995 to 29.1% (26.0-31.2) in 2010-2016 (logrank p<0.001). In patients with metastatic disease, median OS did improve, but not significantly (from 4.4 months (3.6-5.0) to 5.9 months (4.7-7.1); logrank p=0.06). Cancer treatment was an independent prognostic factor for OS among all patients. Conclusion: Both incidence and OS of ampullary cancer increased from 1989 to 2016, which is likely related to the observed increased resection rates and use of adjuvant therapy as well as better diagnostics and centralization of pancreatic surgeries.

The Current Management of Ampullary Cancer: A Survey among Healthcare Workers Worldwide

Purpose: Ampullary adenocarcinoma (AAC) is rare. Therefore, guidelines for the management of patients diagnosed with AAC are not available. To gain insight in the current daily practice of AAC worldwide, this international survey study was performed. Methods: Surgeons and medical oncologists (in training), whom were members of the Dutch Pancreatic Cancer Group (DPCG) or the International Study Group on Ampullary Cancer (ISGACA), or contributed to (peri)ampullary cancer research, were invited through email (January till March 2021). Participants were also approached trough their colleagues and online media platforms. Results: Overall, 57 (72%) surgeons and 22 (28%) oncologists completed the survey. Most respondents work in Europe (81%), and 90% work in a pancreas expertise cancer. When choosing treatment, 94% of the respondents take patients performance status and the presence of metastatic disease into consideration. Neoadjuvant treatment is considered by 20% and adjuvant therapy by 75% of the respondents, with 71% choosing for adjuvant chemotherapeutic treatment alone and 4% choosing for combined adjuvant chemoradiation therapy. The formation of multidisciplinary teams, improvement in surgical and local procedures, increased availability of chemotherapy, and knowledge on tumor biology were interpreted as improvements in the last five years. The necessity for international registries and randomized controlled trials on neoadjuvant and adjuvant chemo(radio)therapy were mentioned frequently. Conclusion: This study highlights the worldwide variation in the management of patients diagnosed with AAC, especially regarding neoadjuvant and/or adjuvant therapy. More data, including randomized controlled trials and international registries are needed to develop evidence-based guidelines for a more standardized surgical, and oncological management.

Journey of a tertiary care hospital at Puducherry, India, into becoming a high-volume centre for pancreaticoduodenectomy - a decade of experience

Background: This study aims to study the outcomes of the Pancreaticoduodenectomy (PD) procedure- at the department of Surgery, JIPMER, Puducherry, which was in the early process of evolving into a high-volume centre for PDs in the last decade. Methods: Details of 147 patients who underwent PDs from 2010-2019, were collected retrospectively from the Medical Records Department from 2010-2017, and prospectively in the last 2 years. Independent perioperative variables were compared to outcome variables - morbidity and mortality rates, and analysed. Results: 29 patients underwent PDs in the first 5-year period, and 118 in the second, with mortality rates decreasing from 27.6% to 10.2% (P-0.029), and to 5.8% in the last year. Overall morbidities remained significantly high, with clinically relevant POPF, DGE and PPH to be 28.2%, 30.1% and 22.6% respectively. Ampullary adenocarcinoma was the commonest malignant tumour (63.3%). Factor significantly associated with perioperative mortality were - the period of surgery (1st vs 2nd 5 year period), ASA scores, Bilirubin levels, Intraop blood loss, CR-POPF, PPH, pneumonia and Sepsis. But variables which significantly increased the risk of mortality by Multivariate Logistic regression were Sepsis (OR - 108.4, p-0.011), and post operative pulmonary complications. Median overall survival was 36 months (19 - 53) months. Conclusion: As we look back in the last decade, there have been significant improvement in the mortality rates of PD, but morbidity still remains high and has to be looked into as the department goes into a new decade as a young high volume centre.

Clinical, operative, and pathologic outcomes following neoadjuvant therapy versus upfront surgery for ampullary, duodenal and distal bile duct adenocarcinoma

Clinical, operative, and pathologic outcomes following neoadjuvant therapy versus upfront surgery for ampullary, duodenal and distal bile duct adenocarcinoma

Comparison of observed vs predicted outcomes from NSQIP for pancreaticoduodenectomy at a pancreatic surgery unit

Introduction: Although the mortality of pancreaticoduodenectomy has decreased significantly over the last few years, with a current 30 day mortality of 1% in NSW hospitals, the morbidity, length of stay and readmission rates remain high when compared to other complex surgical procedures. Our aim was to ascertain accuracy of the ACS NSQIP risk calculator for pancreaticoduodenectomy. Estimating Perioperative risk accurately can allow future patients to make an informed decision about undergoing Pancreaticoduodenectomy; provide a benchmark for safe, high-quality Pancreatic surgery and help target complication-reduction measures for hospital staff. Methods: A retrospective analysis of patients undergoing PancreaticoDuodenectomy at our hospital from July 2015 to July 2017 was performed. Patients found to be inoperable during the procedure or who had subtotal or distal pancreatectomy were excluded. For 5 main parameters, observed outcomes were measured against predicted outcomes using ACS-NSQIP Surgical Risk Calculator for Pancreaticoduodenectomy. Results: During the 24-month period, 45 patients underwent Pancreticodudenectomy for various pathologies, including 16 for pancreatic Adenocarcinoma, 6 for Cholangiocarcinoma, 5 for ampullary adenocarcinoma, 5 NETs, 5 IPMN and 5 others. 30-day mortality was slightly higher than the NSQIP prediction (2 deaths -4.4% vs predicted 1.2% mortality). Return to theatre rate was higher than predicted (8 cases- 17.7% vs 4.3% predicted). There were fewer actual Readmission rates (4.4% vs 11.8% predicted), observed Serious complications (17.7% vs 20.7% predicted) and observed Surgical Site infections (11.1% vs 15.6% predicted). Conclusions: NSQIP Calculator does not accurately predict Observed outcomes for pancreaticoduodenectomy.

The Use of Inflammatory Biomarkers in the Early Identification of Post-operative Pancreatic Fistulae Following Pancreaticoduodenectomy

Purpose: Pancreaticoduodenectomy(PD) is associated with a significant risk of post-operative complications, including pancreatic fistulae(POPF). The utility and interpretation of peri-operative inflammatory biomarkers in predicting such complications remains unclear. This study aimed to evaluate the role of pre-operative neutrophil-lymphocyte ratio(NLR) and post-operative c-reactive protein(CRP) in the early identification of POPF following PD. Method: An analysis of consecutive patients undergoing PD between 2012 and 2020 at a single tertiary centre was performed. Data were derived from a combination of prospective electronic databases, retrospective case-notes and computer records. Patients were excluded if data were incomplete. Results: 96 male and 80 female patients(median age 68 years) underwent PD; 67(38.1%%) for pancreatic adenocarcinoma, 45(25.6%%) for ampullary adenocarcinoma, 26(14.8%) for biliary/duodenal adenocarcinoma and 38(21.6%) for a combination of other benign/malignant indications. 63(35.8%) patients were diagnosed with POPF and 42(23.8%) with clinically-relevant POPF(CR-POPF; ISGPS Grade B/C). Median pre-operative NLR was 2.73 in POPF patients, 2.74 in CR-POPF patients and 2.66 in non-POPF patients(t-test; p>0.05). Median post-operative peak CRP was 305mg/L in POPF patients, 330mg/L in CR-POPF patients and 182mg/L in non-POPF patients(t-test; p = 0.0001). Median and mode post-operative peak CRP occurred on day 3 in POPF and CR-POPF patients, and on day 2 in non-POPF patients. Conclusion: There was a non-significant trend towards higher pre-operative NLR in patients with POPF. Patients with serum CRP that continues to rise on post-operative day 3 above approximately 300mg/L are at risk of CR-POPF. Such data may help to guide early administration of antibiotics or targeted use of cross-sectional imaging.

MUC5AC Expression in Various Tumor Types and Nonneoplastic Tissue: A Tissue Microarray Study on 10 399 Tissue Samples

Background: Mucin 5AC (MUC5AC) belongs to the glycoprotein family of secreted gel-forming mucins and is physiologically expressed in some epithelial cells. Studies have shown that MUC5AC is also expressed in several cancer types suggesting a potential utility for the distinction of tumor types and subtypes. Methods: To systematically determine MUC5AC expression in normal and cancerous tissues, a tissue microarray containing 10 399 samples from 111 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Results: MUC5AC was expressed in normal mucus-producing cells of various organs. At least weak MUC5AC positivity was seen in 44 of 111 (40%) tumor entities. Of these 44 tumor entities, 28 included also tumors with strong positivity. MUC5AC immunostaining was most commonly seen in esophageal adenocarcinoma (72%), colon adenoma (62%), ductal adenocarcinoma of the pancreas (64%), mucinous carcinoma of the ovary (46%), diffuse gastric adenocarcinoma (44%), pancreatic ampullary adenocarcinoma (41%), intestinal gastric adenocarcinoma (39%), and bronchioloalveolar carcinoma (33%). Clinically relevant tumors with complete or almost complete absence of MUC5AC staining included small cell carcinoma of the lung (0% of 17), clear cell renal cell carcinoma (0% of 507), papillary thyroid carcinoma (0% of 359), breast cancer (2% of 1097), prostate cancer (2% of 228), soft tissue tumors (0.1% of 968), and hematological neoplasias (0% of 111). Conclusion: The highly standardized analysis of a broad range of cancers identified a ranking order of tumors according to their relative prevalence of MUC5AC expression.

Pancreatoduodenectomy for Ampullary Cancer after Roux-en-Y Gastric Bypass – An Extremely Rare Case Report

Introduction: Obesity is a known risk factor for periampullary carcinoma. However we have identified in the international literature only 1 case of a patient with ampullary carcinoma and history of gastric bypass submitted to curative surgery. And it is considered a surgery challenge. We present here the second case. Methods: This clinical case describes a female patient, 70 years old, clinically classified as a periampullary neoplasia with resectability criteria and without metastization evidence (cT2N0M0). This patient has a surgical history of a laparoscopic Roux-en-Y gastric bypass in 2017. This clinical case was discussed in the multidisciplinary hepatobilopancreatic meeting, resulting in a curative surgery as proposal. Results: The patient was subjected to a pancreatoduodenectomy (with a terminolateral pancreatojejunal anastomosis and a terminolateral hepaticojejunal anastomosis) with remnant gastrectomy in December of 2020. Postoperative care had no complications, resulting in a clinical discharge thirteen days later. The histological result of the surgical piece showed an ampullary adenocarcinoma moderately differentiated with invasion of peripancreatic adipose tissue, with surgical margins free of neoplasia and 29 nodes were removed (6 with metastasis) (pT4, pN1). Conclusion: There are multiple types of possible reconstruction for patients after a Roux-en-Y gastric bypass. The rarity of clinical cases is the main factor for the poor evidence to the best clinical practice and for the big surgical challenge that it presents.

Can we improve the classification of ampullary adenocarcinoma? the value of histomolecular classification and clinicopatothological features on prognosis

Can we improve the classification of ampullary adenocarcinoma? the value of histomolecular classification and clinicopatothological features on prognosis

Validation of the Eighth Edition of the American Joint Committee on Cancer (AJCC) TNM Staging System in Patients with Resected Ampullary Adenocarcinoma

Validation of the Eighth Edition of the American Joint Committee on Cancer (AJCC) TNM Staging System in Patients with Resected Ampullary Adenocarcinoma

Survival Benefit of Adjuvant Chemotherapy After Pancreatoduodenectomy for Ampullary Adenocarcinoma: a Propensity-Matched National Cancer Database (NCDB) Analysis

BackgroundThe benefit of adjuvant chemotherapy (AC) after pancreatoduodenectomy (PD) for ampullary adenocarcinoma is uncertain. We aimed to evaluate the association of AC with survival in patients with resected ampullary adenocarcinoma. MethodsUsing the National Cancer Database (NCDB) data from 2004 to 2016, patients with non-metastatic ampullary adenocarcinoma who underwent PD were identified. Patients with neoadjuvant radiotherapy and chemotherapy and survival < 6 months were excluded. Propensity score matching was used to account for treatment selection bias. A multivariable Cox proportional hazards model was then used to analyze the association of AC with survival. ResultsOf 3186 (43%) AC and 4172 (57%) no AC (noAC) patients, 1720 AC and 1720 noAC patients remained in the cohort after matching. Clinicopathologic variables were well balanced after matching. After matching, AC was associated with improved survival (median 47.5 vs 39.6 months, p = 0.003), which remained after multivariable adjustment (HR: 0.83, CI95%: 0.76–0.91, p < 0.001). Multivariable interaction analyses showed that this benefit was seen irrespective of nodal status: N0 (HR: 0.81, CI95%: 0.68–0.97, p < 0.001), N1 (HR: 0.65, CI95%: 0.61–0.70, p < 0.001), N2 (HR: 0.73, CI95%: 0.59–0.90, p = 0.003), N3 (HR: 0.59, CI95%: 0.44–0.78, p < 0.001); and margin status: R0 (HR: 0.85, CI95%: 0.77–0.94, p < 0.001), R1 (HR: 0.69, CI95%: 0.48–1.00, p < 0.001). Stratified analyses by nodal and margin status demonstrated consistent results. ConclusionIn this large retrospective cohort study, AC after resected ampullary adenocarcinoma was associated with a survival benefit in patients, including patients with node-negative and margin-negative disease.

Tissue microarray-chip featuring computerized immunophenotypical characterization more accurately subtypes ampullary adenocarcinoma than routine histology.

BACKGROUNDAmpullary adenocarcinomas (AACs) are heterogeneous tumors currently classified into three important sub-classes (SC): Intestinal (INT), Pancreato-Biliary (PB) and Mixed-Type (MT). The different subgroups have similar clinical presentation and are treated by pancreatoduodenectomy with curative intent. However, they respond differently to chemotherapy and have different prognostic outcomes. The SC are often difficult to identify with conventional histology alone. The clinical outcome of all three remains unclear, particularly for MT.AIMTo identify two main subtypes of AACs, using an immunohistochemical (IHC) score based on CDX2, CK7 and CK20.METHODSTissue samples from 21 patients who had undergone resection of AAC were classified by HE histology and IHC expression of CDX2, CK7 and CK 20. An IHC score was obtained for each marker by counting the number of positive cells (0 = no stained cells; 1 < 25%; 2 < 50% and 3 > 50%) and their intensity (1 = weak; 2 = moderate and 3 = strong). A global score (GS) was then obtained by summation of the IHC scores of each marker. The MT tumors were grouped either with the INT or PB group based on the predominant immuno-molecular phenotype, obtaining only two AACs subtypes. The overall survival in INT and PB patients was obtained by Kaplan-Meier methods.RESULTSHistological parameters defined the AACs subtypes as follows: 15% INT, 45% PB and 40% MT. Using IHC expression and the GS, 75% and 25% of MT samples were assigned to either the INT or the PB group. The mean value of the GS was 9.5 (range 4-16). All INT samples had a GS above the average, distinct from the PB samples which had a GS score significantly below the average (P = 0.0011). The INT samples were identified by high expression of CDX2 and CK20, whereas PB samples exhibited high expression of CK7 and no expression of CK20 (P = 0.0008). The INT group had a statistically significant higher overall survival than in the PB group (85.7 mo vs 20.3 mo, HR: 8.39; 95%CI: 1.38 to 18.90; P = 0.0152).CONCLUSIONThe combination of histopathological and molecular criteria enables the classification of AACs into two clinically relevant histo-molecular phenotypes, which appear to represent distinct disorders with potentially significant changes to the current therapeutic strategies.

Abstract PO-102: A novel disseminated tumor cell identified in myriad cancer harbors tumor initiating properties

Abstract The identification of a disseminated tumor cell generated by heterotypic cell fusion, a circulating hybrid cell (CHCs) is a biologically relevant analyte of disease across myriad of cancers. Detected at elevated levels in peripheral blood, this novel population can be leveraged to understand mechanisms driving metastatic progression and predict metastatic spread. Our long term goal is to leverage evolving knowledge of mechanisms of metastatic progression to identify biologically relevant tumor markers for clinical disease assessment strategies. We therefore detected and delineated the role of CHCs as a measure of disease across a multitude of solid tumors. Human blood specimens were collected and analyzed with IRB approved protocols. Peripheral blood was obtained from patients with cancer in 14 different organ sites: ampullary adenocarcinoma, breast adenocarcinoma, cholangiocarcinoma, colon adenocarcinoma, esophageal cancer, high grade glioma (pediatric &amp; adult), head and neck squamous cell carcinoma, pancreatic ductal adenocarcinoma, pancreatic neuroendocrine tumor, prostate adenocarcinoma, rectal adenocarcinoma and uveal melanoma and healthy subjects. Peripheral blood mononuclear cells were isolated and prepared for flow cytometry or immunofluorescence microscopy analyses with antibodies to CD45 and panCytokeratin, EpCAM, NKI Beteb, chromogranin A (CHGA)/synaptophysin (SYP) or glial fibrillary acid protein (GFAP). Discrete cellular populations including CHCs and circulating tumor cells (CTCs) were identified by protein expression. Cyclic immunofluorescence (cycIF) techniques were performed on a subset of specimens, for indepth interrogation of phenotypic heterogeneity in both the tumor and among CHCs. CHCs, defined by co-expression of CD45+ and a tumor associated protein were detected in all subjects across all disease sites at statistically significantly higher numbers than in controls samples using both detection paradigms. Furthermore, higher levels of CHCs compared with CTCs (that were CD45-) across disease sites. CycIF analysis of tumor tissue and dissemnated tumor cells from a triple negative breast cancer subject revealed a heterogeneous population of CHCs as well as complex tumor ecosystem. The phenotypic diversity of CHCs included CD44 and androgen receptor (AR) expression, which aligned with those detected in the proliferative tumor compartment. AR expression in triple negative breast cancer is known to correlate with treatment resistance and indeed, our subject rapidly succumb to disease. Taken together, these data suggest that tumors disseminate a heterogeneous population of CHCs that reflect the overall phenotype of viable tumor, supporting the value of phenotypically profiling CHCs for liquid biopsy to anticipate disease evolution and treatment resistance. This study established an isolation and detection platform for measuring CHCs in myriad of cancers and methods of phenotypic profiling CHC heterogeneity to identify discrete subpopulations. Citation Format: Matthew S. Dietz, Thomas Sutton, Brett Walker, Young Hwan Chang, Koei Chin, Melissa H. Wong. A novel disseminated tumor cell identified in myriad cancer harbors tumor initiating properties [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-102.

Characteristics of benign and malignant lesions of ampullary polyps and the accuracy of forceps biopsy

OBJECTIVE To distinguish the endoscopic and clinical features of ampullary polyps, to investigate the endoscopic cancer risk factors of ampullary polyps based on the compared differences of benign lesions and adenocarcinoma, and to assess the accuracy of forceps biopsy. METHODS Authors retrospectively analyzed the data extracted from patients treated with endoscopic papillectomy (EP) from January 2009 to May 2019 in the Department of Gastroenterology, Peking University Third Hospital. Endoscopic pictures and pathology reports were reevaluated and analyzed. Differences between benign and cancer groups were conducted. RESULTS In the study, 42 cases were involved, 35 to 83 years old, containing 83.3% older than 50 years old patients. The histological types were as follows, 2 for inflammatory polyps (4.8%), 1 for neuroendocrine tumor (2.4%), 1 for hyperplastic polyp (2.4%), 5 for grade Ⅰ adenoma (11.9%), 10 for grade Ⅱ adenoma (23.8%), 4 for grade Ⅲ adenoma (9.5%) and 19 for adenocarcinoma (45.2%), and 90.5% were adenoma or adenocarcinoma. The average age of benign group (inflammatory polyps and adenomas) was (56.7±9.2), which was significantly younger than that of adenocarcinoma group [(66.0±9.8), P=0.004]. Tumor diameter in adenocarcinoma group[(2.3±0.8) cm] was significantly larger than that in benign group[(1.6±0.6) cm, P=0.002]. Benign lesions only showed Yamada type Ⅰ(57.1%)and type Ⅱ(42.9%). The percentage of Yamada type Ⅰ (36.8%)and type Ⅱ(31.6%) in adenocarcinoma group was lower than that in benign group. Moreover, Yamada type Ⅲ (31.5%) was only found in the adenocarcinoma group. Significant differences were observed between the two groups in Yamada types (P=0.046). Most of the benign lesions had clear boundary(18/21, 85.7%). The percentage of clear boundary in adenocarcinoma group (2/19, 10.5%) was significantly lower than that in the benign group (P < 0.001). No significant differences were investigated in color (P=0.353) and surface (P=0.324) between benign and adenocarcinoma lesions. Pooling age, lesion diameter, Yamada type and clear boundary into Logistic regression analysis, only age (OR=1.186, 95%CI 1.025-1.373, P=0.022) and clear boundary (OR=66.218, 95%CI 3.421-1 281.840, P=0.006) were the independent cancer risk factors. Only 2 (10.5%) in the 19 cancer patients had positive biopsy results before EP. As compared with post-EP, 55.3% (21/38) biopsies were under-estimated, including 17 (17/19, 89.5%) adenocarcinomas and 4 (4/10, 40%) grade Ⅱ adenomas. CONCLUSION adenoma and adenocarcinoma were the major histological type of ampullary po-lyps. Age and unclear boundary were the independent risk factors of ampullary adenocarcinoma. Forceps biopsy was not enough for ampullary polyp differentiation.