Development of a Second Primary Lung Cancer Following a Primary Breast Cancer: A Case Series.

Breast cancer (BC) accounts for 24.2% of all women's malignant tumors, with rising survival rates due to advancements in chemotherapy and targeted treatments. However, second primary cancers, particularly lung cancer (LC), have become more prevalent, often emerging approximately 10 years after BC treatment. This study presents a case series of 9 women diagnosed with second primary LC following BC, treated at a high-complexity hospital in Colombia between 2014 and 2019. All initial BCs were ductal carcinomas, 7 were triple negative, 1 was human epidermal growth factor receptor 2 positive, and 1 was estrogen and progesterone positive. Each patient had undergone radiation therapy, and 7 had received chemotherapy, increasing their LC risk. The second primary LCs, all adenocarcinomas, were confirmed using immunohistochemical stains for thyroid transcription factor-1 (TTF-1), Napsin A, and estrogen receptor (ER) status. The interval between treatments and LC detection ranged from 1 to 17 years, with 4 cases identified after 10 years and 3 within 1 to 3 years, underscoring the need for prolonged surveillance. Seven LCs were ipsilateral to the BC and radiation site, while 2 were contralateral, highlighting the necessity of monitoring both sides for potential LC development. This case series enhances the local epidemiological understanding, showing that prior radiotherapy for BC and histological analysis are key in characterizing second primary LC patients. The study emphasizes the critical role of accurate histological diagnosis in guiding treatment approaches for lung lesions in BC survivors.

Flurbiprofen inhibits cAMP transport by MRP4/ABCC4 increasing the potency of gemcitabine treatment in PDAC cell models.

Pancreatic ductal adenocarcinoma (PDAC) remains a highly malignant cancer with a grim prognosis due to its early metastasis and resistance to current chemotherapies, such as Gemcitabine (GEM). We have previously demonstrated that cAMP exclusion by MRP4 is critical for PDAC cell proliferation, establishing this transporter as a promising prognostic marker and therapeutic target. In search for novel therapeutic options to improve GEM efficacy, we conducted a drug repositioning screening to identify potential inhibitors of cAMP transport by MRP4. Several non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit the transport of certain MRP4 substrates. In this study, we assessed the efficacy of sixteen NSAIDs in inhibiting cAMP transport mediated by MRP4, identifying seven potent inhibitors based on their IC50 values. The most potent inhibitors were further tested for their effect on cell proliferation and migration. Flurbiprofen emerged as the most potent inhibitor of both MRP4-mediated cAMP transport and cell proliferation. Overexpression of MRP4 in BxPC-3 cells significantly increased GEM resistance, and co-administration of flurbiprofen with GEM markedly enhanced the latter's potency inhibiting PDAC cells proliferation. These findings position flurbiprofen as a potent inhibitor of cAMP transport by MRP4 and a promising adjunctive therapy to enhance GEM effectiveness in PDAC treatment.

5-nitro-thiophene-thiosemicarbazone derivative induces cell death, cell cycle arrest, and phospho-kinase shutdown in pancreatic ductal adenocarcinoma cells.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options. This study explores the potential of novel 5-nitro-thiophene-thiosemicarbazone derivatives as therapeutic agents for PDAC. METHODS: We evaluated the cytotoxicity of seven derivatives in peripheral blood mononuclear cells (PBMCs) and PDAC cell lines. Promising candidates (PR12 and PR17) were further analyzed for their effects on colony formation, cell cycle progression, and reactive oxygen species (ROS) production. PR17, the most promising derivative, was subjected to additional investigation, including analysis of autophagy-related genes and protein kinase inhibition. RESULTS: Three derivatives (PR16, PR19, and PR20) displayed cytotoxicity towards PBMCs. PR12 reduced colony formation and G0/G1 cell cycle arrest in PDAC cells. Notably, PR17 exhibited potent activity in MIA PaCa-2 cells, inducing S-phase cell cycle arrest, downregulating autophagy genes, and inhibiting key protein kinases. CONCLUSION: PR17, a 5-nitro-thiophene-thiosemicarbazone derivative, demonstrates promising antineoplastic activity against PDAC cells by potentially modulating cell cycle progression, autophagy, and protein kinase signaling. Further studies are warranted to elucidate the detailed mechanism of action and explore its efficacy in vivo.

Evaluation of tumor infiltrating lymphocytes as a prognostic biomarker in patients with ductal carcinoma in situ of the breast.

PURPOSE: To assess the association between tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ (DCIS) samples and disease recurrence. METHODS: This retrospective cohort study included women aged 18 years and older who underwent treatment between January 2007 and December 2020. Male patients, individuals diagnosed with invasive or microinvasive disease based on anatomopathological examination of surgical specimens, and those with a personal history of any other cancers were excluded. Additionally, the presence of "touching TILs" (lymphocytes in direct contact with tumor cells) and periductal desmoplasia were evaluated as complementary methods to represent the immunological microenvironment. The primary outcome was relapse-free survival based on TIL quantification adjusted for potential confounders. Pathologists assessed TILs in the sample with the highest tumor representation and quantified them as a percentage. Survival was evaluated using Kaplan‒Meier curves, log-rank tests, and Cox regression models. RESULTS: A total of 191 patients met the eligibility criteria. The mean follow-up duration was 77.2 months, with a recurrence rate of 9.2%. Patients with TILs ≥ 17% had a greater risk of recurrence (HR 2.97, 95% CI 1.17-7.51; p = 0.02). Additionally, focal necrosis (HR 6.4, 95% CI 1.39-34.71; p = 0.018) or comedonecrosis (HR 4.53, 95% CI 1.34-15.28; p = 0.015) were associated with increased recurrence risk. According to the multivariate model, comedonecrosis and TILs ≥ 17% were significantly associated with recurrence (p = 0.034 and p = 0.035, respectively). Regarding the evaluations of "touching TILs" and periductal desmoplasia, no statistical significance was found when assessing their association with disease recurrence. CONCLUSION: In our cohort, a high percentage of TILs (≥ 17%) and the presence of comedonecrosis were independently associated with DCIS recurrence.

Laparoscopic Versus Open Pancreatoduodenectomy for Periampullary Tumors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: Laparoscopic pancreatoduodenectomy (LPD) has emerged as an alternative to open technique in treating periampullary tumors. However, the safety and efficacy of LPD compared to open pancreatoduodenectomy (OPD) remain unclear. Thus, we conducted an updated meta-analysis to evaluate the efficacy and safety of LPD versus OPD in patients with periampullary tumors, with a particular focus on the pancreatic ductal adenocarcinoma patient subgroup. METHODS: According to PRISMA guidelines, we searched PubMed, Embase, and Cochrane Library in December 2023 for randomized controlled trials (RCTs) that directly compare LPD versus OPD in patients with periampullary tumors. Endpoints and sensitive analysis were conducted for short-term endpoints. All statistical analysis was performed using R software version 4.3.1 with a random-effects model. RESULTS: Five RCTs yielding 1018 patients with periampullary tumors were included, of whom 511 (50.2%) were randomized to the LPD group. Total follow-up time was 90 days. LPD was associated with a longer operation time (MD 66.75; 95% CI 26.59 to 106.92; p = 0.001; I2 = 87%; Fig. 1A), lower intraoperative blood loss (MD - 124.05; 95% CI - 178.56 to - 69.53; p < 0.001; I2 = 86%; Fig. 1B), and shorter length of stay (MD - 1.37; 95% IC - 2.31 to - 0.43; p = 0.004; I2 = 14%; Fig. 1C) as compared with OPD. In terms of 90-day mortality rates and number of lymph nodes yield, no significant differences were found between both groups. CONCLUSION: Our meta-analysis of RCTs suggests that LPD is an effective and safe alternative for patients with periampullary tumors, with lower intraoperative blood loss and shorter length of stay.

HPV Detection in Breast Tumors and Associated Risk Factors in Northeastern Brazil.

Breast cancer risk factors include lifestyle, genetic-hormonal influences, and viral infections. Human papillomavirus (HPV), known primarily as the etiological agent of cervical cancer, also appears active in breast carcinogenesis, as evidenced in our study of 56 patients from northeastern Brazil. We assessed the clinical and sociodemographic characteristics, correlating them with various breast cancer tumor types. HPV detection involved amplifying the L1 region, with viral load measured using the E2/E6 ratio and viral activity indicated by E5 oncogene expression. Predominantly, patients over 56 years of age with healthy lifestyles showed a high incidence of invasive ductal carcinoma and triple-negative breast cancer. HPV was detected in 35.7% of cases, mostly HPV16, which is associated with high viral loads (80 copies per cell) and significant E5 expression. These results hint at a possible link between HPV and breast carcinogenesis, necessitating further studies to explore this association and the underlying viral mechanisms.

Mortalidad post operatoria de la duodenopancreatectomía cefálica en una unidad de cuidados intensivos

Introducción: La duodenopancreatectomía cefálica o cirugía de Whipple ha sido el procedimiento quirúrgico electivo como tratamiento de las patologías neoplásicas de páncreas, duodeno y vías biliares. A pesar de los avances en técnicas quirúrgicas continúa siendo un gran desafío el manejo multidisciplinario. Materiales y Métodos: Estudio analítico, retrospectivo, de corte transversal, de pacientes postoperados de duodenopancreatectomía cefálica mayores de 18 años, ingresados a una unidad de Cuidados Intensivos, de enero de 2022 a julio de 2023. Variables evaluadas: características sociodemográficas (edad, sexo); comorbilidades asociadas; variables de interés en UCI (SOFA, APACHE, días de internación en UTI, días de internación hospitalaria, requerimiento de Intubación orotraqueal IOT, días de IOT, requerimiento de vasopresores), desenlace en UTI; variables de interés quirúrgicas: duración de la cirugía, complicaciones quirúrgicas. Resultados: Se incluyeron 24 pacientes. La media de edad: 66 años (mín:35; Máx: 85; RIC: 59-77); 14 (58%) sexo femenino. Comorbilidades más frecuentes: Hipertensión arterial 17 (71%), Diabetes Mellitus 26 (25%), Cardiopatía 3. SOFA al ingreso media de 4; (mín:1; Máx: 11; DS:3); APACHE al ingreso: media de 15; (mín:6; Máx: 24; DS: 4); media de internación en UTI fue de 6 días (mín:1; Máx: 68; DS: 14). Se constataron 5 (21%) óbitos. Factores asociados a la mortalidad el uso de vasopresores (p=0,013), insuficiencia renal aguda (p=0,009), infección del sitio quirúrgico (p=0,023), y una media de SOFA estimada en 9 (p=0,0012). Conclusión: Es fundamental el manejo multidisciplinario de pacientes sometidos a cirugía de Whipple a fin de optimizar los resultados, previniendo la aparición de complicaciones, y disminuyendo de esta forma la morbimortalidad de los mismos.

Introduction: Cephalic pancreaticoduodenectomy or Whipple surgery has been the elective surgical procedure as a treatment for neoplastic pathologies of the pancreas, duodenum and bile ducts. Despite advances in surgical techniques, multidisciplinary management continues to be a great challenge. Materials and Methods: Analytical, retrospective, cross-sectional study of postoperative cephalic duodenal-pancreatectomy patients over 18 years of age, admitted to an Intensive Care unit, from January 2022 to July 2023. Variables evaluated: sociodemographic characteristics (age, sex); associated comorbidities; variables of interest in the ICU (SOFA, APACHE, days of ICU admission, days of hospitalization, requirement for orotracheal intubation IOT, days of IOT, requirement for vasopressors), outcome in ICU; surgical variables of interest: duration of surgery, surgical complications. Results: 24 patients were included. Median age: 66 years (min: 35; Max: 85; IQR: 59-77); 14 (58%) female. Most frequent comorbidities: High blood pressure 17 (71%), Diabetes Mellitus 26 (25%), Heart disease 3. SOFA at admission average of 4; (min:1; Max: 11; DS:3); APACHE upon admission: average of 15; (min:6; Max: 24; DS: 4); Mean ICU stay was 6 days (min: 1; Max: 68; SD: 14). There were 5 (21%) deaths. Factors associated with mortality were the use of vasopressors (p=0.013), acute renal failure (p=0.009), surgical site infection (p=0.023), and a mean estimated SOFA of 9 (p=0.0012). Conclusion: Multidisciplinary management of patients undergoing Whipple surgery is essential in order to optimize results, preventing the appearance of complications, and thus reducing their morbidity and mortality.

Pancreatic ductal adenocarcinoma: exploring clinicopathological trends and racial disparities in a comprehensive U.S. population-based study.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy about 50% of PDAC are metastatic at presentation. In this study, we evaluated PDAC demographics, annual trend analysis, racial disparities, survival rate, and the role of different treatment modalities in localized and metastatic disease. METHODS: A total of 144,824 cases of PDAC were obtained from the SEER database from 2000 to 2018. RESULTS: The median age was 69 years, with a slightly higher incidence in males (52%) and 80% of all cases were white. Among cases with available data, 43% were grade III tumors and 57% were metastatic. The most common site of metastasis was the liver (15.7%). The annual incidence has increased steadily from 2000 to 2018. The overall observed (OS) 5-year survival rate was 4.4% (95% CI 4.3-4.6%), and 5 years cause-specific survival (CSS) was 5% (95% CI 5.1-5.4%). The 5-year survival with multimodal therapy (chemotherapy, surgery, and radiation) was 22% (95% CI 20.5-22.8%). 5-year CSS for the blacks was lower at 4.7% (95% CI 4.2-5.1%) compared to the whites at 5.3% (95% CI 5.1-5.4%). Multivariate analysis found male gender and black race associated with worse prognosis. Kaplan-Meier survival analysis found multimodal therapy to have the best outcomes in all three stages. CONCLUSION: PDAC is an aggressive malignancy with male gender and black race are associated with a poor prognosis. Surgery with chemoradiation was associated with the best overall survival. With steadily increasing rates of PDAC, improved treatment modalities are paramount to improving survival in these patients.

Thermosensitive Polymeric Nanoparticles for Drug Co-Encapsulation and Breast Cancer Treatment.

Despite advances in breast cancer treatment, there remains a need for local management of noninvasive, low-grade ductal carcinoma in situ (DCIS). These focal lesions are well suited for local intraductal treatment. Intraductal administration supported target site drug retention, improved efficacy, and reduced systemic exposure. Here, we used a poly(N-isopropyl acrylamide, pNIPAM) nanoparticle delivery system loaded with cytotoxic piplartine and an MAPKAP Kinase 2 inhibitor (YARA) for this purpose. For tumor environment targeting, a collagen-binding peptide SILY (RRANAALKAGELYKSILYGSG-hydrazide) was attached to pNIPAM nanoparticles, and the nanoparticle diameter, zeta potential, drug loading, and release were assessed. The system was evaluated for cytotoxicity in a 2D cell culture and 3D spheroids. In vivo efficacy was evaluated using a chemical carcinogenesis model in female Sprague-Dawley rats. Nanoparticle delivery significantly reduced the IC50 of piplartine (4.9 times) compared to the drug in solution. The combination of piplartine and YARA in nanoparticles further reduced the piplartine IC50 (~15 times). Treatment with these nanoparticles decreased the in vivo tumor incidence (5.2 times). Notably, the concentration of piplartine in mammary glands treated with nanoparticles (35.3 ± 22.4 µg/mL) was substantially higher than in plasma (0.7 ± 0.05 µg/mL), demonstrating targeted drug retention. These results indicate that our nanocarrier system effectively reduced tumor development with low systemic exposure.

Chloroxine inhibits pancreatic cancer progression through targeted antagonization of the PI3K/AKT/mTOR signaling pathway.

BACKGROUND: Patients with pancreatic cancer have a dismal prognosis due to tumor cell infiltration and metastasis. Many reports have documented that EMT and PI3K-AKT-mTOR axis control pancreatic cancer cell infiltration and metastasis. Chloroxine is an artificially synthesized antibacterial compound that demonstrated anti-pancreatic cancer effects in our previous drug-screening trial. We have explored the impact of chloroxine on pancreatic cancer growth, infiltration, migration, and apoptosis. METHODS: The proliferation of pancreatic cancer cell lines (PCCs) treated with chloroxine was assessed through real-time cell analysis (RTCA), colony formation assay, CCK-8 assay, as well as immunofluorescence. Chloroxine effects on the infiltrative and migratory capacities of PCCs were assessed via Transwell invasion and scratch experiments. To assess the contents of EMT- and apoptosis-associated proteins in tumor cells, we adopted Western immunoblotting as well as immunofluorescence assays, and flow cytometry to determine chloroxine effects on PCCs apoptosis. The in vivo chloroxine antineoplastic effects were explored in nude mice xenografts. RESULTS: Chloroxine repressed pancreatic cancer cell growth, migration, and infiltration in vitro, as well as in vivo, and stimulated apoptosis of the PCCs. Chloroxine appeared to inhibit PCC growth by Ki67 downregulation; this targeted and inhibited aberrant stimulation of the PI3K-AKT-mTOR signaling cascade, triggered apoptosis in PCC via mitochondria-dependent apoptosis, and modulated the EMT to inhibit PCC infiltration and migration. CONCLUSIONS: Chloroxine targeted and inhibited the PI3K-AKT-mTOR cascade to repress PCCs growth, migration, as well as invasion, and triggered cellular apoptosis. Therefore, chloroxine may constitute a potential antineoplastic drug for the treatment of pancreatic cancer.

Intravenous prostaglandin E1 (alprostadil) bolus in ductus arteriosus-dependent CHD: valid or absolutely contraindicated?

The use of prostaglandin E1 is well documented in ductus arteriosus-dependent CHD or in neonatal pulmonary pathologies that cause severe pulmonary hypertension. The intravenous infusion is well established in loading infusion and maintenance with an onset of action of 30 minutes until 2 hours or even more. Our aim is to report three patients with pulmonary atresia that presented hypercyanotic spell due to a ductal spasm during cardiac catheterisation in whom the administration of a bolus of alprostadil reversed the spasm and increased pulmonary flow, immediately stabilising the condition of the patients allowing subsequent successful stent placement with no serious complications or sequelae after the administration of the bolus. More studies are needed to make a recommendation regarding the use of alprostadil in bolus in cases where the ductal spasm might jeopardise the life of the patient.

Sobrevida del adenocarcinoma ductal de páncreas

El objetivo de este trabajo es analizar la presentación epidemiológica y la sobrevida de los pacientes con adenocarcinoma ductal de páncreas de acuerdo con su estadío clínico y al tipo de intervención realizada, en una cohorte de pacientes atendidos en una clínica en Lima, Perú. Estudio de cohortes retrospectivas que evaluó desde enero del 2015 a febrero del 2021 a pacientes con diagnóstico de adenocarcinoma ductal de páncreas considerando diversos factores epidemiológicos, radiológicos, estadiaje oncológico, haber recibido quimioterapia neoadyuvante o adyuvante, haber sido sometidos a cirugía y la sobrevida posterior a alguna de las intervenciones realizadas. De los 249 pacientes analizados, se encontró que 75 de ellos requerían cirugía resectiva. Entre los principales resultados obtenidos, se observó que aquellos con un nivel de CA 19-9 menor a 200 U/mL presentaban una media de sobrevida más alta en comparación con aquellos cuyo nivel de CA 19-9 era superior a 200 U/mL (HR: 1,96; IC95%: 0,18-0,53; p≤0,001). Asimismo, al comparar a los pacientes según su etapa, se encontró que aquellos con tumores resecables tenían una media de sobrevida de 37,72 meses, mientras que aquellos con tumores localmente avanzados tenían una media de sobrevida de 13,47 meses y aquellos con tumores metastásicos tenían una media de sobrevida de 7,69 meses (HR: 0,87; IC95%: 0,31-0,25; p≤0,001). Igualmente, se observó que recibir tratamiento neoadyuvante se asociaba con un mejor pronóstico de sobrevida para los pacientes (HR: 0,32; IC95%: 0,19-0,53; p≤0,001). Asimismo, se llevaron a cabo 5 pancreatectomías con resección metastásica en pacientes oligometastásicos tratados con quimioterapia de rescate, y se encontró que la media de sobrevida para estos pacientes fue de 22,51 meses. Conclusión: La cirugía resectiva en un estadío clínico temprano , presentar valores de CA 19-9 por debajo de 200 U/mL y haber recibido quimioterapia neoadyuvante se correlaciona estadísticamente con una mayor esperanza de sobrevida.

The objective of this study is to analyze the epidemiological presentation and survival of patients with pancreatic ductal adenocarcinoma according to their clinical stage and the type of intervention performed, in a cohort of patients treated at a clinic in Lima, Peru. A retrospective cohort study evaluated patients diagnosed with pancreatic ductal adenocarcinoma from January 2015 to February 2021, considering various epidemiological factors, radiological findings, oncological staging, receipt of neoadjuvant or adjuvant chemotherapy, undergoing surgery, and post-intervention survival. Out of the 249 patients analyzed, 75 of them required resective surgery. Among the main findings, it was observed that those with a CA 19-9 level below 200 U/mL had a higher median survival compared to those with a CA 19-9 level above 200 U/mL (HR: 1.96; 95% CI: 0.18-0.53; p≤0.001). Furthermore, when comparing patients according to their stage, those with resectable tumors had a median survival of 37.72 months, while those with locally advanced tumors had a median survival of 13.47 months, and those with metastatic tumors had a median survival of 7.69 months (HR: 0.87; 95% CI: 0.31-0.25; p≤0.001). Additionally, receiving neoadjuvant treatment was associated with a better prognosis of survival for patients (HR: 0.32; 95% CI: 0.19-0.53; p≤0.001). Furthermore, 5 pancreatectomies with metastatic resection were performed in oligometastatic patients treated with salvage chemotherapy, and the median survival for these patients was 22.51 months. Conclusion: Resective surgery at an early clinical stage, CA 19-9 levels below 200 U/mL, and receiving neoadjuvant chemotherapy are statistically correlated with a higher overall survival.

A more radical perspective on surgical approach and outcomes in pancreatic cancer-a narrative review.

Background and Objective: Pancreatic adenocarcinoma remains a dismal disease and is expected to become an even greater burden in the near future. This review focuses on the different surgical aspects for pancreaticoduodenectomy (PD), distal and total pancreatectomy (TP), incorporating lessons from both the western and eastern visions in treating pancreatic cancer. Methods: We conducted an extensive literature review through PubMed, prioritizing papers published in the last 5 years, but older emblematic papers were also included. We included articles that explored the treatment of pancreatic adenocarcinoma, with focus on the surgical aspect and strategies to improve outcomes. References of selected articles were also reviewed to identify any missed studies. Only papers in English were included. Key Content and Findings: As evidence continues to build, it is clear that both systemic and surgical therapies have a fundamental and complementary role. State of art surgical treatment encompasses complete mesopancreas excision for radical lymphadenectomy. Preoperative planning of dissection planes, extensive knowledge of vascular anatomic variations, oncological principles and expertise for vascular resections are mandatory to perform a more radical operation, in pursuit of improved outcomes. Conclusions: Based on current data, patient selection remains key and a more radical surgical approach brings more accomplishing results bringing as to believe that more is better.

Incidence and Clinical Implications of Anatomical Variations in the Pancreas and Its Ductal System: A Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review analyzes the anatomical variants in the pancreas and its ductal system to report on their association with pancreatic pathologies. METHODS: We conducted a search of the MEDLINE, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS databases from their inception to July 2023. The methodological quality was assessed with the Anatomical Quality Assessment (AQUA) tool. Finally, the pooled prevalence was estimated using a random effects model. RESULTS: 55 studies were found that met the eligibility criteria. The overall prevalence of pancreas divisum (PD) was 18% (95% CI = 15-21%). The prevalence of PD associated with pancreatitis was 30% (95% CI = 1-61%). CONCLUSIONS: An anatomical variant of the pancreas such as PD may be the cause of bile duct obstruction, resulting in various clinical complications, such as pancreatitis. Hence, knowing this variant is extremely important for surgeons, especially for those who treat the gastroduodenal region.

Comprehensive analysis and identification of prognostic biomarkers and immunotherapeutic targets in the NADPH oxidase family (and its regulatory subunits) in pancreatic ductal adenocarcinoma.

PURPOSE: This study aimed to evaluate the role of NADPH in pancreatic ductal adenocarcinoma using bioinformatic analyses and experimental validations. METHODS: We compared the expression levels, performed GO and KEGG analysis of NADPH oxidase family and its regulatory subunits, and determined the survival of patients with pancreatic ductal adenocarcinoma by GEPIA, David and KM plotter. The relationship between their expression with immune infiltration levels, phagocytotic/NK cell immune checkpoints, recruitment-related molecules were detected by Timer 2.0 and TISIDB, respectively. Subsequently, their correlation with NK cell infiltration level was verified by immunohistochemistry. RESULTS: The expression of some members of the NADPH oxidase family and its regulatory subunits was significantly increased in pancreatic ductal adenocarcinoma tissues compared to that in normal tissues and was positively correlated with natural killer (NK) cell infiltration. Furthermore, the NADPH oxidase family and its regulatory subunits were associated with survival and immune status in patients with pancreatic ductal adenocarcinoma, including chemokines, immune checkpoints, and immune infiltration levels of NK cells, monocytes, and myeloid-derived suppressor cells. CONCLUSIONS: These results suggest the NADPH oxidase family and its regulatory subunits might serve as indicators for predicting the responsiveness to immunotherapy and outcome of patients with pancreatic ductal adenocarcinoma, providing a new perspective or strategy for immunotherapy in pancreatic ductal adenocarcinoma.

Transcriptomic Profile of Canine Mammary Ductal Carcinoma.

Dogs can be excellent models for spontaneous studies about breast cancers, presenting similarities in clinical behavior and molecular pathways of the disease. Thus, analyses of the canine transcriptome can identify deregulated genes and pathways, contributing to the identification of biomarkers and new therapeutic targets, benefiting humans and animals. In this context, this study aimed to determine the transcriptional profile of canine mammary ductal carcinoma and contribute to the clarification of the importance of deregulated molecules in the molecular pathways involved in the disease. Therefore, we used mammary ductal carcinoma tissue samples and non-tumor mammary tissue from the radical mastectomy of six female dogs. Sequencing was performed on the NextSeq-500 System platform. A comparison of carcinoma tissue and normal tissue revealed 633 downregulated and 573 upregulated genes, which were able to differentiate the groups by principal component analysis. Gene ontology analysis indicated that inflammatory, cell differentiation and adhesion, and extracellular matrix maintenance pathways were mainly deregulated in this series. The main differentially expressed genes observed in this research can indicate greater disease aggressiveness and worse prognosis. Finally, the study of the canine transcriptome indicates that it is an excellent model to generate information relevant to oncology in both species.

Technical Implications for Surgical Resection in Locally Advanced Pancreatic Cancer.

Pancreatic ductal adenocarcinoma remains a global health challenge and is predicted to soon become the second leading cause of cancer death in developed countries. Currently, surgical resection in combination with systemic chemotherapy offers the only chance of cure or long-term survival. However, only 20% of cases are diagnosed with anatomically resectable disease. Neoadjuvant treatment followed by highly complex surgical procedures has been studied over the last decade with promising short- and long-term results in patients with locally advanced pancreatic ductal adenocarcinoma (LAPC). In recent years, a wide variety of complex surgical techniques that involve extended pancreatectomies, including portomesenteric venous resection, arterial resection, or multi-organ resection, have emerged to optimize local control of the disease and improve postoperative outcomes. Although there are multiple surgical techniques described in the literature to improve outcomes in LAPC, the comprehensive view of these strategies remains underdeveloped. We aim to describe the preoperative surgical planning as well different surgical resections strategies in LAPC after neoadjuvant treatment in an integrated way for selected patients with no other potentially curative option other than surgery.

Role of imaging in the applicability of irreversible electroporation for the management of pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma is one of the most aggressive malignant neoplasms, with a one-year survival rate below 20%. Axial methods (computed tomography and magnetic resonance imaging) play a fundamental role in the diagnosis and staging of the disease, because they provide adequate anatomical resolution in the assessment of key structures, mainly vascular structures. Pancreatic ductal adenocarcinoma is most often discovered in advanced stages, when surgical resection is no longer feasible. In that scenario, minimally invasive treatment alternatives have been developed in attempts to change the natural history of the disease. Irreversible electroporation, an interventional procedure that minimizes deleterious effects on adjacent tissues, has proven useful for the treatment of tumors traditionally considered unresectable. Despite the growing acknowledgment of this technique as a tool for the management of pancreatic ductal adenocarcinoma, it is still relatively unknown among radiologists. In this study, we sought to provide an overview of the main characteristics and eligibility criteria that must be considered for the indication of irreversible electroporation in cases of pancreatic ductal adenocarcinoma.

O adenocarcinoma ductal de pâncreas é uma das neoplasias malignas mais agressivas, com taxas de sobrevivência anuais inferiores a 20%. Os métodos axiais (tomografia computadorizada e ressonância magnética) têm papel fundamental no diagnóstico e estadiamento da doença, por fornecerem adequada resolução anatômica na avaliação de estruturas-chave, principalmente vasculares. O adenocarcinoma ductal de pâncreas é frequentemente descoberto em estágios avançados e sem viabilidade de ressecção cirúrgica, e nesse cenário o desenvolvimento de alternativas terapêuticas minimamente invasivas tem sido ainda mais importante para a mudança de sua história natural. A eletroporação irreversível, procedimento intervencionista que minimiza efeitos deletérios nos tecidos adjacentes, vem se destacando no tratamento de lesões tradicionalmente consideradas irressecáveis. Essa técnica, apesar de ganhar cada vez mais espaço no manejo terapêutico do adenocarcinoma ductal de pâncreas, ainda é pouco familiar aos radiologistas. Neste estudo, buscamos expor, de forma sucinta e didática, os fundamentos da técnica, as principais características de imagem e os critérios de elegibilidade que devem ser considerados para indicação da eletroporação irreversível nessa doença.

New thoughts and findings on invasion and metastasis of pancreatic ductal adenocarcinoma (PDAC) from comparative proteomics: multi-target therapy.

As one of the most aggressive malignant tumors, pancreatic ductal adenocarcinoma (PDAC) ranks as the fourth cancer-related mortality in the world. The extremely low survival rate is closely related to early invasion and distant metastasis. However, effective target therapy for weakening its malignant behavior remains limited. Over the past decades, many proteins correlating with invasion and metastasis of PDAC have been discovered using proteomics. The discovery of these proteins gives us a deeper understanding of the invasive and migratory processes of PDAC. This review is a systemic integration of these proteomics findings over the past 10 years. The discovered proteins were typically associated with the glycolytic process, hypoxic microenvironment, post-translational modification, extracellular matrix, exosomes, cancer stem cells, and immune escape. Some proteins were found to have multiple functions, and, cooperation between different proteins in the invasive and metastatic processes was found. This cooperation, and not just single protein function, may play a more significant role in the poor prognosis of PDAC. Therefore, multi-target therapy against these cooperative networks should be a primary choice in the future.