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Gastroenterology May 2024Over half of pancreatic ductal adenocarcinomas (PDAC) recur within 12 months after curative-intent resection. The aim of this systematic review and meta-analysis was to...
BACKGROUND AND AIMS
Over half of pancreatic ductal adenocarcinomas (PDAC) recur within 12 months after curative-intent resection. The aim of this systematic review and meta-analysis was to identify all reported prognostic factors for early recurrence in resected PDAC.
METHODS
Following a systematic literature search, meta-analysis was conducted using a random-effects model. Separate analyses were performed for adjusted vs unadjusted effect estimates as well as reported odds ratios (OR) and hazard ratios (HR). Risk of bias was assessed using the QUIPS tool and evidence rated according to GRADE recommendations.
RESULTS
After screening 2,903 abstracts, 65 studies were included. Twenty-eight (43.1%) studies defined early recurrence as evidence of recurrence within 6 months, while 34 (52.3%) defined it as evidence of recurrence within 12 months after surgery. Other definitions were uncommon. Analysis of unadjusted OR and HR revealed 41 and 5 prognostic factors for early recurrence within 6 months, respectively. When exclusively considering adjusted data, 25 and 10 prognostic factors were identified based on OR and HR, respectively. Using a 12-month definition, 38 (OR) and 15 (HR) prognostic factors were identified from unadjusted data and 38 (OR) and 30 (HR) prognostic factors from adjusted data, respectively. Based on frequency counts of adjusted data, preoperative CA19-9, N status, non-delivery of adjuvant therapy, grading, and tumor size based on imaging were identified as key prognostic factors for early recurrence.
CONCLUSION
Reported prognostic factors of early recurrence vary considerably. Identified key prognostic factors could aid in the development of a risk stratification framework for early recurrence. However, prospective validation is necessary.
PubMed: 38825047
DOI: 10.1053/j.gastro.2024.05.028 -
Heliyon Apr 2024Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, often diagnosed at an advanced stage. Systemic chemotherapy is the primary treatment, but direct comparisons... (Review)
Review
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, often diagnosed at an advanced stage. Systemic chemotherapy is the primary treatment, but direct comparisons of different regimens are limited. This study conducted a systematic review and network meta-analysis (NMA) to compare the efficacy and safety of various chemotherapy regimens, with the unique advantage of only including Phase III randomized controlled trials (RCTs).
METHODS
NMA was conducted regarding the searched phase III RCTs by comparing overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) of different chemotherapy protocols.
RESULTS
The analysis included 24 studies with 11470 patients across 25 treatment modalities. Among the chemotherapy regimens evaluated, FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin) demonstrated the highest OS and PFS, with a risk ratio (logHR) of 4.5 (95 % confidence interval 4.32-4.68) compared to gemcitabine monotherapy. The PEFG regimen (cisplatin, epirubicin, 5-fluorouracil, and gemcitabine) exhibited the highest ORR, with an odds ratio (OR) of 6.67 (2.08-20) compared to gemcitabine monotherapy. Notably, gemcitabine plus sorafenib was associated with the lowest hematological toxicity, with an odds ratio (OR) of 0.1 (0.02-0.48).
CONCLUSION
Combination therapies may offer greater benefits but also cause more toxic effects. However, combinations with targeted agents seem to have fewer adverse reactions.
PubMed: 38681566
DOI: 10.1016/j.heliyon.2024.e27679 -
PloS One 2024Familial Pancreatic Cancer (FPC) presents a notable risk, with 3-10% of pancreatic adenocarcinoma cases having a family history. Studies link FPC to syndromes like HBOC,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Familial Pancreatic Cancer (FPC) presents a notable risk, with 3-10% of pancreatic adenocarcinoma cases having a family history. Studies link FPC to syndromes like HBOC, suggesting BRCA1/BRCA2 mutations play a role. BRCA gene functions in DNA repair impact FPC management, influencing sensitivity to therapies like PARP inhibitors. Identifying mutations not only aids FPC treatment but also reveals broader cancer risks. However, challenges persist in selectively applying genetic testing due to cost constraints. This Systematic Review focuses on BRCA1/BRCA2 significance in FPC, diagnostic criteria, prognostic value, and limitations.
METHOD
Original articles published from 2013 to January 2023 were sourced from databases such as Scopus, PubMed, ProQuest, and ScienceDirect. Inclusion criteria comprised observational cohort or diagnostic studies related to the role of BRCA1/2 mutation in correlation to familial pancreatic cancer (FPC), while article reviews, narrative reviews, and non-relevant content were excluded. The assessment of bias used ROBINS-I, and the results were organized using PICOS criteria in a Google spreadsheet table. The systematic review adhered to the PRISMA 2020 checklist.
RESULT
We analyzed 9 diagnostic studies encompassing 1325 families and 4267 patients from Italy, USA, and Poland. Despite the limitation of limited homogenous PICO studies, our findings effectively present evidence. BRCA1/2 demonstrates benefits in detecting first-degree relatives FPC involvement with 2.26-10 times higher risk. These mutation findings also play an important role since with the BRCA1/2 targeted therapy, Poly-ADP Ribose Polymerase inhibitors (PARP) may give better outcomes of FPC treatment. Analysis of BRCA1 and BRCA2 administration's impact on odds ratio (OR) based on six and five studies respectively. BRCA1 exhibited non-significant effects (OR = 1.26, P = 0.51), while BRCA2 showed significance (OR = 1.68, P = 0.04). No heterogeneity observed, indicating consistent results. Further research on BRCA1 is warranted.
CONCLUSION
Detecting the BRCA1/2 mutation gene offers numerous advantages, particularly in its correlation with FPC. For diagnostic and prognostic purposes, testing is strongly recommended for first-degree relatives, who face a significantly higher risk (2.26-10 times) of being affected. Additionally, FPC patients with identified BRCA1/2 mutations exhibit a more favorable prognosis compared to the non-mutated population. This is attributed to the availability of targeted BRCA1/2 therapy, which maximizes treatment outcomes.
Topics: Humans; Pancreatic Neoplasms; Germ-Line Mutation; BRCA2 Protein; BRCA1 Protein; Genetic Predisposition to Disease; Carcinoma
PubMed: 38809921
DOI: 10.1371/journal.pone.0299276 -
Annals of Surgical Oncology Jul 2024Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer...
Differences in Lymph Node Metastases Patterns Among Non-pancreatic Periampullary Cancers and Histologic Subtypes: An International Multicenter Retrospective Cohort Study and Systematic Review.
BACKGROUND
Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer (NPPC), ampullary adenocarcinoma (AAC), distal cholangiocarcinoma (dCCA), or duodenal adenocarcinoma (DAC). This study aimed to compare the patterns of lymph node metastases among the different NPPCs in a large series and in a systematic review to guide the discussion on surgical lymphadenectomy and pathology assessment.
METHODS
This retrospective cohort study included patients after pancreatoduodenectomy for NPPC with at least one lymph node metastasis (2010-2021) from 24 centers in nine countries. The primary outcome was identification of lymph node stations affected in case of a lymph node metastasis per NPPC. A separate systematic review included studies on lymph node metastases patterns of AAC, dCCA, and DAC.
RESULTS
The study included 2367 patients, of whom 1535 had AAC, 616 had dCCA, and 216 had DAC. More patients with pancreatobiliary type AAC had one or more lymph node metastasis (67.2% vs 44.8%; P < 0.001) compared with intestinal-type, but no differences in metastasis pattern were observed. Stations 13 and 17 were most frequently involved (95%, 94%, and 90%). Whereas dCCA metastasized more frequently to station 12 (13.0% vs 6.4% and 7.0%, P = 0.005), DAC metastasized more frequently to stations 6 (5.0% vs 0% and 2.7%; P < 0.001) and 14 (17.0% vs 8.4% and 11.7%, P = 0.015).
CONCLUSION
This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC.
Topics: Humans; Lymphatic Metastasis; Retrospective Studies; Ampulla of Vater; Pancreaticoduodenectomy; Common Bile Duct Neoplasms; Duodenal Neoplasms; Male; Female; Pancreatic Neoplasms; Adenocarcinoma; Lymph Node Excision; Cholangiocarcinoma; Aged; Middle Aged; Prognosis; Follow-Up Studies; Lymph Nodes; Bile Duct Neoplasms; Carcinoma, Pancreatic Ductal
PubMed: 38602578
DOI: 10.1245/s10434-024-15213-z -
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 Mar 2024Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer; however, the superiority of neoadjuvant chemotherapy (nCT) or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer; however, the superiority of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) is unclear. Therefore, a discussion of these two modalities is necessary.
AIM
To investigate the benefits and complications of neoadjuvant modalities.
METHODS
To address this concern, predefined criteria were established using the PICO protocol. Two independent authors performed comprehensive searches using predetermined keywords. Statistical analyses were performed to identify significant differences between groups. Potential publication bias was visualized using funnel plots. The quality of the data was evaluated using the Risk of Bias Tool 2 (RoB2) and the GRADE approach.
RESULTS
Ten articles, including 1928 patients, were included for the analysis. Significant difference was detected in pathological complete response (pCR) [ < 0.001; odds ratio (OR): 0.27; 95%CI: 0.16-0.46], 30-d mortality ( = 0.015; OR: 0.4; 95%CI: 0.22-0.71) favoring the nCRT, and renal failure ( = 0.039; OR: 1.04; 95%CI: 0.66-1.64) favoring the nCT. No significant differences were observed in terms of survival, local or distal recurrence, or other clinical or surgical complications. The result of RoB2 was moderate, and that of the GRADE approach was low or very low in almost all cases.
CONCLUSION
Although nCRT may have a higher pCR rate, it does not translate to greater long-term survival. Moreover, nCRT is associated with higher 30-d mortality, although the specific cause for postoperative complications could not be identified. In the case of nCT, toxic side effects are suspected, which can reduce the quality of life. Given the quality of available studies, further randomized trials are required.
Topics: Humans; Neoadjuvant Therapy; Quality of Life; Adenocarcinoma; Chemoradiotherapy; Esophageal Neoplasms
PubMed: 38617451
DOI: 10.3748/wjg.v30.i11.1621 -
World Journal of Gastrointestinal... May 2024Colorectal signet-ring cell carcinoma (CSRCC) is a rare clinical entity which accounts for approximately 1% of all colorectal cancers. Although multiple studies...
BACKGROUND
Colorectal signet-ring cell carcinoma (CSRCC) is a rare clinical entity which accounts for approximately 1% of all colorectal cancers. Although multiple studies concerning this specific topic have been published in the past decades, the pathogenesis, associated risk factors, and potential implications on treatment are still poorly understood. Besides the low incidence, historically confusing histological criteria have resulted in confusing data. Nevertheless, the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis, highlight the actual interest to synthesize the known literature regarding CSRCC.
AIM
To provide an updated overview of risk factors, prognosis, and management of CSRCC.
METHODS
A literature search in the MEDLINE/PubMed database was conducted with the following search terms used: 'Signet ring cell carcinoma' and 'colorectal'. Studies in English language, published after January 1980, were included. Studies included in the qualitative synthesis were evaluated for content concerning epidemiology, risk factors, and clinical, diagnostic, histological, and molecular features, as well as metastatic pattern and therapeutic management. If possible, presented data was extracted in order to present a more detailed overview of the literature.
RESULTS
In total, 67 articles were included for qualitative analysis, of which 54 were eligible for detailed data extraction. CSRCC has a reported incidence between 0.1%-2.4% and frequently presents with advanced disease stage at the time of diagnosis. CSRCC is associated with an impaired overall survival (5-year OS: 0%-46%) and a worse stage-corrected outcome compared to mucinous and not otherwise specified adenocarcinoma. The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised. Surgery is the mainstay of treatment, although the rates of curative resection in CSRCC (21%-82%) are lower compared to those in other histological types. In case of peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should only be proposed in selected patients.
CONCLUSION
CSRCC is a rare clinical entity most often characterized by young age and advanced disease at presentation. As such, diagnostic modalities and therapeutic approach should be tailored accordingly.
PubMed: 38764832
DOI: 10.4251/wjgo.v16.i5.2141 -
Urologic Oncology Jul 2024Urachal cancer (UrC) is a rare disease with limited availability of representative incidence and clinical data. Although, the prevalence is accounting for less than 1%... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Urachal cancer (UrC) is a rare disease with limited availability of representative incidence and clinical data. Although, the prevalence is accounting for less than 1% of bladder tumors, the 5-year survival rate is around only 50% for patients with resectable tumors, and even worse for patients with metastatic disease. Due to the lack of comprehensive prospective studies, our current knowledge of UrC is still limited.
OBJECTIVE
The present study aimed to summarize the available registry-based studies with unselected UrC patients to evaluate its incidence and clinicopathological characteristics.
MATERIAL AND METHODS
We conducted a systematic literature search of registry-based UrC publications on the 15th of May 2023 in 5 databases, which identified 4,748 publications. After duplicate removal and selection by 2 independent investigators, 6 publications proved to be appropriate for the final meta-analysis. Estimated incidence and clinicopathological parameters were extracted.
RESULTS
Estimated incidence ranged between 0.022 and 0.060/ 100.000 person-years, with the highest occurrence in Japan and the lowest in Canada, while the random effect model calculated an overall incidence rate of 0.04 (95%CI: 0.03-0.05) 100.000 person-years. The median age at first diagnosis was 60 years (range: 58-64). The female to male ratio was 2:3. Lymph node or distant metastases were present in 9% and 14% of patients. The predominant tumour type was adenocarcinoma (86%) followed by urothelial carcinoma (12%) and squamous cell carcinoma (2%). The 5-year survival rate was 51.0% with 95%CI: 45.2-57.4.
CONCLUSIONS
Our study provides an up-to-date comparison of estimated incidence rates between 6 countries of 3 continents based on rigorously selected registry-based studies. The results suggest low incidence rates for UrC with considerable geographic differences. The present meta-analysis provides unbiased registry-based data on the incidence, clinicopathological parameters and survival of UrC.
Topics: Humans; Urinary Bladder Neoplasms; Registries; Incidence; Male
PubMed: 38627107
DOI: 10.1016/j.urolonc.2024.03.011 -
International Journal of Surgery... Jan 2024Hilar cholangiocarcinoma (HCCA) is widely considered to have a poor prognosis. In particular, combined caudate lobe resection (CLR) as a strategy for radical resection...
Hilar cholangiocarcinoma (HCCA) is widely considered to have a poor prognosis. In particular, combined caudate lobe resection (CLR) as a strategy for radical resection in HCCA is important for improving the R0 resection rate. However, the criteria for R0 resection, necessity of CLR, optimal extent of hepatic resection, and surgical approach are still controversial. This review aimed to summarize the findings and discuss the controversies surrounding CLR. Numerous clinical studies have shown that combined CLR treatment for HCCA improves the R0 resection rate and postoperative survival time. Whether surgery for Bismuth type I or II is combined with CLR depends on the pathological type. Considering the anatomical factors, total rather than partial CLR is recommended to achieve a higher R0 resection rate. In the resection of HCCA, a proximal ductal margin greater than or equal to 10 mm should be achieved to obtain a survival benefit. Although there is no obvious boundary between the right side (especially the paracaval portion) and the right posterior lobe of the liver, Peng's resection line can serve as a reference marker for right-sided resection. Laparoscopic resection of the caudate lobe may be safer, more convenient, accurate, and minimally invasive than open surgery, but it needs to be completed by experienced laparoscopic doctors.
Topics: Humans; Klatskin Tumor; Cholangiocarcinoma; Hepatectomy; Bile Duct Neoplasms; Liver; Bile Ducts, Intrahepatic; Treatment Outcome; Retrospective Studies
PubMed: 37738006
DOI: 10.1097/JS9.0000000000000795 -
Advances in Clinical and Experimental... Aug 2023Which systemic therapy should be administered following sorafenib failure for patients with advanced hepatocellular carcinoma (HCC) is still a debated issue in clinical... (Meta-Analysis)
Meta-Analysis
Which systemic therapy should be administered following sorafenib failure for patients with advanced hepatocellular carcinoma (HCC) is still a debated issue in clinical practice. This study aimed to compare regorafenib with nivolumab after sorafenib failure in patients with HCC. MEDLINE via PubMed, Scopus and Embase databases were searched for studies published until December 2021. The risk of bias (RoB) was evaluated using the Cochrane Collaboration tool for assessing risk of bias in randomized trials. From a total of 2120 articles, 3 papers were included in this meta-analysis. We found a statistically significant difference in the patient's objective response rate between the regorafenib and nivolumab groups (odds ratio (OR): 0.296, 95% confidence interval (95% CI): 0.161-0.544, p = 0.000). A statistically significant difference between regorafenib and nivolumab was not found for disease control rate after sorafenib failure in patients with advanced HCC (OR: 1.111, 95% CI: 0.793-1.557, p = 0.541) nor the number of progressive disease events (OR: 0.972, 95% CI: 0.693-1.362, p = 0.867). Overall survival (OS) and progression-free survival (PFS) were not calculable. The heterogeneity of the included data was low. Nivolumab monotherapy appears superior to regorafenib after sorafenib failure in patients with advanced HCC.
Topics: Humans; Carcinoma, Hepatocellular; Sorafenib; Liver Neoplasms; Nivolumab
PubMed: 37140014
DOI: 10.17219/acem/158488