Towards the characterization of the tumor microenvironment through dictionary learning-based interpretable classification of multiplexed immunofluorescence images.

Objective.Histology image analysis is a crucial diagnostic step in staging and treatment planning, especially for cancerous lesions. With the increasing adoption of computational methods for image analysis, significant strides are being made to improve the performance metrics of image segmentation and classification frameworks. However, many developed frameworks effectively function as black boxes, granting minimal context to the decision-making process. Thus, there is a need to develop methods that offer reasonable discriminatory power and a biologically-informed intuition to the decision-making process.Approach.In this study, we utilized and modified a discriminative feature-based dictionary learning (DFDL) paradigm to generate a classification framework that allows for discrimination between two distinct clinical histologies. This framework allows us (i) to discriminate between 2 clinically distinct diseases or histologies and (ii) provides interpretable group-specific representative dictionary image patches, or 'atoms', generated during classifier training. This implementation is performed on multiplexed immunofluorescence images from two separate patient cohorts- a pancreatic cohort consisting of cancerous and non-cancerous tissues and a metastatic non-small cell lung cancer (mNSCLC) cohort of responders and non-responders to an immunotherapeutic treatment regimen. The analysis was done at both the image-level and subject-level. Five cell types were selected, namely, epithelial cells, cytotoxic lymphocytes, antigen presenting cells, HelperT cells, and T-regulatory cells, as our phenotypes of interest.Results.We showed that DFDL had significant discriminant capabilities for both the pancreatic pathologies cohort (subject-level AUC-0.8878) and the mNSCLC immunotherapy response cohort (subject-level AUC-0.7221). The secondary analysis also showed that more than 50% of the obtained dictionary atoms from the classifier contained biologically relevant information.Significance.Our method shows that the generated dictionary features can help distinguish patients presenting two different histologies with strong sensitivity and specificity metrics. These features allow for an additional layer of model interpretability, a highly desirable element in clinical applications for identifying novel biological phenomena.

Successful Outcome of Metastatic Pancreatoblastoma in an Adolescent: A Case Report and Review of the Literature.

Pancreatoblastoma, an orphan disease, is the most common malignant epithelial neoplasm of the pancreas in children. With vague clinical features, diagnosis is made by radiological suggestions and histopathology. The presence of metastatic disease and inoperable/incomplete excision remains the poor prognostic markers. We present a rare instance of an adolescent who has survived metastatic pancreatoblastoma after neoadjuvant chemoreduction/complete surgical excision.

Nutritional treatment is associated with longer survival in patients with pancreatic disease and concomitant risk of malnutrition.

BACKGROUND: Pancreatic diseases involve complex nutritional challenges. Despite this, conflicting evidence exists regarding the clinical relevance of detecting the risk of malnutrition and implementing systematic nutrition support for these patients. Thus, our aims were to investigate whether screening for malnutrition risk and initiating nutrition support are predictive of mortality for hospitalized patients with pancreatic diseases. DESIGN: From 2008 to 2018, 34 prevalence surveys of nutrition were conducted at Haukeland University Hospital (HUH), Norway. Risk of malnutrition was defined by a score of ≥3 in Nutritional Risk Screening 2002 (NRS 2002). Primary outcomes included overall, one-year, and one-month mortality, and were compared according to malnutrition risk and nutrition support for adult patients with ICD-10 codes of K85: acute pancreatitis, K86: other diseases of pancreas, and C25: malignant neoplasm of pancreas. Length of hospital stay (LOS) was included as a secondary outcome. RESULTS: Of the 283 patients investigated, risk of malnutrition was present in 61.5%. Risk of malnutrition was associated with higher overall mortality (Hazard Ratio (HR) = 1.67, 95% confidence interval (CI): 1.2-2.4, P = 0.003) and one-year mortality (HR = 1.89, 95% CI: 1.2-2.9, P = 0.004) compared to patients not at risk. Not receiving nutrition support for at-risk patients was associated with higher overall mortality (HR = 1.60, 95% CI: 1.1-2.4, P = 0.019) and one-year mortality (HR = 1.64, 95% CI: 1.04-2.6, P = 0.034) compared to patients at risk who received nutrition support. Patients at risk of malnutrition had increased LOS (20.5 nights vs 15.2 nights, P = 0.044) compared to patients not at risk of malnutrition. CONCLUSION: This study of hospitalized patients with pancreatic disease suggests that risk of malnutrition may be associated with higher mortality rates, whereas nutrition support may decrease mortality rates. CLINICAL TRIAL REGISTRY: Not registered.

Correlation of Multi-Detector Computed Tomography and Intraoperative Variations of the Celiac Trunk and Hepatic Artery in Resectable Hepatobiliary Pancreatic Cancers.

Introduction Knowledge of celiac artery variations is imperative to perform complex hepato-biliary pancreatic surgical procedures to avoid inadvertent complications. Multi-detector computed tomographic (MDCT) angiography aids in detecting these variations preoperatively. Surgical confirmation is considered the gold standard. Aims and objectives Preoperative assessment of celiac artery variations by MDCT angiography and surgical confirmation intraoperatively in resectable hepato-biliary pancreatic cancers. Patients and methods MDCT angiography was performed in 40 patients with clinical evidence of resectable hepato-biliary-pancreatic cancers. Three dimensional (3D) reconstructions were performed to confirm the celiac artery variations. Surgery was performed as per the institute's protocol in all these patients for resection of tumor and confirmation of celiac artery anatomy. Variations were confirmed surgically that were identified through imaging. Results MDCT angiography identified normal trifurcated celiac artery anatomy in 33 (82.5%) patients and variant anatomy in seven (17.5%) patients. The most common variation was a replaced right hepatic artery (r-RHA) from the superior mesenteric artery (SMA) in four (10%) of patients. A replaced left hepatic artery (r-LHA) from the celiac trunk, a common hepatic artery (CHA) from the abdominal aorta, and an accessory right hepatic artery (ac-RHA) from the proper hepatic artery itself were identified in one (2.5%) patient each, respectively. All these findings were confirmed intraoperatively. There was a 100% statistical correlation between imaging and surgical findings. Conclusion Surgical confirmation of radiological data of celiac artery variations is the gold standard to avoid disastrous complications such as inadvertent vascular bleeds, biliary injuries, and hepatic necrosis. Since the presence of variations warrants the preservation or excision of the arterial system without oncological compromise and minimizing surgical complications.

Pancreatic resections in elderly patients with high American Society of Anesthesiologists' risk score: a view from a tertiary care center.

BACKGROUND: More than 60% of patients affected by pancreatic cancer are ≥ 65 years of age. Surgery represents the only potentially curative treatment for malignant pancreatic neoplasia and a useful treatment for benign diseases. AIM: To evaluate outcomes in elderly patients with ASA risk score 4 who underwent pancreatic resection compared to younger patients and elderly patients with lower anesthesiological risk. METHODS: A consecutive series of 345 patients underwent pancreatic resection between 2010 and 2017 was reviewed. We compared three groups based on age at the time of surgery: < 65 years (group A), 65-74 years (group B), and ≥ 75 years (group C). Patients in group C were split into two subgroups, ASA 1-3 versus ASA 4, and compared. RESULTS: Group A consisted of 117 (34%) patients, group B 128 (37%) patients, and group C 100 (29%) patients. Group C had a significantly higher incidence of comorbidity and ASA 4 status (p < 0.05), and of overall post-operative complications (p < 0.01), because of the higher incidence of post-operative medical complications. No differences in terms of overall surgical complications and post-operative mortality were reported. The mean overall survival was significantly lower for group C (p < 0.01), with no difference in mortality for cancer. Within group C, no differences were reported regarding surgical complications (p = 0.59), mortality (p = 0.34), and mean overall survival (p = 0.53) between ASA 1-3 and ASA 4 patients. CONCLUSIONS: Advanced age should not preclude elderly patients with pancreatic diseases from being treated surgically, and ASA 4 in subjects aged ≥ 75 years should not be an absolute contraindication.

Concordancia entre la tomografía axial computarizada de abdomen, la ultrasonografía endoscópica y la punción por aspiración con aguja fina en el diagnóstico de lesiones sólidas sugestivas de neoplasias malignas de páncreas / Diagnostic concordance of abdominal CT scans, Endoscopic Ultrasonography and Fine Needle Puncture Aspiration for solid pancreatic lesions suggestive of malignant neoplasms

Resumen Introducción y objetivo: la realización de pruebas para el diagnóstico de lesiones sólidas de páncreas conduce frecuentemente a resultados discordantes, lo que genera confusión y retraso en las decisiones terapéuticas. La concordancia entre los resultados de la tomografía axial computarizada de abdomen con contraste (TAC), la ultrasonografía endoscópica (USE) biliopancreática y la punción por aspiración con aguja fina guiada por ultrasonografía endoscópica (PAAF-USE) no ha sido evaluada en nuestro medio. Materiales y métodos: se evaluó una serie de pacientes adultos con masas sólidas del páncreas sospechosas de malignidad, atendidos en el Hospital Universitario San Ignacio (HUSI) de Bogotá (Colombia), en los cuales se realizaron, por lo menos, dos de las siguientes pruebas: TAC, USE o PAAF-USE. Se evaluó la concordancia de los resultados, definidos como compatibles con neoplasia, no compatibles con neoplasia o resultado no conclusivo. Resultados: se incluyeron 57 pacientes. Un alto porcentaje de estos, con USE compatible con neoplasia, tuvieron resultados discordantes con la TAC (33,3 %) y con la PAAF-USE (52,5 %). La concordancia entre imágenes y PAAF-USE fue mínima (kappa = 0,02; intervalo de confianza [IC] 95 %, 0,04-0,08). La probabilidad de detectar un compromiso vascular fue significativamente mayor en la USE (42,1 % frente a 23,8 %, p = 0,06) a diferencia del compromiso ganglionar, que fue detectado más frecuentemente por imágenes (TAC/resonancia magnética nuclear [RMN]) (23,8 % frente a 7,1 %, p = 0,01). Conclusiones: los resultados de este estudio sugieren un pobre acuerdo entre los diferentes métodos diagnósticos y advierten que es necesario implementar mejoras como la elastografía y medios de contraste, nuevas modalidades de aguja para la toma de muestras o la presencia de un citopatólogo in situ.

Abstract Introduction and objective: Diagnostic tests for solid pancreatic lesions frequently produce discordant results which lead to confusion and delays of therapeutic decisions. Concordance among abdominal computed tomography with contrast, endoscopic ultrasound (EUS) pancreatobiliary and EUS guided fine needle aspiration had not previously been evaluated in Colombia. Materials and methods: We evaluated a series of adult patients with solid pancreatic masses suspected of malignancy treated at the San Ignacio University Hospital in Bogotá, Colombia. At least two of the following tests were performed: CT scans, EUS, and EUS guided fine needle aspiration. Results were defined as compatible with neoplasia, not compatible with neoplasia or inconclusive. Concordance of results was then evaluated. Results: Fifty-seven patients were included. A high percentage EUS results compatible with neoplasia were discordant with CT scan results and with EUS guided fine needle aspiration results (33.3% and 52.5%, respectively). Agreement between imaging and EUS guided fine needle aspiration results was minimal (Kappa 0.02; 95% CI:-0.04 to 0.08). The probability of detecting vascular compromises was significantly higher for EUS (42.1% vs. 23.8%, p: 0.06), but lymph node compromises were detected more frequently by imaging (CT or MRI) (23.8% vs. 7.1%, p: 0.01). Conclusions: The results of this study suggest poor agreement between these diagnostic methods implying a need for improvements such as elastography and contrast media, new needle modalities for sampling, and/or the an on-site cytopathologist.

Imaging of neuroendocrine tumors of the pancreas.

Pancreatic neuroendocrine tumors (PNETs) are rare and represent a heterogeneous disease. PNET can be functioning or non-functioning with different clinical presentations and different prognosis based on WHO and pTNM classifications. The role of imaging includes the localization of small functioning tumor, differentiation of these tumors from adenocarcinoma, identification of signs of malignancy and evaluation of extent. PNETs have a broad spectrum of appearance. On CT and MRI, most of functioning PNETs are well defined small tumors with intense and homogeneous enhancement on arterial and portal phases. However, some PNETs with a more fibrous content may have a more delayed enhancement that is best depicted on the delayed phase. Other PNETs can present as purely cystic, complex cystic and solid tumors and calcified tumors. Non-functioning PNETs are larger with less intense and more heterogeneous enhancement. Functional imaging is useful for disease staging, to detect disease recurrence or the primary but also to select patient candidate for peptide receptor radiometabolic treatment. Somatostatin receptor scintigraphy (SRS) (Octreoscan®) is still the most available technique. Gallium 68-SST analogue PET have been demonstrated to be more sensitive than SRS-SPEC and it will be the future of functional imaging for NET. Finally, 18FDG PET/CT is indicated for more aggressive PNET as defined either by negative SRS and huge tumor burden or ki67 above 10% or poorly differentiated PNEC tumors.

Squamous cell carcinoma of the pancreas.

Pancreatic malignancies can be subdivided into endocrine and non-endocrine processes. Of the non-endocrine tumours, ductal carcinoma is the most common, and the ductal carcinomas can be further subdivided into adenocarcinomas and squamous cell carcinomas. The adenocarcinomas constitute most of the non-endocrine pancreatic malignancies, and the treatment options for these, although limited in efficacy, are relatively well established. The squamous cell carcinoma pathology is a rare entity, and few reports of it are found in the literature. As a result, treatment options for squamous cell carcinoma of the pancreas are poorly understood. Here, we report the presentation of a 48-year-old woman with metastatic squamous cell carcinoma of the pancreas. The subsequent investigations, treatment, and outcome are described.