Pancreatic Head Research Articles

Robot-Assisted Pancreaticoduodenectomy Using the Anterior Superior Mesenteric Artery-First Approach for Pancreatic Cancer.

The superior mesenteric artery (SMA)-first approach for pancreatic cancer (PC) is common surgical technique in pancreaticoduodenectomy. To date, few studies have reported SMA-first approach in robot-assisted pancreaticoduodenectomy (RPD). Herein, we present the anterior SMA-first approach for PC during RPD. A 75-year-old man with resectable PC underwent RPD after neoadjuvant chemotherapy. As pancreatic head tumor contacted with the superior mesenteric vein (SMV), the anterior SMA approach was applied. After the mesenteric Kocher maneuver, the jejunum was divided and the left side of the SMA was dissected. Subsequently, the anterior plane of the SMA was dissected. Following the division of branches from the mesenteric vessels, the SMA was taped, and the circumferential dissection around the SMA was performed to detach the pancreatic neck from the SMA completely. Finally, the dissection between the SMV and the tumor was performed under vascular control to remove the specimen. The anterior SMA-first approach can be optional in patients with PC undergoing RPD. This unique approach allows for the circumferential dissection around the SMA during RPD.

Endoscopic biliary drainage for distal bile duct obstruction due to pancreatic cancer.

Approximately 60% of pancreatic cancers occur in the pancreatic head and may present as obstructive jaundice due to bile duct invasion. Obstructive jaundice often leads to poor general conditions and acute cholangitis, interfering with surgery and chemotherapy and requiring biliary drainage. The first choice of treatment for biliary drainage is the endoscopic transpapillary approach. In unresectable tumors, self-expandable metal stents (SEMSs) are most commonly used and are classified into uncovered and covered SEMSs. Recently, antireflux metal stents and large- or small-diameter SEMSs have become commercially available, and their usefulness has been reported. Plastic stents are infrequently used in patients with resectable biliary obstruction; however, owing to the recent trend in preoperative chemotherapy, SEMSs are frequently used because of the long time to recurrent biliary obstruction. Endoscopic ultrasound-guided biliary drainage (EUS-BD) is often performed in patients who are not eligible for the transpapillary approach, and favorable outcomes have been reported. Different EUS-BD techniques and specialized stents have been developed and can be safely used in high-volume centers. The indications for EUS-BD are expected to further expand in the future.

Rare complications of acute pancreatitis: Clinical cases

Background. Acute pancreatitis is recognized as a common disease, occasionally accompanied by the development of local complications that require surgical debridement. Rare complications of pancreatitis may occur in clinical practice, which is one of the reasons for their untimely diagnosis and treatment. Pancreaticopleural fistula and high small bowel obstruction develop in less than 1% of acute pancreatitis cases. Therefore, possible options for management of these complications are considered valuable. Description of clinical cases. The clinical examples, provided in the present paper, describe pancreaticopleural fistula and high small bowel obstruction that develop against the peripancreatic mass in the abdominal cavity. Patient K., 44, was hospitalized to the Regional Clinical Hospital of Emergency Medical Care, Krasnodar Krai, and preliminary diagnosed with bilateral hydrothorax and type II respiratory failure; pleural puncture was performed. Following the extended examination, a clinical diagnosis was made as follows: “Acute necrotic pancreatitis spreading to a pancreatic tail cyst. Reactive double pleurisy”. The postoperative period was indicated with repeated recurrence of right hydrothorax, and pancreaticopleural fistula (diagnosed by measuring amylase activity in the brown fluid effused from the right pleural cavity, which appeared to be 41216 IU/l (not normally determined)). The right pleural cavity and pseudocyst of the pancreatic tail were drained, resulting in obliteration of the pancreatbcopleural fistula. Patient V., 50, was hospitalized and transferred to the surgical department of the Regional Clinical Hospital No. 2, Krasnodar Krai, and diagnosed with “pancreonecrosis, extensive purulent-necrotic peripancreatitis.” The patient underwent puncture-drainage treatment. The postoperative period was complicated by acute small bowel obstruction. Surgical treatment involved Braun enteroesterostomy. The patient recovered. Conclusion. Pancreaticopleural fistula refers to a rare complication of acute pancreatitis, manifested by hydrothorax. Its diagnosis is based on the determination of amylase activity in the effusion. Drainage of the pleural cavity and pancreatic pseudocyst contributes to obliteration of the fistula. The intestinal obstruction, another complication of pancreatitis, requires open surgical treatment when a conservative therapy appears ineffective.

Tuberculosis masquerading as a pancreatic cyst in a patient with cirrhosis

Cystic lesions of the pancreas are being increasingly diagnosed incidentally in recent decades due to easy availability of abdominal imaging. They may be neoplastic or benign. Tuberculosis, the great masquerader, may rarely involve the pancreas mimicking pancreatic malignancy, cyst, or abscess. Identification of this rare entity is crucial to avoid potentially risky surgery as anti-tubercular pharmacotherapy is highly effective. We report a case of a 40-year old cirrhotic man who presented with a cystic hypodense lesion in the pancreatic tail and was subsequently diagnosed with pancreatic tuberculosis. Apart from the rarity of diagnosis, our case also highlights the utility of endoscopic ultrasound for minimally invasive assessment of pancreatic lesions.

Laparoscopic Duodenum and Spleen-Preserving Subtotal or Total Pancreatectomy: A Parenchyma-Sparing Strategy for Main Duct Intraductal Papillary Mucinous Neoplasms (with Video)

Abstract Background For premalignant main duct intraductal papillary mucinous neoplasms (MD-IPMN), laparoscopic duodenum and spleen-preserving subtotal or total pancreatectomy (LDSP-STP/TP) seems to be a viable option for parenchyma-sparing pancreatectomy. Patients and Methods On the basis of the imaging features, family history, genomic alterations, intraoperative ultrasound examination, and frozen section evaluation, we have proposed patient selection strategies for the LDSP-STP/TP technique for the first time. Additionally, a comprehensive step-by-step overview of this technique has been provided. To date, we have performed five LDSP-STP procedures and one LDSP-TP procedure. Results We successfully performed selective resection of the affected pancreatic parenchyma while preserving the duodenum, common bile duct (CBD), spleen, and splenic artery and vein. The operation time ranged from 295 to 495 min, with blood loss ranging from 100 to 300 mL. Postoperative pathological results revealed low-grade dysplasia in the resected pancreatic samples and margins. The patients resumed eating within 3–5 days after surgery, and all postoperative complications were classified as grade I according to the Clavien–Dindo classification. At the 3-month follow-up, there were no cases of CBD ischemic stenosis, splenic ischemia, or pseudocyst formation observed. For patients who received LDSP-STP, the longitudinal diameter of the remaining pancreatic tail ranged from 2.2 to 4.6 cm, and they demonstrated satisfactory long-term blood glycemic control. Conclusions LDSP-STP/TP demonstrates technical feasibility and safety. It allows for the selective resection of the affected pancreatic parenchyma, thereby minimizing the impact of pancreatic functional impairment. However, it is crucial to validate this technique through long-term prospective observations.

Image J as the quantification tool in endosonography strain elastography may be reflected in the disturbance of endocrine pancreatic dysfunction.

Pancreatic fibrosis is one of the main pathological features of chronic pancreatitis (CP), suggesting a strong relationship between CP and pancreatic ductal cancer. There was no available data about pancreatic fibrosis and pancreatic dysfunction in the early CP (ECP) using endosonography (EUS). Asymptomatic patients with pancreatic enzyme abnormalities (AP-P; n = 56) and patients with ECP (n = 21) were determined by the absence of abnormal findings on upper gastrointestinal endoscopy, abdominal ultrasonography, and abdominal computed tomography. An Olympus EUS (GF-UCT 260; Olympus) was used to perform EUS. Open software "Image J", developed by NIH, was used to measure the surface area fraction of the designated elastic blue region. The maximum value among the pancreatic head, pancreatic body, and pancreatic tail was defined as the ELST-blue score. The exocrine and endocrine pancreatic functions were evaluated using the N-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA) test and homeostasis model assessment of β-cell function (HOMA-β) value, respectively. EUS score, lobularity, and hyperechoic foci/strands in patients with ECP were significantly (p < 0.001) higher than those in patients with AP-P. In addition, there were no significant differences in the BT-PABA test (73.1 ± 25.5, 68.5 ± 15.6) and HOMA-β (93.1 ± 67.4, 73.5 ± 139.7) between patients with ECP and AP-P. The ELST-blue score measured by image J as the quantification tool in EUS strain elastography in patients with ECP was significantly higher (p = 0.002) than that in patients with AP-P. Interestingly, the ELST-blue score was significantly associated with HOMA-β in patients with ECP. The ELST-blue score may be a useful tool for the evaluation of endocrine pancreatic dysfunction in the ECP.

Pancreatoduodenectomy after Ivor-Lewis Santi oesophagectomy with gastric tube reconstruction. An European multicentre experience

BackgroundPancreaticoduodenectomy (PD) is the standard surgery to treat tumors and other conditions affecting the head of the pancreas. PD involves the division of the gastroduodenal artery (GDA) and its branches, to allow for complete dissection of lymph nodes. However, PD in patients with prior esophageal resection presents challenges due to altered anatomy and risks compromising gastric tube vascularization. GDA preservation becomes crucial to avoid ischemia, although this may pose oncological risks by potentially leaving behind regional lymph nodes. This article reviews European surgical center experiences and techniques for PD in patients with prior esophageal surgery, focusing on short-term outcomes. MethodsWe have collected all the experiences carried out in European surgical centers and evaluated the techniques applied for PD in patients who had prior esophageal surgery while analyzing short-term outcomes. ResultsEight patients from 5 European centers were identified. Six patients were diagnosed with pancreatic adenocarcinoma, including one borderline case. Intraoperatively, the gastroduodenal artery (GDA) was preserved in all cases, with portal vein reconstruction required in only one instance due to tumor invasion. No ischemia or venous congestion of the gastric tube was observed during the surgical procedure. Post-operative complications that occurred included POPF type C in 1 (12.5 %), PPH type C in 1 (12.5 %). The median number of harvested lymph nodes was 21 [14–24]. with a median of 1.5 positive lymph nodes. R1 resection was present in 62.5 % of cases. ConclusionPerforming pancreaticoduodenectomy subsequent to Ivor Lewis esophagectomy is a technical challenge, but seems feasiable and safe in selected patients. GDA-preserving pancreaticoduodenectomy emerges as a valuable and time-efficient variation of the conventional procedure, it can be considered oncologically appropriate, but studies confirming its long-term impact on radicality are still needed.

The value of a nomogram model based on CT imaging features in differentiating duodenal gastrointestinal stromal tumors from pancreatic head neuroendocrine tumors

The value of a nomogram model based on CT imaging features in differentiating duodenal gastrointestinal stromal tumors from pancreatic head neuroendocrine tumors

Laparoscopic Central Pancreatectomy with Modified Blumgart Pancreatojejunostomy for Pancreatic Neuroendocrine Tumor.

This report with a video describes a laparoscopic central pancreatectomy with modified Blumgart pancreatojejunostomy for pancreatic neuroendocrine tumor. A 71-year-old woman presented with a single 17 mm lesion in the pancreatic neck, responsible for dilatation of the main pancreatic duct. Cancer staging showed no additional location. Somatostatin receptor imaging was positive. After a multidisciplinary discussion in the French national reference network for the management of neuroendocrine tumor (RENATEN) surgery with central pancreatectomy was decided. The operation time was 320 min and the estimated blood loss was less than 100 ml. Final pathology confirmed a pancreatic NET of 13 mm staged as T1 N0 M0 R0 G1 with a Ki-67 of 2%. After lymph node dissection, five nodes were analyzed and were found to be noninvaded. The postoperative course was uneventful. Laparoscopic central pancreatectomy is an excellent alternative for sparing pancreatic parenchyma.

Robotic Central Pancreatectomy

Central pancreatectomy is an excellent alternative to left pancreatectomy for symptomatic benign or premalignant lesions of the pancreatic body or tail. A key advantage of this technique lies in the preservation of pancreatic parenchyma, resulting in a lower rate of postoperative diabetes mellitus. However, this procedure requires more complex reconstruction, which in turn is associated with an increased risk of morbidity.Insulinoma in the pancreatic body.Robot-assisted central pancreatectomy with pancreaticojejunostomy using a modified Blumgart technique.Central pancreatectomy is a generally rare and challenging pancreatic procedure, but clearly plays a significant role in modern pancreatic surgery due to its functional advantages. When appropriate and technically feasible, central pancreatectomy should be preferred to the alternative of left pancreatectomy and whenever possible, performed minimally invasively.

Total Venous Control and Vein-to-the-Right Superior Mesenteric Artery Approach in Robotic Pancreatoduodenectomy.

Robotic pancreatoduodenectomy is an increasingly accepted alternative for the treatment of pancreatic ductal adenocarcinoma (PDAC).1 However, the ability to perform a meticulous robotic-assisted superior mesenteric artery (SMA) dissection to obtain a margin-negative resection remains unknown.2 PDAC within the head of the pancreas (HOP) that involves the superior mesenteric vein (SMV) and portal vein (PV) requires total venous control (TVC) and a 'vein-to-the-right' (or anterior artery-first) approach to SMA dissection to minimize venous congestion and operative blood loss.3-5 Here, we demonstrate a robotic pancreatoduodenectomy with TVC and a 'vein-to-the-right' approach. A 70-year-old woman with cT2N0M0 HOP PDAC with lateral SMV involvement and right gastroepiploic vein occlusion underwent robotic pancreatoduodenectomy after neoadjuvant chemotherapy. After transecting the pancreas, we achieved TVC by dividing the small venous tributaries and encircling the SMV, splenic vein, and PV. We then proceeded with a 'vein-to-the-right' approach. The inferior pancreatoduodenal arteries were divided to minimize HOP inflow and decrease specimen bleeding. Once the specimen was dissected off the periadventitial plane of the distal SMA, the SMV dissection was carefully performed using a partial side-wall vein resection using a vascular stapler. Total operative time was 7.5h and estimated blood loss was 25mL. The patient recovered well postoperatively and was discharged on postoperative day 3. Final pathology exhibited a 2.4cm, moderately to poorly differentiated adenocarcinoma with negative margins (ypT2N1, 2/38 lymph nodes positive). For tumors with lateral vein involvement, robotic pancreatoduodenectomy can be safely performed via TVC and a 'vein-to-the-right' approach.

Minimally invasive treatment of an internal pancreaticopleural fistula with massive pleural effusion: a case report

BackgroundA pancreatic duct rupture can lead to various complications such as a fistula, pseudocyst, ascites, or walled-off necrosis. Due to pleural effusion, pancreaticopleural fistula typically causes dyspnea and chest pain. Leaks of enzyme-rich pancreatic fluid forming a pleural effusion can be verified in a thoracocentesis following radiological imaging such as computed tomography or magnetic resonance tomography. While management strategies range from a conservative to endoscopic and surgical approach, we report a case with successful minimally invasive treatment of pancreaticopleural fistula and effusion.Case presentationWe present a case of a patient with pancreaticopleural fistula and successful minimally invasive surgical treatment. A 62-year old Caucasian man presented with acute chest pain and dyspnea. A computed tomography scan identified a left-sided cystoid formation, extending from the abdominal cavity into the left hemithorax with concomitant pleural effusion. Pleural effusion analysis indicated significantly elevated pancreatic enzymes. Magnetic resonance cholangiopancreatography revealed a rupture of the pancreatic duct and nearby fluid accumulation. Endosonography later confirmed proximity to the tail of the pancreas, suggesting a pancreatic pseudocyst with visible tract into the pancreas. We assumed a pancreatic duct rupture with a fistula from the tail of the pancreas transdiaphragmatically into the left hemithorax with a commencing pleural empyema. A visceral and parietal decortication on the left hemithorax and a laparoscopic distal pancreatectomy with splenectomy was performed. The suspected diagnosis of a fistula arising from the pancreatic duct was confirmed histologically.ConclusionPancreaticopleural fistulas often have a long course and may remain undiagnosed for a long time. At this point diagnostic management and therapy demand a high level of expertise. In instances of unclear symptomatic pleural effusion, considering an abdominal focus is crucial. If endoscopic treatment is not feasible, minimally invasive surgery should strongly be considered, especially when located in the distal pancreas.

Abstract B053: SUMOylation and TIGIT inhibition: a novel immunotherapy combination for pancreatic cancer

Abstract Introduction: Immune checkpoint inhibitors have shown promise in many other solid tumors but have been disappointing in pancreatic ductal adenocarcinoma (PDAC). Preclinical work demonstrates that the immune checkpoint receptor TIGIT plays a key role in PDAC immune evasion and may be a better therapeutic target than the PD1 or CTLA4 axes. Post-translational small-ubiquitin-like modification (SUMOylation) regulates the activity of numerous proteins involved in cell proliferation. Our laboratory has shown that inhibition of SUMOylation with small molecule TAK-981 favorably modulates the PDAC immune microenvironment and specifically increases the expression of TIGIT binding partners CD226 on immune cells and CD155 on tumor cells. We hypothesized that inhibition of SUMOylation with small molecule TAK-981 would synergize with anti-TIGIT antibody therapy to induce anti-tumor immunity. Methods:All studies utilized a murine PDAC organoid line (KPC46) derived from a liver metastasis in a genetically engineered mouse model (KPC). KPC46 consistently metastasizes to the liver when implanted orthotopically into the tail of the pancreas in immunocompetent mice. Following tumor implantation, mice were surveilled by ultrasound until tumors reached 5-7 mm in diameter, then randomized to one of two treatment groups: TAK-981 + anti-TIGIT or vehicle control (n=10/group). Monotherapies were not included, as each drug alone did not produce significant responses in prior studies using this model. The treatment cohort received 15 mg/kg of TAK-981 and 100 micrograms of anti-TIGIT antibody via intraperitoneal injection every 48 hours starting 14 and 15 days, respectively, post-implantation, for a total of 4 weeks. Complete responders were defined as absence of disease after 2 months of observation. Complete responders and age-matched controls (n=3/group) were rechallenged with subcutaneous tumor injection and monitored for tumor development. Results:Survival of PDAC mice was significantly prolonged in the combination group when compared to the control group (median survival 81 vs 42 days, P&amp;lt;0.05). A total of 4 mice (40%) were deemed complete responders after 2 months of monitoring. The re-challenge experiment produced tumors in all three control mice but none of the treated mice by 4 weeks after implantation. Conclusion:In this study, we explored the combination of two promising immunotherapy agents for PDAC which demonstrated significant additive effects generating durable and complete responses. We were able to confirm the presence of protective immunity. These results are rarely seen in PDAC experiments. Further experiments to better understand and optimize these effects are underway. These drugs are currently in clinical trials for solid tumors and could feasibly be studied in the near future in PDAC. Citation Format: Jorge R de la Torre Medina, Utsav Joshi, Jaynath Shankara Narayanan, Herve Tiriac, Yuan Chen, Rebekah White. SUMOylation and TIGIT inhibition: a novel immunotherapy combination for pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B053.

Abstract B078: A comprehensive spatial atlas of neoadjuvant chemoradiation therapy in resected pancreatic cancer identifies cellular &amp; microenvironmental determinants of persister populations

Abstract Background The molecular pathways involved in the response to radiation therapy (RT) in pancreatic ductal adenocarcinoma (PDAC) remain poorly understood. Despite extensive molecular stratification efforts, improvements in molecularly informed RT-based therapeutic strategies in the neoadjuvant setting have been limited. This study aims to elucidate the adaptive mechanisms and interactions within PDAC to identify new combinatorial therapeutic targets with RT. MethodsWe constructed a high-resolution molecular landscape of the cellular subtypes and spatial communities that constitute PDAC. Single-cell RNA sequencing (scRNA- seq) was performed on 16 PDAC biopsies of matched pre- and post-treatment samples from a Phase I/II dose-escalation clinical trial of pancreatic stereotactic body radiation therapy (SBRT). Additionally, Visium spatial transcriptomics (ST) was conducted on biopsies from primary PDAC patients collected at the time of surgery. These patients received either no neoadjuvant therapy (n = 8) or neoadjuvant chemoradiation (chemoRT) (n = 20). Cell type profiles were determined from scRNA-seq to compare changes in cell type proportions and signatures before and after RT. From these profiles, we employed robust cell type decomposition to analyze cell type signatures in our ST dataset. ResultsChemoRT induced several significant effects compared to controls within the tumor microenvironment, including an increase in the proportion of myofibroblasts, specifically senescent cancer-associated fibroblasts (CAFs), with signatures consistent with immune cell dysfunction. We observed an increase in CD8 and CD4 effector memory cells with RT; however, this occurred alongside a rise in immunosuppressive alternatively activated tumor-associated macrophages. Additionally, RT upregulated pathways related to HIF, cytokine production, B cell proliferation, and negative regulation of lymphocytes. Patients with increased infiltration of NK, memory B, and CD8 effector memory cells demonstrated improved overall survival outcomes. Inference of copy number variations enabled us to identify cancer subclones as either responsive or resistant in matched pre and post RT biopsies. Resistance was characterized by augmented hypoxia, KRAS activation, epithelial- mesenchymal transition, and interferon-gamma response signaling. Conversely, responders exhibited increased oxidative phosphorylation signaling and pathway enrichment associated with cell proliferation and cell cycle progression. Interestingly, RT induced a decrease in cancer cells characterized as harboring a chemoresistant basal-like molecular subtype. ConclusionThrough both longitudinal and therapy stratified tumor biopsies, we were able to observe significant selection pressures on stromal and cancer cells following RT. This includes upregulation of innate and adaptive immune pathways with a compensatory immunosuppressive response driven by myeloid cells and CAFs. This may provide opportunities for development of clinical trials to therapeutically target specific cellular phenotypes and their interactions. Citation Format: Vincent Bernard, Galia Jacobson, Kimal Rajapakshe, Jimin Min, Guangsheng Pei, Daniel Lin, Ayush Suresh, Dadi Jiang, Ching-Wei Tzeng, Manoop S Bhutani, Linghua Wang, Paola A Guerrero, Ethan B Ludmir, Albert C Koong, Anirban Maitra, Cullen M Taniguchi, Eugene J Koay. A comprehensive spatial atlas of neoadjuvant chemoradiation therapy in resected pancreatic cancer identifies cellular &amp; microenvironmental determinants of persister populations [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B078.

Abstract A035: 3D High-Density Collagen I Improves the Modeling of Aggressive Pancreatic Cancer

Abstract Background: Fibrillar collagen type I constitutes the majority of the extracellular matrix in pancreatic ductal adenocarcinoma (PDAC), yet most in vivo murine models involve the use of basement membrane extracts, which instead contain collagen type IV, as matrices to embed PDAC cells. Type I collagen in the PDAC tumor microenvironment has been associated with worse prognosis. Our hypothesis is that PDAC cells grown in 3D high-density collagen I (HDC) gels behave more aggressively compared to the same cells grown using conventional basement membrane matrix (BMM). Methods: The KPC1199 2D cell line was previously generated from a tumor-bearing male KPC mouse. KPC1199 cells were cultured in vitro in HDC or BMM for one week. Orthotopic tumors were established by embedding KPC1199 cells in HDC (N=10) or BMM (N=10) in the pancreatic tail of syngeneic C57BL/6J mice via laparotomy. Half of the tumors were collected five weeks after tumor implantation, and the other half utilized for a survival study. Collagen was imaged by second harmonic generation (SHG) microscopy. Results: In vitro imaging of single KPC1199 cells grown in HDC revealed an aggressive phenotype with clonal network-like structures compared to a spheroidal, non-aggressive phenotype for cells grown in BMM over the course of seven days. SHG imaging confirmed consistent formation and organization of collagen in HDC tumors but minimal to faint collagen formation in BMM tumors. Gross examination of HDC mice showed 60% with visible liver metastasis compared with none in the BMM mice. In the survival study, the entire HDC group died before the BMM group (p-value &amp;lt; 0.01). Conclusions: Our pilot study is the first, to our knowledge, to successfully generate orthotopic PDAC tumors using 3D high-density collagen I in a mouse model. KPC1199 cells embedded in HDC showed an aggressive phenotype in vitro, and resultant tumors demonstrated more robust collagen organization compared to the same cells grown in the BMM substrate. This aggressive phenotype translated to visible liver metastasis within five weeks in the HDC mice and prior to death from primary tumor burden. This is not typical for most KPC-derived cell lines but is typical for human PDAC patients. Our preliminary findings support the use of HDC as an alternative substrate for better modeling of this aggressive cancer. Citation Format: Kim Nguyen-Ta, Sural Ranamukhaarachchi, Jeffrey Turner, Utsav Joshi, Himangshu Sonowal, Jorge de la Torre Medina, Herve Tiriac, Stephanie Fraley, Rebekah White. 3D High-Density Collagen I Improves the Modeling of Aggressive Pancreatic Cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A035.

Main challenges on the curation of large scale datasets for pancreas segmentation using deep learning in multi-phase CT scans: Focus on cardinality, manual refinement, and annotation quality

Accurate segmentation of the pancreas in computed tomography (CT) holds paramount importance in diagnostics, surgical planning, and interventions. Recent studies have proposed supervised deep-learning models for segmentation, but their efficacy relies on the quality and quantity of the training data. Most of such works employed small-scale public datasets, without proving the efficacy of generalization to external datasets. This study explored the optimization of pancreas segmentation accuracy by pinpointing the ideal dataset size, understanding resource implications, examining manual refinement impact, and assessing the influence of anatomical subregions. We present the AIMS-1300 dataset encompassing 1,300 CT scans. Its manual annotation by medical experts required 938 h. A 2.5D UNet was implemented to assess the impact of training sample size on segmentation accuracy by partitioning the original AIMS-1300 dataset into 11 smaller subsets of progressively increasing numerosity. The findings revealed that training sets exceeding 440 CTs did not lead to better segmentation performance. In contrast, nnU-Net and UNet with Attention Gate reached a plateau for 585 CTs. Tests on generalization on the publicly available AMOS-CT dataset confirmed this outcome. As the size of the partition of the AIMS-1300 training set increases, the number of error slices decreases, reaching a minimum with 730 and 440 CTs, for AIMS-1300 and AMOS-CT datasets, respectively. Segmentation metrics on the AIMS-1300 and AMOS-CT datasets improved more on the head than the body and tail of the pancreas as the dataset size increased. By carefully considering the task and the characteristics of the available data, researchers can develop deep learning models without sacrificing performance even with limited data. This could accelerate developing and deploying artificial intelligence tools for pancreas surgery and other surgical data science applications.

A rare case of pancreatic pseudocyst-portal vein fistula in a patient with chronic pancreatitis.

A 60-year-old female with chronic pancreatitis and a history of splenectomy presented with epigastric pain, vomiting, and asthenia. Elevated pancreatic enzymes and CT imaging revealed a pseudocyst in the pancreatic head with suspected communication to the portal vein, confirmed by MR Cholangiopancreatography and endoscopic ultrasound (EUS). EUS-guided puncture revealed high amylase levels. Given her manageable symptoms, a conservative approach was adopted, leading to symptomatic relief and pseudocyst size reduction. Pancreatic pseudocyst-portal vein fistula is a rare pancreatitis complication, challenging to diagnose, with no gold-standard treatment. Endoscopic stenting offers a promising alternative to surgery for severe cases.

Laparoscopic enucleation of tumors embedded in the pancreatic head: Safety and feasibility

BackgroundSurgical treatment for a benign or low-grade malignant tumor in the pancreatic head remains a challenge at present. As an organ-sparing procedure, enucleation is ideal. However, it is still controversial whether laparoscopic enucleation (LapEN) can be safely performed for a pancreatic head tumor, especially a deeply embedded one. MethodsThe cases who underwent LapEN of a pancreatic tumor from January 2014 to September 2022 in our hospital were collected and analyzed. ResultsA total of 151 cases were collected. The incidence of pancreatic fistula (PF, grade B) was 21.9%. No patient developed PF (grade C) or died. Compared with enucleating a tumor in the distal pancreas (N = 98), enucleating a tumor in the pancreatic head (N = 53) showed a longer operation time and a higher incidence of conversion. The cases with a tumor in the pancreatic head were then divided into the group with a deeply embedded tumor (N = 32) and the group with a superficial tumor (N = 21). The embedded group had a smaller tumor size and a higher proportion of insulinoma. There were no statistical differences in the parameters of operation time, blood loss and incidence of complications between the two groups. The outcomes of enucleating a tumor deeply embedded in the proximal and distal pancreas were further analyzed, which indicated no statistical differences in clinical parameters between the two groups. ConclusionLapEN of a tumor in the pancreatic head is feasible and safe, even for a deeply embedded tumor.

Outcomes of proton therapy to infradiaphragmatic sites in pediatric patients with Hodgkin lymphoma.

Proton therapy (PT) has potential advantages in pediatric Hodgkin lymphoma (pHL). However, there are limited data on PT, specifically to infradiaphragmatic targets. We report on PT planning details, doses achieved to organs at risk (OARs), and clinical and toxicity outcomes for patients with pHL who received PT to infradiaphragmatic regions. This is a retrospective study including patients treated between 2011 and 2022. Demographic and clinical factors were collected, and toxicity was reported using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Dosimetric and clinical factors associated with key outcomes were assessed via Cox regression. Photon plans were generated for all patients, and the paired t-tests or Wilcoxon signed rank sum tests were used for dosimetric comparisons. Twenty-one patients comprising 22 PT courses were included. Median follow-up was 5.0years, and mean age was 14.2years. Median dose was 21 Gray equivalent (GyE) over 14 fractions. Top acute grade 1 (G1) toxicities included fatigue (59%) and anorexia (36%). Rates of acute G2 and G3+ toxicity were 18% and 0%, respectively. After PT, no local or marginal failures occurred. Five percent experienced disease progression, who were all successfully salvaged, and all patients were alive and disease-free at last follow-up. No secondary malignancies developed. Compared to photon radiotherapy, PT achieved significantly lower doses to the bowels, stomach, spleen, pancreatic tail, liver, kidneys, and pelvic bones. PT is well-tolerated and leads to excellent oncologic and toxicity outcomes with long-term follow-up. PT confers dosimetric advantages when compared to photons.

Informing Decision-making for Transected Margin Reresection in Intraductal Papillary Mucinous Neoplasm-derived PDAC: An International Multicenter Study.

To assess the prognostic impact of margin status in patients with resected intraductal papillary mucinous neoplasms (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) and to inform future intraoperative decision-making on handling differing degrees of dysplasia on frozen section. The ideal oncologic surgical outcome is a negative transection margin with normal pancreatic epithelium left behind. However, the prognostic significance of reresecting certain degrees of dysplasia or invasive cancer at the pancreatic neck margin during pancreatectomy for IPMN-derived PDAC is debatable. Consecutive patients with resected and histologically confirmed IPMN-derived PDAC (2002-2022) from six international high-volume centers were included. The prognostic relevance of a positive resection margin (R1) and degrees of dysplasia at the pancreatic neck margin were assessed by log-rank test and multivariable Cox-regression for overall survival (OS) and recurrence-free survival (RFS). Overall, 832 patients with IPMN-derived PDAC were included with 322 patients (39%) having an R1-resection on final pathology. Median OS (mOS) was significantly longer in patients with an R0 status compared to those with an R1 status (65.8 vs. 26.3mo P<0.001). Patients without dysplasia at the pancreatic neck margin had similar OS compared to those with low-grade dysplasia (mOS: 78.8 vs. 66.8 months, P=0.344). However, high-grade dysplasia (mOS: 26.1mo, P=0.001) and invasive cancer (mOS: 25.0mo, P<0.001) were associated with significantly worse OS compared to no or low-grade dysplasia. Patients who underwent conversion of high-risk margins (high-grade or invasive cancer) to a low-risk margin (low-grade or no dysplasia) after intraoperative frozen section had significantly superior OS compared to those with a high-risk neck margin on final pathology (mOS: 76.9 vs. 26.1mo P<0.001). In IPMN-derived PDAC, normal epithelium or low-grade dysplasia at the neck have similar outcomes while pancreatic neck margins with high-grade dysplasia or invasive cancer are associated with poorer outcomes. Conversion of a high-risk to low-risk margin after intraoperative frozen section is associated with survival benefit and should be performed when feasible.