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Cancers Apr 2023To systematically review all studies comparing multi-agent to single-agent chemotherapy in the first and second-line setting for unresectable pancreatic adenocarcinoma,... (Review)
Review
PURPOSE
To systematically review all studies comparing multi-agent to single-agent chemotherapy in the first and second-line setting for unresectable pancreatic adenocarcinoma, so as to compare the outcomes of young and elderly patients.
METHODS
This review searched three databases for relevant studies. The inclusion criteria were diagnosis of locally advanced or metastatic pancreatic adenocarcinoma, comparison of an elderly versus young population, comparison of single-agent versus multi-agent chemotherapy, data on survival outcomes, and randomised controlled trials. The exclusion criteria were phase I trials, incomplete studies, retrospective analyses, systematic reviews, and case reports. A meta-analysis was performed on second-line chemotherapy in elderly patients.
RESULTS
Six articles were included in this systematic review. Three of these studies explored first-line treatment and three explored second-line treatment. In the subgroup analysis, the meta-analysis showed statistically improved overall survival for elderly patients receiving single-agent second-line treatment.
CONCLUSIONS
This systematic review confirmed that combination chemotherapy improved survival in the first-line treatment of advanced pancreatic adenocarcinoma, regardless of age. The benefit of combination chemotherapy in second-line studies for elderly patients with advanced pancreas cancer was less clear.
PubMed: 37190218
DOI: 10.3390/cancers15082289 -
International Journal of Molecular... Aug 2018Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumours, and its incidence is rising worldwide. Although survival can be improved by surgical... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumours, and its incidence is rising worldwide. Although survival can be improved by surgical resection when these tumours are detected at an early stage, this cancer is usually asymptomatic, and disease only becomes apparent after metastasis. Several risk factors are associated with this disease, the most relevant being chronic pancreatitis, diabetes, tobacco and alcohol intake, cadmium, arsenic and lead exposure, certain infectious diseases, and the mutational status of some genes associated to a familial component. PDAC incidence has increased in recent decades, and there are few alternatives for chemotherapeutic treatment. Endoplasmic reticulum (ER) stress factors such as GRP78/BiP (78 kDa glucose-regulated protein), ATF6α (activating transcription factor 6 isoform α), IRE1α (inositol-requiring enzyme 1 isoform α), and PERK (protein kinase RNA-like endoplasmic reticulum kinase) activate the transcription of several genes involved in both survival and apoptosis. Some of these factors aid in inducing a non-proliferative state in cancer called dormancy. Modulation of endoplasmic reticulum stress could induce dormancy of tumour cells, thus prolonging patient survival. In this systematic review, we have compiled relevant results concerning those endoplasmic reticulum stress factors involved in PDAC, and we have analysed the mechanism of dormancy associated to endoplasmic reticulum stress and its potential use as a chemotherapeutic target against PDAC.
Topics: Activating Transcription Factor 6; Animals; Antibodies; Carcinoma, Pancreatic Ductal; Communicable Diseases; Deoxycytidine; Diabetes Complications; Disease Models, Animal; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Endoribonucleases; Gene Expression Regulation; Heat-Shock Proteins; Humans; Pancreatic Neoplasms; Pancreatitis, Chronic; Protein Serine-Threonine Kinases; RNA, Small Interfering; Risk Factors; Sulfones; eIF-2 Kinase; Gemcitabine
PubMed: 30134550
DOI: 10.3390/ijms19092468 -
International Journal of Clinical and... 2015CD133 is one of the most commonly used markers of pancreatic cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity.... (Meta-Analysis)
Meta-Analysis Review
CD133 is one of the most commonly used markers of pancreatic cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. Although the expression of CD133 has been reported to correlate with poor prognosis of PDAC in most literatures, some controversies still exist. In this study, we aimed to investigate the correlation between CD133 expression and prognosis and clinicopathological features in PDAC. A search in the Medline, EMBASE and Chinese CNKI (China National Knowledge Infrastructure) database (up to 1 March 2015) was performed using the following keywords pancreatic cancer, CD133, AC133, prominin-1 etc. Data from eligible studies were extracted and included into meta-analysis using a random effects model. Outcomes included overall survival and various clinicopathological features. We performed a final analysis of 723 patients from 11 evaluable studies for prognostic value and 687 patients from 12 evaluable studies for clinicopathological features. Our study shows that the pooled hazard ratio (HR) of overexpression CD133 for overall survival in PDAC was 0.58 (95% confidence interval (CI): 0.49-0.67) by univariate analysis and 0.73 (95% CI: 0.52-1.03) by multivariate analysis. With respect to clinicopathological features, CD133 overexpression by immunohistochemistry (IHC) method was closely correlated with clinical TNM stage (TNM stage III+IV, OR=0.32, 95% CI: 0.19-0.54), tumor differentiation (poor differentiation, OR=0.56, 95% CI: 0.37-0.83), and lymph node metastasis (N1, 3.15, 95% CI: 1.56-6.36) in patients with PDAC. Our meta-analysis results suggest that CD133 is an efficient prognostic factor in PDAC. Overexpression of CD133 was significantly associated with clinical TNM stage, tumor differentiation and lymph node metastasis.
Topics: AC133 Antigen; Antigens, CD; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Glycoproteins; Humans; Neoplastic Stem Cells; Pancreatic Neoplasms; Peptides; Prognosis
PubMed: 26722393
DOI: No ID Found -
Archives of Pathology & Laboratory... Jul 2020Preoperative neoadjuvant therapy has been increasingly used to treat patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant therapy...
CONTEXT.—
Preoperative neoadjuvant therapy has been increasingly used to treat patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant therapy often induces extensive fibrosis in tumor, adjacent pancreatic parenchyma, and peripancreatic tissue. Histopathologic evaluations and histologic tumor response grading (HTRG) of posttherapy pancreatectomy specimens are very difficult and challenging. Studies on prognostic significance of posttherapy pathologic staging, optimal system for HTRG, and other pathologic parameters in treated PDAC patients are limited.
OBJECTIVE.—
This review is to provide a timely update of the prognostic values of posttherapy pathologic staging, HTRG, and other pathologic parameters in PDAC patients who received neoadjuvant therapy and pancreas resection.
DATA SOURCES.—
Systemic review of major studies on pathologic evaluation and its clinicopathologic implications in treated PDAC patients.
CONCLUSIONS.—
Systemic pathologic examination, histologic tumor regression grading, pathologic evaluation of the margins, tumor involvement of superior mesenteric vein/portal vein, accurate pathologic staging, and reporting of posttherapy pancreatectomy specimens provide highly valuable prognostic information for postoperative patient care. Our findings suggest for the first time that tumor size of 1.0 cm, instead of 2.0 cm, is a better cutoff for ypT2 in PDAC patients. The newly proposed 3-tier MD Anderson HTRG system not only has proved to be an independent prognostic marker for PDAC patients who received neoadjuvant therapy and pancreatectomy, but also improves interobserver agreement among pathologists in evaluation of tumor response. This grading system should be considered in future editions of the College of American Pathologists protocol for PDAC.
Topics: Biopsy; Carcinoma, Pancreatic Ductal; Humans; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Staging; Observer Variation; Pancreatectomy; Pancreatic Neoplasms; Predictive Value of Tests; Reproducibility of Results; Treatment Outcome
PubMed: 32023088
DOI: 10.5858/arpa.2019-0477-RA -
BMC Gastroenterology Jul 2018Laparoscopic pancreaticoduodenectomy (LPD) remains to be established as a safe and effective alternative to open pancreaticoduodenectomy (OPD) for pancreatic-head and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Laparoscopic pancreaticoduodenectomy (LPD) remains to be established as a safe and effective alternative to open pancreaticoduodenectomy (OPD) for pancreatic-head and periampullary malignancy. The purpose of this meta-analysis was to compare LPD with OPD for these malignancies regarding short-term surgical and long-term survival outcomes.
METHODS
A literature search was conducted before March 2018 to identify comparative studies in regard to outcomes of both LPD and OPD for the treatment of pancreatic-head and periampullary malignancies. Morbidity, postoperative pancreatic fistula (POPF), mortality, operative time, estimated blood loss, hospitalization, retrieved lymph nodes, and survival outcomes were compared.
RESULTS
Among eleven identified studies, 1196 underwent LPD, and 8247 were operated through OPD. The pooled data showed that LPD was associated with less morbidity (OR = 0.57, 95%CI: 0.41~ 0.78, P < 0.01), less blood loss (WMD = - 372.96 ml, 95% CI, - 507.83~ - 238.09 ml, P < 0.01), shorter hospital stays (WMD = - 197.49 ml, 95% CI, - 304.62~ - 90.37 ml, P < 0.01), and comparable POPF (OR = 0.85, 95%CI: 0.59~ 1.24, P = 0.40), and overall survival (HR = 1.03, 95%CI: 0.93~ 1.14, P = 0.54) compared to OPD. Operative time was longer in LPD (WMD = 87.68 min; 95%CI: 27.05~ 148.32, P < 0.01), whereas R0 rate tended to be higher in LPD (OR = 1.17; 95%CI: 1.00~ 1.37, P = 0.05) and there tended to be more retrieved lymph nodes in LPD (WMD = 1.15, 95%CI: -0.16~ 2.47, P = 0.08), but these differences failed to reach statistical significance.
CONCLUSIONS
LPD can be performed as safe and effective as OPD for pancreatic-head and periampullary malignancy with respect to both surgical and oncological outcomes. LPD is associated with less intraoperative blood loss and postoperative morbidity and may serve as a promising alternative to OPD in selected individuals in the future.
Topics: Adenocarcinoma; Ampulla of Vater; Blood Loss, Surgical; Common Bile Duct Neoplasms; Humans; Laparoscopy; Length of Stay; Lymphatic Metastasis; Operative Time; Pancreatic Fistula; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Survival Analysis
PubMed: 29969999
DOI: 10.1186/s12876-018-0830-y -
Clinics (Sao Paulo, Brazil) 2022The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose... (Review)
Review
INTRODUCTION
The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose to analyze new findings on the association between microbiota and Pancreatic Ductal Adenocarcinoma (PDAC) or Cholangiocarcinoma (CCA).
METHODS
This systematic review was carried out according to the items of Preferred Reports for Systematic Reviews and Protocol Meta-Analysis (PRISMA-P). This study was registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020192748 before the review was carried out. Articles were selected from the PUBMED, EMBASE, and Cochrane databases.
RESULTS
Most studies (86.67%) used 16s rRNA as a sequencing method. The main comorbidities found were diabetes mellitus, systemic arterial hypertension, and dyslipidemia. Many studies were limited by the small number of participants, but the biases were mostly low. There was very little concordance about the composition of the microbiome of different sites, for both case and control groups when compared to other studies' results. Bile sample analysis was the one with a greater agreement between studies, as three out of four studies found Escherichia in cases of CCA.
CONCLUSION
There was great disagreement in the characterization of both the microbiota of cases and control groups. Studies are still scarce, making it difficult to adequately assess the data in this regard. It was not possible to specify any marker or to associate any genus of microbiota bacteria with PDAC or CCA.
Topics: Carcinoma, Pancreatic Ductal; Humans; Microbiota; Pancreatic Neoplasms; RNA, Ribosomal, 16S; Syndrome
PubMed: 36122499
DOI: 10.1016/j.clinsp.2022.100101 -
Journal of B.U.ON. : Official Journal... 2019Vasoactive intestinal peptide (VIP) secreting tumor (VIPoma) constitutes a rare functional neuroendocrine tumor that most often originates from pancreatic islet cells...
PURPOSE
Vasoactive intestinal peptide (VIP) secreting tumor (VIPoma) constitutes a rare functional neuroendocrine tumor that most often originates from pancreatic islet cells and presents as a sporadic, solitary neoplasm of the pancreas. The purpose of this study was to systematically review the literature of pancreatic VIPomas and report clinicopathologic data and treatment modalities for this rare entity.
METHODS
A systematic literature search was performed. The reviewed clinical series and case reports were included if they reported surgical treatment and also analyzed oncological outcomes on individual patients. Data extraction was performed using a standard registry pro-forma.
RESULTS
The search resulted in 53 case reports and 2 case series including 65 patients in total. Median age reported was 54 years. The predominant pancreatic location was the pancreatic tail. The most common clinical symptom was watery diarrhea. Serum VIP levels were remarkably elevated in all patients. Distal pancreatectomy with or without splenectomy was the most commonly applied surgical procedure. Overall survival associated with pancreatic VIPoma was 67.7%, recurrence rate 40.4% and relevant median disease-free interval was 16 months.
CONCLUSIONS
VIPomas are functional tumors that secrete excessive amounts of VIP. Clinically, production of VIP causes refractory watery diarrhea, hypokalemia and achlorydria. As far as diagnosis is concerned, elevated VIP plasma levels are required. Moreover, the majority of VIPomas are malignant or have already metastasized on diagnosis. Despite recent research on the therapeutic strategies against pancreatic VIPoma, surgical resection appears as the only potentially curative approach.
Topics: Adult; Aged; Disease-Free Survival; Female; Humans; Islets of Langerhans; Male; Middle Aged; Neoplasm Recurrence, Local; Pancreatectomy; Pancreatic Neoplasms; Vasoactive Intestinal Peptide; Vipoma
PubMed: 31127985
DOI: No ID Found -
Therapeutic Advances in Medical Oncology 2020There are no randomized data to guide treatment decisions for patients with advanced pancreatic adenocarcinoma following first-line FOLFIRINOX. We performed a systematic...
BACKGROUND
There are no randomized data to guide treatment decisions for patients with advanced pancreatic adenocarcinoma following first-line FOLFIRINOX. We performed a systematic review and meta-analysis of studies using gemcitabine-based chemotherapy after FOLFIRINOX to assess treatment efficacy and toxicity.
METHODS
We included studies published between 2011 and 2018 that evaluated the efficacy and toxicity of gemcitabine-based chemotherapy after FOLFIRINOX in patients with advanced pancreatic adenocarcinoma. We searched PubMed, Embase, Scopus, and Web of Science. Primary outcomes were objective response rate (ORR), disease control rate (DCR), any grade 3/4 toxicity rate, and progression-free survival (PFS). We used the random-effects model to generate pooled estimates for proportions.
RESULTS
Sixteen studies met the eligibility criteria. Overall, ORR was 10.8%, DCR was 41.1%, and any grade 3/4 toxicity rate was 28.6%. In subgroup analyses, gemcitabine plus nab-paclitaxel was associated with superior ORR (14.4 8.4%; = 0.038) and DCR (53.5 30.5%; < 0.001) compared with single-agent gemcitabine. Median PFS ranged from 1.9 to 6.4 months and numerically favored gemcitabine plus nab-paclitaxel.
CONCLUSIONS
Our study suggests gemcitabine-based chemotherapy likely outperforms best supportive care after FOLFIRINOX in advanced pancreatic cancer. Also, gemcitabine plus nab-paclitaxel seems to be more active than single-agent gemcitabine (CRD42018100421).
PubMed: 32165927
DOI: 10.1177/1758835920905408 -
Journal of B.U.ON. : Official Journal... 2018Pancreatic and periampullary adenocarcinoma have not generally been included in the tumour types considered for metastasectomy. However, there is an increasing interest... (Meta-Analysis)
Meta-Analysis
PURPOSE
Pancreatic and periampullary adenocarcinoma have not generally been included in the tumour types considered for metastasectomy. However, there is an increasing interest that metastasectomy in well-selected patients can prolong survival. This review aims to establish the recent evidence on the surgical management of oligometastatic disease and survival outcome in patients who underwent metastasectomy focusing on isolated hepatic and pulmonary metastases.
METHODS
A systematic search was performed in the PubMed database to identify all original articles on the role of metastasectomy for oligometastasis of pancreatic and periampullary adenocarcinoma. Data on methodologies used, 1,3,5 - year survival and median overall survival were summarized, and used to address relevant clinical questions related to the survival outcome in patients who underwent metastasectomy.
RESULTS
Sixteen studies were included in this review. All the studies included were retrospective and heterogenous in nature and did not have a uniform reporting on survival outcomes.
CONCLUSION
There is insufficient evidence to support a change of current practice in managing metastatic pancreatic and periampullary cancer. However, patients with ampullary cancer as the primary and any patients with first recurrence as isolated pulmonary metastases had better prognosis than patients with synchronous metastasis or metastases to the liver. This need to be explored in future studies.
Topics: Adenocarcinoma; Ampulla of Vater; Common Bile Duct Neoplasms; Humans; Metastasectomy; Neoplasms; Pancreatic Neoplasms; Prognosis; Survival Rate
PubMed: 30610789
DOI: No ID Found -
Cancers Nov 2021The impact of postoperative pancreatic fistula (POPF) on survival after resection for pancreatic ductal adenocarcinoma (PDAC) remains unclear. (Review)
Review
BACKGROUND
The impact of postoperative pancreatic fistula (POPF) on survival after resection for pancreatic ductal adenocarcinoma (PDAC) remains unclear.
METHODS
The MEDLINE, Scopus, Embase, Web of Science, and Cochrane Library databases were searched for studies reporting on survival in patients with and without POPF. A meta-analysis was performed to investigate the impact of POPF on disease-free survival (DFS) and overall survival (OS).
RESULTS
Sixteen retrospective cohort studies concerning a total of 5019 patients with an overall clinically relevant POPF (CR-POPF) rate of 12.63% (n = 634 patients) were considered. Five of eleven studies including DFS data reported higher recurrence rates in patients with POPF, and one study showed a higher recurrence rate in the peritoneal cavity. Six of sixteen studies reported worse OS rates in patients with POPF. Sufficient data for a meta-analysis were available in 11 studies for DFS, and in 16 studies for OS. The meta-analysis identified a shorter DFS in patients with CR-POPF (HR 1.59, = 0.0025), and a worse OS in patients with POPF, CR-POPF (HR 1.15, = 0.0043), grade-C POPF (HR 2.21, = 0.0007), or CR-POPF after neoadjuvant therapy.
CONCLUSIONS
CR-POPF after resection for PDAC is significantly associated with worse overall and disease-free survival.
PubMed: 34830957
DOI: 10.3390/cancers13225803