Journal of Pancreatic Cancer最新文献

Introduction: The incidence of pancreatic cancer is around 5 in 100,000, and the 5-year survival is poor. Pancreatic cancer patients have a high disease-specific burden of symptoms, and palliative chemotherapy has varying side effects. The American Society of Clinical Oncology (ASCO) suggests integrating specialized palliative care (SPC) with standard oncological treatment for pancreatic cancer patients at stage ≥III. This study investigated the effects of enrollment into SPC >30 days before death.

Materials and methods: This retrospective study included 170 patients with histopathologically verified pancreatic adenocarcinoma who received palliative chemotherapy at Skåne University Hospital and died between February 1, 2015, and December 31, 2017.

Results: Of the 170 patients, 151 were enrolled within the SPC unit; 97 of them for >30 days before death (group A). The remainder (group B) received SPC for ≤30 days before death (n = 54) or not at all (n = 19). Patients in groups A and B lived a median of 73 and 44 days, respectively, after the last palliative chemotherapy treatment (p < 0.001), but did not differ in terms of median overall survival (11.2 months vs. 10.9 months). Death in the hospital occurred in 84% of patients never admitted to SPC and 2% of patients ever admitted to SPC.

Conclusion: Enrollment in SPC for longer than 30 days may lower the risk of receiving futile palliative chemotherapy at the end of life, compared with patients enrolled in SPC for 30 days or less before death. Enrollment in SPC lowers the risk of dying in a hospital.

Purpose: Resectability in localized pancreatic ductal adenocarcinoma (PDAC) is deemed through radiological criteria. Despite initial evaluation classifying tumors as "resectable," they often have ill-defined borders that can result in more extensive cancer than predicted on final pathology analysis. We attempt to categorize these tumors radiologically and define them as "infiltrative" and contrast them to more well-defined or "mass-forming" tumors and assess their correlation with surgical oncological outcomes. We hypothesize that mass-forming lesions will result in fewer positive resection margins.

Methods: Patients diagnosed with PDAC of the head of the pancreas and who underwent subsequent curative intent resection between 2016 and 2018 were included. A retrospective chart review of patients was conducted and computed tomography images at the time of diagnosis were reviewed by two radiologists and scored as "mass forming" or "infiltrative" using a newly developed classification system. These classifications were then correlated with margin status.

Results: Sixty-eight consecutive pancreatoduodenectomies performed for PDAC from 2016 to 2018 were identified. After screening, 54 patients were eligible for inclusion. Radiologically defined mass-forming lesions had a trend toward a lower rate of positive resection margins (35.7% vs. 50.0%; p = 0.18), specifically the bile duct margin and pancreas margin as well as an overall larger size (4.03 cm vs. 3.25 cm, p = 0.02) compared with infiltrative lesions.

Conclusion: We propose a new radiological definition of PDAC into "mass forming" and "infiltrative," a nomenclature that resonates with other tumor sites. Infiltrative lesions trended toward a higher rate of positive resection margins. This classification may help tailor therapy for infiltrative tumors toward a neoadjuvant approach even if they appear resectable.

Background: The impact of the do-not-resuscitate (DNR) order on patients with pancreatic cancer remains uncertain. In this study, we evaluated whether DNR status was associated with in-hospital mortality and costs for inpatient stay among patients hospitalized with pancreatic cancer.

Methods: Data were obtained from the National Inpatient Sample, Healthcare Cost and Utilization Project, which represents ∼20% of all discharges from US community hospitals; 40,246 pancreatic cancer admissions between 2011 and 2016 were included. Mortality was modeled using a logistic regression model; costs for inpatient stay were modeled using a multivariable generalized linear regression model.

Results: The sample included 6041 (15%) patients with a documented DNR order. After controlling for covariates, patients with a DNR order had approximately six times greater odds of mortality compared with patients without a DNR order (odds ratio 5.90, p < 0.0001). Compared with patients who survived without a DNR order during the hospital stay, patients who had a DNR order and died during the hospital stay had significantly lower costs (-US$983; p = 0.0270), and patients who died without a DNR order during the hospital stay had significantly higher costs (US$5638; p < 0.0001). Patients who survived with a DNR order had costs that were not significantly different from patients who survived without a DNR order.

Conclusions: The presence of a DNR order among patients with pancreatic cancer was significantly associated with higher mortality risk as well as lower costs for patients who died during the hospital stay. However, DNR status was not significantly associated with costs for pancreatic cancer patients who were discharged alive.

Purpose: Hepaticojejunostomy leak and bile fistula after pancreaticoduodenectomy (PD) are less frequent than pancreatic leaks. Patients with biliary fistula (BF) have an increased risk of serious complications and an extended hospital stay. This study has investigated the occurrence and outcome of BF. Methods: All patients who underwent a PD from January 1st, 2015 to December 31st, 2019 were included. The significance of multiple risk factors was examined. Univariate analysis was used to identify predictive variables for postoperative BF. Results: Of the 552 patients who underwent PD, 38 patients (6.7%) developed a BF. Patients with nonmalignant diagnoses and malignancies without bile duct obstruction had a greater risk of developing BF. BF did not increase the mortality, though most patients had complications, including surgical site infections, intraabdominal abscesses, and an extended hospital stay. Conclusion: BF after PD leads to an increased risk of subsequent complications and an extended hospital stay but does not increase mortality. Patients with nonmalignant diagnoses and malignancies without bile duct obstruction have an increased risk of BF.

Background and Presentation: In this study, we present the case of a 64-year-old female with a chief complaint of abdominal pain and bloating, which had been persistent over a period of 4 months. Imaging revealed a 6.1-cm left-sided pancreatic mass as well as a 19.1-cm multiloculated cystic lesion in the pelvis, later revealed to be replacing the left ovary. The pancreatic mass was biopsied through endoscopic ultrasound-guided fine needle aspiration, and diagnosed as adenocarcinoma by cytology. The patient was treated with neoadjuvant chemotherapy and radiation before laparotomy for resection of the pancreas and left adnexal mass. Her response to treatment was followed radiologically and biochemically with cancer antigen (CA) 19-9 (114-35 U/mL), carcinoembryonic antigen (12-4.8 ng/mL), and CA-125 (119-15.3 U/mL) levels. She subsequently underwent an Appleby procedure, and resection of left pelvic mass and bilateral oophorectomy. Permanent sections revealed residual pancreatic ductal carcinoma with treatment effect, and a multicystic epithelial neoplasia of the left ovary for which the differential was primary ovarian carcinoma versus metastatic disease. Conclusions: Molecular mutational analysis was performed on sections of both the ovarian tumor and the pancreatic tumor to aid in diagnosis. The ovarian tumor in this case showed exactly the same mutations, KRAS G12R and TP53 G245S, as in the treated pancreatic cancer. This raised the high probability that these tumors originated from the same clonal event. The findings suggested that the ovarian tumor was an isolated metastasis of the pancreatic primary, despite the morphologic ambiguity between the two sites of neoplasia.

Purpose: The KRAS proto-oncogene is involved in the RAS/MAPK pathway. KRAS is present in the wild type or mutated forms. The oncogene KRAS is frequently mutated in various cancers. At the time that amino acid glycine is mutated, KRAS protein acquires oncogenic properties that result in the tumor cell growth, proliferation, and cancer progression. There has been limited understanding of the different mutations at codon 12. The consequences of such mutations is not fully understood. Various G12X mutations in pancreatic cancer patients have been examined, with the most common mutations being G12D (40%), G12V (30%), and G12R (15-20%). Now we are understanding that G12X mutations in the KRAS are not all equal. Methods: In a single-arm exploratory study, we accrued 13 KRAS-G12X-mutated pancreatic patients (KRAS G12D, G12V, and G12R). They were divided into two groups: group 1 consisted of seven patients with G12D and G12V and group 2 included six patients with the KRAS G12R mutation. All patients were treated with the combination of gemcitabine at 1250 mg/m² intravenous weekly for 3 weeks and oral cobimetinib 20 mg b.i.d. for 3 weeks. This was followed by a week of rest before the initiation of the next cycle. Results: In the first cohort, seven patients were on treatment, all of whom progressed and died within the 2 months of the study. In the second cohort, one of six patients achieved partial response, and five achieved stable disease. Median progression-free survival was 6 months (9% confidence interval 3.0-9.3 months) and overall survival has been reached at 8 months. Common adverse reactions included rash, fatigue, nausea, and vomiting (grades 2 and 3). Cancer antigen CA19-9 decreased by >50% in all group 2 patients. Conclusion: Our pancreatic cancer patients were heavily pretreated (all had received FOLFIRINOX and gemcitabine/nab-paclitaxel) before the entry into our trial. Upon entry into our trial, all patients were treated with the combination of gemcitabine and oral cobimetinib. Therefore, this constituted the second exposure of the patients to gemcitabine. This study illustrates a new discovery, which can potentially target 15-20% of pancreatic cancer patients and allow for a significant improvement in their prognosis. We will be conducting randomized phase II trials to substantiate our findings.

Background: Undifferentiated carcinoma with osteoclast-like giant cells/osteoclast-like giant cell reaction (UC-OGC) is a rare form of pancreatic cancer historically associated with a poor prognosis. Molecular tumor profiling provides new information about tumor origins and a more nuanced understanding of the potential efficacy of different chemotherapeutic agents. Presentation: A 69-year-old man presented with a 13-cm periampullary pancreatic mass. Biopsy of a neighboring lymph node was consistent with adenocarcinoma. After neoadjuvant chemoradiation, the patient underwent resection and the tumor was consistent with UC-OGC. Next-generation sequencing was performed with genomic and proteomic analyses analyzed by a molecular tumor board review. These analyses revealed genetic alterations similar to those seen in pancreatic ductal adenocarcinoma, as well as potential therapeutic targets for the patient's subsequent therapy. Conclusions: Understanding a tumor's genetic changes allows for better understanding of its biology and may improve treatment efficacy. We believe that future study in tumor profiling will improve our understanding of rare cancers such as UC-OGC and also pave the way for the use of novel therapies to specifically target mutations in a broad range of more common tumors.

Background: The association between Helicobacter pylori (H. pylori) infection and pancreatic cancer (PC) risk remains inconclusive. We examined the association between H. pylori antibodies and PC risk in a case-control study at a comprehensive cancer center. Methods: Multiplex serology using a glutathione S-transferase capture immunosorbent assay in conjunction with fluorescent bead technology was used to measure antibodies to 15 H. pylori proteins in serum or plasma from 131 incident cases with PC or a PC precursor and 131 healthy controls. Reactivity to ≥4 H. pylori proteins was defined as the overall seroprevalence. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for age at diagnosis/interview, gender, and race. Results: The majority of the sample was 50 years or older, and from the white race group. Half of the sample were women. Seroprevalence ≥4 of H. pylori proteins was 11.1%. Overall, H. pylori seroprevalence was not associated with PC risk (OR: 0.59; 95% CI: 0.25-1.40). The prevalence of several H. pylori-specific proteins HP537 (OR: 1.78; 95% CI: 0.30-10.51), HP305 (OR: 1.38; 95% CI: 0.61-3.16), and HP410 (OR: 1.31; 95% CI: 0.44-3.96) increased the odds of PC. Similarly, H. pylori-specific proteins HP522 (OR: 0.25; 95% CI: 0.04-1.66), HyuA (OR: 0.49; 95% CI: 0.21-1.14), and HP1564 (OR: 0.63; 95% CI: 0.27-1.51) decreased the odds of PC. However, these findings were not statistically significant at α = 0.05. Conclusions: Our findings do not support an association between H. pylori and PC risk. Further evaluation of this lack of association is recommended.

Purpose: For incurable pancreatic cancer, the therapeutic goal is to prolong survival and maintain the quality of life (QOL). Unexpected outpatient consultation (OCT) and emergency hospitalization lead to QOL deterioration. The National Comprehensive Cancer Network (NCCN) guidelines recommend 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) and gemcitabine plus albumin-bound paclitaxel (nabPTX+GEM) as the preferred first-line regimens. Japanese clinical practice guidelines further recommend GEM and tegafur/gimeracil/oteracil potassium (S-1). Currently, no treatment strategy considers QOL at any stage during a patient's clinical course. Methods: In this study, hospital-free survival (HFS), defined as the period without hospitalization and OCT, was introduced as a new indicator of the qualitative aspect of overall survival (OS). We compared OS, length of hospitalization (LOH), OCT, and HFS for the four first-line chemotherapy groups. Results: No significant difference was observed in the median OS and HFS, nor was there a strong correlation between OS and LOH, based on the four first-line chemotherapy groups. In contrast, there were strong correlations between OS and OCT and between OS and HFS in all first-line chemotherapy groups. The ratio of OCT to OS was similar for mFOLFIRINOX and nabPTX+GEM. S-1 had the lowest OCT-to-OS ratio. The ratio of HFS to OS declined from highest to lowest in the order S-1, nabPTX+GEM, mFOLFIRINOX, and GEM. Conclusion: Our findings suggested existence of correlation differences between OS and HFS between first-line mFOLFIRINOX and first-line nabPTX+GEM. In addition, a good HFS was obtained with S-1 alone in some cases. In the future, clinical trials for chemotherapy should examine QOL during the entire clinical course.

Background: Sonic Hedgehog (Shh) is a tightly regulated membrane-associated morphogen and a known driver of tumorigenesis in pancreatic ductal adenocarcinoma (PDAC). After processing, Shh remains at the plasma membrane of Shh producing cells, thereby limiting its distribution and signal strength. In PDAC, the release of Shh from tumor cells is necessary to promote a tumor-permissive microenvironment. Mechanisms regulating Shh sequestration and/or release from tumor cells to signal distant stromal cells are not well known. Previously, our laboratory demonstrated that the Drosophila transmembrane protein Boi, sequesters Hh at the membrane of Hh-producing cells. In response to dietary cholesterol or in the absence of boi, Hh is constitutively released to promote proliferation in distant cells. In this study, we investigated the conservation of this mechanism in mammals by exploring the role of the human boi homolog, CDON, in PDAC. Methods: Using PDAC cell-lines BxPC-3, Capan-2, and MIA PaCa-2, along with normal pancreatic epithelial cells (PDEC), we investigated Shh expression via Immunoblot and real-time, quantitative polymerase chain reaction in addition to Shh release via enzyme-linked immunoassay following cholesterol treatment and/or transfection with either RNA interference to reduce CDON expression or with human CDON to increase expression. Results: Consistent with our Boi model, CDON suppresses Shh release, which is alleviated in response to dietary cholesterol. However, over-expressing CDON suppresses cholesterol-mediated Shh release in some PDAC contexts, which may be relative to the mutational burden of the cells. Conclusion: Identifying mechanisms that either sequester or stimulate Shh release from the tumor cell membrane may provide new avenues to reduce signaling between the tumor and its surrounding environment, which may restrain tumor development.