Assessment of Patient-Derived Xenograft Growth and Antitumor Activity: The NCI PDXNet Consensus Recommendations.

Although patient-derived xenografts (PDXs) are commonly used for preclinical modeling in cancer research, a standard approach to in vivo tumor growth analysis and assessment of antitumor activity is lacking, complicating comparison of different studies and determination of whether a PDX experiment has produced evidence needed to consider a new therapy promising. We present consensus recommendations for assessment of PDX growth and antitumor activity, providing public access to a suite of tools for in vivo growth analyses. We expect that harmonizing PDX study design and analysis and access to a suite of analytical tools will enhance information exchange and facilitate identification of promising novel therapies and biomarkers for guiding cancer therapy.

A Gravid Situation: General Surgery Faculty Support for Pregnant Surgical Residents.

INTRODUCTION: The perceptions of teaching faculty toward pregnant general surgery residents have been overlooked despite the daily interactions amongst these groups. METHODS: A 32-question survey designed to measure general surgery teaching faculty perceptions toward pregnant residents was distributed electronically from March 2022 to April 2022 to general surgery teaching faculty in the United States. Descriptive statistics were used to characterize responses and differences in perceptions, and qualitative analysis identified recurring themes from free-text responses. RESULTS: Among 163 respondents included in the final analysis, 58.5% were male and 41.5% were female. Despite 99.4% of surgeons feeling comfortable if a resident told them they were pregnant, 22.4% of surgeons disagreed that their institutions have supportive cultures toward pregnancy. Almost half (45.4%) have witnessed negative comments about pregnant residents and half (50.3%) believe that pregnant surgical residents are discriminated against by their coresidents. Nearly two-thirds of surgeons (64.8%) believe that someone should have a child whenever they wish during training. Given recent reports, 80.2% of surgeons recognized that female surgeons have increased risks of infertility and pregnancy complications. Recurring themes of normalizing pregnancy, improving policies, and creating a culture change were expressed. CONCLUSIONS: In this national survey, although there appears to be positive perceptions of pregnancy in surgical training amongst those surveyed, there is acknowledged necessity of further normalizing pregnancy and improving policies to better support pregnant residents. These data provide further evidence that though perceptions may be improving, changes are still needed to better support pregnancy during training.

Tension Distribution in Articular Surfaces of the Rotator Cable and Crescent: A Cadaveric Study.

BACKGROUND: The rotator cable functions as a stress and/or load transfer structure. Some studies suggested that a disruption of the cable negatively affects shoulder function and tendon integrity in patients with rotator cuff tears, while others found no functional impairment regardless of rotator cable tear severity. Although anatomical studies have identified distinct regions within the rotator cuff muscles, the strain distribution within the articular sides of the rotator cuff tendons that results from the tension in each region remains unknown. We hypothesized that the posterior region of the supraspinatus (SSP) muscle and the middle region of the infraspinatus (ISP) muscle, with their firm capsular attachments to the cable, transmit 3D strains, and thus tension, to the whole cable, leading to differences in tension within the cable. METHODS: The 3D strain distributions in the articular sides of the SSP and ISP tendons of 8 fresh-frozen cadaveric intact shoulders were determined when tension was applied to the various SSP and ISP muscle regions. RESULTS: Loading the anterior SSP muscle region yielded significantly higher strains in the anterior third of the cable compared with the posterior third (p < 0.05). Loading the posterior SSP muscle region yielded no significant differences among the cable and crescent regions. Loading the middle ISP muscle region yielded higher strains in the anterior and posterior thirds of the cable compared with the middle third (p < 0.01). Loading the superior ISP muscle region yielded no significant differences among the cable and crescent regions (p > 0.05). CONCLUSIONS: Tension generated from the posterior region of the SSP muscle and middle region of the ISP muscle was evenly distributed to the anterior and posterior attachments of the rotator cable, while the tension generated from other SSP and ISP muscle regions was locally transmitted to the respective attachment area. CLINICAL RELEVANCE: The rotator cable and crescent serve pivotal roles in transmitting tension generated from the deep regions of the rotator cuff muscles, i.e., the posterior SSP and middle ISP. These findings indicate that both the rotator cable and the rotator crescent play crucial roles as tension transmitters for the deep regions of the rotator cuff muscles. This information could have important implications for developing anatomically relevant repair techniques and enhancing rehabilitation protocols.

Oncogene-induced matrix reorganization controls CD8+ T cell function in the soft-tissue sarcoma microenvironment.

CD8+ T cell dysfunction impedes antitumor immunity in solid cancers, but the underlying mechanisms are diverse and poorly understood. Extracellular matrix (ECM) composition has been linked to impaired T cell migration and enhanced tumor progression; however, impacts of individual ECM molecules on T cell function in the tumor microenvironment (TME) are only beginning to be elucidated. Upstream regulators of aberrant ECM deposition and organization in solid tumors are equally ill-defined. Therefore, we investigated how ECM composition modulates CD8+ T cell function in undifferentiated pleomorphic sarcoma (UPS), an immunologically active desmoplastic tumor. Using an autochthonous murine model of UPS and data from multiple human patient cohorts, we discovered a multifaceted mechanism wherein the transcriptional coactivator YAP1 promotes collagen VI (COLVI) deposition in the UPS TME. In turn, COLVI induces CD8+ T cell dysfunction and immune evasion by remodeling fibrillar collagen and inhibiting T cell autophagic flux. Unexpectedly, collagen I (COLI) opposed COLVI in this setting, promoting CD8+ T cell function and acting as a tumor suppressor. Thus, CD8+ T cell responses in sarcoma depend on oncogene-mediated ECM composition and remodeling.

Infiltration of CD3+ and CD8+ lymphocytes in association with inflammation and survival in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins. METHODS: Tissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath. Levels of inflammation-associated proteins were quantified by multiplexed, enzyme-linked immunosorbent assay panels on matching tumor and tissue samples. RESULTS: Our findings revealed a significant increase in both CD3+ and CD8+ lymphocytes populations in PDAC compared with non-PDAC tissue, except when comparing CD8+ percentages in PDAC versus intraductal papillary mucinous neoplasms (IPMN) (p = 0.5012). Patients with quantitatively assessed CD3+ low tumors (lower 50%) had shorter survival (median 273 days) compared to CD3+ high tumors (upper 50%) with a median overall survival of 642.5 days (p = 0.2184). Patients with quantitatively assessed CD8+ low tumors had significantly shorter survival (median 240 days) compared to CD8+ high tumors with a median overall survival of 1059 days (p = 0.0003). Of 41 proteins assessed in the inflammation assay, higher levels of IL-1B and IL-2 were significantly associated with decreased CD3+ infiltration (r = -0.3704, p = 0.0187, and r = -0.4275, p = 0.0074, respectively). Higher levels of IL-1B were also significantly associated with decreased CD8+ infiltration (r = -0.4299, p = 0.0045), but not IL-2 (r = -0.0078, p = 0.9616). Principal component analysis of the inflammatory analytes showed diverse inflammatory responses in PDAC. CONCLUSION: In this work, we found a marked heterogeneity in infiltrating CD3+ and CD8+ lymphocytes and individual inflammatory responses in PDAC. Future mechanistic studies should explore personalized therapeutic strategies to target the immune and inflammatory components of the tumor microenvironment.

Cooperation between PRMT1 and PRMT6 drives lung cancer health disparities among Black/African American men.

Lung cancer is the third most common cancer with Black/AA men showing higher risk and poorer outcomes than NHW men. Lung cancer disparities are multifactorial, driven by tobacco exposure, inequities in care access, upstream health determinants, and molecular determinants including biological and genetic factors. Elevated expressions of protein arginine methyltransferases (PRMTs) correlating with poorer prognosis have been observed in many cancers. Most importantly, our study shows that PRMT6 displays higher expression in lung cancer tissues of Black/AA men compared to NHW men. In this study, we investigated the underlying mechanism of PRMT6 and its cooperation with PRMT1 to form a heteromer as a driver of lung cancer. Disrupting PRMT1/PRMT6 heteromer by a competitive peptide reduced proliferation in non-small cell lung cancer cell lines and patient-derived organoids, therefore, giving rise to a more strategic approach in the treatment of Black/AA men with lung cancer and to eliminate cancer health disparities.

Metastatic Uterine Leiomyosarcoma presenting as small bowel intussusception at two independent visits.

•Metastatic disease to the small bowel may present with intussusception.•Clinical decision making for malignant bowel obstruction is difficult and individual specific.•Malignant bowel obstruction due to metastatic year has an average life expectancy of less than 200 days.

Heterogeneity of weight loss and transcriptomic signatures in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is highly associated with cachexia and weight loss, which is driven by the tumour's effect on the body. Data are lacking on differences in these metrics based on PDAC anatomic location. We hypothesize that the primary tumour's anatomic region influences the prevalence and severity of unintentional weight loss. METHODS: Treatment naïve patients with PDAC who underwent pancreatectomy at a single institution between 2012 and 2020 were identified retrospectively. Patients with pancreatic head or distal tumours were matched by sex, age, N and T stage. Serologic and anthropometric variables were obtained at the time of diagnosis. Skeletal muscle index (SMI), muscle radiation attenuation (MRA) and adiposity were measured. The primary outcome was presence of significant weight loss [>5% body weight (BW) loss in past 6 months]. Signed rank tests, Cochran Mantel Haenszel tests and Kaplan-Meier survival analysis are presented. RNA-seq of tumours was performed to explore enriched pathways related to cachexia and weight loss. RESULTS: Pancreatic head tumours (n = 24) were associated with higher prevalence (70.8% vs. 41.7%, P = 0.081) and degree of weight loss (7.9% vs. 2.5%, P = 0.014) compared to distal tumours (n = 24). BMI (P = 0.642), SMI (P = 0.738) and MRA (P = 0.478) were similar between groups. Combining BW loss, SMI and MRA into a composite score, patients with pancreatic head cancers met more criteria associated with poor prognosis (P = 0.142). Serum albumin (3.9 vs. 4.4 g/dL, P = 0.002) was lower and bilirubin (4.5 vs. 0.4 mg/dL, P < 0.001) were higher with pancreatic head tumours. Survival differed by tumour location (P = 0.014) with numerically higher median overall survival with distal tumours (11.1 vs. 21.8 months; P = 0.066). Transcriptomic analysis revealed inactivation of appetite stimulation, weight regulation and nutrient digestion/metabolism pathways in pancreatic head tumours. CONCLUSIONS: Resectable pancreatic head PDAC is associated with higher prevalence of significant weight loss and more poor prognosis features. Pancreaticobiliary obstruction and hypoalbuminemia in patients with head tumours suggests compounding effects of nutrient malabsorption and systemic inflammation on molecular drivers of cachexia, possibly contributing to shorter survival. Therefore, PDAC-associated cachexia is a heterogenous syndrome, which may be influenced by the primary tumour location. Select patients with resectable pancreatic head tumours may benefit from nutritional rehabilitation to improve outcomes.

Discovery of KRB-456, a KRAS G12D Switch-I/II Allosteric Pocket Binder That Inhibits the Growth of Pancreatic Cancer Patient-derived Tumors.

Currently, there are no clinically approved drugs that directly thwart mutant KRAS G12D, a major driver of human cancer. Here, we report on the discovery of a small molecule, KRB-456, that binds KRAS G12D and inhibits the growth of pancreatic cancer patient-derived tumors. Protein nuclear magnetic resonance studies revealed that KRB-456 binds the GDP-bound and GCP-bound conformation of KRAS G12D by forming interactions with a dynamic allosteric binding pocket within the switch-I/II region. Isothermal titration calorimetry demonstrated that KRB-456 binds potently to KRAS G12D with 1.5-, 2-, and 6-fold higher affinity than to KRAS G12V, KRAS wild-type, and KRAS G12C, respectively. KRB-456 potently inhibits the binding of KRAS G12D to the RAS-binding domain (RBD) of RAF1 as demonstrated by GST-RBD pulldown and AlphaScreen assays. Treatment of KRAS G12D-harboring human pancreatic cancer cells with KRB-456 suppresses the cellular levels of KRAS bound to GTP and inhibits the binding of KRAS to RAF1. Importantly, KRB-456 inhibits P-MEK, P-AKT, and P-S6 levels in vivo and inhibits the growth of subcutaneous and orthotopic xenografts derived from patients with pancreatic cancer whose tumors harbor KRAS G12D and KRAS G12V and who relapsed after chemotherapy and radiotherapy. These results warrant further development of KRB-456 for pancreatic cancer. SIGNIFICANCE: There are no clinically approved drugs directly abrogating mutant KRAS G12D. Here, we discovered a small molecule, KRB-456, that binds a dynamic allosteric binding pocket within the switch-I/II region of KRAS G12D. KRB-456 inhibits P-MEK, P-AKT, and P-S6 levels in vivo and inhibits the growth of subcutaneous and orthotopic xenografts derived from patients with pancreatic cancer. This discovery warrants further advanced preclinical and clinical studies in pancreatic cancer.

Case report: Buschke-Lowenstein tumor, a giant anal condyloma acuminata.

24-year-old man with positive HIV, with a giant exofitic anal condyloma, with a clinical presentation of a painfull suppurative anal condyloma with a pathology report of an in situ squamous cell carcinoma. The purpose of the investigation is a case report and the procedure was observational. The finding was a Buschke-Lowenstein tumor.

Varón de 24 años, con infección por el virus de la inmunodeficiencia humana, que presenta una tumoración exofítica, dolorosa y supurativa, con reporte positivo de virus de papiloma humano y reporte histopatológico de carcinoma espinocelular sin evidencia de diseminación (in situ). El propósito de la investigación es un reporte de caso y el procedimientos fue observacional. El hallazgo fue un tumor de Buschke-Lowenstein.

Cytoplasmic-delivery of polyinosine-polycytidylic acid inhibits pancreatic cancer progression increasing survival by activating Stat1-CCL2-mediated immunity.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer without effective therapies and with poor prognosis, causing 7% of all cancer-related fatalities in the USA. Considering the lack of effective therapies for this aggressive cancer, there is an urgent need to define newer and more effective therapeutic strategies. Polyinosine-polycytidylic acid (pIC) is a synthetic double-stranded RNA (dsRNA) which directly activates dendritic cells and natural killer cells inhibiting tumor growth. When pIC is delivered into the cytoplasm using polyethyleneimine (PEI), pIC-PEI, programmed-cell death is induced in PDAC. Transfection of [pIC]PEI into PDAC cells inhibits growth, promotes toxic autophagy and also induces apoptosis in vitro and in vivo in animal models. METHODS: The KPC transgenic mouse model that recapitulates PDAC development in patients was used to interrogate the role of an intact immune system in vivo in PDAC in response to [pIC]PEI. Antitumor efficacy and survival were monitored endpoints. Comprehensive analysis of the tumor microenvironment (TME) and immune cells, cytokines and chemokines in the spleen, and macrophage polarization were analyzed. RESULTS: Cytosolic delivery of [pIC]PEI induces apoptosis and provokes strong antitumor immunity in vivo in immune competent mice with PDAC. The mechanism underlying the immune stimulatory properties of [pIC]PEI involves Stat1 activation resulting in CCL2 and MMP13 stimulation thereby provoking macrophage polarization. [pIC]PEI induces apoptosis via the AKT-XIAP pathway, as well as macrophage differentiation and T-cell activation via the IFNγ-Stat1-CCL2 signaling pathways in PDAC. In transgenic tumor mouse models, [pIC]PEI promotes robust and profound antitumor activity implying that stimulating the immune system contributes to biological activity. The [pIC]PEI anti-PDAC effects are enhanced when used in combination with a standard of care (SOC) treatment, that is, gemcitabine. CONCLUSIONS: In summary, [pIC]PEI treatment is non-toxic toward normal pancreatic cells while displaying strong cytotoxic and potent immune activating activities in PDAC, making it an attractive therapeutic when used alone or in conjunction with SOC therapeutic agents, potentially providing a safe and effective treatment protocol with translational potential for the effective therapy of PDAC.

CellNeighborEX: deciphering neighbor-dependent gene expression from spatial transcriptomics data.

Cells have evolved their communication methods to sense their microenvironments and send biological signals. In addition to communication using ligands and receptors, cells use diverse channels including gap junctions to communicate with their immediate neighbors. Current approaches, however, cannot effectively capture the influence of various microenvironments. Here, we propose a novel approach to investigate cell neighbor-dependent gene expression (CellNeighborEX) in spatial transcriptomics (ST) data. To categorize cells based on their microenvironment, CellNeighborEX uses direct cell location or the mixture of transcriptome from multiple cells depending on ST technologies. For each cell type, CellNeighborEX identifies diverse gene sets associated with partnering cell types, providing further insight. We found that cells express different genes depending on their neighboring cell types in various tissues including mouse embryos, brain, and liver cancer. Those genes are associated with critical biological processes such as development or metastases. We further validated that gene expression is induced by neighboring partners via spatial visualization. The neighbor-dependent gene expression suggests new potential genes involved in cell-cell interactions beyond what ligand-receptor co-expression can discover.

Changing Practice Patterns and Improving Survival for Patients with Pancreatic Ductal Adenocarcinoma.

Over the last two decades, there have been many reported advances in the clinical management of pancreatic ductal adenocarcinoma (PDAC). We sought to evaluate changes in survival for patients diagnosed with PDAC between 2004 and 2017. The National Cancer Database was queried for patients diagnosed with PDAC between 2004 and 2017. There were 55,401 patients who underwent surgery and 109,477 patients who underwent non-surgical treatment for PDAC between 2004 and 2017. Patients were categorized into four groups by year of diagnosis. Median survival improved from 15.5 months to 25.3 months for patients treated with surgery between the years 2016 and 2017 compared with between 2004 and 2007 (p < 0.001). Median survival improved from 7.2 months to 10.1 months for patients treated without surgery during the same years (p < 0.001). On multivariable analysis, the hazard ratio for death was estimated to multiply by 0.975 per year for patients treated with surgery and 0.959 per year for patients treated without surgery (p < 0.001). This increase in survival in the setting of evolving care validates continued efforts aimed at improving survival for patients with this devastating disease.

Race and Ethnicity Impacts Overall Survival of Patients with Appendiceal Cancer Who Undergo Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

Appendiceal cancer treatment may include cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). We investigated whether patient race/ethnicity influences outcomes and overall survival for patients with appendiceal cancer who undergo CRS/HIPEC. We queried the National Cancer Database for adult patients with appendiceal cancer treated with CRS/HIPEC from 2006 to 2018. Patients were stratified by race/ethnicity: non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic, and Other. Sociodemographics and outcomes were compared using descriptive statistics. Kaplan-Meier survival analysis and Log-rank tests assessed differences in overall survival (OS). Cox Multivariate Regression evaluated factors associated with OS. In total, 2532 patients were identified: 2098 (82.9%) NHW, 186 (7.3%) NHB, 127 (5.0%) Hispanic, and 121 (4.8%) Other patients. The sociodemographics were statistically different across groups. The perioperative and postoperative outcomes were similar. OS was significantly different by race/ethnicity (p = 0.0029). NHB patients compared to Hispanic patients had the shortest median OS (106.7 vs. 145.9 months, p = 0.0093). Race/ethnicity was independently associated with OS: NHB (HR: 2.117 [1.306, 3.431], p = 0.0023) and NHW (HR: 1.549 [1.007, 2.383], p = 0.0463) patients compared to Hispanic patients had worse survival rates. Racial/ethnic disparities exist for patients with appendiceal cancer undergoing CRS/HIPEC. Despite having similar tumor and treatment characteristics, OS is associated with patient race/ethnicity.

Racial/Ethnic Disparities in the Era of Minimally Invasive Surgery for Treatment of Colorectal Cancer.

BACKGROUND: Minimally invasive (laparoscopic and robotic) surgery (MIS) for colorectal cancer is associated with improved outcomes. We sought to characterize possible disparities in surgical approach and outcomes. PATIENTS AND METHODS: In this cross-sectional study, colorectal adenocarcinoma cases among non-Hispanic white (NHW), non-Hispanic Black (NHB), and Hispanic patients were identified using the National Cancer Database (2010-2017). Logistic and Poisson regressions, generalized logit models, and Cox proportional hazards were used to assess outcomes, with reclassification of surgery type if converted to open. RESULTS: NHB patients were less likely to undergo robotic surgery. After multivariable analysis, NHB patients were 6% less likely, while Hispanic patients were 12% more likely to undergo a MIS approach. Lymph node retrieval was higher (> 1.3% more, p < 0.0001) and length of stay was shorter (> 17% shorter, p < 0.0001) for MIS approaches. Unplanned readmission was lower for MIS colon cancer operations compared with open operations, but not for rectal cancer. Race/ethnicity-adjusted risk of death was lower with MIS approaches for colon as well as rectal cancer. After adjusting for surgery type, risk of death was 12% lower for NHB and 35% lower for Hispanic patients compared with NHW patients. Hispanic patients had 21% lower risk of death, while NHB patients had 12% higher risk of death than NHW patients with rectal cancer, after adjusting for surgery type. CONCLUSIONS: Racial/ethnic disparities exist in utilization of MIS for colorectal cancer treatment, disproportionately affecting NHB patients. Since MIS has the potential to improve outcomes, suboptimal access may contribute to harmful and thus unacceptable disparities in survivorship.

Moment arms of the anatomical subregions of the rotator cuff muscles during shoulder rotation.

BACKGROUND: Rotator cuff muscles are responsible for humeral rotation. Moment arms of different regions of these muscles during humeral rotation were analyzed in neutral and abducted positions. METHODS: In eight cadaveric shoulders, subregions of the rotator cuff muscles were identified and their excursion during humeral rotation was measured in neutral and abducted positions from an internal rotation of 30° to an external rotation of 45°, with 15° increments, using a 3-D digitizing system. Statistical tests were used to assess differences between subregions within a single muscle. FINDINGS: The posterior-deep subregion of the supraspinatus muscle had greater moment arms compared to the anterior-superficial and anterior-middle subregions in both positions (p < 0.001). The middle and inferior subregions of the infraspinatus muscle and the teres minor muscle showed differences in moment arms compared to the superior region in an abducted position (p < 0.042). The superior subregion of the subscapularis muscle showed differences in moment arms compared to the middle and inferior subregions in an abducted position (p < 0.001). INTERPRETATION: The posterior-deep subregion of the supraspinatus muscle behaved similar to the infraspinatus muscle, as an external rotator. The anterior-superficial and anterior-middle subregions of the supraspinatus muscle showed a biphasic behavior during rotation at a neutral position, but acted as pure external rotators during rotation at an abducted position. Inferior subregions of the infraspinatus and subscapularis muscles showed the largest moment arms compared to superior subregions. These findings support distinct functional roles of the rotator cuff muscle subregions.

In vivo models of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high mortality rate. Within the next decade, PDAC is projected to become the second leading cause of cancer-associated death in the United States. Understanding the pathophysiology of PDAC tumorigenesis and metastases is crucial toward developing new therapeutics. One of the challenges in cancer research is generating in vivo models that closely recapitulate the genomic, histological, and clinical characteristics of human tumors. An ideal model for PDAC not only captures the tumor and stromal environment of human disease, but also allows for mutational control and is easy to reproduce in terms of time and cost. In this review, we highlight evolution of in vivo models for PDAC including spontaneous tumors models (i.e., chemical induction, genetic modification, viral delivery), implantation models including patient derived xenografts (PDX), and humanized PDX. We discuss the implementation of each system and evaluate the benefits and shortcomings of these models. Overall, this review provides a broad overview of prior and current techniques of in vivo PDAC modeling and their associated challenges.

Translocation of Oral Microbiota into the Pancreatic Ductal Adenocarcinoma Tumor Microenvironment.

Oral dysbiosis has long been associated with pancreatic ductal adenocarcinoma (PDAC). In this work, we explore the relationship between the oral and tumor microbiomes of patients diagnosed with PDAC. Salivary and tumor microbiomes were analyzed using a variety of sequencing methods, resulting in a high prevalence and relative abundance of oral bacteria, particularly Veillonella and Streptococcus, within tumor tissue. The most prevalent and abundant taxon found within both saliva and tumor tissue samples, Veillonella atypica, was cultured from patient saliva, sequenced and annotated, identifying genes that potentially contribute to tumorigenesis. High sequence similarity was observed between sequences recovered from patient matched saliva and tumor tissue, indicating that the taxa found in PDAC tumors may derive from the mouth. These findings may have clinical implications in the care and treatment of patients diagnosed with PDAC.