Tumors Of Pancreas Research Articles

Abstract B030: Spatial coupling of microbes and immune cells shapes the tumor microenvironment in human cancers

Abstract Microbes play a crucial role in the tumor microenvironment, yet the factors governing their presence within tumors remain poorly understood. In this study, we employed advanced in situ spatial-profiling technologies to investigate the relationship between microbial and immune cell heterogeneity in human lung and pancreas cancers. We observed a spatial coupling between microbes and immune cells, which was also replicated in mouse models of pancreatic cancer. Within the tumor, distinct niches characterized by T cell abundance or scarcity exhibited varied microbial diversity and compositions associated with immunologically active and quiescent phenotypes. Interestingly, gut microbiome are similar between mice bearing T cell- enriched or T cell-poor pancreas tumors. Depletion of intra-tumoral bacteria resulted in reduced tumor growth specifically in T cell-poor tumors and altered the phenotype and presence of myeloid and B cells in T cell-enriched tumors, without affecting T cell infiltration. Conversely, depletion of T cells disrupted the immunological state of tumors and led to a decrease in intra-tumoral bacteria. Our findings highlight a tight interplay between microbes and T cells in the tumor microenvironment, where spatially defined immune-microbial communities differentially influence tumor biology. Citation Format: Yan Li, Renee B. Chang, Meredith L. Stone, Yuqing Xue, Heather Coho, Kelly Markowitz, Dhruv Patel, Veronica M. Herrera, Joey H. Li, Devora Delman, Liti Zhang, Shaanti Choi-Bose, Michael Giannone, Jae W. Lee, Gregory Beatty. Spatial coupling of microbes and immune cells shapes the tumor microenvironment in human cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B030.

Evaluation of prediction power of fukuoka guideline for malignancy in intraductal papillary mucinous tumor (IPMN) of pancreas: a retrospective study in a single institution

Evaluation of prediction power of fukuoka guideline for malignancy in intraductal papillary mucinous tumor (IPMN) of pancreas: a retrospective study in a single institution

Solid pseudopapillary tumor of pancreas: experience from a tertiary center in Kerala

Solid pseudopapillary tumor of pancreas: experience from a tertiary center in Kerala

A modified UNet-based semantic segmentation architecture for pancreas tumour detection

A modified UNet-based semantic segmentation architecture for pancreas tumour detection

Qualitative and quantitative imaging features of solid pancreas tumours in portal venous phase CT: are they useful in determining tumour type and grade?

Solid pancreatic lesions might have overlapping findings in portal venous phase computed tomography (CT). In this study, we aimed to investigate the quantitative and qualitative imaging features of solid pancreas lesions based on subtype and grade. The study group consisted of 159 patients with solid pancreatic tumours detected after exclusion criteria. According to the pathology results, the patients were divided into 3 groups as PDAC (pancreatic ductal adenocarcinoma, n = 137), PNET (pancreatic neuroendocrine tumour, n = 15), and SC (sarcomatoid carcinoma, n = 7). PDAC and PNET lesions were evaluated in 3 subgroups according to grade. There was no difference between the groups in terms of age, gender, tumour localisation, and internal structure (p = 0.23, p = 0.81, p = 0.19, and p = 0.94, respectively). Qualitative features significantly differed in terms of tumour margin feature, visual tumour density, presence of cystic component, and presence of necrosis (p = 0.01, p = 0.0001, p = 0.002, and p = 0.004, respectively). Tumour size, Tmden, Tmden/VPden, and Tmden/PanPden showed differences between groups (p = 0.0001, p = 0.002, p = 0.0001, p = 0.0001, respectively). The presence of cystic density in PDAC patients differed according to grade (p = 0.01). While ill-defined irregular margins, hypodense visual tumour density, no cystic component, low value of Tmden, and low ratios of Tmden/VPden and Tmden/PanPden indicate PDAC, regular margins, iso-or hyperdense visual tumour density, cystic component, high value of Tmden, and high ratios of Tmden/VPden and Tmden/PanPden indicate PNET. SC can be differentiated from them by containing necrosis and reaching larger sizes. The presence of a cystic component in PDAC patients indicates high grade.

Basic ctDNA Panel Promises Affordable Clinical Validity in Colon Cancer Patients but Not in Pancreas Cancer Patients.

The potential of circulating tumor DNA (ctDNA) as a biomarker to assess the progression of various solid tumors has been explored extensively. In this study, we investigated the feasibility of utilizing a ctDNA sequencing panel specifically designed to target the most frequently mutated genomic regions in colon and pancreas cancers. Through somatic analysis of colon and pancreas tumors, we targeted 27 regions within eight genes. By employing PCR amplification and Illumina NGS, we ensured that each region was adequately covered with a minimum of 5000 reads (with an average of 12,000 reads). Our method exhibited reproducibility with repetition and dilutions. The positive detection threshold for ctDNA was set at a cutoff value of 0.5% ctDNA of the total reads using IGV. Among the samples analyzed, 71% of colon cancer cases displayed somatic mutations covered by the targeted regions. Within this group, detectable ctDNA was observed in 34% of the cases. Conversely, in pancreatic cancer, 55% of mutations were covered by the panel's regions, but only 13% of these cases exhibited detectable ctDNA. In follow-ups with the patients, changes in ctDNA percentages demonstrated complete concordance with changes in the clinical condition in 88% of the cases. Our findings suggest that employing a basic ctDNA-targeted panel can serve as a cost-effective and reliable approach for repeated monitoring of the efficacy of colon cancer therapy. However, in the case of pancreatic cancer, ctDNA showed limited utility, and alternative biomarkers may offer superior diagnostic value. Additionally, we found that a negative ctDNA test is not a guarantee for a relapse-free recovery; thus, we recommend a continuous follow-up with the patient on a long-term basis.

Successful In Situ Targeting of Pancreatic Tumors in a Novel Orthotopic Porcine Model Using Histotripsy.

New therapeutic strategies and paradigms are direly needed to treat pancreatic cancer. The absence of a suitable pre-clinical animal model of pancreatic cancer is a major limitation to biomedical device and therapeutic development. Traditionally, pigs have proven to be ideal models, especially in the context of designing human-sized instruments, perfecting surgical techniques and optimizing clinical procedures for use in humans. However, pig studies have typically focused on healthy tissue assessments and are limited to general safety evaluations because of the inability to effectively model human tumors. Here, we establish an orthotopic porcine model of human pancreatic cancer using RAG2/IL2RG double-knockout immunocompromised pigs and treat the tumors ex vivo and in vivo with histotripsy. Using these animals, we describe the successful engraftment of Panc-1 human pancreatic cancer cell line tumors and characterize their development. To illustrate the utility of these animals for therapeutic development, we determine for the first time, the successful targeting of in situ pancreatic tumors using histotripsy. Treatment with histotripsy resulted in partial ablation in vivo and reduction in collagen content in both in vivo tumor in pig pancreas and ex vivo patient tumor. This study presents a first step toward establishing histotripsy as a non-invasive treatment method for pancreatic cancer and exposes some of the challenges of ultrasound guidance for histotripsy ablation in the pancreas. Simultaneously, we introduce a highly robust model of pancreatic cancer in a large mammal model that could be used to evaluate a variety biomedical devices and therapeutic strategies.

Strongly representative semantic-guided segmentation network for pancreatic and pancreatic tumors

Accurate and reliable segmentation of the pancreas and its lesions on computed tomography (CT) images is crucial in medical imaging for preoperative diagnosis, surgical planning, and postoperative monitoring. However, there are limited studies that address simultaneous segmentation of the pancreas and pancreatic tumors. Moreover, existing studies have not fully utilized the feature potential of the original images and have neglected the exploration of semantic information with strong representation. To overcome these limitations, we propose the Strongly Representative Semantic-guided Segmentation Network (SRSNet). Specifically, we employ intermediate semantic information to generate strongly representative high-resolution pre-segmented images, effectively reducing channel redundancy across different resolutions. We utilize various mechanisms to extract distinct representative features, and with the guidance of these features, SRSNet effectively supplements high-resolution detailed information for features of different resolutions, provides auxiliary features for the pixel decision phase of the network, and detects large-scale changes in the pancreas and pancreatic tumors. Additionally, we design a loss function that enhances SRSNet’s sensitivity to boundary pixels and attenuates the effect of class imbalance. Our method is evaluated on Task07 Pancreas and NIH Pancreas datasets. In the experiment of combined pancreas and tumor segmentation in the MSD dataset, we achieved Dice, Recall, Precision, and MIoU scores of 78.60%, 79.64%, 81.72%, and 71.47%, respectively. Extensive experiments demonstrate that our algorithm not only outperforms state-of-the-art algorithms for pancreas segmentation but also exhibits excellent performance for pancreas and pancreatic tumor segmentation.

S151 Characteristics and Outcomes of Solid Pseudopapillary Tumors of Pancreas: A US Multicenter Retrospective Study

S151 Characteristics and Outcomes of Solid Pseudopapillary Tumors of Pancreas: A US Multicenter Retrospective Study

1655P Nampt inhibitors re-sensitize MAP17 expressing pancreas tumors

1655P Nampt inhibitors re-sensitize MAP17 expressing pancreas tumors

Patient-Reported Adverse Effects in 15-Fraction Pancreatic Cancer Radiation Therapy

Fifteen-fraction radiotherapy (RT) regimens have emerged as a standard option in the treatment of patients with pancreas cancer. Patient-reported outcomes (PROs) during and after pancreas cancer RT have not been well characterized. There is an even greater paucity of data among patients treated with 15-fraction regimens. We aimed to characterize gastrointestinal (GI) PROs in a cohort of patients treated with 15-fraction pancreas RT. This was an IRB-approved retrospective cohort study including patients with primary pancreas tumors treated with pre-operative or definitive 15-fraction RT from 2013 to 2022. PROs, including anorexia, nausea, diarrhea, stool incontinence, and abdominal pain, were prospectively collected and characterized per PRO-common terminology criteria for adverse events (PRO-CTCAE). Acute PROs were defined as occurring during RT through 110 days post-RT but prior to oncological surgery. Grade 3 or 4 PROs were respectively scored as "quite a bit" or "very much" in symptom interference questions, "frequently" or "almost constantly" in symptom frequency questions, and "severe" or "very severe" in symptom severity questions. A total of 330 patients were analyzed. Patient characteristics included a median age of 67 years (IQR: 60 - 72), ECOG 0-1 (96%), and male sex (56%). Most patients had pancreatic ductal adenocarcinoma (96%). Resectability status included resectable (12%), borderline resectable (46%), and locally advanced (42%). 37% had lymph node involvement. 97% of patients received neoadjuvant chemotherapy and 98% received concurrent chemotherapy, most commonly with 5-fluorouracil or capecitabine (88%) or gemcitabine (11%). 99% were treated with intensity modulated RT. Median RT dose was 4500 cGy (IQR 4500 - 4500) to gross disease with margin and 3750 cGy (IQR 3750 - 3750) to elective nodal regions. 59% proceeded with oncologic resection. Grade 3 or higher acute PROs are demonstrated in the table. Often considered more sensitive than physician assessments, PROs provide vital metrics that allow for a better understanding of the patient experience during cancer treatment. We report a comprehensive assessment of prospectively collected PROs per standardized PRO-CTCAE with the goals of raising awareness of the patient experience during 15-fraction pancreas cancer RT and helping guide future clinical trial designs focused on patient quality of life endpoints.

Utility of Wnt family member 9b (Wnt9b) immunohistochemistry inthe cytologic diagnosis of metastatic breast carcinoma.

Wnt family member 9b (Wnt9b) has been demonstrated as a valuable marker for breast cancer diagnosis in surgical pathology. In this study, we examined the utility of Wnt9bin diagnosing metastatic breast carcinomaincytologysamples. Cell blocks from fine needle aspirations (FNA) and fluid specimens of 96 metastatic breast carcinomasand 123 primary and metastatic non-breast neoplasms from various organ systems were evaluated by Wnt9band GATA3 immunohistochemistry (IHC). Wnt9b and GATA3 were positive in 81.3%and 92.7%ofmetastaticbreast carcinomas, respectively. Conversely, 93.5%and 90.0%of non-breast, non-urothelial carcinomas were negative for Wnt9b and GATA3, respectively. Wnt9b expression was positive in rare gastrointestinal, gynecological, lung, pancreas, and salivary gland tumors. All twenty-eight urothelial carcinomas were negative for Wnt9b, while twenty-six (92.9%) were positive for GATA3. Wnt9b was slightly less sensitive but more specific than GATA3 in diagnosing metastatic breast cancer in cytology samples. Particularly, Wnt9b shows higher specificity in differentiating breast and urothelial primaries. The combined use of Wnt9b and GATA3 may increase diagnostic accuracy.

Severe gastroenteritis as presentation of a neuroendocrine tumor of pancreas

Pancreatic neuroendocrine tumors (PanNETs) are a very rare entity, corresponding to 1-2% of all pancreatic neoplasms, although incidence and prevalence are rising. According to hormonal production, they can be functional or nonfunctional, leading to a subset of symptoms. A 45-year-old man, came to our emergency department complaining of vomiting and profuse non-bloody diarrhea for a week, with asthenia and no improvement with medication. He presented with diminished muscular strength and severe electrolytic changes with electrocardiographic repercussion. Patient was admitted to our intensive care unit (ICU) for hypovolemic and distributive shock due to a severe gastroenteritis. Further research studies were carried out which have shown a nodular structure of 5x4cm in the pancreas tail on computed tomography scan. A biopsy was made, and a histopathological exam revealed a pancreatic well differentiated neuroendocrine tumor. Hormonal analysis showed an elevation on vasoactive intestinal polypeptide (VIP). On 68Ga-DOTA-NOC PET/CT, there were 2 nodular lesions with anomalous overexpression of somatostatin receptors, one in the pancreatic tail near splenic hilum and another in the pancreatic head. Patient underwent a total pancreaticoduodenectomy with en bloc splenectomy. Postoperative period was uneventful. Mostly, this kind of pancreatic neuroendocrine tumors are indolent, but till 39% can have an aggressive course, so they have variable prognosis.

APPLICATION OF ENDOSCOPIC ULTRASOUND GUIDED FNAC(EUS-FNAC) IN DIAGNOSING PANCREATIC MASS LESIONS

Introduction: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNAC) has become an important modality for identification of pancreatic masses. It is a minimally invasive procedure that provides excellent cell yield even in deep seated lesions. The preoperative diagnosis of pancreatic mass by EUS-FNAC can help the surgeons in early detection and confirmation of neoplasm as pancreatic mass lesions are highly concerning for pancreatic carcinoma. This study was aimed at application of EUS-FNAC in diagnosing pancreatic mass lesions. Methods: A study was conducted for 20 cases who underwent EUS guided FNAC for pancreatic mass lesions. EUS-FNAC was performed by using a curvilinear array echo endoscope. The technique was carried out by a skilled endoscopist, and the glass slides were used to make smears from fluid that was aspirated containing corpuscular fractions. The slides were air dried before being examined cytopathologically. Results: Out of 20 cases,10 were of pancreatic Ductal adenocarcinoma, 3 of Neuroendocrine tumor of pancreas, 2 of Acinar cell carcinoma, 1 of Solid pseudopapillary tumor, 2 of Serous cystadenoma and 2 of Mucinous cystadenoma. This was confirmed later, on further Immunocytochemical stains. Conclusions:Out of 20 cases, 16 were malignant and 4 were benign. EUS-FNAC can help in early diagnosis and can improve the patient outcome. It is safe, cost-effective and reliable. It not only gives precise cytological diagnosis, but it also allows for the exact site of tiny lesions.

Perivascular epithelioid cell tumor of pancreas on the background of chronic liver disease: a case report and review of literature

Perivascular epithelioid cell tumours, known as PEComas, of the pancreas are an extremely rare group of neoplasms. This heterogenous entity includes angiomyo­lipo­ma (AML), clear cell sugar tumour (CCST), lymphangioleio­myoma (LAM), and another group of lesions originating from the soft tissues and organs with similar histological and immunophenotype characteristics. To date, only 23 cases have been reported throughout the world with different clinical presentations. We report a 52-year-old lady who presented with a symptomatic mass in the body of the pancreas on the background of hepatitis B virus (HBV)-related chronic liver disease (CLD). She presented with abdominal pain of 2 months' duration. On initial computed tomography (CT) imaging, it revealed a homogenously enhancing lesion in the body of the pancreas. It was T2 isointense on magnetic resonance imaging (MRI), and there was no uptake present in the 68Ga DOTONAC scan. Endoscopic ultrasound with fine needle aspiration (FNA) showed paucicellular material with occasional dysplastic cells. On account of suspicion of a non-functional neuroendocrine tumour, she underwent a distal pancreatosplenectomy. Intra-operatively, the lesion was encapsulated and hard in consistency, and the rest of the pancreas was soft with an undilated MPD. She had a smooth postoperative recovery. Final histopathology revealed benign PEComa of the distal body and tail of the pancreas with HMB 45 and SMA positivity on IHC. Currently, she has been on regular follow up for the last 12 months. PEComas usually present as a histological surprise and are a diagnosis of exclusion. However, knowledge of this exceptionally rare tumour makes diagnosis at the pre-operative level more certain. Resection must be considered, as it leads to a good prognosis and survival.

Sound speed and attenuation of human pancreas and pancreatic tumors and their influence on focused ultrasound thermal and mechanical therapies.

There is increasing interest in using ultrasound for thermal ablation, histotripsy, and thermal or cavitational enhancement of drug delivery for the treatment of pancreatic cancer. Ultrasonic and thermal modelling conducted as part of the treatment planning process requires acoustic property values for all constituent tissues, but the literature contains no data for the human pancreas. This study presents the first acoustic property measurements of human pancreatic samples and provides examples of how these properties impact a broad range of ultrasound therapies. Data were collected on human pancreatic tissue samples at physiological temperature from 23 consented patients in cooperation with a hospital pathology laboratory. Propagation of ultrasound over the 2.1-4.5MHz frequency range through samples of various thicknesses and pathologies was measured using a set of custom-built ultrasonic calipers, with the data processed to estimate sound speed and attenuation. The results were used in acoustic and thermal simulations to illustrate the impacts on extracorporeal ultrasound therapies for mild hyperthermia, thermal ablation, and histotripsy implemented with a CE-marked clinical system operating at 0.96MHz. The mean sound speed and attenuation coefficient values for human samples were well below the range of values in the literature for non-human pancreata, while the human attenuation power law exponents were substantially higher. The simulated impacts on ultrasound mediated therapies for the pancreas indicated that when using the human data instead of the literature average, there was a 30% reduction in median temperature elevation in the treatment volume for mild hyperthermia and 43% smaller volume within a 60°C contour for thermal ablation, all driven by attenuation. By comparison, impacts on boiling and intrinsic threshold histotripsy were minor, with peak pressures changing by less than 15% (positive) and 1% (negative) as a consequence of the counteracting effects of attenuation and sound speed. This study provides the most complete set of speed of sound and attenuation data available for the human pancreas, and it reiterates the importance of acoustic material properties in the planning and conduct of ultrasound-mediated procedures, particularly thermal therapies.

Cytomorphologic, immunophenotypical and molecular features of pancreatic acinar cell carcinoma.

As a rare tumor in pancreas, pancreatic acinar cell carcinoma (PACC) possesses a distinct molecular feature from pancreatic ductal carcinoma (PDAC). Though the diagnosis of PACC is often established based on cytology specimens, its cytologic diagnosis can be challenging. Furthermore, the correlation between PACC cytomorphology and its unique different molecular alterations have not been fully explored. Cytology features were analyzed in 8 histologically proven PACC and cytohistological correlation was performed. Immunocytochemistry for trypsin, chymotrypsin, BCL10, synaptophysin, chromogranin A, INSM1, β-catenin, and Ki-67 was assessed. Comprehensive molecular profiling and additional targetable treatment biomarker assessment were also performed. The cohort included 4 mixed acinar-neuroendocrine carcinomas, 3 pure PACCs, and 1 mixed acinar-ductal carcinoma. Immunophenotypical features are consistent with diagnoses of PACC or PACC with neuroendocrine features. Identified genetic alterations included somatic mutations of CTNNB1, TP53, MAP2K1, PTEN, RAC1, germline mutations of NBN and BRAC2, and gene fusion of CCDC6-RET. The current study is the first attempt to explore the correlation between the cytomorphology characteristics and molecular features of PACC and a few intriguing findings were observed. Further validation in larger cohorts is warranted.

Solid Pseudopapillary Tumor of Pancreas in a 14-year-old Adolescent Presenting With Melena: A Case Report

Background: The incidence of pancreatic neoplasms in infants and children is 1.8 cases per 1000000. Three of children’s most common primary pancreatic neoplasms are pancreatoblastoma, solid pseudopapillary neoplasm of the pancreas, and pancreatic endocrine neoplasms. Solid pseudopapillary neoplasm of the pancreas is a low-grade malignant tumor. Solid pseudopapillary neoplasm in children is presented with a palpable mass (60%), followed by abdominal pain (33.3%). Although duodenal invasion frequently occurs in patients with pancreatic cancer, massive gastrointestinal bleeding is seldom encountered. The most helpful imaging technique is the CT scan. Surgical resection is the treatment of choice for solid pseudopapillary neoplasms. Case Presentations: A 14 years old male adolescent was presented to our pediatric emergency department with fatigue, dizziness, fever, vomiting, and tachycardia. He had melena 5 days before admission. Crystalloids, pantoprazole, and packed red blood cells were administered to stabilize the patient. As the initial resuscitation measures stabilized the patient, endoscopic gastroduodenoscopy was performed, and a vascular lesion measuring 60×70 mm was noted in the second part of the duodenum. CT scan of the abdomen with intravenous and oral contrast showed a mass with solid and cystic components measuring 75×52 mm between the head of the pancreas and gallbladder origination from the head of the pancreas. The patient underwent Whipple surgery. The diagnosis of the pathologic evaluation was a solid pseudopapillary tumor of the pancreas. Conclusions: Most pediatric pseudopapillary tumors of the pancreas present with a palpable mass and abdominal pain, and gastrointestinal bleeding is a rare presentation not mentioned in previous case reports.

COMPARISON OF CLINICAL PARAMETERS AND PATHOLOGICAL FEATURES OF INTESTINAL AND PANCREATOBILIARY HISTOLOGIC PHENOTYPES OF PERIAMPULLARY CARCINOMA

Background: Identification of the exact origin in large sized tumors of periampullary region is very difficult grossly and microscopically. The purpose of the study was to compare the two histological phenotypes of periampullary carcinoma in terms of their preoperative clinical parameters and pathological features. Methods: This was a prospective observational study done in patients diagnosed as periampullary carcinoma in specimen after pancreatoduodenectomy, between May 2018 and July 2019 at a Tertiary Teaching Hospital of Nepal. Relevant patient clinical characteristics, biochemical parameters including CEA and CA 19.9, immuno-histochemical markers (CK-20 and MUC-1) expression and histopathological details were recorded. Student t-test, ANOVA, median test, Kruskal Wallis test, binary logistic regression tests were used for analysis in SPSS version 20. P-value < 0.05 was considered significant. Results: Thirty-nine patients with periampullary adenocarcinoma in Pancreatoduodenectomy specimen were included in the study with mean age of 58.6 years. Ampullary tumors (53.8%) were common in this study. Pancreatobiliary phenotype (61.5% versus 38.5%), was more common in head of pancreas and distal CBD tumors and was associated with significantly higher lymph node ratio (0.174 ± 0.173 versus 0.069±0.096), higher rates of lymphovascular invasion (66.7% versus 33.3%) and perineural invasion (75% versus 26.7%) on univariate analysis. On multivariate analysis, Perineural invasion was associated with Pancreatobiliary phenotype (Odds ratio of 10.46). Conclusions: Pancreatobiliary phenotype of periampullary tumors was associated with poor prognostic pathologic features like high lymph node ratio, lymphovascular invasion and perineural invasion. Perineural invasion had the strongest association of all.

Treatment with long term follow-up of solid pseudopapillary tumor of pancreas - A single center experience from India

Treatment with long term follow-up of solid pseudopapillary tumor of pancreas - A single center experience from India