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Cancers Sep 2023Despite advances in treatment, the prognosis of resectable pancreatic adenocarcinoma remains poor. Neoadjuvant therapy (NAT) has gained great interest in hopes of... (Review)
Review
BACKGROUND
Despite advances in treatment, the prognosis of resectable pancreatic adenocarcinoma remains poor. Neoadjuvant therapy (NAT) has gained great interest in hopes of improving survival. However, the results of available studies based on different treatment approaches, such as chemotherapy and chemoradiotherapy, showed contrasting results. The aim of this systematic review and meta-analysis is to clarify the benefit of NAT compared to upfront surgery (US) in primarily resectable pancreatic adenocarcinoma.
METHODS
A PRISMA literature review identified 139 studies, of which 15 were finally included in the systematic review and meta-analysis. All data from eligible articles was summarized in a systematic summary and then used for the meta-analysis. Specifically, we used HR for OS and DFS and risk estimates (odds ratios) for the R0 resection rate and the N+ rate. The risk of bias was correctly assessed according to the nature of the studies included.
RESULTS
From the pooled HRs, OS for NAT patients was better, with an HR for death of 0.80 (95% CI: 0.72-0.90) at a significance level of less than 1%. In the sub-group analysis, no difference was found between patients treated with chemoradiotherapy or chemotherapy exclusively. The meta-analysis of seven studies that reported DFS for NAT resulted in a pooled HR for progression of 0.66 (95% CI: 0.56-0.79) with a significance level of less than 1%. A significantly lower risk of positive lymph nodes (OR: 0.45; 95% CI: 0.32-0.63) and an improved R0 resection rate (OR: 1.70; 95% CI: 1.23-2.36) were also found in patients treated with NAT, despite high heterogeneity.
CONCLUSIONS
NAT is associated with improved survival for patients with resectable pancreatic adenocarcinoma; however, the optimal treatment strategy has yet to be defined, and further studies are required.
PubMed: 37760596
DOI: 10.3390/cancers15184627 -
Cancers Dec 2023Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide. While population-wide screening recommendations for PDAC in asymptomatic... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide. While population-wide screening recommendations for PDAC in asymptomatic individuals are not achievable due to its relatively low incidence, pancreatic cancer surveillance programs are recommended for patients with germline causative variants in PDAC susceptibility genes or a strong family history. In this study, we sought to determine the prevalence and significance of germline alterations in major genes (, , , , , , , , , , , ) involved in PDAC susceptibility. We performed a systematic review of PubMed publications reporting germline variants identified in these genes in PDAC patients. Overall, the retrieved articles included 1493 PDAC patients. A high proportion of these patients ( = 1225/1493, 82%) were found to harbor alterations in genes (, , , ) involved in the homologous recombination repair (HRR) pathway. Specifically, the remaining PDAC patients were reported to carry alterations in genes playing a role in other cancer pathways (, , ; = 181/1493, 12.1%) or in the mismatch repair (MMR) pathway (, , , ; = 87/1493, 5.8%). Our findings highlight the importance of germline genetic characterization in PDAC patients for better personalized targeted therapies, clinical management, and surveillance.
PubMed: 38201484
DOI: 10.3390/cancers16010056 -
BMC Cancer Aug 2023The association between gastrointestinal cancer and types of meat consumption, including red meat, processed meat, or a combination of both, remains disputable.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The association between gastrointestinal cancer and types of meat consumption, including red meat, processed meat, or a combination of both, remains disputable. Therefore, we performed a systematic review and meta-analysis of prospective cohort studies to estimate the association between meat consumption and gastrointestinal cancer risk.
METHODS
PubMed, EmBase, and the Cochrane library databases were searched systematically for eligible studies that investigated the relation between meat consumption and the risk of developing gastrointestinal cancers, including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), colon cancer (CC), rectal cancer (RC), pancreatic cancer (PC), and hepatocellular carcinoma (HCC) throughout February, 2023. The pooled relative risk (RR) with 95% confidence interval (CI) was assigned as an effect estimate and calculated using a random-effects model with inverse variance weighting.
RESULTS
Forty cohorts comprising 3,780,590 individuals were selected for the final quantitative analysis. The summary results indicated that a higher red meat consumption was associated with an increased risk of CRC (RR: 1.09; 95% CI: 1.02-1.16; P = 0.007) and CC (RR: 1.13; 95% CI: 1.03-1.25; P = 0.011). Moreover, a higher processed meat consumption was associated with an increased risk of CRC (RR: 1.19; 95% CI: 1.13-1.26; P < 0.001), CC (RR: 1.24; 95% CI: 1.13-1.26; P < 0.001), and RC (RR: 1.24; 95% CI: 1.08-1.42; P = 0.002). Furthermore, a higher total consumption of red and processed meat was associated with an increased risk of CRC (RR: 1.13; 95% CI: 1.06-1.20; P < 0.001), CC (RR: 1.17; 95% CI: 1.04-1.33; P = 0.012), and RC (RR: 1.20; 95% CI: 1.04-1.39; P = 0.016). Finally, the strength of higher consumption of total red and processed meat with the risk of GC, and higher consumption of red meat with the risk of RC in subgroup of high adjusted level was lower than subgroup of moderate adjusted level, while the strength of higher consumption of processed meat with the risk of RC and HCC in subgroup of follow-up ≥ 10.0 years was higher than subgroup of follow-up < 10.0 years.
CONCLUSIONS
This study found that meat consumption was associated with an increased risk of CRC, CC, and RC, and dietary intervention could be considered an effective strategy in preventing CRC.
Topics: Humans; Carcinoma, Hepatocellular; Prospective Studies; Liver Neoplasms; Gastrointestinal Neoplasms; Stomach Neoplasms; Meat; Colonic Neoplasms
PubMed: 37612616
DOI: 10.1186/s12885-023-11218-1 -
Translational Gastroenterology and... 2023Surgical resection is a part of the treatment pathways for the management of pancreatic cancer with arterial involvement. Arterial resection in this context is however... (Review)
Review
BACKGROUND
Surgical resection is a part of the treatment pathways for the management of pancreatic cancer with arterial involvement. Arterial resection in this context is however not widely supported due to the paucity and diversity of the reported evidence in the literature. The aim of this systematic review is the presentation and analysis of the current evidence in the field.
METHODS
A systematic literature search of PubMed, MEDLINE and the Cochrane Library was performed for eligible studies, following the PRISMA guidelines. Information on baseline characteristics, peri-operative outcomes, survival outcomes and histopathological findings were extracted for pooling and analysis.
RESULTS
Eight studies with a total of 170 patients were included in the analysis. One hundred and thirty-five patients had a pancreaticoduodenectomy (PD) and 35 had a total pancreatectomy (TP) with arterial resection. Perioperative morbidity was 43.5% and mortality was 4.5%. Median overall survival (OS) was 12.7 months (range, 10.5-22.2 months). Overall 3- and 5-year survival for this cohort was reported at 6.6% (range, 0-42.4%) and 3.3% (range, 0-6.6%) respectively. Resection margins were clear (R0) in a median of 75% of patients. Only a median of 45% of patients received neo-adjuvant chemotherapy.
CONCLUSIONS
Arterial resection can be performed with an acceptable peri-operative morbidity and mortality. However, survival outcomes are still not convincing and future efforts should concentrate on patient and disease biology selection.
PubMed: 38021362
DOI: 10.21037/tgh-23-33 -
Annals of Surgical Oncology Jul 2024Improved systemic therapy has made long term (≥ 5 years) overall survival (LTS) after resection of pancreatic ductal adenocarcinoma (PDAC) increasingly common.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Improved systemic therapy has made long term (≥ 5 years) overall survival (LTS) after resection of pancreatic ductal adenocarcinoma (PDAC) increasingly common. However, a systematic review on predictors of LTS following resection of PDAC is lacking.
METHODS
The PubMed, Embase, Scopus, and Cochrane CENTRAL databases were systematically searched from inception until March 2023. Studies reporting actual survival data (based on follow-up and not survival analysis estimates) on factors associated with LTS were included. Meta-analyses were conducted by using a random effects model, and study quality was gauged by using the Newcastle-Ottawa Scale (NOS).
RESULTS
Twenty-five studies with 27,091 patients (LTS: 2,132, non-LTS: 24,959) who underwent surgical resection for PDAC were meta-analyzed. The median proportion of LTS patients was 18.32% (IQR 12.97-21.18%) based on 20 studies. Predictors for LTS included sex, body mass index (BMI), preoperative levels of CA19-9, CEA, and albumin, neutrophil-lymphocyte ratio, tumor grade, AJCC stage, lymphovascular and perineural invasion, pathologic T-stage, nodal disease, metastatic disease, margin status, adjuvant therapy, vascular resection, operative time, operative blood loss, and perioperative blood transfusion. Most articles received a "good" NOS assessment, indicating an acceptable risk of bias.
CONCLUSIONS
Our meta-analysis pools all true follow up data in the literature to quantify associations between prognostic factors and LTS after resection of PDAC. While there appears to be evidence of a complex interplay between risk, tumor biology, patient characteristics, and management related factors, no single parameter can predict LTS after the resection of PDAC.
Topics: Humans; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Survival Rate; Prognosis; Pancreatectomy
PubMed: 38710910
DOI: 10.1245/s10434-024-15281-1 -
International Journal of Surgery... Nov 2023Hepatocellular carcinoma (HCC) is the third-most lethal malignant tumor worldwide. The rapid development of immunotherapy utilizing immune checkpoint inhibitors for... (Meta-Analysis)
Meta-Analysis
Clinico-characteristics of patients which correlated with preferable treatment outcomes in immunotherapy for advanced hepatocellular carcinoma: a systematic review and meta-analysis.
BACKGROUND AND AIMS
Hepatocellular carcinoma (HCC) is the third-most lethal malignant tumor worldwide. The rapid development of immunotherapy utilizing immune checkpoint inhibitors for advanced HCC patients has been witnessed in recent years, along with numerous randomized clinical trials demonstrating the survival benefits for these individuals. This systematic review and meta-analysis aimed to identify specific clinico-pathological characteristics of advanced HCC patients that may lead to preferable responses to immunotherapy in terms of overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).
METHODS
The included clinical trials were retrieved from PubMed, Embase, the Cochrane library, and the Web of Science databases published in English between 1 January 2002 and 20 October 2022. A systematic review and meta-analysis for first-line and second-line phase II/III studies were conducted on immunotherapy for patients with advanced HCC by using OS as the primary outcome measure, and PFS and ORR as the secondary outcome measures to obtain clinico-pathological characteristics of patients which might be preferable responses to programmed death-1 (PD-1) and programmed cell death-Ligand 1 (PD-L1) inhibitors. Toxicity and specific treatment-related adverse events (TRAEs) were also determined.
RESULTS
After screening 1392 relevant studies, 12 studies were included in this systematic review and meta-analysis to include 5948 patients. Based on the analysis of interaction, the difference in OS after first-line immunotherapy between the subgroups of viral hepatitis [hazard ratio (HR)=0.73 vs 0.87, P for interaction=0.02] and macrovascular invasion and/or extrahepatic spread (HR=0.73 vs 0.89, P for interaction=0.02) were significant. The difference in PFS between the subgroups of viral hepatitis was highly significant (pooled HR=0.55 vs 0.81, P for interaction=0.007). After second-line immunotherapy, the difference in ORR between the subgroups of Barcelona Clinic Liver Cancer was significant (pooled ES=0.12 vs 0.23, P for interaction=0.04). Compared with PD-L1 inhibitors, PD-1 inhibitors may have a higher probability to cause TRAEs. Diarrhea, increased aspartate aminotransferase, and hypertension were the top three TRAEs.
CONCLUSIONS
This systematic review and meta-analysis represents the first pilot study aimed at identifying crucial clinico-pathological characteristics of patients with advanced HCC that may predict favorable treatment outcomes in terms of OS, PFS, and ORR to immunotherapy. Findings suggest that patients with viral hepatitis positivity (especially hepatitis B virus) and macrovascular invasion and/or extrahepatic spread may benefit more in OS when treated with PD-1/PD-L1 immune checkpoint inhibitors.
Topics: Humans; Carcinoma, Hepatocellular; B7-H1 Antigen; Immune Checkpoint Inhibitors; Pilot Projects; Programmed Cell Death 1 Receptor; Liver Neoplasms; Treatment Outcome; Immunotherapy; Hepatitis, Viral, Human; Lung Neoplasms
PubMed: 37598406
DOI: 10.1097/JS9.0000000000000652 -
Cureus Oct 2023Barrett's esophagus (BE) remains a significant precursor to esophageal adenocarcinoma, requiring accurate and efficient diagnosis and management. The increasing... (Review)
Review
Barrett's esophagus (BE) remains a significant precursor to esophageal adenocarcinoma, requiring accurate and efficient diagnosis and management. The increasing application of machine learning (ML) technologies presents a transformative opportunity for diagnosing and treating BE. This systematic review evaluates the effectiveness and accuracy of machine learning technologies in BE diagnosis and management by conducting a comprehensive search across PubMed, Scopus, and Web of Science databases up to the year 2023. The studies were organized into five categories: computer-aided systems, natural language processing and text-based systems, deep learning on histology and biopsy images, real-time and video analysis, and miscellaneous studies. Results indicate high sensitivity and specificity across machine learning applications. Specifically, computer-aided systems showed sensitivities ranging from 84% to 100% and specificities from 64% to 90.7%. Natural language processing and text-based systems achieved an accuracy as high as 98.7%. Deep learning techniques applied to histology and biopsy images displayed sensitivities up to greater than 90% and a specificity of 100%. Furthermore, real-time and video analysis technologies demonstrated high performance with assessment speeds of up to 48 frames per second (fps) and a mean average precision of 75.3%. Overall, the reviewed literature underscores the growing capability and efficiency of machine learning technologies in diagnosing and managing Barrett's esophagus, often outperforming traditional diagnostic methods. These findings highlight the promising future role of machine learning in enhancing clinical practice and improving patient care for Barrett's esophagus.
PubMed: 38021699
DOI: 10.7759/cureus.47755 -
Journal of Cancer 2023The incidence of gastroesophageal junction adenocarcinoma has gradually increased. Proximal gastrectomy or total gastrectomy is recommended for early gastric cancer of... (Review)
Review
The incidence of gastroesophageal junction adenocarcinoma has gradually increased. Proximal gastrectomy or total gastrectomy is recommended for early gastric cancer of the upper third of the stomach. Because total gastrectomy is often accompanied by body mass loss and nutrient absorption disorders, such as severe hypoproteinemia and anemia, Proximal gastrectomy is more frequently recommended by researchers for early upper gastric cancer (T1N0M0) and Siewert II gastroesophageal junction cancer less than 4 cm in length. Although some functions of the stomach are retained after proximal gastrectomy, the anatomical structure of the gastroesophageal junction can be destroyed, and the anti-reflux effect of the cardia is lost. In recent years, as various reconstruction methods for anti-reflux function have been developed, some functions of the stomach are retained, and serious reflux esophagitis is avoided after proximal gastrectomy. In this article, we summarized the indications, advantages, and disadvantages of various classic reconstruction methods and latest improved reconstruction method including esophageal and residual stomach anastomosis, tubular gastroesophageal anastomosis, muscle flap anastomosis, jejunal interposition, and double-tract reconstruction.
PubMed: 37859825
DOI: 10.7150/jca.87315 -
Journal of Clinical Medicine Dec 2023Pancreatic ductal adenocarcinoma (PDAC) is a cancer with one of the highest mortality rates in the world. Several studies have been conductedusing preclinical... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is a cancer with one of the highest mortality rates in the world. Several studies have been conductedusing preclinical experiments in mice to find new therapeutic strategies. Experimental ultrasound, in expert hands, is a safe, multifaceted, and relatively not-expensive device that helps researchers in several ways. In this systematic review, we propose a summary of the applications of ultrasonography in a preclinical mouse model of PDAC. Eighty-eight studies met our inclusion criteria. The included studies could be divided into seven main topics: ultrasound in pancreatic cancer diagnosis and progression (n: 21); dynamic contrast-enhanced ultrasound (DCE-US) (n: 5); microbubble ultra-sound-mediated drug delivery; focused ultrasound (n: 23); sonodynamic therapy (SDT) (n: 7); harmonic motion elastography (HME) and shear wave elastography (SWE) (n: 6); ultrasound-guided procedures (n: 9). In six cases, the articles fit into two or more sections. In conclusion, ultrasound can be a really useful, eclectic, and ductile tool in different diagnostic areas, not only regarding diagnosis but also in therapy, pharmacological and interventional treatment, and follow-up. All these multiple possibilities of use certainly represent a good starting point for the effective and wide use of murine ultrasonography in the study and comprehensive evaluation of pancreatic cancer.
PubMed: 38137745
DOI: 10.3390/jcm12247677 -
Cureus Aug 2023Pancreatic ductal adenocarcinoma (PDAC) is a significant challenge due to its silent progression and well-advanced, unresectable, complicated presentation. Detecting... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is a significant challenge due to its silent progression and well-advanced, unresectable, complicated presentation. Detecting this disease early on is crucial, and researchers have been investigating various potential biological markers, such as carbohydrate antigen 19-9 (CA 19-9), hoping to find indicators that can aid in its early detection. The primary focus of this review is on the diagnostic usefulness of CA 19-9 in detecting pancreatic cancer (PC) in the beginning stage and its usefulness in predicting progression. The database search of articles from PubMed, PMC, the Cochrane Library, and Google Scholar identified 227 articles published from 2013 to 2023. The keyword mix used in the search technique included terms like "CA 19-9," "pancreatic cancer," "diagnosis," and "early detection." This study provides evidence of CA 19-9's ability in detecting PDAC in the pre-diagnostic stage. But since the outcomes were inconsistent among the included trials, further analysis is required to develop standardized diagnostic criteria and methodologies. Furthermore, because of the variability of the study, it is not easy to make firm conclusions on CA 19-9's sensitivity as well as specificity in the first stage of pancreatic neoplasm. This in-depth overview of the available literature provides new insights into using CA 19-9 as a biological marker for detecting undiagnosed PC before progressing into the advanced stage, and was proven beneficial. However, this has to be shown in broader research with adequate sample size. Although it shows promise as a diagnostic tool, further study is required to confirm these findings.
PubMed: 37671217
DOI: 10.7759/cureus.44382