Presence Of Invasive Carcinoma Research Articles

Incidental finding of invasive lobular carcinoma within a borderline phyllodes tumour of the breast: a case report

Background: Phyllodes tumours (PTs) are rare neoplasms of the breast with similar clinical and radiological features to fibroadenomas. The presence of invasive carcinoma within a PT occurs in less than 1% of cases. Furthermore, the presence of invasive lobular carcinoma (ILC) within a borderline PT has only been reported once before in a female under the peak incidence age of 45 years, making the case presented here exceedingly rare. The incidental finding of ILC highlights the importance of the multidisciplinary team’s (MDT) collaborative expertise and rigorous investigative work-up where inconsistencies in the breast triple assessment are identified.

The effects of clinicopathological and imaging findings on recurrence and survival in mammary Paget's disease.

Mammary Paget's disease (MPD) is a rare presentation type of breast cancer. The aim of this study was to evaluate the clinicopathological and imaging features affecting the invasive component, loco-regional recurrence, prognosis, and survival of MPD. Patients who had undergone surgery due to MPD in a 10-year period were included. Parameters including mammography and magnetic resonance imaging (MRI) findings, tumor stage, molecular subtype, axillary involvement, presence of invasive carcinoma, loco-regional recurrence, overall survival (OS), and disease-free survival (DFS) were recorded and statistically analyzed. P<0.05 was determined as statistically significant. The study group consisted of 49 women with a mean age of 67.05±14.43 (range: 23-90) years. There was a significant association between the presence of invasive carcinoma and a mass lesion in the MRI (p=0.002). The frequency of sentinel lymph node (SLN) metastasis was significantly higher in patients with multicentric tumors (p=0.029; p<0.05). Locoregional recurrence and distant metastasis were significantly more frequent in patients with axillary involvement (p=0.0336; p<0.05). The mean DFS was 115.02±7.28 months, while the mean OS was 119.29±6.57 months. The presence of a mass lesion on MRI was determined to be significant in recognizing invasive carcinoma in MPD. The rate of SLN metastasis was higher in patients with multicentric tumors than in patients with unifocal tumors. Axillary involvement was associated with impaired DFS.

Automated medical chart review for breast cancer outcomes research: a novel natural language processing extraction system

BackgroundManually extracted data points from health records are collated on an institutional, provincial, and national level to facilitate clinical research. However, the labour-intensive clinical chart review process puts an increasing burden on healthcare system budgets. Therefore, an automated information extraction system is needed to ensure the timeliness and scalability of research data.MethodsWe used a dataset of 100 synoptic operative and 100 pathology reports, evenly split into 50 reports in training and test sets for each report type. The training set guided our development of a Natural Language Processing (NLP) extraction pipeline system, which accepts scanned images of operative and pathology reports. The system uses a combination of rule-based and transfer learning methods to extract numeric encodings from text. We also developed visualization tools to compare the manual and automated extractions. The code for this paper was made available on GitHub.ResultsA test set of 50 operative and 50 pathology reports were used to evaluate the extraction accuracies of the NLP pipeline. Gold standard, defined as manual extraction by expert reviewers, yielded accuracies of 90.5% for operative reports and 96.0% for pathology reports, while the NLP system achieved overall 91.9% (operative) and 95.4% (pathology) accuracy. The pipeline successfully extracted outcomes data pertinent to breast cancer tumor characteristics (e.g. presence of invasive carcinoma, size, histologic type), prognostic factors (e.g. number of lymph nodes with micro-metastases and macro-metastases, pathologic stage), and treatment-related variables (e.g. margins, neo-adjuvant treatment, surgical indication) with high accuracy. Out of the 48 variables across operative and pathology codebooks, NLP yielded 43 variables with F-scores of at least 0.90; in comparison, a trained human annotator yielded 44 variables with F-scores of at least 0.90.ConclusionsThe NLP system achieves near-human-level accuracy in both operative and pathology reports using a minimal curated dataset. This system uniquely provides a robust solution for transparent, adaptable, and scalable automation of data extraction from patient health records. It may serve to advance breast cancer clinical research by facilitating collection of vast amounts of valuable health data at a population level.

ABO blood group distribution and risk of malignancy in patients undergoing resection for intraductal papillary mucinous neoplasm (IPMN)

BackgroundThe ABO blood type has been associated with risk of development of several malignancies, including pancreatic cancer. Data regarding IPMN is equivocal. To investigate this further, we analyzed the association between the ABO blood group and the presence of malignancy in a large cohort of resected IPMN and its influence in survival. Methods819 patients who underwent pancreatic resection for IPMN in the Massachusetts General Hospital (MGH) and Cambridge University Hospitals NHS Foundation Trust (CUH) from January 1993 to December 2020 were identified from prospective institutional databases. Pathological characteristics and blood type were correlated. ResultsThe distribution of blood types A, B, AB and O was 384 (47%), 92 (11%), 44 (5%) and 299 (37%), respectively. This blood type distribution was different than the reference population of the MGH and the CUH, which is 55% non-O blood group, and 45% type O. There was a significant predominance of non-O blood types when compared with O-blood type in patients with malignant IPMN (i.e. patients with high-grade dysplasia and invasive cancer) (67% vs 33%, OR 1.31 95%CI: 0.98–1.75, p = 0.069). The association was stronger for IPMN with invasive cancer (OR 1.43 95%CI: 1.01–2.02, p = 0.039). Blood group did not influence survival. ConclusionNon-O blood type is associated with need for resection in IPMN and with presence of invasive carcinoma.

147 Association of Estrogen Receptor and Porgesteron Receptor Positivity with Nodal Involvement, Menopause Status and Stage of Primary Invasive Carcinoma of Breast Among Patients Presenting to Fauji Foundation Hospital, Islamabad

Abstract Aim To determine the percentage of estrogen and progesterone receptor positivity along with histological variants, stage, and menopausal status among carcinoma breast patients in our setup. Method This was a retrospective observational study. Data from records of patients with breast carcinoma presenting at Oncology Department Fauji Foundation Hospital, Islamabad was evaluated. H+E stained slides from 431 cases with carcinoma breast, patients over the age of 18 years, were reviewed and the presence of invasive carcinoma was confirmed in all cases. Patients with metastases were excluded. Paraffin blocks were assessed immunohistochemically for estrogen and progesterone receptor expression. Histological subtypes, stages of tumors, and nodal involvement were also noted. Data were analyzed using SPSS. Results Records of 431 patients were evaluated. The median age was 53 years. The most common histological variant was invasive ductal carcinoma. 4.6% of patients had stage I, 33.4% had stage II, 40% had Stage III and 22% had Stage IV disease. Overall, 62% had node-positive disease. Overall ER+, PR+, ER+/PR+, ER+/PR-, ER-/PR+ and ER-/PR- percentages were 52%, 54%, 42%, 11%, 12% and 35% respectively. 38% of patients were premenopausal, 59% were postmenopausal and 3% were perimenopausal. Patients with node positive diseases were 51% ER+,55% PR+, 43% ER+/PR+, 8% ER+/PR-, 12% ER-/PR+ and 37% ER-/PR-. Conclusions The percentage of ER/PR+ is the highest in our study. Pre-menopausal patients showed approximately equal positivity to post-menopausal patients. Node positive enrolments had increased positivity of ER/PR receptor.

Does every woman require a post-lumpectomy mammogram and ultrasound before radiotherapy when negative margins?

PurposeMost studies regarding the value of post lumpectomy imaging (PLI) studies rely on mammography alone and are often focused on patients that present with suspicious microcalcifications or in situ disease. This way, its true benefit remains controversial, which explained the heterogeneity between centers. This is the first study to evaluate the role of mammography with breast and axillary ultrasound undertaken before radiotherapy in patients with conservatively managed invasive and/or in situ carcinoma with negative margins. Materials and MethodsIn this retrospective study, medical records for patients referred to our External Radiotherapy Unit between January 2018 and December 2019 were reviewed. ResultsA total of 1251 patients (1262 breasts) were analyzed. A total of 3.4% had suspicious findings for local residual breast disease, with 1.0% having a re-excision positive for residual malignancy. Presentation with microcalcifications alone (OR=4.854), extension of microcalcifications>3cm (OR=13.500), histologic subtype pure ductal carcinoma in situ (OR=12.348), presence of invasive carcinoma≤1mm of the pathological margins (OR=4.630), stage pTis (5.630), and absence of invasive component (OR=4.629), were associated with an increased risk for residual malignancy. Only one patient (0.1%) had nodal residual involvement. ConclusionPLI detected residual local cancer in 1.0% of the patients. PLI plays an important role in the evaluation of patients undergoing breast-conserving therapy with negative margins. The major question that remains is whether it changes survival outcomes.

ENDOSCOPIC PAPILLECTOMY FOR EARLY AMPULLARY NEOPLASTIC LESIONS - A CASE SERIES ANALYSIS.

Endoscopic papillectomy has been conceived as a less invasive therapeutic option for treatment of early neoplastic lesions located at the major duodenal papilla. Evaluating patients with early ampullary lesions who underwent curative intent endoscopic papillectomy related to technical success (histopathological tumor margin assessment) and safety (adverse event rate). A retrospective study including consecutive patients who underwent curative intent endoscopic papillectomy for demographic, histopathological and pre-/post-procedural clinical assessment. Endpoints were technical success (histopathological residual tumor assessment) and adverse events rates. A total of 21 medical records patients with a female predominance (13 cases, 61.9%) were included. The tumor was incidental in 8 (38%) cases. Negative residual tumor resection margin rate was 72% (15 cases); three of these cases confirmed high-grade dysplasia in the resected specimen, and six cases were invasive neoplasia. Tumoral recurrence was seen in two cases, and median follow-up time was 12 months, with a 23% loss rate (five patients). Six (28.5%) patients had adverse events, all of them early (bleeding and pancreatitis); none of them required surgical intervention and there was no mortality. Endoscopic papillectomy allowed for technical successful procedure with complete removal of ampullary neoplastic lesions in the majority of cases with acceptable adverse event rates. Recurrence rate should be carefully assessed in further studies. There was a recent increase in the number of procedures. There was also a low correlation between pre- and post-histopathological assessment regarding the presence of invasive carcinoma and adenoma with high grade dysplasia, with a predominance of superficial neoplastic adenomatous lesions.

Abstract P2-14-09: A novel nipple aleolar complex involvement predictive index (NACPI) for indicating nipple sparing mastectomy in breast cancer patients

Abstract Background: While Preservation of NAC is concerned to increase the risk of local recurrences in the retroareolar glandular tissue, nipple sparing mastectomy (NSM) is increasing in patients with breast cancer and has been shown to result in better cosmetic outcome and the benefit for quality-of-life. It is necessary to predict accurately NAC involvement in order to select which patients may be candidates to NSM. The distance from the nipple to the tumor (DNT) is proposed as one of the best criteria to select the patient. The purpose of this study is to identify the predictors of NAC involvement retrospectively and to develop a clinical predictive model to select the patients who can be offered preservation of NAC.Methods: A total of 168 patients with primary operable breast cancer who received subcutaneous mastectomy for breast reconstruction at Saitama Medical Center during July 2013 to December 2017 were selected from the hospital's surgical database. NAC involvement was defined by the presence of invasive carcinoma and/or ductal carcinoma in situ at the subareolar margin. Results: Of the 148 patients who were preserved NAC, 89.9% (133/148) were NAC involvement negative and 10.1% (15/148) were positive in permanent pathological specimens. Of the 20 patients who were resected NAC, NAC involvement positivity was only 50.0% (10/20). This revealed that NAC involvement with a sensitivity (SN) of 40.0%, a specificity (SP) of 93.0%, a positive predictive value (PPV) of 50.0% and a negative predictive value (NPV) of 89.9% (AUC=0.665, 95%CI: 0.5345-0.796). In 140 patients who were performed intraoperative sub-nipple frozen section biopsy, the findings was significantly associated with NAC involvement (P&amp;lt;0.001), and which predict the NAC involvement with a SN of 93.3%, a SP of 89.6%, a PPV of 51.9%, and a NPV of 99.1% (AUC=0.915, 95%CI: 0.835-0.994). In the concordance rate between frozen section findings and definitive pathologic results, DCIS was 53% (9/17), atypical cell was 50% (2/4) and invasive ductal carcinoma was 100% (3/3). Correlation between NAC involvement and clinicopathological factors, tumor size ≥4cm (P&amp;lt;0.001), DNT &amp;lt;1cm by MMG (P=0.002), DNT &amp;lt;1cm by MRI (P&amp;lt;0.001), nipple contrast findings by MRI (P&amp;lt;0.001), tumor in central portion (P&amp;lt;0.001), multicentirc/focal lesion (P&amp;lt;0.001), c(N) positive (P=0.014) were significant relation with NAC involvement. Each predictors were scored 0 or 1, and the total score of 0-3 points was defined as low risk, 4 points as intermediate risk, and 5-7 points as high risk. Depending on this categorized classification, the NAC involvement rate was 3.5% (5/142) in low risk, 68.7% (11/16) in intermediate risk, 90.0% (9/10) in high risk and there was a significant correlation between the risk group and NAC involvement (P &amp;lt;0.001). Notably, assuming that NAC is preserved for low risk patients and is resected for intermediate and high risk patients, NACPI contributes to improve the accuracy of selecting the surgical procedures (SN 80.0%, SP 95.8%, PPV 76.9%, NPV 96.5% (AUC=0.879, 95%CI: 0.784-0.974)).Conclusion: This study suggests that NACPI can help us indicating subcutaneous mastectomy for the breast cancer patients who request preserve NAC with more oncological safety. Citation Format: Seki H, Sakurai T, Shimizu K, Mizuno S, Tokuda T, Kaburagi T, Seki M, Karahashi T, Nakajima K. A novel nipple aleolar complex involvement predictive index (NACPI) for indicating nipple sparing mastectomy in breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-09.

Suggestion of new nomogram including inflammatory marker for predicting invasive carcinoma in intraductal papillary mucinous neoplasm of the pancreas.

204 Background: Previous studies have analyzed that inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and advanced lung cancer inflammation index (ALI), associated with the presence of invasive carcinoma in patients with intraductal papillary mucinous neoplasm (IPMN). This study aimed to evaluate the correlation between the inflammatory markers and the invasive carcinoma in IPMN and propose a nomogram including inflammatory markers for predicting invasive IPMN. Methods: From 1995 to 2016, total 468 patients who underwent surgical resection at four institutions for histologically confirmed IPMN and the data were reviewed retrospectively. The patients with history of pancreatitis, other malignancies and without CA19-9 data or lymphocyte counts were excluded, the study cohort consisted of 365 patients. Variables with P &lt; 0.05 in risk factor analysis were included in the nomogram. Results: Of 365 patients, 98 (26.8%) patients had invasive IPMN. In univariate analysis, high body mass index (BMI) ( P = 0.037), pre-operative bilirubin level ( P = 0.001), CA19-9 ( P &lt; 0.001), NLR ( P = 0.019), PLR ( P = 0.002), ALI ( P = 0.001), main duct type (P &lt; 0.001), the presence of solid portion ( P &lt; 0.001) and tumor size (P = 0.086) were identified as risk factors for invasive IPMN. In multivariate analysis, pre-operative bilirubin level (P = 0.003), CA19-9 (P = 0.002), main duct type (P = 0.034) and the presence of solid portion (P &lt; 0.001) were independent predictive markers for invasive IPMN. The nomogram was developed including all factors of risk factor analysis. Conclusions: The inflammatory markers were the risk factors for the presence of IPMN-associated invasive carcinoma. This nomogram may be useful in identifying patients with IPMN at risk of malignancy and for selecting which patients should undergo surgery. Further validation studies are needed to assess the predictive ability of nomogram including inflammatory markers.

Pancreatic Intraductal Papillary Mucinous Neoplasm With Elevated Pre-Operative Cystic Carcinoembryonic Antigen Level: A Histopathologic Correlation.

BackgroundTo study the relationship between carcinoembryonic antigen (CEA) level, intraductal papillary mucinous neoplasm (IPMN) subtype, and the presence of invasive carcinoma.MethodsCystic CEA level and the following pathologic variables: subtypes of IPMN, size of cystic lesion, presence of dysplasia or carcinoma, and main or branch duct involvement from 45 IPMN cases were analyzed.ResultsThere was a significant correlation between pre-operative cystic fluid CEA level and the intensity of luminal CEA staining. However, there was no correlation between CEA level and cystic mucinous secretions or mucinous epithelial cytoplasm CEA staining, mucin glycoprotein expression, size of lesion, grade of dysplasia or presence of invasive carcinoma. CEA level was neither sensitive nor specific for the presence of invasive carcinoma.ConclusionsCystic CEA level may not be a reliable determinant of the presence or absence of invasive carcinoma in IPMNs, and its use to assess risk of malignancy may be limited.

Pre- and Intraoperative Factors Influencing Omission of Planned Intraoperative Radiation Therapy As a Boost for Breast Cancer Patients Undergoing Breast Conserving Treatment

Ongoing trials are investigating the efficacy of intraoperative radiotherapy (IORT) using photon radiosurgery system as a tumor bed boost for high-risk breast cancer patients undergoing breast conserving treatment. We evaluated preoperative and intraoperative variables influencing the decision to abort the planned IORT boost. A phase II IORT boost trial began in August 2014, and eligible patients were women who were aged 20 years or older, were compatible for lumpectomy, and had ductal carcinoma in situ (DCIS) or invasive carcinoma (Stage I-III). All patients underwent MRI evaluation and were discussed in a multidisciplinary conference for eligibility. The presence of invasive carcinoma and DCIS in resection margins were intraoperatively assessed by the frozen pathologic examination. Optically stimulated luminescence dosimeter detected radiation dose delivered to the skin during IORT. Pre- and intraoperative variables were compared between patients undergoing IORT and those whose planned IORT was cancelled due to anatomical reasons. A total of 434 patients were eligible and underwent a surgery with intension to carry out IORT between August 2014 and December 2017. IORT was cancelled in 90 patients for anatomical reasons including repeated positive margins causing large tumor cavity or total mastectomy (n = 27), insufficient cavity-skin distance (n = 14), satellite lesions causing large tumor cavity or total mastectomy (n = 12), large primary tumor or uncertain tumor margins in MRI causing large tumor cavity (n = 6), tumor cavity geometry unsuitable for IORT (n = 6), subareolar extension (n = 6), tumor abutting pectoralis muscle (n = 3), and non-anatomical reasons including patient’s refusal (n = 5), bilateral breast cancer (n = 3) or benign pathology (n = 3) confirmed during surgery, device malfunction (n = 3), and scheduling difficulty (n = 2). The percentage of IORT omission was 23.8% in 2015, 20.9% in 2016, and 19.3% in 2017. Primary tumor >2.0 cm (n = 0.033) and positive frozen section (n = 0.013) were significantly associated with omission of planned IORT, while breast size, tumor location, DCIS pathology were not. The median skin dose measured during IORT was 2.10 Gy (range, 0.33-10.89 Gy), and acute toxicity after IORT and whole breast irradiation was observed in 16% of the patients (seroma requiring repeated aspiration 13.5% and wound complication 2.7%). A successful IORT procedure depended on preoperative imaging evaluation and status of surgical margins. MRI-based patient selection allowed restriction of skin dose and tolerable acute toxicity.

Neutrophil-to-lymphocyte Ratio is a Predictive Marker for Invasive Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas.

To evaluate the correlation between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values, and the presence of invasive carcinoma in patients with intraductal papillary mucinous neoplasm (IPMN). NLR and (PLR) are inflammatory markers that have been associated with overall survival in patients with invasive malignancies, including pancreatic cancer. We retrospectively reviewed 272 patients who underwent surgical resection for histologically confirmed IPMN from January 1997 to July 2015. NLR and PLR were calculated and coevaluated with additional demographic, clinical, and imaging data for possible correlation with IPMN-associated carcinoma in the form of a predictive nomogram. NLR and PLR were significantly elevated in patients with IPMN-associated invasive carcinoma (P < 0.001). In the multivariate analysis, NLR value higher than 4 (P < 0.001), IPMN cyst of size more than 3 cm (P < 0.001), presence of enhanced solid component (P = 0.014), main pancreatic duct dilatation of more than 5 mm (P < 0.001), and jaundice (P < 0.001) were statistically significant variables. The developed statistical model has a c-index of 0.895. Implementation of the statistically significant variables in a predictive nomogram provided a reliable point system for estimating the presence of IPMN-associated invasive carcinoma. NLR is an independent predictive marker for the presence of IPMN-associated invasive carcinoma. Further prospective studies are needed to assess the predictive ability of NLR and how it can be applied in the clinical setting.

Serum tumor markers not useful in screening patients with pancreatic mucinous cystic lesions associated with malignant changes

Serum cancer antigen 19-9 (CA19-9) provides additional information about mucinous cystic pancreatic neoplasm (MPN). This study was undertaken to assess both CA19-9 and carcinoembryonic antigen (CEA) serum concentrations in consecutive patients affected by MPNs and other chronic benign and malignant pancreatic diseases. We also evaluated whether serum CA19-9 and CEA determinations provide additional information such as the presence of invasive carcinoma in MPN patients. Serum CA19-9 and CEA from 91 patients with pancreatic diseases were tested by commercially available kits at the time of diagnosis. The upper reference limit of serum CA19-9 was 37 U/mL and that of serum CEA was 3 ng/mL. Thirty-five patients was diagnosed with chronic pancreatitis (CP), 32 with MPN, and 24 with pancreatic ductal adenocarcinoma (PDAC) confirmed histologically. Surgery was carried out in 5 CP patients, in 10 MPN patients (7 of them had severe dysplasia), and in 9 PDAC patients. Serum CA19-9 activity was high in 12 (34.3%) CP patients, in 7 (21.9%) MPN patients, and in 12 (50.0%) PDAC patients (P=0.089). High serum CEA concentrations were noted in 6 (17.1%) CP patients, in 6 (18.8%) MPN patients, and in 12 (50.0%) PDAC patients (P=0.010). In the 7 MPN patients associated with histologically confirmed severe dysplasia, 3 (42.9%) patients had elevated serum activity of serum CA19-9, and 2 (28.6%) patients had high levels of CEA. Serum determination of oncological markers is not useful in selecting MPN patients with malignant changes.

Sa1768 Analysis of the Factors Associated With the Presence of Invasive Carcinoma in Patients With Advanced Adenomas or Serrated Lesions: The Way to a Personalized Surveillance

Sa1768 Analysis of the Factors Associated With the Presence of Invasive Carcinoma in Patients With Advanced Adenomas or Serrated Lesions: The Way to a Personalized Surveillance

Lobular neoplasia detected in MRI-guided core biopsy carries a high risk for upgrade: a study of 63 cases from four different institutions

There are certain criteria to recommend surgical excision for lobular neoplasia diagnosed in mammographically detected core biopsy. The aims of this study are to explore the rate of upgrade of lobular neoplasia detected in magnetic resonance imaging (MRI)-guided biopsy and to investigate the clinicopathological and radiological features that could predict upgrade. We reviewed 1655 MRI-guided core biopsies yielding 63 (4%) cases of lobular neoplasia. Key clinical features were recorded. MRI findings including mass vs non-mass enhancement and the reason for biopsy were also recorded. An upgrade was defined as the presence of invasive carcinoma or ductal carcinoma in situ in subsequent surgical excision. The overall rate of lobular neoplasia in MRI-guided core biopsy ranged from 2 to 7%, with an average of 4%. A total of 15 (24%) cases had an upgrade, including 5 cases of invasive carcinoma and 10 cases of ductal carcinoma in situ. Pure lobular neoplasia was identified in 34 cases, 11 (32%) of which had upgrade. In this group, an ipsilateral concurrent or past history of breast cancer was found to be associated with a higher risk of upgrade (6/11, 55%) than contralateral breast cancer (1 of 12, 8%; P=0.03). To our knowledge, this is the largest series of lobular neoplasia diagnosed in MRI-guided core biopsy. The incidence of lobular neoplasia is relatively low. Lobular neoplasia detected in MRI-guided biopsy carries a high risk for upgrade warranting surgical excision. However, more cases from different types of institutions are needed to verify our results.

Abstract 1572: Sensitive and robust targeted sequencing of pancreatic precancer and tumors using microfluidic single-molecule enrichment

Abstract Pancreatic ductal adenocarcinoma (PDAC) arises from two precursor lesions, pancreatic intraepithelial neoplasias and pancreatic cysts, such as intraductal papillary mucinous neoplasias (IPMNs). Since cyst lesions are readily detected on cross sectional imaging, early diagnosis of IPMN-associated PDAC and intervention may be feasible. However, clinical guidelines dictating which IPMNs are high-risk and require surgical resection are suboptimal. Recently, the genomic signature of IPMN-associated carcinomas has been described opening the possibility for targeted genomic analysis. Previous groups have sought to achieve this using conventional methods. However, since IPMN tissue and cyst fluid are limited in quantity and contain inhibitors of PCR, we developed a novel microfluidics-based approach to achieve sensitive and specific targeted amplification and Illumina library construction. We have optimized a novel method to enrich targeted genomic regions for next generation sequencing (NGS) platforms featuring microfluidic partitioning of the sample into uniform picoliter volume droplets containing single molecules of target DNA. All droplets contain all of the primers and PCR reagents, ensuring that every target molecule from the sample is amplified, and after endpoint PCR results in a highly uniform yield that facilitates efficient use of the NGS platform. In addition, the primers contain ‘Illumina tails’ that enable easy sample indexing and loading directly onto a MiSeq without additional library preparation. Here we detail the successful customization and use of the ThunderBolts Cancer Panel, which targets 230 commonly mutated regions in 50 cancer associated genes, with additional primers for commonly mutated genes in PDAC. Addition of the 37 PDAC-relevant primer pairs to the commercially available core panel was very straightforward and resulted in sequencing metrics similar to those of the core panel alone (100% coverage at 100x depth, mean read depth of 2500). Cyst fluid from 30 patients with IPMN resected under Sendai criteria were analyzed. We describe the mutational signature of cyst fluid and relate the presence and quantity of mutations in KRAS, GNAS and PIK3CA to the presence of invasive carcinoma and high grade dysplasia on pathology. Finally, unbiased and high resolution sequencing was obtained using this protocol with as little as 8ng of input DNA. Using picodroplet PCR technology we were able to achieve unprecedented sequencing performance on ultra-low sample inputs. Given the ease of use and customization of the panel, the same platform may be readily adapted to other applications in which samples are limited or are difficult to amplify. Future studies will utilize this platform for an expanded analysis of pancreatic cyst fluid with additional primers. Citation Format: Angelina I. Londoño-Joshi, Erica Pratt, Robert W. Cowan, Michael L. Samuels, Steve Kotsopoulos, Jeff Olson, Francis Long, Michelle A. Anderson, Diane Simeone, Andrew D. Rhim. Sensitive and robust targeted sequencing of pancreatic precancer and tumors using microfluidic single-molecule enrichment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1572. doi:10.1158/1538-7445.AM2015-1572

Evaluation of intraductal papillary mucinous neoplasms of the pancreas on MDCT and MRI

The purpose of our study was to evaluate the predictive factors of the presence of invasive carcinoma associated with intraductal papillary mucinous neoplasm (IPMN) of the pancreas on MDCT and MRI. Preoperative MDCT or/and MRI of 27 consecutive patients (19 men, 8 women, mean age 61.3 years) who had undergone surgical resection and had a pathological diagnosis of IPMN were retrospectively assessed. The type of ductal involvement, solid appearance of the lesion, location, tumor size of branch duct type and combined type lesions, maximum diameter of the tumor, caliber of the main pancreatic duct and the extent of the common bile duct dilatation were assessed on CT and MRI and correlated with the pathological findings of the invasive carcinoma. Two abdominal radiologists reviewed all the images, and when discrepancies of the findings were found, the consensus was reached by discussion. Pathological analysis revealed carcinoma in situ in two patients and invasive carcinoma in 19 patients arising from the IPMN. The type of ductal involvement (P = 0.038), a solid mass (P = 0.003) and the common bile duct dilatation ( ≥ 15 mm, P = 0.004) were correlated with the presence of associated invasive carcinoma. For the finding of solid and cystic mass in predicting invasive IPMN, the sensitivity was 66.7% (8/12) and specificity was 100.0% (8/8), and for bile duct diameter ≥ 15 mm, the sensitivity was 47.4% (9/19) and specificity was 100.0% (8/8). However, no association was found between the location of the lesion and associated invasive carcinoma. The caliber of the main pancreatic duct of patients with associated invasive carcinoma was significantly larger than that in the cases without invasive carcinoma (8.07 ± 2.23 mm vs. 4.86 ± 1.86 mm, P = 0.002). When using the main pancreatic duct dilatation ≥ 4 mm as the threshold, the sensitivity and specificity in predicting invasive IPMN were 94.7% (18/19) and 37.5% (3/8), respectively. For the branch duct type and combined type, the size of the tumor with associated invasive carcinoma was significantly larger than these without invasive carcinoma (41.35 ± 12.58) mm vs. (23.76 ± 8.06) mm (P = 0.003). When the maximum diameter was ≥ 40 mm, the sensitivity and specificity in predicting invasive IPMN were 50.0% (6/12) and 87.5% (7/8), respectively. The findings of CT and MRI are helpful to predict invasive carcinoma associated with IPMN, which may play an important role in the preoperative evaluation, surgical planning and predicting the prognosis of IPMN.

Ultrasonography Mapping Combined With Mammography Before Breast-Conserving Surgery for Primary Breast Cancer With Microcalcifications: A Novel Approach

IntroductionEvaluation for the spread of breast cancer with microcalcifications is challenging, because the microcalcifications sometimes spread beyond the lesions detectable by ultrasonography (US). An original method for preoperative mapping was performed for such lesions, using US in combination with mammography (MG) (US + MG mapping) before breast-conserving surgery (BCS). Materials and MethodsA total of 885 consecutive patients underwent BCS for primary breast cancer. Of the 885 patients, 154 (17.4%) with ductal carcinoma in situ or invasive carcinoma having microcalcifications underwent US + MG mapping preoperatively. Five patients who received neoadjuvant chemotherapy and 17 patients who were lost to follow-up were excluded. Accordingly, 133 lesions in 132 patients were retrospectively evaluated. The associations among this method, surgical margin (positive, close, or negative), pathologic characteristics, the area of the lesion within the specimen, and local recurrence rate during 5 years of follow-up were analyzed. ResultsThe median age and follow-up duration were 51.3 years (range, 28-80 years) and 71.4 months (range, 60-79 months), respectively. The surgical margin was negative in 96 lesions (72.2%), close in 27 lesions (20.3%), and positive in 10 lesions (7.5%). Local recurrence was noted in 1 patient (0.8%). There was no significant association between surgical margin status and the presence of invasive carcinoma. Larger lesion area was significantly associated with positive or close margin (P = .027). ConclusionUS + MG mapping is useful and results in a high complete-resection rate and an extremely low 5-year local recurrence rate.

Loss of PTEN Expression Is Associated with Poor Prognosis in Patients with Intraductal Papillary Mucinous Neoplasms of the Pancreas

Previously, we reported PIK3CA gene mutations in high-grade intraductal papillary mucinous neoplasms (IPMN). However, the contribution of phosphatidylinositol-3 kinase pathway (PI3K) dysregulation to pancreatic carcinogenesis is not fully understood and its prognostic value unknown. We investigated the dysregulation of the PI3K signaling pathway in IPMN and its clinical implication. Thirty-six IPMN specimens were examined by novel mutant-enriched sequencing methods for hot-spot mutations in the PIK3CA and AKT1 genes. PIK3CA and AKT1 gene amplifications and loss of heterozygosity at the PTEN locus were also evaluated. In addition, the expression levels of PDPK1/PDK1, PTEN, and Ki67 were analyzed by immunohistochemistry. Three cases carrying the E17K mutation in the AKT1 gene and one case harboring the H1047R mutation in the PIK3CA gene were detected among the 36 cases. PDK1 was significantly overexpressed in the high-grade IPMN versus low-grade IPMN (P = 0.034) and in pancreatic and intestinal-type of IPMN versus gastric-type of IPMN (P = 0.020). Loss of PTEN expression was strongly associated with presence of invasive carcinoma and poor survival in these IPMN patients (P = 0.014). This is the first report of AKT1 mutations in IPMN. Our data indicate that oncogenic activation of the PI3K pathway can contribute to the progression of IPMN, in particular loss of PTEN expression. This finding suggests the potential employment of PI3K pathway-targeted therapies for IPMN patients. The incorporation of PTEN expression status in making surgical decisions may also benefit IPMN patients and should warrant further investigation.

Ductal lavage cytology in patients with ductal carcinoma in situ (DCIS).

89 Background: Ductal lavage (DL) is a procedure used to obtain epithelial cells from a breast duct for cytologic evaluation. Previous studies have investigated DL as a potential screening procedure for women at high-risk for cancer. The data, however, does not support a significant correlation between lavage cytology and the presence of invasive carcinoma. It is postulated that an invasive cancer causes destruction of the involved ducts which prevents direct sampling of the malignant intraductal cells. Because ductal carcinoma in-situ (DCIS) does not disrupt the breast ductal structure, DL may yield a more representative cytologic sample in patients with DCIS. Methods: Ductal lavage was performed in the affected breast of 32 women undergoing mastectomy with preoperative diagnosis of DCIS. The lavage procedure was done in the operating room after induction of general anesthesia by cannulating a duct yielding fluid on the nipple and instilling saline which was then aspirated and sent for cytologic evaluation. A cytopathologist classified each sample as insufficient cellular quantity, benign, mild atypia, marked atypia, or malignant. Results: A successful lavage was obtained from 22 (69%) of 32 women undergoing DL in the operating room. Of these 22 cytology samples; 4(18%) had an insufficient cellular quantity, 4 (18%) had mild atypia, 6 (27%) had marked atypia, and 8 (36%) had malignant cells. Twenty one of these 22 women had DCIS in the surgical mastectomy specimen. Seven (32%) patients were found to have invasive ductal cancer in addition to DCIS on final pathology. Conclusions: Our results show that DL reveals markedly atypical or malignant cytology in 64% of patients with DCIS who underwent a successful lavage procedure. As an office procedure, DL may have the ability to obtain viable ductal carcinoma cells repeatedly over time in the same patient. Thus, DL may have an important role in patients with DCIS who are involved in window trial studies investigating response to medical treatments prior to surgical intervention. Further studies to evaluate the reproducibility of the ductal lavage results in patients with DCIS are needed to confirm these findings.