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Scandinavian Journal of Surgery : SJS :... Mar 2020A positive resection margin is considered to be a factor associated with poor prognosis after pancreatic ductal adenocarcinoma resection. However, analysis of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
A positive resection margin is considered to be a factor associated with poor prognosis after pancreatic ductal adenocarcinoma resection. However, analysis of the resection margin is dependent on the pathological slicing technique. The aim of this systematic review and meta-analysis was to study the impact of resection margin on the survival of pancreatic ductal adenocarcinoma patients whose specimens were analyzed using the axial slicing technique.
MATERIAL AND METHODS
A systematic search in the PubMed, Cochrane, and Embase datasets covering the time period from November 2006 to January 2019 was performed. Only studies with axial slicing technique (Leeds Pathology Protocol or Royal College of Pathology Protocol) were included in the final database. Meta-analysis between the marginal distance and survival was performed with the Inverse Variance Method in RevMan.
RESULTS
The systematic search resulted in nine studies meeting the inclusion criteria. The median survival for a resection margin 0 mm ranged from 12.3 to 23.4 months, for resection margin <0.5 mm 16 months, for resection margin <1 mm ranged from 11 to 27.5 months, for resection margin <1.5 mm ranged from 16.9 to 21.2 months, and for resection margin >2 mm ranged from 53.9 to 63.1 months. Five studies were eligible for meta-analysis. The pooled multivariable hazard ratio favored resection margin ⩾1 mm (hazard ratio: 1.32 and 95% confidence interval: 1.03-1.68, p = 0.03).
CONCLUSION
Resection margins ⩾1 mm seem to lead to better survival in pancreatic ductal adenocarcinoma patients than resection margin <1 mm. However, there is not enough data to evaluate the effect of oncologic therapy or to analyze the impact of other resection margin distances on survival.
Topics: Carcinoma, Pancreatic Ductal; Clinical Protocols; Histocytological Preparation Techniques; Humans; Margins of Excision; Pancreatic Neoplasms
PubMed: 32192417
DOI: 10.1177/1457496920911807 -
HPB : the Official Journal of the... Feb 2021The clinical relevance of subdivision of non-metastatic pancreatic ductal adenocarcinoma (PDAC) into locally advanced borderline resectable (LA-BR) and locally advanced... (Meta-Analysis)
Meta-Analysis Review
Survival equivalence in patients treated for borderline resectable and unresectable locally advanced pancreatic ductal adenocarcinoma: a systematic review and network meta-analysis.
BACKGROUND
The clinical relevance of subdivision of non-metastatic pancreatic ductal adenocarcinoma (PDAC) into locally advanced borderline resectable (LA-BR) and locally advanced unresectable (LA-UR) has been questioned. We assessed equivalence of overall survival (OS) in patients with LA-BR and LA-UR PDAC.
METHODS
A systematic review was performed of studies published January 1, 2009 to August 21, 2019, reporting OS for LA-BR and LA-UR patients treated with or without neoadjuvant therapy (NAT), with or without surgical resection. A frequentist network meta-analysis was used to assess the primary outcome (hazard ratio for OS) and secondary outcomes (OS in LA-BR, LA-UR, and upfront resectable (UFR) PDAC).
RESULTS
Thirty-nine studies, comprising 14,065 patients in a network of eight unique treatment subgroups were analysed. Overall survival was better for LA-BR than LA-UR patients following surgery both with and without NAT. Neoadjuvant therapy prior to surgery was associated with longer OS for UFR, LA-BR, and LA-UR tumours, compared to upfront surgery.
CONCLUSION
Survival between the LA-BR and LA-UR subgroups was not equivalent. This subdivision is useful for prognostication, but likely unhelpful in treatment decision making. Our data supports NAT regardless of initial disease extent. Individual patient data assessment is needed to accurately estimate the benefit of NAT.
Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Humans; Neoadjuvant Therapy; Network Meta-Analysis; Pancreatectomy; Pancreatic Neoplasms
PubMed: 33268268
DOI: 10.1016/j.hpb.2020.09.022 -
Histopathology Sep 2022Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a recently recognized pancreatic tumor entity. Here we aimed to determine the most important features with... (Review)
Review
AIMS
Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a recently recognized pancreatic tumor entity. Here we aimed to determine the most important features with a systematic review coupled with an integrated statistical approach.
METHODS AND RESULTS
PubMed, SCOPUS, and Embase were searched for studies reporting data on pancreatic ITPN. The clinicopathological, immunohistochemical, and molecular data were summarized. Then a comprehensive survival analysis and a comparative analysis of the molecular alterations of ITPN with those of pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) from reference cohorts (including the International Cancer Genome Consortium- ICGC dataset and The Cancer Genome Atlas, TCGA program) were conducted. The core findings of 128 patients were as follows: (i) Clinicopathological parameters: pancreatic head is the most common site; presence of an associated adenocarcinoma was reported in 60% of cases, but with rare nodal metastasis. (ii) Immunohistochemistry: MUC1 (>90%) and MUC6 (70%) were the most frequently expressed mucins. ITPN lacked the intestinal marker MUC2; unlike IPMN, it did not express MUC5AC. (iii) Molecular landscape: Compared with PDAC/IPMN, the classic pancreatic drivers KRAS, TP53, CDKN2A, SMAD4, GNAS, and RNF43 were less altered in ITPN (P < 0.001), whereas MCL amplifications, FGFR2 fusions, and PI3KCA mutations were commonly altered (P < 0.001). (iv) Survival analysis: ITPN with a "pure" branch duct involvement showed the lowest risk of recurrence.
CONCLUSION
ITPN is a distinct pancreatic neoplasm with specific clinicopathological and molecular characteristics. Its recognition is fundamental for its clinical/prognostic implications and for the enrichment of potential targets for precision oncology.
Topics: Carcinoma, Pancreatic Ductal; Carcinoma, Papillary; Humans; Pancreas; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Precision Medicine
PubMed: 35583805
DOI: 10.1111/his.14698 -
Frontiers in Oncology 2021To compare perioperative and oncological outcomes of pancreatic duct adenocarcinoma (PDAC) after laparoscopic open pancreaticoduodenectomy (LPD OPD), we performed a...
BACKGROUND
To compare perioperative and oncological outcomes of pancreatic duct adenocarcinoma (PDAC) after laparoscopic open pancreaticoduodenectomy (LPD OPD), we performed a meta-analysis of currently available propensity score matching studies and large-scale retrospective cohorts to compare the safety and overall effect of LPD to OPD for patients with PDAC.
METHODS
A meta-analysis was registered at PROSPERO and the registration number is CRD42021250395. PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched based on a defined search strategy to identify eligible studies before March 2021. Data on operative times, blood loss, 30-day mortality, reoperation, length of hospital stay (LOS), overall morbidity, Clavien-Dindo ≥3 complications, postoperative pancreatic fistula (POPF), blood transfusion, delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), and oncologic outcomes (R0 resection, lymph node dissection, overall survival, and long-term survival) were subjected to meta-analysis.
RESULTS
Overall, we identified 10 retrospective studies enrolling a total of 11,535 patients (1,514 and 10,021 patients underwent LPD and OPD, respectively). The present meta-analysis showed that there were no significant differences in overall survival time, 1-year survival, 2-year survival, 30-day mortality, Clavien-Dindo ≥3 complications, POPF, DGE, PPH, and lymph node dissection between the LPD and OPD groups. Nevertheless, compared with the OPD group, LPD resulted in significantly higher rate of R0 resection (OR: 1.22; 95% CI 1.06-1.40; = 0.005), longer operative time (WMD: 60.01 min; 95% CI 23.23-96.79; = 0.001), lower Clavien-Dindo grade ≥III rate ( = 0.02), less blood loss (WMD: -96.49 ml; 95% CI -165.14 to -27.83; = 0.006), lower overall morbidity rate (OR: 0.65; 95% CI 0.50 to 0.85; = 0.002), shorter LOS (MD = -2.73; 95% CI -4.44 to -1.03; = 0.002), higher 4-year survival time ( = 0.04), 5-year survival time ( = 0.001), and earlier time to starting adjuvant chemotherapy after surgery (OR: -10.86; 95% CI -19.42 to -2.30; = 0.01).
CONCLUSIONS
LPD is a safe and feasible alternative to OPD for patients with PDAC, and compared with OPD, LPD seemed to provide a similar OS.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/#recordDetails.
PubMed: 34778064
DOI: 10.3389/fonc.2021.749140 -
Cancer Epidemiology, Biomarkers &... May 2022Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, and this is attributed to it being diagnosed at an advanced stage. Understanding the pathways involved in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, and this is attributed to it being diagnosed at an advanced stage. Understanding the pathways involved in initial development may improve early detection strategies. This systematic review assessed the association between circulating protein and metabolite biomarkers and PDAC development.
METHODS
A literature search until August 2020 in MEDLINE, EMBASE, and Web of Science was performed. Studies were included if they assessed circulating blood, urine, or salivary biomarkers and their association with PDAC risk. Quality was assessed using the Newcastle-Ottawa scale for cohort studies. Random-effects meta-analyses were used to calculate pooled relative risk.
RESULTS
A total of 65 studies were included. Higher levels of glucose were found to be positively associated with risk of developing PDAC [n = 4 studies; pooled relative risk (RR): 1.61; 95% CI: 1.16-2.22]. Additionally, an inverse association was seen with pyridoxal 5'-phosphate (PLP) levels (n = 4 studies; RR: 0.62; 95% CI: 0.44-0.87). Meta-analyses showed no association between levels of C-peptide, members of the insulin growth factor signaling pathway, C-reactive protein, adiponectin, 25-hydroxyvitamin D, and folate/homocysteine and PDAC risk. Four individual studies also reported a suggestive positive association of branched-chain amino acids with PDAC risk, but due to differences in measures reported, a meta-analysis could not be performed.
CONCLUSIONS
Our pooled analysis demonstrates that higher serum glucose levels and lower levels of PLP are associated with risk of PDAC.
IMPACT
Glucose and PLP levels are associated with PDAC risk. More prospective studies are required to identify biomarkers for early detection.
Topics: Biomarkers; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Glucose; Humans; Pancreatic Neoplasms; Prognosis
PubMed: 34810209
DOI: 10.1158/1055-9965.EPI-21-0616 -
United European Gastroenterology Journal May 2018Data on surveillance for pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs) with "familial pancreatic cancer" (FPC) and specific syndromes are... (Review)
Review
BACKGROUND
Data on surveillance for pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs) with "familial pancreatic cancer" (FPC) and specific syndromes are limited and heterogeneous.
OBJECTIVE
We conducted a systematic review and meta-analysis of PDAC surveillance studies in HRIs.
METHODS
Prevalence of solid/cystic pancreatic lesions and of lesions considered a successful target of surveillance (proven resectable PDAC and high-grade precursors) was pooled across studies. The rate of lesions diagnosed by endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI) and across different HRI groups was calculated.
RESULTS
Sixteen studies incorporating 1588 HRIs were included. The pooled prevalence of pancreatic solid and cystic lesions was 5.8% and 20.2%, respectively. The pooled prevalence of patients with lesions considered a successful target of surveillance was 3.3%, being similar to EUS or MRI and varying across subgroups, being 3% in FPC, 4% in hereditary pancreatitis, 5% in familial melanoma, 6.3% in hereditary breast/ovarian cancer, and 12.2% in Peutz-Jeghers syndrome. The pooled estimated rate of lesions considered a successful target of surveillance during follow-up was 5/1000 person-years.
CONCLUSION
Surveillance programs identify successful target lesions in 3.3% of HRIs with a similar yield of EUS and MRI and an annual risk of 0.5%. A higher rate of target lesions was reported in HRIs with specific DNA mutations.
PubMed: 29881603
DOI: 10.1177/2050640617752182 -
Oncotarget May 2017The impact of histopathologic tumor invasion of the superior mesenteric vein (SMV)/portal vein (PV) on prognosis in patients with pancreatic ductal adenocarcinoma (PDAC)... (Meta-Analysis)
Meta-Analysis Review
Histopathologic tumor invasion of superior mesenteric vein/ portal vein is a poor prognostic indicator in patients with pancreatic ductal adenocarcinoma: results from a systematic review and meta-analysis.
BACKGROUND
The impact of histopathologic tumor invasion of the superior mesenteric vein (SMV)/portal vein (PV) on prognosis in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreatectomy remains controversial. A meta-analysis was performed to assess this issue.
RESULTS
Eighteen observational studies comprising 5242 patients were eligible, of whom 2199 (41.9%) patients received SMV/PV resection. Histopathologic tumor invasion was detected in 1218 (58.1%) of the 2096 resected SMV/PV specimens. SMV/PV invasion was associated with higher rates of poor tumor differentiation (P = 0.002), lymph node metastasis (P < 0.001), perineural invasion (P < 0.001), positive resection margins (P = 0.004), and postoperative tumor recurrence (P < 0.001). SMV/PV invasion showed a significantly negative effect on survival in total patients who underwent pancreatectomy with and without SMV/PV resection (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.08-1.35; P = 0.001) and in patients who underwent pancreatectomy with SMV/PV resection (HR: 1.88, 95% CI, 1.48-2.39; P < 0.001).
MATERIALS AND METHODS
A systematic literature search was performed to identify articles published from January 2000 to August 2016. Data were pooled for meta-analysis using Review Manager 5.3.
CONCLUSIONS
Histopathologic tumor invasion of the SMV/PV is associated with more aggressive biologic behavior and could be used as an indicator of poor prognosis after PDAC resection.
Topics: Carcinoma, Pancreatic Ductal; Female; Humans; Male; Mesenteric Veins; Prognosis; Retrospective Studies; Survival Analysis
PubMed: 28427231
DOI: 10.18632/oncotarget.15938 -
Cancers Mar 2021The prognosis of metastatic pancreatic ductal adenocarcinoma (mPDAC) remains universally poor, requiring new and innovative treatment approaches. In a subset of... (Review)
Review
The prognosis of metastatic pancreatic ductal adenocarcinoma (mPDAC) remains universally poor, requiring new and innovative treatment approaches. In a subset of oligometastatic PDAC patients, locoregional therapy, in addition to systemic chemotherapy, may improve survival. The aim of this systematic review was to explore and evaluate the current evidence on locoregional treatments for mPDAC. A systematic literature search was conducted on locoregional techniques, including resection, ablation and embolization, for mPDAC with a focus on hepatic and pulmonary metastases. A total of 59 studies were identified, including 63,453 patients. Although subject to significant bias, radical-intent local therapy for both the primary and metastatic sites was associated with a superior median overall survival from metastatic diagnosis or treatment (hepatic mPDAC 7.8-19 months; pulmonary mPDAC 22.8-47 months) compared to control groups receiving chemotherapy or best supportive care (hepatic mPDAC 4.3-7.6 months; pulmonary mPDAC 11.8 months). To recruit patients that may benefit from these local treatments, selection appears essential. Most significant is the upfront possibility of local radical pancreatic and metastatic treatment. In addition, a patient's response to neoadjuvant systemic chemotherapy, performance status, metastatic disease load and, to a lesser degree, histological differentiation grade and tumor marker CA19-9 serum levels, are powerful prognostic factors that help identify eligible subjects. Although the exact additive value of locoregional treatments for mPDAC patients cannot be distillated from the results, locoregional primary pancreatic and metastatic treatment seems beneficial for a highly selected group of oligometastatic PDAC patients. For definite recommendations, well-designed prospective randomized controlled trials with strict in- and exclusion criteria are needed to validate these results.
PubMed: 33807220
DOI: 10.3390/cancers13071608 -
International Journal of Surgery... Dec 2019Pancreatic cancer is a disease of the elderly. Surgical resection is usually offered to patients in early stage disease; however, pancreatic resection in the elderly is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatic cancer is a disease of the elderly. Surgical resection is usually offered to patients in early stage disease; however, pancreatic resection in the elderly is controversial.
METHODS
MEDLINE, EMBASE and Cochrane Library, were searched for studies comparing short- and long-term outcomes of elderly (above the age of 70) with non-elderly patients (below the age of 70) following pancreatic resection for pancreatic adenocarcinoma over the period from the inception of electronic database to 2017. Twelve articles documenting 4860 patients were included. A meta-analysis of data on patient characteristics, operative techniques, and perioperative outcomes were analysed. Our primary endpoint was postoperative mortality, defined as 30-day mortality or in-hospitalisation mortality.
RESULTS
There were 919 patients in the elderly group and 3941 patients in the non-elderly group. Elderly patients had worse ASA scores (p < 0.001) and more cardiovascular comorbidities (p = 0.002). Tumour size, T-stage, N-stage and tumour grade were similar between the elderly and non-elderly group (p > 0.05). Fewer elderly patients received a concomitant venous resection with their pancreatectomy (RR0.80, p = 0.003, I2 = 0%), achieved a negative margin status (RR0.76, p = 0.02, I2 = 28%) and underwent adjuvant chemotherapy treatment (RR0.69, p < 0.001, I2 = 42%). Overall complication (RR1.15, p < 0.001, I2 = 47%), in particular, respiratory complications (RR2.33, p = 0.004, I2 = 39%), was higher in the elderly group. There was no difference in postoperative pancreatic fistula formation, postoperative haemorrhage, intraabdominal abscess and length of hospital stay between both groups (p > 0.05). Postoperative mortality was similar between both groups (p = 0.17). Subgroup analysis according to the time of enrolment (<2000, ≥2000) showed a significant subgroup effect (Chi2 = 3.44, p = 0.06, I2 = 70.9%) and revealed that postoperative mortality in the elderly group improved over time (Before 2000: n = 1654, subtotal RR2.27, p = 0.02, I2 = 0%; From 2000 onwards: n = 3206, subtotal RR1.00, p = 0.99, I2 = 0%).
CONCLUSION
Fewer elderly patients received chemotherapy and portal vein resection to achieve a clear margin. Pancreatic resection of pancreatic adenocarcinoma can be performed safely on elderly patients with acceptable risks in experienced centres by specialist hepatobiliary surgeons. Age alone should not be the only determinant for the selection of patients for surgical treatment of pancreatic adenocarcinoma.
Topics: Adenocarcinoma; Chemotherapy, Adjuvant; Comorbidity; Hospital Mortality; Humans; Length of Stay; Pancreatectomy; Pancreatic Fistula; Pancreatic Neoplasms; Portal Vein; Postoperative Complications; Postoperative Hemorrhage
PubMed: 31580919
DOI: 10.1016/j.ijsu.2019.09.030 -
Digestive Surgery 2023A systematic review and meta-analysis of the literature was carried out to determine the clinical and oncological outcome of patients who had enucleation of solitary... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
A systematic review and meta-analysis of the literature was carried out to determine the clinical and oncological outcome of patients who had enucleation of solitary pancreatic metastases from renal cell carcinoma.
METHODS
Operative mortality, postoperative complications, observed survival, and disease-free survival were analyzed. The clinical outcomes of patients who had enucleation were compared to those of 947 patients collected from the literature who had standard or atypical pancreatic resection for the same disease using propensity score matching.
RESULTS
There was no postoperative mortality in the 56 patients who had enucleation of pancreatic metastases from renal cell carcinoma. In 51 patients, postoperative complications could be analyzed. Ten patients (10/51 = 19.6%) had postoperative complications. Three patients (3/51 = 5.9%) had major complications (Clavien-Dindo III or more). Five-year observed survival rates and disease-free survival for patients with enucleation were 92% and 79%, respectively. These results compared favorably with those obtained in patients who had standard resection and other forms of atypical resection (also using propensity score matching). Patients who had partial pancreatic resection (atypical or not) with pancreatic-jejunal anastomosis had increased rates of postoperative complications and local recurrences.
CONCLUSIONS
Enucleation of pancreatic metastases offers a valid solution in selected patients.
Topics: Humans; Carcinoma, Renal Cell; Pancreatic Neoplasms; Pancreas; Pancreatectomy; Postoperative Complications; Kidney Neoplasms; Retrospective Studies; Treatment Outcome
PubMed: 36809760
DOI: 10.1159/000528823