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HPB : the Official Journal of the... May 2020Several randomised controlled trials (RCTs) have reported various systemic adjuvant therapy regimens following resection of pancreatic ductal adenocarcinoma (PDAC). The... (Meta-Analysis)
Meta-Analysis Review
A systematic review and network meta-analysis of phase III randomised controlled trials for adjuvant therapy following resection of pancreatic ductal adenocarcinoma (PDAC).
BACKGROUND
Several randomised controlled trials (RCTs) have reported various systemic adjuvant therapy regimens following resection of pancreatic ductal adenocarcinoma (PDAC). The most commonly applied include modified FOLFRINOX (mFFX), Gemcitabine/Capecitabine (GemCap) and S1, usually compared to gemcitabine (Gem) alone. However, many of these regimens have not been directly compared in RCTs. This network meta-analysis aims to characterise the impact of adjuvant therapies on overall and disease-free survival in patients having resection of PDAC.
METHODS
A systematic review was conducted using MEDLINE, EMBASE, Cochrane Central and American Society of Clinical Oncology (ASCO) abstracts to identify published phase III RCTs articles up to 9th May 2019 that examined adjuvant systemic therapy in resected pancreatic cancer. Data including study characteristics and outcomes including overall survival (OS) and disease-free survival (DFS) were extracted. Indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analyses (NMA) which maintains randomisation within trials.
RESULTS
Twelve phase III RCTs involving 4947 patients and nine different regimens (5-Flourouracil/Folinic acid (5-FU/FA), Gemcitabine, Gemcitabine/Erlotinib (GemErl), GemCap), mFFX, S1, chemoradiotherapy (CRT), CRT with either 5-FU or Gemcitabine) were identified. S1 was ranked best for overall and disease-free survival followed by mFFX. Whilst there were no significant difference between S1 and mFFX for overall survival (mean difference: 1.6 months, p = 0.8), S1 had significantly longer disease-free survival than mFFX (mean difference: 2.8 months, p < 0.001). Furthermore, S1 was ranked best for lowest overall and haematological grade 3/4 toxicities.
CONCLUSION
This network meta-analysis demonstrates that chemotherapy with S1 or mFFX is superior to GemCap for adjuvant treatment for PDAC, improves survival after surgical resection and should be considered as reasonable standard treatment options in the adjuvant setting and as control arm for future adjuvant clinical trials.
Topics: Carcinoma, Pancreatic Ductal; Chemoradiotherapy; Chemotherapy, Adjuvant; Combined Modality Therapy; Humans; Network Meta-Analysis; Pancreatic Neoplasms; Randomized Controlled Trials as Topic
PubMed: 31894014
DOI: 10.1016/j.hpb.2019.12.001 -
International Journal of Environmental... Jan 2023Background: Celiac disease (CD) is an autoimmune enteropathy affecting approximately 1% of the population and is associated with an increased risk of... (Meta-Analysis)
Meta-Analysis Review
Background: Celiac disease (CD) is an autoimmune enteropathy affecting approximately 1% of the population and is associated with an increased risk of enteropathy-associated T-cell lymphoma and small bowel adenocarcinoma, whereas the association between CD and other malignancies is unclear. Since pancreatic cancer (PC) remains one of the most lethal neoplasms and its incidence is increasing despite numerous ongoing research on diagnostic biomarkers and novel therapies, we aimed to investigate whether CD has an impact on the risk of PC. Material and Methods: We performed a systematic review of the literature published from January 2000 to March 2022 in two databases: Web of Science and Scopus and a meta-analysis of eligible studies. Results: Our search identified eight publications included in the systematic review. A total of five studies involving 47,941 patients, including 6399 CD patients with malignancies and 1231 PC cases were included in the meta-analysis and 221 cases of PC in CD patients with other cancers were recognized. The pooled OR for PC was 1.46 (95% CI 1.26−1.7) with significant heterogeneity (89.1%; p < 0.05), suggesting that CD patients with malignancies were at higher risk for PC. Conclusions: The association between CD and PC is uncertain. However, the results of the current meta-analysis may indicate an increased risk of PC in the group of patients with CD and other cancers. Further multicenter studies are warranted.
Topics: Humans; Celiac Disease; Pancreatic Neoplasms; Intestine, Small
PubMed: 36674320
DOI: 10.3390/ijerph20021565 -
BMC Gastroenterology Dec 2023Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas arising from abnormal papillary proliferation of ductal epithelial cells, and is a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas arising from abnormal papillary proliferation of ductal epithelial cells, and is a precancerous lesion of pancreatic malignancy. This study aimed to evaluate associations between acute pancreatitis (AP) and histologic subtypes of IPMN.
METHODS
In the clinical study, patients with IPMN confirmed by surgical resection specimens at our institute between 2009 and 2021 were eligible for inclusion. Associations and predictive accuracy of AP on the presence of HGD were determined by logistic regressions. In addition, a systematic review and meta-analysis was conducted through literatures upon search in PubMed, Embase, CENTRAL, China National Knowledge Infrastructure (CKNI), and Wanfang database, up to June, 2023. Pooled effects of the associations between AP and HGD and intestinal epithelial subtype subtype, shown as odds ratios (ORs) with 95% confidence intervals (CIs), were calculated using random effects model.
RESULTS
The retrospective cohort study included 47 patients (32 males, 15 females) diagnosed with IPMN at our center between 2009 and 2021, including 11 cases with AP (median 62 years) and 36 cases (median 64.5 years) without. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AP in predicting HGD were 78.7%, 57.1%, 82.5%, 36.4%, and 91.7%, respectively. Univariate logistic regression analysis showed that AP group had greater odds of presence of HGD (OR: 6.29,95% CI: 1.14-34.57) than non-AP group. Meta-analysis of five case-control studies in the literature included 930 patients and showed that AP-IPMN patients had higher odds for HGD (OR: 2.13, 95% CI 1.38-3.29) and intestinal epithelial subtype (OR: 5.38, 95% CI: 3.50-8.27) compared to non-AP IPMN.
CONCLUSIONS
AP is predictive of malignancy in patients with IPMN.
Topics: Male; Female; Humans; Carcinoma, Pancreatic Ductal; Pancreatitis; Retrospective Studies; Acute Disease; Pancreatic Intraductal Neoplasms; Adenocarcinoma, Mucinous; Pancreatic Neoplasms
PubMed: 38041073
DOI: 10.1186/s12876-023-02972-4 -
World Journal of Gastroenterology Aug 2015To present a systematic review of techniques and clinical results. (Review)
Review
AIM
To present a systematic review of techniques and clinical results.
METHODS
A systematic review of published literature was performed. Only studies reporting patient outcome after radiosurgery (single fraction) delivered with robotic devices [i.e., robotic radiosurgery (RRS)] have been analyzed.
RESULTS
A total of 96 patients from 5 studies were included. The studies are characterized by small series and different methods in terms of dose, target definition, combination with chemotherapy and/or standard fractionated radiotherapy and evaluation modalities. Preliminary results are positive in terms of tumor response (ORR = 56%) and local control of the tumor (crude rate of local progressions: 19.5%). Results for median overall survival (11.4 mo) seem comparable with the ones of prolonged chemoradiation (range: 8.6-13.0 mo). However, gastrointestinal toxicity seems to be the main limitation of RRS, especially at the duodenal level.
CONCLUSION
RRS allows for local treatment in a shortened time (1 fraction) compared to traditional treatments (about 1 mo), providing the possibility for an easy integration with systemic therapies. Preliminary results did not show any outcome differences compared to standard chemoradiation. Thus, further efforts to reduce gastrointestinal toxicity are strongly needed.
Topics: Chemoradiotherapy; Dose Fractionation, Radiation; Humans; Pancreatic Neoplasms; Radiosurgery; Robotic Surgical Procedures; Treatment Outcome
PubMed: 26309369
DOI: 10.3748/wjg.v21.i31.9420 -
Journal of Gastrointestinal Surgery :... Nov 2023Pancreatic benign, cystic, and neuroendocrine neoplasms are increasingly detected and recommended for surgical treatment. In multiorgan resection pancreatoduodenectomy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic benign, cystic, and neuroendocrine neoplasms are increasingly detected and recommended for surgical treatment. In multiorgan resection pancreatoduodenectomy or parenchyma-sparing, local extirpation is a challenge for decision-making regarding surgery-related early and late postoperative morbidity.
METHODS
PubMed, Embase, and Cochrane Libraries were searched for studies reporting early surgery-related complications following pancreatoduodenectomy (PD) and duodenum-preserving total (DPPHRt) or partial (DPPHRp) pancreatic head resection for benign tumors. Thirty-four cohort studies comprising data from 1099 patients were analyzed. In total, 654 patients underwent DPPHR and 445 patients PD for benign tumors. This review and meta-analysis does not need ethical approval.
RESULTS
Comparing DPPHRt and PD, the need for blood transfusion (OR 0.20, 95% CI 0.10-0.41, p<0.01), re-intervention for serious surgery-related complications (OR 0.48, 95% CI 0.31-0.73, p<0.001), and re-operation for severe complications (OR 0.50, 95% CI 0.26-0.95, p=0.04) were significantly less frequent following DPPHRt. Pancreatic fistula B+C (19.0 to 15.3%, p=0.99) and biliary fistula (6.3 to 4.3%; p=0.33) were in the same range following PD and DPPHRt. In-hospital mortality after DPPHRt was one of 350 patients (0.28%) and after PD eight of 445 patients (1.79%) (OR 0.32, 95% CI 0.10-1.09, p=0.07). Following DPPHRp, there was no mortality among the 192 patients.
CONCLUSION
DPPHR for benign pancreatic tumors is associated with significantly fewer surgery-related, serious, and severe postoperative complications and lower in-hospital mortality compared to PD. Tailored use of DPPHRt or DPPHRp contributes to a reduction of surgery-related complications. DPPHR has the potential to replace PD for benign tumors and premalignant cystic and neuroendocrine neoplasms of the pancreatic head.
Topics: Humans; Pancreatectomy; Pancreas; Pancreaticoduodenectomy; Pancreatic Neoplasms; Duodenum; Neuroendocrine Tumors; Pancreatic Cyst
PubMed: 37670106
DOI: 10.1007/s11605-023-05789-4 -
HPB : the Official Journal of the... May 2022Major abdominal surgery and malignancy lead to a hypercoagulable state, with a risk of venous thromboembolism (VTE) of approximately 3% after pancreatic surgery. No... (Review)
Review
BACKGROUND
Major abdominal surgery and malignancy lead to a hypercoagulable state, with a risk of venous thromboembolism (VTE) of approximately 3% after pancreatic surgery. No guidelines exist to assist surgeons in managing VTE prophylaxis or anticoagulation in patients undergoing elective pancreatic surgery for malignancy or premalignant lesions. A systematic review specific to VTE prophylaxis and anticoagulation after resectional pancreatic surgery is herein provided.
METHODS
Six topic areas are reviewed: pre- and perioperative VTE prophylaxis, early postoperative VTE prophylaxis, extended outpatient VTE prophylaxis, management of chronic anticoagulation, anti-coagulation after vascular reconstruction, and treatment of VTE. A Medline and PubMED search was completed with systematic medical literature review for each topic. Level of evidence was graded and strength of recommendation ranked according to the GRADE (Grades of Recommendation Assessment, Development and Evaluation) system for practice guidelines.
RESULTS
Levels of evidence and strength of recommendations are presented.
DISCUSSION
While strong data exist to guide management of chronic anticoagulation and treatment of VTE, data for anticoagulation after reconstruction is inconclusive and support for perioperative chemoprophylaxis with pancreatic surgery is similarly limited. The risk of post-pancreatectomy hemorrhage often exceeds that of thrombosis. The role of universal chemoprophylaxis must therefore be examined critically, particularly in the preoperative setting.
Topics: Anticoagulants; Blood Coagulation; Hemorrhage; Humans; Neoplasms; Risk Factors; Venous Thromboembolism
PubMed: 35063354
DOI: 10.1016/j.hpb.2021.12.010 -
Journal of Hepato-biliary-pancreatic... Nov 2022Previous systematic reviews have shown that radical antegrade modular pancreatosplenectomy (RAMPS) had favorable outcomes including prognosis. However, recent large... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/PURPOSE
Previous systematic reviews have shown that radical antegrade modular pancreatosplenectomy (RAMPS) had favorable outcomes including prognosis. However, recent large studies have shown opposite results, thus necessitating clarification of RAMPS efficacy. We aimed to update existing evidence on the clinical outcomes of RAMPS for left-sided pancreatic cancer by comparing them to those of the conventional approach.
METHODS
Electronic databases and registries were searched until August 2021 to perform random-effect meta-analysis. Methodological quality was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The protocol was registered at protocols.io (https://doi.org/10.17504/protocols.io.bxhfpj3n).
RESULTS
Thirteen cohort studies (1641 patients) and four ongoing randomized controlled trials (RCTs) were identified. RAMPS increased disease-free survival (hazard ratio [HR] 0.62, 95% confidence interval [CI] = 0.42-0.91), but it had little effect on overall survival (HR 0.92, 95% CI = 0.79-1.09) and recurrence-free survival (HR 0.72, 95% CI = 0.37-1.38) with low certainty of evidence.
CONCLUSION
The meta-analysis of recent studies suggests that RAMPS may have little effect on clinical outcomes. These findings highlight the necessity of further studies, including RCTs to determine the efficacy and subsequent indication of RAMPS in clinical cases.
Topics: Humans; Pancreatectomy; Splenectomy; Lymph Node Excision; Pancreatic Neoplasms; Prognosis
PubMed: 35092177
DOI: 10.1002/jhbp.1120 -
International Journal of Surgery... Jul 2023The best approach for treating benign or low-grade malignant lesions localized in the pancreatic neck or body remains debatable. Conventional pancreatoduodenectomy and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The best approach for treating benign or low-grade malignant lesions localized in the pancreatic neck or body remains debatable. Conventional pancreatoduodenectomy and distal pancreatectomy (DP) are associated with a risk of impairment of pancreatic function at long-term follow-up. With advances in technology and surgical skills, the use of central pancreatectomy (CP) has gradually increased.
OBJECTIVES
The objective was to compare the safety, feasibility, and short-term and long-term clinical benefits of CP and DP in matched cases.
METHODS
The PubMed, MEDLINE, Web of Science, Cochrane, and EMBASE databases were systematically searched to identify studies published from database inception to February 2022 that compared CP and DP. This meta-analysis was performed using R software.
RESULTS
Twenty-six studies matched the selection criteria, including 774 CP and 1713 DP cases. CP was significantly associated with longer operative time ( P <0.0001), less blood loss ( P <0.01), overall and clinically relevant pancreatic fistula ( P <0.0001), postoperative hemorrhage ( P <0.0001), reoperation ( P =0.0196), delayed gastric emptying ( P =0.0096), increased hospital stay ( P =0.0002), intra-abdominal abscess or effusion ( P =0.0161), higher morbidity ( P <0.0001) and severe morbidity ( P <0.0001) but with a significantly lower incidence of overall endocrine and exocrine insufficiency ( P <0.01), and new-onset and worsening diabetes mellitus ( P <0.0001) than DP.
CONCLUSIONS
CP should be considered as an alternative to DP in selected cases such as without pancreatic disease, length of the residual distal pancreas is more than 5 cm, branch-duct intraductal papillary mucinous neoplasms, and a low risk of postoperative pancreatic fistula after adequate evaluation.
Topics: Humans; Pancreatectomy; Pancreatic Fistula; Retrospective Studies; Pancreas; Pancreatic Neoplasms; Postoperative Complications
PubMed: 37300889
DOI: 10.1097/JS9.0000000000000326 -
Langenbeck's Archives of Surgery Aug 2023Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity... (Meta-Analysis)
Meta-Analysis Review
The clinical implication of minimally invasive versus open pancreatoduodenectomy for non-pancreatic periampullary cancer: a systematic review and individual patient data meta-analysis.
BACKGROUND
Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC).
METHODS
A systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015-12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS).
RESULTS
Overall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group.
CONCLUSIONS
This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately.
PROTOCOL REGISTRATION
PROSPERO (CRD42021277495) on the 25th of October 2021.
Topics: Humans; Pancreaticoduodenectomy; Duodenal Neoplasms; Prospective Studies; Pancreas; Postoperative Complications; Laparoscopy; Pancreatic Neoplasms; Retrospective Studies
PubMed: 37581763
DOI: 10.1007/s00423-023-03047-4 -
HPB : the Official Journal of the... May 2014Over the last decade laparoscopic pancreatic surgery (LPS) has emerged as an alternative to open pancreatic surgery (OPS) in selected patients with neuroendocrine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Over the last decade laparoscopic pancreatic surgery (LPS) has emerged as an alternative to open pancreatic surgery (OPS) in selected patients with neuroendocrine tumours (NET) of the pancreas (PNET). Evidence on the safety and efficacy of LPS is available from non-comparative studies.
OBJECTIVES
This study was designed as a meta-analysis of studies which allow a comparison of LPS and OPS for resection of PNET.
METHODS
Studies conducted from 1994 to 2012 and reporting on LPS and OPS were reviewed. Studies considered were required to report on outcomes in more than 10 patients on at least one of the following: operative time; hospital length of stay (LoS); intraoperative blood loss; postoperative morbidity; pancreatic fistula rates, and mortality. Outcomes were compared using weighted mean differences and odds ratios.
RESULTS
Eleven studies were included. These referred to 906 patients with PNET, of whom 22% underwent LPS and 78% underwent OPS. Laparoscopic pancreatic surgery was associated with a lower overall complication rate (38% in LPS versus 46% in OPS; P < 0.001). Blood loss and LoS were lower in LPS by 67 ml (P < 0.001) and 5 days (P < 0.001), respectively. There were no differences in rates of pancreatic fistula, operative time or mortality.
CONCLUSIONS
The nature of this meta-analysis is limited; nevertheless LPS for PNET appears to be safe and is associated with a reduced complication rate and shorter LoS than OPS.
Topics: Chi-Square Distribution; Humans; Laparoscopy; Length of Stay; Neuroendocrine Tumors; Odds Ratio; Pancreatectomy; Pancreatic Neoplasms; Postoperative Complications; Risk Factors; Time Factors; Treatment Outcome
PubMed: 24245906
DOI: 10.1111/hpb.12162