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To develop and validate a deep learning (DL)-based method for pancreas segmentation on CT and automatic measurement of pancreatic volume in pancreatic cancer. This retrospective study used 3D nnU-net architecture for fully automated pancreatic segmentation in patients with pancreatic cancer. The study used 851 portal venous phase CT images (499 pancreatic cancer and 352 normal pancreas). This dataset was divided into training (n = 506), internal validation (n = 126), and external test set (n = 219). For the external test set, the pancreas was manually segmented by two abdominal radiologists (R1 and R2) to obtain the ground truth. In addition, the consensus segmentation was obtained using Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm. Segmentation performance was assessed using the Dice similarity coefficient (DSC). Next, the pancreatic volumes determined by automatic segmentation were compared to those determined by manual segmentation by two radiologists. The DL-based model for pancreatic segmentation showed a mean DSC of 0.764 in the internal validation dataset and DSC of 0.807, 0.805, and 0.803 using R1, R2, and STAPLE as references in the external test dataset. The pancreas parenchymal volume measured by automatic and manual segmentations were similar (DL-based model: 65.5 ± 19.3 cm3 and STAPLE: 65.1 ± 21.4 cm3; p = 0.486). The pancreatic parenchymal volume difference between the DL-based model predictions and the manual segmentation by STAPLE was 0.5 cm3, with correlation coefficients of 0.88. The DL-based model efficiently generates automatic segmentation of the pancreas and measures the pancreatic volume in patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

The outcomes of patients with intraepithelial neoplasia at the pancreatic transection margin after pancreatic cancer surgery remain unclear. We evaluated the clinical impact of pancreatic transection margin status. This retrospective observational study included 171 patients who underwent surgery for pancreatic ductal adenocarcinoma between January 2008 and December 2019. Patients were classified into three groups: negative pancreatic transection margin (group N), positive low-grade (group L), and positive high-grade (group H) intraepithelial neoplasia. The clinicopathological findings and prognoses were analyzed for each group. There were 140, 14, and 9 patients in groups N, L, and H, respectively. The median age was significantly higher in group H (p = 0.035). There were no significant differences in male ratio, preoperative chemotherapy administration rate, pretreatment tumor markers, operative procedure, operative time, or blood loss. Overall survival and recurrence-free survival were not significantly different; however, the cumulative risk of recurrence in the remnant pancreas was significantly higher in group H (p = 0.018). Intraepithelial neoplasia at the pancreatic transection margin did not affect overall/recurrence-free survival. As patients with high-grade intraepithelial neoplasia at the pancreatic transection margin have an increased risk of recurrence in the remnant pancreas, careful postoperative follow-up is required. [ABSTRACT FROM AUTHOR]

To investigate the exact relationship between CT tumor size and the microscopic tumor size in PDAC. We enrolled 310 patients with pathologically confirmed PDAC without preoperative adjuvant therapies who underwent CT examination from June 2016 and December 2018. Smooth curve fitting and a segmented regression model were used to analyze the threshold effect between CT tumor size and the microscopic tumor size. The tumor size was 2.93±1.15 cm under the microscope and 3.00±1.23 cm in CT. The mean bias was 0.067 cm between CT and microscopic assessments. The accuracy of CT T stages was 61.02% (36/59), 79.41% (162/204) and 57.45% (27/47) in T1, T2 and T3, respectively. A non-linear relationship was detected between CT tumor size and the microscopic tumor size, with a turning point of 4.3 cm. On the left of the inflection point, the effect size, 95% confidence interval, and p value were 0.51, 0.40 to 0.63, and <0.0001, respectively. However, we observed no relationship between CT size and microscopic tumor size on the right of the inflection point (0.22, 0 to 0.44, 0.053). The relationship between CT and the microscopic tumor size is non-linear. When the CT tumor size was <4.3 cm, every 1-cm increase in CT tumor size was associated with a 0.56 cm increase in microscopic tumor size. When the CT tumor size was >4.3 cm, every 1-cm increase in CT tumor size was associated with a 0.91 cm increase in microscopic tumor size. • A non-linear relationship was detected between CT tumor size and microscopic tumor size, with a turning point of 4.3 cm. • When the CT tumor size was < 4.3 cm, every 1-cm increase in CT tumor size was associated with a 0.56 cm increase in microscopic tumor size. • when the CT tumor size was > 4.3 cm, every 1-cm increase in CT tumor size was associated with a 0.91 cm increase in microscopic tumor size. • The approximate value of microscopic tumor size can be estimated, which provides doctors with a new approach for the rapid identification of the microscopic tumor size. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) has substantial heterogeneity in biophysical features and in outcomes of patients. Identifying reliable pretreatment imaging biomarkers for PDAC with distant metastases (stage IV) is a key imperative. Our objective was to determine whether visual tumor enhancement pattern on enhanced computed tomography (CT) can be used as a prognostic factor in stage IV PDAC treated with chemotherapy. This is a retrospective cohort study of 133 patients with stage IV PDAC who underwent multiphasic enhanced CT before systemic chemotherapy. The enhancement pattern of PDAC was qualitatively categorized as hypoattenuation, isoattenuation, or hyperattenuation on each of the pancreatic, portal venous, and delayed phases. The effects of clinical prognostic factors and the visual tumor enhancement pattern on progression-free survival (PFS) and overall survival (OS) were assessed in univariate and multivariate analyses using Cox proportional hazards models. On univariate analysis, the number of metastatic organs and the visual tumor enhancement pattern during the delayed phase were significantly associated with PFS (p = 0.003 and < 0.001, respectively) and OS (p = 0.005 and < 0.001, respectively). Multivariate analysis identified the number of metastatic organs (PFS, p = 0.021; OS, p = 0.041) and visual tumor enhancement pattern during the delayed phase (PFS, p < 0.001; OS, p < 0.001) as independent predictors of PFS and OS. Visual enhancement pattern of PDAC on delayed phase enhanced CT appears to be associated with outcomes and could be a useful prognostic factor in stage IV PDAC, despite the need to add the delayed phase to CT protocol for pancreatic disease. [ABSTRACT FROM AUTHOR]

Background Long-term survival of patients with operated pancreatic ductal adenocarcinoma (PDAC) has been associated with resection status, disease stage and centralisation. However, no previous reports are available about long-term survivors of PDAC with confirmed histology covering an entire nation. Our aim was to analyze retrospectively confirmed long-term survivors of PDAC operated on in Finland 2000–2008. Method PDAC patients operated between 2000 and 2008 were selected from Finnish patient registers and archives. Histological slides of patients with over four-year survival were re-evaluated by an expert pancreatic pathologist. From the confirmed PDAC patients, demographic, oncologic and operative parameters were recorded. The cut-point of survival was 31.12.2013. Results Out of the 598 patients operated on and originally diagnosed with PDAC, 52 of the long-term survivors (LTS) were confirmed as having had true PDAC. The four-year survival rate in high volume centres (HVC) was 13.0% and 6.7% elsewhere (p = 0.017). Five-year survival rate was 7.2%. After multivariate analysis only the size of the tumour persisted as prognostic factor for over four-year survival. Among LTSs, 50% of patients had stage IIB tumour and 40% had a R1 resection without difference with patients with shorter survival. The use of adjuvant therapy did not differ between the groups. Conclusion This is the largest single-nationwide cohort of long-term survivors with confirmed PDAC. Comprehensive pathological evaluation is mandatory for an adequate PDAC diagnosis and true survival analysis. Long-term survival can be achieved even in T3 patients with nodal involvement and may be explained by favorable tumour biology. [ABSTRACT FROM AUTHOR]

In the past decade, insightful preclinical research has led to important breakthroughs in our understanding of pancreatic cancer. Even though the vast majority of pancreatic cancers are KRAS mutated, not all pancreatic cancer tumors are "KRAS equal"; there seems to be varying dependencies on the KRAS pathway. While KRAS-targeting therapies have been disappointing in the clinic, 'synthetic lethal' approaches hold promise in this setting. The pancreatic cancer stromal microenvironment appears to have contradictory roles. While there is evidence to suggest that stromal barrier prevents drug delivery, in other circumstances, stroma can play a protective role and its disruption enhances tumor dissemination. Clinical trials aimed at manipulating the various stromal components are in progress. BRCA mutation-related pancreatic tumors illustrate a unique subtype with enhanced susceptibility to DNA damaging agents and PARP-inhibition. DNA repair defects in cancer extend beyond germ line BRCA mutation and may extend the indications for DNA repair-targeting agents. Immune strategies are an area of active investigation in pancreatic cancer. Although the initial trials of single-agent checkpoint inhibitors have been negative, combinational approaches using immune-modifying agents and vaccines appear promising and goal is to identify an 'immune-therapy responsive' profile in pancreatic cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: The effects of diabetes mellitus (DM) on sensitivity of fluorine-18 fluorodeoxyglucose positron emission tomography coupled with computed tomography (18F-FDG PET/CT) for diagnosing pancreatic ductal adenocarcinomas (PDACs) is not well known. This study was aimed to evaluate the effects of DM on the validity of 18F-FDG PET/CT in PDAC. METHODS: A total of 173 patients with PDACs who underwent 18F-FDG PET/CT were enrolled (75 in the DM group and 98 in the non-DM group). The maximum standardized uptake values (SUVsmax) were compared. RESULTS: The mean SUVmax was significantly lower in the DM group than in the non-DM group (4.403 vs 5.998, P 5.001). The sensitivity of SUVmax (cut-off value 4.0) was significantly lower in the DM group than in the non-DM group (49.3% vs 75.5%, P < .001) and also lower in normoglycemic DM patients (n 524) than in non-DM patients (54.2% vs 75.5%, P 5 .038).CONCLUSION: DM contributes to a lower SUVmax of 18F-FDG PET/CT in patients with PDACs. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer, which commonly metastasizes to the liver. The current standard of care for metastatic PDAC is systemic chemotherapy, however there are limited emerging data regarding surgical resection of pancreatic oligometastases in select patients. Here we review the literature addressing resection of PDAC liver oligometastases. • Pancreatic ductal adenocarcinoma (PDAC) commonly metastasizes to the liver. • We review the data regarding resection of pancreatic liver oligometastases. • There may be a role for selective metastaectomy, however further study is required. [ABSTRACT FROM AUTHOR]

Abstract: The presence of neurotensin and neurotensin receptors has been demonstrated in human pancreatic carcinomas using autoradiography and Northern blot analysis. In vitro studies have reported that the neurotensin antagonist SR 48692 could inhibit the growth of MIA PaCa-2 cells in a neurotensin mediated fashion, and neurotensin could overcome this inhibition or stimulate proliferation. However, it is currently unknown whether such actions are exerted on PANC-1 cells. In addition, the immunolocation of neurotensin and neurotensin receptors is still unclear in human pancreatic ductal carcinoma tissues. Immunohistochemistry was applied to detect the distribution of neurotensin and neurotensin receptor subtype-1 in human pancreatic ductal carcinoma and normal pancreatic tissues. Furthermore, an in vitro study was carried out to test the pharmacological profile of neurotensin and SR 48692 in human pancreatic ductal carcinoma cell line PANC-1. Compared with normal pancreatic tissues, pancreatic ductal carcinoma tissues have higher neurotensin and neurotensin receptor subtype-1 expression rates. Pancreatic ductal carcinomas (32/40) bear the expression of both neurotensin and neurotensin receptor subtype-1. We observed that neurotensin (10−11–10−7 M) significantly stimulated the proliferation of PANC-1 and SR 48692 (10−11–10−7 M) alone had no effect on the growth of PANC-1 cells; however, SR 48692 (10−10–10−6 M) inhibited the stimulatory effect of neurotensin (10−9 M). Considering the overexpression of both neurotensin and neurotensin receptor subtype-1 in pancreatic ductal carcinomas, it could enable us to develop markers for pancreatic cancer diagnosis. As SR 48692 could inhibit neurotensin induced cell growth, neurotensin receptor subtype-1 may serve as a therapeutic target for the therapy of pancreatic carcinomas. Furthermore, our study indicates that the counteraction of neurotensin and neurotensin receptor subtype-1 regulates the genesis and development of pancreatic carcinomas. [Copyright &y& Elsevier]

Abstract: Background: Peritoneal lavage cytology in the staging of pancreatic cancer is not widely used given improvements in computed tomography (CT). The aim of this study was to determine the utility of peritoneal lavage cytology in predicting survival in locally advanced pancreatic cancer. Methods: Between 2000 and 2008, 202 patients with biopsy-proven pancreatic cancer who were determined by pancreas protocol CT to be locally advanced and not currently resectable underwent diagnostic laparoscopy and peritoneal lavage for cytology (DL-PLC). Results: DL-PLC upstaged 58 of 202 patients (29%) to stage IV, who had a significantly worse median survival of 11 months versus 16 months (P = .03). Positive cytology was an independent predictor of worse survival (P = .02). Discussion: Positive peritoneal cytology (stage IV disease) in locally advanced pancreatic cancer is common and predicts worse survival. This survival difference suggests that peritoneal cytology status might be useful in deciding treatment regimens in patients with locally advanced disease based on CT. [Copyright &y& Elsevier]

Background Breast cancer (BC) is the third most common cancer in the world and is the most common cancer in Iran in both sexes. Worldwide, there will be about 2.1 million newly diagnosed female breast cancer cases in 2018, accounting for almost 1 in 4 cancer cases among women. The aim of this study was to provide recent data on the BC incidence and distribution in East Azerbaijan, Iran. Methods East Azerbaijan is the largest and most populous province in the northwest of Iran, which more than 95% of the population is of Azeri ethnicity. Data of the patients diagnosed with confirmed BC as registered in the East Azerbaijan population based cancer registry between 2015 and 2017, were linked to the main data sources. The age standardized incidence rates (ASIRs) for BC were estimated. Results We had overall 1410 primary breast cancer cases during two years, in both sexes, which accounted 10.3% of cancer cases. The mean age of our patients was 51.07(±13.29), with the age range of 21 to 99 years old. About 98.2% of BC was female, and 1.7% of them were male. The most common morphology was ductal carcinoma (n = 1077, 76.4%), and most of our BC patient were in grade II of disease (35.9%). In 31.2% of patients had lymphatic Invasion, 17.8 % vascular invasion, and 8.7% of them had neural invasion. Also, our results showed that breast cancer was the most common cancer among female, with slightly increasing of ASRs from 31.1 to 31.7 per 100,000 women during 2 years. There were two age peaks of ASRs in women, first in approximately 45-55 years and second in 60-70 years old groups. Conclusions We observed slightly increase in incidence of BC, which might be explained by the improvement of compliance to the cancer registration, compared with previous reports of our region. However, the low tumor stages and improved knowledge and attitude of women to early diagnosis and screening, which we have recently addressed in our ongoing screening programs in the province, may have played important roles in these results. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Breast cancer is a heterogeneous disease and patients with advanced breast cancer who are resistant to Anthracycline and Taxane chemotherapeutic agents present a major obstacle to therapy and left with very few effective treatment options. Eribulin, a microtubule polymerization inhibitor, is a single agent chemotherapy which has shown survival benefits and therapeutic safety and efficacy in patients with metastatic disease who has received prior Taxane and Anthracycline. Data of Eribulin efficacy and safety is sparse and there is very little evidence in Asian population. The present study was undertaken to assess the efficacy of Eribulin in advanced breast cancer patients treated at a tertiary cancer care centre in India. Methods During the study period October 2013 to June 2018, a total of 82 advanced breast cancer female patients with metastatic disease received Eribulin. The clinico-pathological data including treatment details, patient outcome and survival was recorded and evaluated. Results The mean age of the patients was 49 years and 52% patients were premenopausal. 94% patient has classical infiltrating ductal carcinoma and 45% patients were negative for ER, PR and HER2 neu receptor status. Around 46% patients had metastatic disease at presentation. Eribulin was given as second, third, fourth and fifth line of treatment in 44, 32, 5 and 1 patient, respectively. The median progression free survival was 13.5 months. 83.7% patients had progressive disease and 12% patients expired during the course of the study. The overall survival was 65% at 231 months whereas the progression free survival was 0% at 185 months (calculated from date of registration). Conclusion The present study establishes the safety and efficacy of Eribulin administration in breast cancer patients with advanced disease. The experience at our centre showed clinical outcomes similar to real world data and reemphasizes the importance of Eribulin in this subset of patients. [ABSTRACT FROM AUTHOR]