Early initiation of chemotherapy after histological diagnosis to improve the prognosis of metastatic pancreatic ductal adenocarcinoma.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 273-273 ◽  
Author(s):  
Rei Suzuki ◽  
Tadayuki Takagi ◽  
Takuto Hikichi ◽  
Ai Sato ◽  
Ko Watanabe ◽  
...  

273 Background: Since pancreatic ductal adenocarcinoma (PDAC) shows aggressive progression, we speculate that prolonged waiting time after detection of disease until initiation of treatment may relate to prognosis of patients with advanced diseases. Methods: We included patients diagnosed to have metastatic PDAC in Fukushima Medical University between September 2006 and January 2014. All patients underwent more than 2 cycles of gemcitabine treatment (1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle) after confirming histological diagnosis. We classified waiting time as Time A (detection-to-diagnosis waiting time) and Time B (diagnosis-to-treatment waiting time). Each period was further divided into 2 groups (shorter [-short] or longer [-long] waiting time than median length of each waiting time group). Kaplan-Meier methods, log-rank test and Cox proportional hazard methods were used to analyze overall survival (OS). Results: Twenty three patients were included. Median age was 64 (49-75) and length of waiting time was 19.5 days (4-78) in Time A and 9.0 days (2-34) in Time B. Regarding Time A, there was no significant difference in median OS between Time A-short and Time A-long (198.5 vs. 197.0 days; hazard ration [HR] 1.096; 95% confidential interval [CI] 0.4822-2.537; P=0.81). On the other hand, median OS was significantly better in Time B-short than Time B-long (median OS 290 vs. 160 days; HR, 0.381; 95% CI, 0.096-0.622; P= 0.0078). Conclusions: We foundthat waiting time between disease detection and diagnosis didn’t impact on prognosis of metastatic PDAC contrary to our speculation. However, patients with short waiting time (less than 9 days) after diagnosis until initiation of first chemotherapy had better prognosis than patients who had long waiting time. These findings suggest that early initiation of chemotherapy after histological diagnosis can improve the prognosis of metastatic PDAC.

2014 ◽  
Vol 80 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Clancy J. Clark ◽  
Janani S. Arun ◽  
Rondell P. Graham ◽  
Lizhi Zhang ◽  
Michael Farnell ◽  
...  

Anaplastic pancreatic cancer (APC) is a rare undifferentiated variant of pancreatic ductal adenocarcinoma with poor overall survival (OS). The aim of this study was to evaluate the clinical outcomes of APC compared with differentiated pancreatic ductal adenocarcinoma. We conducted a retrospective review of all patients treated at the Mayo Clinic with pathologically confirmed APC from 1987 to 2011. After matching with control subjects with pancreatic ductal adenocarcinoma, OS was evaluated using Kaplan-Meier estimates and log-rank test. Sixteen patients were identified with APC (56.3% male, median age 57 years). Ten patients underwent exploration of whom eight underwent pancreatectomy. Perioperative morbidity was 60 per cent with no mortality. The median OS was 12.8 months. However, patients with APC who underwent resection had longer OS compared with those who were not resected, 34.1 versus 3.3 months ( P = 0.001). After matching age, sex, tumor stage, and year of operation, the median OS was similar between patients with APC and those with ductal adenocarcinoma treated with pancreatic resection, 44.1 versus 39.9 months, ( P = 0.763). Overall survival for APC is poor; however, when resected, survival is similar to differentiated pancreatic ductal adenocarcinoma.


2020 ◽  
Author(s):  
Gokce Askan ◽  
Ibrahim Halil Sahin ◽  
Joanne F. Chou ◽  
Aslihan Yavas ◽  
Marinela Capanu ◽  
...  

Abstract Background: Herein, we investigate the relationship between pancreatic stem cell markers (PCSC markers), CD44, and epithelial-specific antigen (ESA), tumor stroma, and the impact on recurrence outcomes in pancreatic ductal adenocarcinoma (PDAC) patients.Methods: PDAC patients who underwent surgical resection between 01/2012 -06/2014 were identified. CD44 and ESA expression was assessed by immunohistochemistry. Stroma was classified as loose, moderate, and dense based on fibroblast content. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared between subgroups by log-rank test. The association between PCSC markers and stroma type was assessed by Fisher`s exact test. Results: N= 93 PDAC patients were identified. The number of PDAC patients with dense, moderate density, and loose stroma was 11 (12%), 51 (54%), and 31 (33%) respectively. PDAC with CD44+/ESA- had highest rate of loose stroma (63%) followed by PDAC CD44+/ESA+ (50%), PDAC CD44-/ESA+ (35%), CD44-/ESA- (9%) (p=0.0033). No local recurrence was observed in patients with dense stroma and 9 had distant recurrence. The highest rate of cumulative local recurrence observed in patients with loose stroma. No statistically significant difference in RFS and OS were observed among subgroups (P=0.089). Conclusions: These data indicate PCSCs may have an important role in stroma differentiation in PDAC. Although not reaching statistical significance, we observed more local recurrences in patients with loose stroma, and no local recurrence was seen in patients with dense stroma suggesting tumor stroma may influence the recurrence pattern in PDAC patients.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gokce Askan ◽  
Ibrahim Halil. Sahin ◽  
Joanne F. Chou ◽  
Aslihan Yavas ◽  
Marinela Capanu ◽  
...  

Abstract Background Herein, we investigate the relationship between pancreatic stem cell markers (PCSC markers), CD44, and epithelial-specific antigen (ESA), tumor stroma, and the impact on recurrence outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. Methods PDAC patients who underwent surgical resection between 01/2012–06/2014 were identified. CD44 and ESA expression was assessed by immunohistochemistry. Stroma was classified as loose, moderate, and dense based on fibroblast content. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared between subgroups by log-rank test. The association between PCSC markers and stroma type was assessed by Fisher’s exact test. Results N = 93 PDAC patients were identified. The number of PDAC patients with dense, moderate density, and loose stroma was 11 (12%), 51 (54%), and 31 (33%) respectively. PDAC with CD44+/ESA− had highest rate of loose stroma (63%) followed by PDAC CD44+/ESA+ (50%), PDAC CD44−/ESA+ (35%), CD44−/ESA− (9%) (p = 0.0033). Conversely, lack of CD44 and ESA expression was associated with the highest rate of moderate and dense stroma (91% p = 0.0033). No local recurrence was observed in patients with dense stroma and 9 had distant recurrence. The highest rate of cumulative local recurrence was observed in patients with loose stroma. No statistically significant difference in RFS and OS was observed among subgroups (P = 0.089). Conclusions These data indicate PCSCs may have an important role in stroma differentiation in PDAC. Our results further suggest that tumor stroma may influence the recurrence pattern in PDAC patients.


2020 ◽  
Vol 14 ◽  
pp. 117955492093660
Author(s):  
Rossana Berardi ◽  
Silvia Rinaldi ◽  
Giulio Belfiori ◽  
Stefano Partelli ◽  
Stefano Crippa ◽  
...  

Objectives: Hyponatraemia represents a negative prognostic factor in patients with cancer. The aim of this study was to assess, for the first time, the role of hyponatraemia in patients undergoing radical surgery for pancreatic ductal adenocarcinoma. Methods: A total of 89 patients with stage I-III pancreatic ductal adenocarcinoma underwent radical surgery between November 2012 and October 2014. Relapse-free survival (RFS) and disease-specific survival (DSS) were estimated using Kaplan-Meier method. A Cox regression model was carried out for univariate and multivariate analyses. Fisher exact test was used to estimate correlation between variables. Results: In total, 12 patients (14%) presented with hyponatraemia at diagnosis. The median DSS was 20 months in patients with hyponatraemia and not reached in patients with eunatraemia ( P < .1073), while a statistical significant difference was observed in terms of median RFS (10 months vs 17 months, respectively; P = .0233). Considering clinical features (hyponatraemia, smoke and alcoholic habit, diabetes, pain, and jaundice), patients with 4 or more of these factors had a worse prognosis (mDSS: 30 months vs not reached; hazard ratio [HR]: 0.40, 95% confidence interval [CI] = 0.16-0.80; P = .0120). Conclusions: The presence of hyponatraemia and its prompt correction at the diagnosis time should be considered for the correct management of patients with pancreatic carcinoma.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8811
Author(s):  
Ankang Wang ◽  
Bo Sun ◽  
Min Wang ◽  
Hao Shi ◽  
Zhiwei Huang ◽  
...  

Background The preoperative controlling nutritional status (CONUT) score and serum carbohydrate antigen 199 (CA199) levels are individually correlated with the prognosis of pancreatic ductal adenocarcinoma (PDAC). The objective of this study aimed to investigate the efficacy of CONUT score and CA199 (CONUT-CA199) combination in predicting the prognosis of PDAC patients undergoing radical surgery. Methods We retrospectively analyzed the preoperative CONUT scores and serum CA199 levels of 294 patients with PDAC who underwent radical resection at the Affiliated Hospital of Southwest Medical University between March 2012 and July 2019. Patients were divided into four groups on the basis of their preoperative CONUT scores and serum CA199 levels: CONUTlow/CA199low (1), CONUTlow/CA199high (2), CONUThigh/CA199low (3) and CONUThigh/CA199high (4). The prognostic effects were compared among the groups. Results CONUThigh was more frequent in patients with positive peripancreatic infiltration and Clavien–Dindo classification of ≥IIIa (P < 0.001). Kaplan–Meier analysis revealed obvious difference in overall survival (OS) and recurrence-free survival (RFS) among patients with PDAC having CONUT-CA199 scores of 1, 2, 3 and 4 (P < 0.001). Peripancreatic infiltration, lymph node metastasis, pTNM stage, CONUT score, serum CA199 levels and CONUT-CA199 classification were found to be the independent prognostic factors for OS and RFS in multivariate analyses. In time-dependent receiver operating characteristic (ROC) analyses, the area of the CONUT-CA199 score under the ROC curve (AUC) was higher than that of the preoperative CONUT score or serum CA199 levels for the prediction of OS and RFS. Conclusion CONUT-CA199 classification may be more effective in predicting the postoperative prognosis of PDAC patients.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Andrés Moreno Roca ◽  
Luciana Armijos Acurio ◽  
Ruth Jimbo Sotomayor ◽  
Carlos Céspedes Rivadeneira ◽  
Carlos Rosero Reyes ◽  
...  

Abstract Objectives Pancreatic cancers in most patients in Ecuador are diagnosed at an advanced stage of the disease, which is associated with lower survival. To determine the characteristics and global survival of pancreatic cancer patients in a social security hospital in Ecuador between 2007 and 2017. Methods A retrospective cohort study and a survival analysis were performed using all the available data in the electronic clinical records of patients with a diagnosis of pancreatic cancer in a Hospital of Specialties of Quito-Ecuador between 2007 and 2017. The included patients were those coded according to the ICD 10 between C25.0 and C25.9. Our univariate analysis calculated frequencies, measures of central tendency and dispersion. Through the Kaplan-Meier method we estimated the median time of survival and analyzed the difference in survival time among the different categories of our included variables. These differences were shown through the log rank test. Results A total of 357 patients diagnosed with pancreatic cancer between 2007 and 2017 were included in the study. More than two-thirds (69.9%) of the patients were diagnosed in late stages of the disease. The median survival time for all patients was of 4 months (P25: 2, P75: 8). Conclusions The statistically significant difference of survival time between types of treatment is the most relevant finding in this study, when comparing to all other types of treatments.


Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 349
Author(s):  
Nausika Betriu ◽  
Juan Bertran-Mas ◽  
Anna Andreeva ◽  
Carlos E. Semino

Pancreatic Ductal Adenocarcinoma (PDAC) is a fatal disease with poor prognosis because patients rarely express symptoms in initial stages, which prevents early detection and diagnosis. Syndecans, a subfamily of proteoglycans, are involved in many physiological processes including cell proliferation, adhesion, and migration. Syndecans are physiologically found in many cell types and their interactions with other macromolecules enhance many pathways. In particular, extracellular matrix components, growth factors, and integrins collect the majority of syndecans associations acting as biochemical, physical, and mechanical transducers. Syndecans are transmembrane glycoproteins, but occasionally their extracellular domain can be released from the cell surface by the action of matrix metalloproteinases, converting them into soluble molecules that are capable of binding distant molecules such as extracellular matrix (ECM) components, growth factor receptors, and integrins from other cells. In this review, we explore the role of syndecans in tumorigenesis as well as their potential as therapeutic targets. Finally, this work reviews the contribution of syndecan-1 and syndecan-2 in PDAC progression and illustrates its potential to be targeted in future treatments for this devastating disease.


2021 ◽  
pp. 1-9
Author(s):  
Leonard Naymagon ◽  
Douglas Tremblay ◽  
John Mascarenhas

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mitch Kampmeyer ◽  
Clifton W Callaway

Recent research supports the use of cold IV fluid as a method for initiating therapeutic hypothermia in post-cardiac arrest resuscitation. However, prehospital care programs employing this treatment have encountered various difficulties. Barriers to prehospital induced hypothermia protocols include the lack of effective or economically reasonable methods to maintain cold saline in the field. Objective. Determine the time that a standard commercial cooler can maintain two 1-liter normal saline solution (NSS) bags below 4°C in 3 different environments. Methods. Environments simulating an ambulance compartment were created for the experiment. NSS temperatures were continuously recorded inside a standard commercial cooler with or without ice packs (IPs) under one of three scenarios: ambient room temperature (25°C) without (IPs), ambient room temperature with IPs and 50°C ambient temperature with IPs. Four trials under each condition were performed. Time to warm to 4°C was compared using Kaplan-Meier log rank test. Results. In a room temperature environment with IPs, the NSS warmed to 4°C in a mean interval of 29 hrs 53 mins versus in ambient room temperature without IPs (1 hr 21 mins) versus in constant hot environment of 50°C with IPs (10 hrs 50 mins). A significant difference was found between the three environments (log-rank =17.90, dF =2, p =0.0001). Conclusions. Low technology methods in the form of a cooler and IPs can provide cold NSS storage for longer than a full 24 hour shift in a room temperature ambulance. In hot ambient conditions, 4°C NSS can be maintained for nearly 11 hours using this method. This model exhibits an economical, easily deployable cold saline storage unit.


2021 ◽  
Author(s):  
Yuichi Kojima ◽  
Sho Nakakubo ◽  
Keisuke Kamada ◽  
Yu Yamashita ◽  
Nozomu Takei ◽  
...  

SummaryBackgroundAlthough biological agents, tocilizumab and baricitinib, have been shown to improve the outcomes of patients with COVID-19, a comparative evaluation has not been performed.MethodsA retrospective, single-center study was conducted using the data of patients with COVID-19 admitted to the Hokkaido University hospital between April 2020 and September 2021, who were treated with tocilizumab or baricitinib. The clinical characteristics of patients who received each drug were compared. Univariate and multivariate logistic regression models were performed against the outcomes of all-cause mortality and the improvement in respiratory status. The development of secondary infection events was analyzed using the Kaplan–Meier analysis and the log-rank test.ResultsThe use of tocilizumab or baricitinib was not associated with all-cause mortality and the improvement in respiratory status within 28 days of drug administration. Age, chronic renal disease, and comorbid respiratory disease were independent prognostic factors for all-cause mortality, while anti-viral drug use and severity of COVID-19 at baseline were associated with the improvement in respiratory status. There was no significant difference in the infection-free survival between patients treated with tocilizumab and those with baricitinib.ConclusionThere were no differences in efficacy and safety between tocilizumab and baricitinib for the treatment of COVID-19.


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