Journal of Pancreatic Cancer最新文献

Background: Immunotherapy (IT) has led to improved survival in several common cancers but success in pancreatic ductal adenocarcinoma (PDAC) has been limited. We analyzed if combination IT-chemotherapy (IT-CT) is associated with improved survival compared with chemotherapy alone (CT) in patients with metastatic PDAC. Methods: The National Cancer Database (2004-2016) was queried for patients who were diagnosed with metastatic PDAC. Patients were categorized by treatment group: CT only and IT-CT. Patients were excluded if they received radiation or a surgical procedure. The primary outcome was overall survival. Results: A total of 59,289 patients were identified, of whom 58,947 (99.4%) received CT and 342 (0.6%) received IT-CT. The IT-CT group was younger, had fewer comorbidities, and was more often treated at an academic center. The utilization of multiagent CT was similar between the groups. Median survival of patients treated with IT-CT was longer than CT alone (7.9 months vs. 6.3 months, p = 0.005). On multivariable analysis, receipt of IT-CT was associated with a survival advantage as compared with CT (hazard ratio = 0.86, 95% confidence intervals 0.76-0.97) when adjusting for demographics and type of CT regimen. Conclusion: In patients with metastatic PDAC, it appears that combination IT-CT may perhaps be associated with a survival advantage compared with CT alone.

Purpose: Current literature reports increased incidence of postpancreaticoduodenectomy (PD) nonalcoholic fatty liver disease (NAFLD), a precursor for nonalcoholic steatohepatitis and cirrhosis. The incidence of and risk factors (RFs) for NAFLD in the PD population, however, are not well elucidated. Methods: A cohort of 421 patients from a single institution who underwent PD for carcinoma and followed for at least 6 months were assessed retrospectively for age, gender, pathology, surgical complications (operative blood loss and length of stay [LOS]), comorbidities (diabetes, hypertension, hyperlipidemia, obesity), tobacco use, pre- and postoperative nutritional status (albumin and body mass index [BMI]), use of pancreatic enzyme replacement, and perioperative laboratory values (hemoglobin and liver function test). Cox proportional hazards model was used to examine these potential RFs as predictors of time to development of post-PD NAFLD. Results: Sixty (14.3%) patients developed post-PD NAFLD. Patients with NAFLD were younger (61.10 vs. 65.01 years old) and had higher preoperative BMI (28.92 vs. 26.61). Multivariate Cox proportional hazard model identified higher preoperative BMI, shorter postoperative LOS, and female gender as RFs for post-PD NAFLD. After excluding 12 patients with rare histology, there was a lower unadjusted hazard of developing NAFLD (p-value = 0.018) in the adenocarcinoma group than in the neuroendocrine and periampullary tumor groups. There was no statistically significant association between post-PD NAFLD and other characteristics. Conclusion: Female gender, higher preoperative BMI, and shorter LOS deserve closer monitoring for earlier detection and management of NAFLD.

Background: Both primary pancreatic lymphoma (PPL) and primary splenic lymphoma (PSL) represent rare entities. PPL typically arises in the head of the pancreas but may arise in other locations also. PSL usually presents with nonspecific symptoms, including left upper quadrant pain, weight loss, and fever. This report describes a patient with a large left upper quadrant mass, which initially was believed to be a primary pancreatic mass, but which on final pathology appeared to be consistent with a PSL. Presentation: The patient is a 64-year-old woman who initially presented with symptoms of left upper quadrant abdominal pain and distension; she subsequently was found to have an 18 cm heterogeneous mass arising from the pancreatic tail. She underwent a distal pancreatectomy with splenectomy. Final pathology confirmed a diffuse large B cell lymphoma arising from the splenic parenchyma. Conclusions: Both PPL and PSL are rare causes of left upper quadrant masses. In this case, we describe a large lymphoma that appeared to arise from the tail of the pancreas, but on final pathology was found to be splenic in origin. Differentiating these two clinical entities is important for prognostication and treatment. A multimodal approach with surgical resection followed by chemotherapy is preferred.

Purpose: GI-4000, a series of recombinant yeast expressing four different mutated RAS proteins, was evaluated in subjects with resected ras-mutated pancreas cancer. Methods: Subjects (n = 176) received GI-4000 or placebo plus gemcitabine. Subjects' tumors were genotyped to identify which matched GI-4000 product to administer. Immune responses were measured by interferon-γ (IFNγ) ELISpot assay and by regulatory T cell (Treg) frequencies on treatment. Pretreatment plasma was retrospectively analyzed by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-ToF) mass spectrometry for proteomic signatures predictive of GI-4000 responsiveness. Results: GI-4000 was well tolerated, with comparable safety findings between treatment groups. The GI-4000 group showed a similar pattern of median recurrence-free and overall survival (OS) compared with placebo. For the prospectively defined and stratified R1 resection subgroup, there was a trend in 1 year OS (72% vs. 56%), an improvement in OS (523.5 vs. 443.5 days [hazard ratio (HR) = 1.06 [confidence interval (CI): 0.53-2.13], p = 0.872), and increased frequency of immune responders (40% vs. 8%; p = 0.062) for GI-4000 versus placebo and a 159-day improvement in OS for R1 GI-4000 immune responders versus placebo (p = 0.810). For R0 resection subjects, no increases in IFNγ responses in GI-4000-treated subjects were observed. A higher frequency of R0/R1 subjects with a reduction in Tregs (CD4⁺/CD45RA⁺/Foxp3^low) was observed in GI-4000-treated subjects versus placebo (p = 0.033). A proteomic signature was identified that predicted response to GI-4000/gemcitabine regardless of resection status. Conclusion: These results justify continued investigation of GI-4000 in studies stratified for likely responders or in combination with immune check-point inhibitors or other immunomodulators, which may provide optimal reactivation of antitumor immunity. ClinicalTrials.gov Number: NCT00300950.

Background: Primary pancreatic signet ring cell carcinoma (PPSRCC) is a rare (<1%) poorly reported histopathological variant of pancreatic cancer with ill-defined treatment guidelines. Herein, we describe a case of nonmetastatic PPSRCC in a 45-year-old female. Presentation: A 45-year-old female presented with 3 weeks of abdominal pain radiating to her back. Other pertinent positives included a 20-pound (9.1-kilogram) weight loss and jaundice, with a known 30-pack-year smoking history. CT scan revealed a 4.6 × 3.6 cm hypoattenuating mass in the head of the pancreas (HOP) with dilatation of the common bile duct. Total bilirubin at presentation was elevated, and a biliary stent was placed endoscopically. Subsequent endoscopic ultrasonography revealed a periampullary ulcerated mass involving the HOP and second portion of the duodenum, with pathology revealing poorly differentiated adenocarcinoma with mucinous background and focal signet ring cells. A classic pancreatoduodenectomy (Whipple procedure) was performed. Final pathology revealed a poorly differentiated (G3) pT3/pN2/pM0 PPSRCC with 11 of 16 positive specimen lymph nodes. The tumor had evidence of both KRAS and TP53 mutations and expressed an MUC1+/MUC2-/MUC5AC+ immunophenotype. Medical oncology recommended a 6-month course of adjuvant modified-dose FOLFIRINOX therapy. Conclusion: This report highlights the need for further research into the pathogenesis of gastrointestinal signet ring cell carcinoma to identify and study therapeutic targets that can eventually be translated to PPSRCC treatment. Given the paucity of PPSRCC, adjuvant therapy candidates follow the current literature on more common pancreatic cancer subtypes to guide treatment.

Background: As treatment of esophageal carcinomas continues to improve, we have seen an increasing population of long-term survivors giving rise to the observation of additional primary malignancies not previously seen. Esophagogastrectomy for previously treated esophageal carcinoma presents unique anatomic changes providing further technical difficulties for surgical management of new primary malignancies. Presentation: A 65-year-old male with a history of esophagogastrectomy for esophageal adenocarcinoma presents with a pancreatic head mass consistent with pancreatic adenocarcinoma. Our case report describes a pylorus sparing pancreaticoduodenectomy with preservation of the right gastric and right gastroepiploic vessels in order to preserve blood supply to the gastric conduit. Conclusion: Here we demonstrate that in select cases where location of the pancreatic head tumor is favorable, pancreaticoduodenectomy can be performed in the context of prior esophagogastrectomy with preservation of the native blood supply to the gastric conduit. Pancreaticoduodenectomy may have yet been possible if the tumor involved the gastroduodenal artery via vascular reconstruction to the right gastroepiploic artery or sacrifice of the gastric conduit with reconstruction using small or large intestine.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is the most common cancer found in the pancreas. It has a dismal prognosis and current therapeutic options, including surgical resection, provide only a temporary or limited response due to the development of treatment resistance. Methods: A narrative review of studies investigating poly (ADP-ribose) polymerase (PARP) pathway inhibitors in metastatic PDAC to highlight recent advances. Results: Mutations in BRCA genes confer a higher risk of PDAC, while germ line mutations are found in 4-7% of individuals harboring pancreatic cancer. Although solid tumors with defective DNA damage repair defect (DDR) genes such as BRCA show heightened sensitivity to platinum agents, tumors can exploit the PARP pathway as salvage pathways. Therefore, blocking this pathway will trigger cell death in vulnerable tumor cells with BRCA/DNA repair deficiency. Several drugs with inhibitory activity on the PARP pathway have been approved for breast and ovarian tumors harboring germ line or somatic BRCA mutations. Based on these results, the phase III POLO study showed a significant improvement in progression-free survival compared with placebo in BRCA mutant pancreatic tumors and highlighted the importance of germ line testing in everyone diagnosed with pancreatic cancer. In addition, expansion of the PARP inhibitor indication beyond BRCA mutations to other genes involved in DDR such as ATM and PALB2 merits attention. Conclusion: PARP inhibitors represent a safe and efficacious treatment for a subset of PDAC patients with BRCA mutations. Ongoing trials are evaluating PARP inhibitors in PDAC patients with non-BRCA DDR gene deficiencies as well as PARP inhibitors in combination with other agents, notably immune checkpoint inhibitors to expand the group of patients that derive benefit from this treatment.

Background: The CA 19-9 tumor marker is commonly used alongside imaging to trend chemotherapy response in patients with pancreatic ductal adenocarcinoma. Presentation: We describe an unusual clinical case of metastatic pancreatic cancer who achieved a marked decline in CA 19-9 but paradoxically developed widespread pulmonary lymphangitic carcinomatosis leading to rapid clinical decline and death. Conclusions: This case highlights the limitations of using the CA 19-9 tumor marker in isolation.

Background: Liver parenchyma that resides outside of the normal hepatic confines is defined as accessory liver if in communication with the native biliary tree, or ectopic liver (EL) if it is not. EL can develop in a variety of tissues, including but not limited to the gallbladder, the hepatic ligaments, the pancreas, and retroperitoneum. EL has an increased propensity for malignant degeneration resulting in hepatocellular carcinoma (HCC). Presentation: A 67-year-old Korean male presented with epigastric discomfort and was found to have an elevation in his transaminases. Cross-sectional imaging demonstrated a 1.3 cm solid mass in the body of the pancreas with features concerning for either a pancreatic ductal adenocarcinoma or pancreatic neuroendocrine tumor. Subsequent endoscopic ultrasound and fine needle aspiration demonstrated cells of epithelial origin with hepatocellular differentiation. A robotic-assisted distal pancreatectomy and splenectomy was performed with final pathology demonstrating a well-differentiated HCC. Conclusions: EL with malignant degeneration resulting in HCC requires surgical excision. The majority of patients reported with EL resulting in HCC in the pancreas have had the tumors located in the body and tail. Therefore, definitive treatment requires distal pancreatectomy and splenectomy. Herein, we describe the presentation, workup, and definitive treatment of HCC arising in the pancreas.

Background: Underutilization of operative management of early stage pancreatic cancer is associated with sociodemographic variables, including age, race, facility type, insurance, and education. It is currently unclear how these variables are associated with survival in patients who undergo surgery. Methods: Patients with clinical stage I pancreatic adenocarcinoma were identified within the National Cancer Database (2010-2016). Utilization of surgery and nonoperative management was determined. Nonclinical factors associated with nonoperative management were identified by multivariable analysis. The association between nonclinical factors and survival was assessed in patients who received operative management. Results: A total of 17,833 patients with clinical stage I pancreatic cancer were identified, and 41.2% underwent operative intervention. Approximately 46% of nonoperatively managed patients lacked a contraindication. Operatively managed patients had longer overall survival (OS) than those who were nonoperatively managed or untreated (25.1 months vs. 11.1 months vs. 5.1 months, p < 0.0001). Factors associated with nonoperative management included age, black/Hispanic race, nonacademic facilities, nonprivate health insurance, lower education level, and lower income. In operatively managed patients, nonclinical factors associated with lower OS included Medicaid (hazard ratio [HR] 1.27) and treatment at nonacademic facilities (HR 1.20-1.22). Patients on Medicaid received less adjuvant therapy and had higher 30- and 90-day mortality rates. Patients treated at nonacademic facilities received less neoadjuvant therapy, had worse pathologic outcomes, and had higher 30- and 90-day mortality rates. Conclusions: Surgical management is underutilized in clinical stage I pancreatic cancer. Primary insurance payor and facility type appear to be associated with OS in patients who undergo operative management.