To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and ...constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient's prognosis, although this-to date-has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging.
Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major ...hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC).
The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity.
On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 0.84–1.29, p = 0.711 and HR 1.18 0.95–1.46, p = 0.13 respectively) or OS (HR 0.96 0.79–1.17, p = 0.67 and HR 1.48 1.16–1.88, p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 1.02–1.74, p = 0.037) and OS (HR 1.26 1.03–1.53, p = 0.022). Furthermore, EBDR (OR 2.86 2.3–3.52, p < 0.0010), resection of additional organs (OR 2.22 1.62–3.02, p < 0.0010) and major hepatectomy (OR 3.81 2.55–5.73, p < 0.0010) were all associated with increased morbidity and mortality. Compared to LMIC, patients in HIC were associated with poorer RFS (HR 1.18 1.02–1.37, p = 0.031) but not OS (HR 1.05 0.91–1.22, p = 0.48). Adjuvant and neoadjuvant treatments were infrequently used.
In this large, multicentre analysis of GBC surgical outcomes, liver resection was not conclusively associated with improved survival, and extended resections were associated with greater morbidity and mortality without oncological benefit. Aggressive upfront resections do not benefit higher stage GBC, and international collaborations are needed to develop evidence-based neoadjuvant and adjuvant treatment strategies to minimise surgical morbidity and prioritise prognostic benefit.
Cambridge Hepatopancreatobiliary Department Research Fund.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives:
To determine the reproducibility of the National Comprehensive Cancer Network (NCCN) resectability status classification for pancreatic cancer.
Background:
The NCCN classification defines ...3 resectability classes (resectable, borderline resectable, locally advanced), according to vascular invasion. It is used to recommend different approaches and stratify patients during clinical trials.
Methods:
Prospective, multicenter, observational study (trial ID: NCT03673423). Main outcome measure was the interobserver agreement of tumor assignment to different resectability classes and quantification of vascular invasion degrees. Agreement was measured by Fleiss’ k (k = 1 perfect agreement; k = 0 agreement by chance). Sixty-nine computed tomography (CT) scans of pathologically confirmed pancreatic adenocarcinoma were independently reviewed in a blinded fashion by 22 observers from 11 hospitals (11 surgeons and 11 radiologists). Rating differences between surgeons or radiologists and between hospitals with different volumes (≥60 or <60 resections/year) were assessed.
Results:
Complete agreement among 22 observers was recorded in 5 CT scans (7.2%), whereas 25 CT scans (36.2%) were variously assigned to all 3 resectability classes. Interobserver agreement varied from fair to moderate (Fleiss’ k range: 0.282–0.555), with the lowest agreement for borderline resectable tumors. Assessing vascular contact ≤180° had the lowest agreement for all vessels (k range: 0.196–0.362). The highest concordance was recorded for venous invasion >180° (k range: 0.619–0.756). Neither reviewers’ specialty nor hospital volume influenced the agreement.
Conclusions:
There is high variability in the assignment to resectability categories, which may compromise the reliability of treatments recommendations and the evidence of trials stratifying patients in resectability classes. Criteria should be revised to allow a reproducible classification.
Objectives:. To determine the reproducibility of the National Comprehensive Cancer Network (NCCN) resectability status classification for pancreatic cancer. Background:. The NCCN classification ...defines 3 resectability classes (resectable, borderline resectable, locally advanced), according to vascular invasion. It is used to recommend different approaches and stratify patients during clinical trials. Methods:. Prospective, multicenter, observational study (trial ID: NCT03673423). Main outcome measure was the interobserver agreement of tumor assignment to different resectability classes and quantification of vascular invasion degrees. Agreement was measured by Fleiss’ k (k = 1 perfect agreement; k = 0 agreement by chance). Sixty-nine computed tomography (CT) scans of pathologically confirmed pancreatic adenocarcinoma were independently reviewed in a blinded fashion by 22 observers from 11 hospitals (11 surgeons and 11 radiologists). Rating differences between surgeons or radiologists and between hospitals with different volumes (≥60 or <60 resections/year) were assessed. Results:. Complete agreement among 22 observers was recorded in 5 CT scans (7.2%), whereas 25 CT scans (36.2%) were variously assigned to all 3 resectability classes. Interobserver agreement varied from fair to moderate (Fleiss’ k range: 0.282–0.555), with the lowest agreement for borderline resectable tumors. Assessing vascular contact ≤180° had the lowest agreement for all vessels (k range: 0.196–0.362). The highest concordance was recorded for venous invasion >180° (k range: 0.619–0.756). Neither reviewers’ specialty nor hospital volume influenced the agreement. Conclusions:. There is high variability in the assignment to resectability categories, which may compromise the reliability of treatments recommendations and the evidence of trials stratifying patients in resectability classes. Criteria should be revised to allow a reproducible classification.
MicroRNA‐221 (miR‐221) is one of the most frequently and consistently up‐regulated microRNAs (miRNAs) in human cancer. It has been hypothesized that miR‐221 may act as a tumor promoter. To ...demonstrate this, we developed a transgenic (TG) mouse model that exhibits an inappropriate overexpression of miR‐221 in the liver. Immunoblotting and immunostaining confirmed a concomitant down‐regulation of miR‐221 target proteins. This TG model is characterized by the emergence of spontaneous nodular liver lesions in approximately 50% of male mice and by a strong acceleration of tumor development in 100% of mice treated with diethylnitrosamine. Similarly to human hepatocellular carcinoma, tumors are characterized by a further increase in miR‐221 expression and a concomitant inhibition of its target protein‐coding genes (i.e., cyclin‐dependent kinase inhibitor Cdkn1b/p27, Cdkn1c/p57, and B‐cell lymphoma 2–modifying factor). To validate the tumor‐promoting effect of miR‐221, we showed that in vivo delivery of anti‐miR‐221 oligonucleotides leads to a significant reduction of the number and size of tumor nodules. Conclusions: This study not only establishes that miR‐221 can promote liver tumorigenicity, but it also establishes a valuable animal model to perform preclinical investigations for the use of anti‐miRNA approaches aimed at liver cancer therapy. (HEPATOLOGY 2012;56:1025–1033)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ...ciRrhosis (ANSWER) study was designed to clarify this issue.
We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008–000625–19, and ClinicalTrials.gov, number NCT01288794.
From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 95% CI 0·40–0·95). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3–4 non-liver related adverse events.
In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis.
Italian Medicine Agency.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Massive changes have occurred in our diet. A growing consumption of vegetal oils rich in omega-6 (ω-6) and a depletion of omega-3 (ω-3) fatty acids (FAs) in our food has led to an imbalance between ...ω-3 and ω-6. In particular, eicosapentaenoic (EPA)/arachidonic acid (AA) ratio seems to be an indicator of this derangement, whose reduction is associated to the development of metabolic diseases, such as diabetes mellitus. Our aim was therefore to investigate the literature on the effects of ω-3 and ω-6 FAs on glucose metabolism. We discussed emerging evidence from pre-clinical studies and from clinical trials. Notably, conflicting results emerged. Source of ω-3, sample size, ethnicity, study duration and food cooking method may be responsible for the lack of univocal results. High EPA/AA ratio seems to be a promising indicator of better glycemic control and reduced inflammation. On the other hand, linoleic acid (LA) appears to be also associated to a minor incidence of type 2 diabetes mellitus, although it is still not clear if the outcome is related to a reduced production of AA or to its intrinsic effect. More data derived from multicenter, prospective randomized clinical trials are needed.
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