Diagnosis and Management of Cystic Lesions of the Pancreas

Pancreatic cysts are challenging lesions to diagnose and to treat. Determining which of the five most common diagnoses—pancreatic pseudocyst, serous cystic neoplasm (SCN), solid pseudopapillary neoplasm (SPN), mucinous cystic neoplasm (MCN), and intraductal mucinous papillary neoplasm (IPMN)—is likely the correct one requires the careful integration of many historical, radiographic, laboratory, and other factors, and management is markedly different depending on the type of cystic lesion of the pancreas. Pseudocysts are generally distinguishable based on historical, clinical and radiographic characteristics, and among the others, the most important differentiation is between the mucin-producing MCN and IPMN (high risk for cancer) versus the serous SCN and SPN (low risk for cancer). EUS with FNA and cyst-fluid analysis will continue to play an important role in diagnosis. Among mucinous lesions, those that require treatment (resection currently) are any MCN, any MD IPMN, and BD IPMN larger than 3 cm, symptomatic, or with an associated mass, with the understanding that SCN or pseudocysts may be removed inadvertently due to diagnostic inaccuracy, and that a certain proportion of SPN will indeed be malignant at the time of removal. The role of ethanol ablation is under investigation as an alternative to resection in selected patients

Global Survey on Pancreatic Surgery During the COVID-19 Pandemic

This global survey among members of seven international pancreatic associations and study groups elucidates the role of pancreatic surgery during the COVID-19 pandemic, regarding patient selection for the surgical and oncological treatment of pancreatic diseases to support clinical decision-making and creating a starting point for further discussion

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Young cademic surgeons participating in laboratory and translational research

In the past 5 to 10 years, it seems that there has been a dramatic shift in emphasis by young academic surgical faculty members and trainees from participating in laboratory and translational research to epidemiological and outcomes research. This increased emphasis on outcomes research will undoubtedly result in an increased standard of care and more critical review of our results. It will also enable us to scientifically describe our results with the proper amount of statistical rigor that we sometimes lack. Perhaps most importantly, it will inform the proper design of clinical trials that test competing treatment options. There is, however, still a need for the surgeon-scientist who both cares for surgical patients and participates in a laboratory or translational research program. To many, a laboratory or translational research program does not seem compatible with a surgical practice. However, if properly set up by the chair . .

Newly Emerging Immune Checkpoints: Promises for Future Cancer Therapy

Cancer immunotherapy has been a great breakthrough, with immune checkpoint inhibitors leading the way. Despite the clinical effectiveness of certain immune checkpoint inhibitors, the overall response rate remains low, and the effectiveness of immunotherapies for many tumors has been disappointing. There is substantial interest in looking for additional immune checkpoint molecules that may act as therapeutic targets for cancer. Recent advances during the last decade have identified several novel immune checkpoint targets, including lymphocyte activation gene-3 (LAG-3), B and T lymphocyte attenuator (BTLA), programmed death-1 homolog (PD-1H), T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIM-3)/carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), and the poliovirus receptor (PVR)-like receptors. The investigations into these molecules have generated promising results in preclinical studies. Herein, we will summarize our current progress and understanding of these newly-characterized immune checkpoints and their potential application in cancer immunotherapy

Anaplastic Pancreatic Carcinoma Arising Within a Mucinous Cystic Neoplasm of the Pancreas: A Case Report and a Brief Review of the Literature

Background: Anaplastic pancreatic carcinomas (APCs) are among the least frequently encountered pancreatic malignancies, ranging from 0.5% to 7% of all nonendocrine pancreatic malignancies. Furthermore, few cases of APCs have been described arising within a pancreatic mucinous cystic neoplasm (MCN). Case Presentation: A 36-year-old female presented with left upper quadrant pain and a 10 × 8 cm complex cystic mass in the pancreatic tail. Fine needle aspiration of the cyst showed papillary clusters of cells with mild cytological atypia, cyst fluid carcinoembryonic antigen >4000 ng/mL, and amylase of 25 U/L. After an open distal pancreatectomy and splenectomy, the specimen revealed an MCN with multifocal microscopic foci of invasive well-differentiated adenocarcinoma. After additional sampling, foci of undifferentiated malignancy—morphologically resembling sarcomas but with immunohistochemical staining consistent with anaplastic carcinoma—were identified. The patient had an uneventful recovery and is currently undergoing a regimen of gemcitabine-based adjuvant chemotherapy; she remains disease-free at 5 months after initial diagnosis. Conclusions: In this study, we describe a rare case of APC originating from a large pancreatic MCN lesion. This case underlines the importance of scrupulous pathological evaluation of the entire MCN epithelium and adds to the limited world literature of APC originating from pancreatic MCN lesions

Anaplastic Pancreatic Carcinoma Arising Within a Mucinous Cystic Neoplasm of the Pancreas: A Case Report and a Brief Review of the Literature

Background: Anaplastic pancreatic carcinomas (APCs) are among the least frequently encountered pancreatic malignancies, ranging from 0.5% to 7% of all nonendocrine pancreatic malignancies. Furthermore, few cases of APCs have been described arising within a pancreatic mucinous cystic neoplasm (MCN). Case Presentation: A 36-year-old female presented with left upper quadrant pain and a 10 × 8 cm complex cystic mass in the pancreatic tail. Fine needle aspiration of the cyst showed papillary clusters of cells with mild cytological atypia, cyst fluid carcinoembryonic antigen >4000 ng/mL, and amylase of 25 U/L. After an open distal pancreatectomy and splenectomy, the specimen revealed an MCN with multifocal microscopic foci of invasive well-differentiated adenocarcinoma. After additional sampling, foci of undifferentiated malignancy—morphologically resembling sarcomas but with immunohistochemical staining consistent with anaplastic carcinoma—were identified. The patient had an uneventful recovery and is currently undergoing a regimen of gemcitabine-based adjuvant chemotherapy; she remains disease-free at 5 months after initial diagnosis. Conclusions: In this study, we describe a rare case of APC originating from a large pancreatic MCN lesion. This case underlines the importance of scrupulous pathological evaluation of the entire MCN epithelium and adds to the limited world literature of APC originating from pancreatic MCN lesions