Pancreatic cystic lesions (PCLs) are frequent incidental findings. As most PCLs require costly diagnostic evaluation and active surveillance, it is important to clarify their prevalence in ...asymptomatic individuals. We therefore aimed at performing a systematic review and meta-analysis to determine it.
Methods: a systematic search was conducted and studies meeting inclusion criteria were included. The prevalence of PCLs was pooled across studies. A random effect model was used with assessment of heterogeneity.
17 studies, with 48,860 patients, were included. Only 3 were prospective; 5 studies were conducted in the US, 7 in Europe, 4 in Asia and 1 in Brazil. The pooled prevalence of PCLs was 8% (95% CI 4–14) with considerable heterogeneity (I2 = 99.5%). This prevalence was higher in studies of higher quality, examining older subjects, smaller cohorts, and employing MRCP (24.8% vs 2.7% with CT-scan). The pooled rate of PCLs was four times higher in studies conducted in the US than in Asia (12.6% vs 3.1%). 7 studies reported the prevalence of mucinous lesions, with a pooled rate of 4.3% (95% CI 2–10; I2 = 99.2%), but of 0.7% only for worrisome features or high risk stigmata.
The rate of incidentally detected PCLs is of 8%. Mucinous lesions are the most common incidentally detected PCLs, although they rarely present with potential indication for surgery. The observed different rates in the US and other geographic Areas suggest that different protocols might be necessary to help balancing costs and effectiveness of follow-up investigations in asymptomatic subjects.
Abstract
Introduction
Four clinical phenotypes of IgG4-related disease (IgG4-RD) have been recently identified by latent class analysis (LCA): pancreato-biliary (group 1); retroperitoneum/aortitis ...(group 2); head and neck limited (group 3); and Mikulicz/systemic (group 4). The reproducibility of this classification in clinical practice and its relevance for patient management, however, remain unknown.
Methods
The study included 179 patients. Four IgG4-RD experts were asked to classify a validation cohort of 40 patients according to published LCA-derived phenotypes based on clinical judgement. Agreement between LCA and clinical clustering was calculated. To assess differences among disease phenotypes, the following variables were recorded on an additional 139 patients: serum IgG4 and IgE; inflammatory markers; eosinophils; plasmablasts; IgG4-RD responder index (RI); history of atopy, diabetes, osteoporosis, relapses and malignancy; cumulative dose of glucocorticoids; and use of rituximab.
Results
Clinical judgement replicated LCA classification with strong agreement among IgG4-RD experts (κ = 0.841, P < 0.0005). At disease onset, group 1 showed the highest levels of serum IgG4 and IgE. Groups 2 and 4 had the lowest and highest IgG4-RD RI, respectively. At 2 years’ follow-up, group 3 received the highest cumulative dose of glucocorticoids, but higher incidences of diabetes mellitus were observed in groups 1 and 4, consistent with the higher likelihood of pancreatic involvement in groups 1 and 4. No difference among the four groups was observed in terms of disease recurrence, time to relapse and frequency of rituximab infusion.
Conclusion
Clinical phenotypes of IgG4-RD reflect differences in epidemiological features and prognostic outcomes.
Earlier detection is key to reducing cancer deaths. Here, we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in ...cell-free DNA. We applied this test, called CancerSEEK, to 1005 patients with nonmetastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69 to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was greater than 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.
Purpose
To assess the ability of radiomic features (RF) extracted from contrast-enhanced CT images (ceCT) and non-contrast-enhanced (non-ceCT) in discriminating histopathologic characteristics of ...pancreatic neuroendocrine tumors (panNET).
Methods
panNET contours were delineated on pre-surgical ceCT and non-ceCT. First- second- and higher-order RF (adjusted to eliminate redundancy) were extracted and correlated with histological panNET grade (G1 vs G2/G3), metastasis, lymph node invasion, microscopic vascular infiltration. Mann–Whitney with Bonferroni corrected
p
values assessed differences. Discriminative power of significant RF was calculated for each of the end-points. The performance of conventional-imaged-based-parameters was also compared to RF.
Results
Thirty-nine patients were included (mean age 55-years-old; 24 male). Mean diameters of the lesions were 24 × 27 mm. Sixty-nine RF were considered. Sphericity could discriminate high grade tumors (AUC = 0.79,
p
= 0.002). Tumor volume (AUC = 0.79,
p
= 0.003) and several non-ceCT and ceCT RF were able to identify microscopic vascular infiltration: voxel-alignment, neighborhood intensity-difference and intensity-size-zone families (AUC ≥ 0.75,
p
< 0.001); voxel-alignment, intensity-size-zone and co-occurrence families (AUC ≥ 0.78,
p
≤ 0.002), respectively). Non-ceCT neighborhood-intensity-difference (AUC = 0.75,
p
= 0.009) and ceCT intensity-size-zone (AUC = 0.73,
p
= 0.014) identified lymph nodal invasion; several non-ceCT and ceCT voxel-alignment family features were discriminative for metastasis (
p
< 0.01, AUC = 0.80–0.85). Conventional CT ‘necrosis’ could discriminate for microscopic vascular invasion (AUC = 0.76,
p
= 0.004) and ‘arterial vascular invasion’ for microscopic metastasis (AUC = 0.86,
p
= 0.001). No conventional-imaged-based-parameter was significantly associated with grade and lymph node invasion.
Conclusions
Radiomic features can discriminate histopathology of panNET, suggesting a role of radiomics as a non-invasive tool for tumor characterization.
Trial registration number
: NCT03967951, 30/05/2019
Background In 2005, the International Study Group of Pancreatic Fistula developed a definition and grading of postoperative pancreatic fistula that has been accepted universally. Eleven years later, ...because postoperative pancreatic fistula remains one of the most relevant and harmful complications of pancreatic operation, the International Study Group of Pancreatic Fistula classification has become the gold standard in defining postoperative pancreatic fistula in clinical practice. The aim of the present report is to verify the value of the International Study Group of Pancreatic Fistula definition and grading of postoperative pancreatic fistula and to update the International Study Group of Pancreatic Fistula classification in light of recent evidence that has emerged, as well as to address the lingering controversies about the original definition and grading of postoperative pancreatic fistula. Methods The International Study Group of Pancreatic Fistula reconvened as the International Study Group in Pancreatic Surgery in order to perform a review of the recent literature and consequently to update and revise the grading system of postoperative pancreatic fistula. Results Based on the literature since 2005 investigating the validity and clinical use of the original International Study Group of Pancreatic Fistula classification, a clinically relevant postoperative pancreatic fistula is now redefined as a drain output of any measurable volume of fluid with an amylase level >3 times the upper limit of institutional normal serum amylase activity, associated with a clinically relevant development/condition related directly to the postoperative pancreatic fistula. Consequently, the former “grade A postoperative pancreatic fistula” is now redefined and called a “biochemical leak,” because it has no clinical importance and is no longer referred to a true pancreatic fistula. Postoperative pancreatic fistula grades B and C are confirmed but defined more strictly. In particular, grade B requires a change in the postoperative management; drains are either left in place >3 weeks or repositioned through endoscopic or percutaneous procedures. Grade C postoperative pancreatic fistula refers to those postoperative pancreatic fistula that require reoperation or lead to single or multiple organ failure and/or mortality attributable to the pancreatic fistula. Conclusion This new definition and grading system of postoperative pancreatic fistula should lead to a more universally consistent evaluation of operative outcomes after pancreatic operation and will allow for a better comparison of techniques used to mitigate the rate and clinical impact of a pancreatic fistula. Use of this updated classification will also allow for more precise comparisons of surgical quality between surgeons and units who perform pancreatic surgery.
Introduction
Surgery is the only cure for neuroendocrine tumors (NETs), with R0 resection being critical for successful tumor removal. Early detection of residual disease is key for optimal ...management, but both imaging and current biomarkers are ineffective post-surgery. NETest, a multigene blood biomarker, identifies NETs with >90% accuracy. We hypothesized that surgery would decrease NETest levels and that elevated scores post-surgery would predict recurrence.
Methods
This was a multicenter evaluation of surgically treated primary NETs (
n
= 153). Blood sampling was performed at day 0 and postoperative day (POD) 30. Follow-up included computed tomography/magnetic resonance imaging (CT/MRI), and messenger RNA (mRNA) quantification was performed by polymerase chain reaction (PCR; NETest score: 0–100; normal ≤20). Statistical analyses were performed using the Mann–Whitney U-test, Chi-square test, Kaplan–Meier survival, and area under the receiver operating characteristic curve (AUROC), as appropriate. Data are presented as mean ± standard deviation.
Results
The NET cohort (
n
= 153) included 57 patients with pancreatic cancer, 62 patients with small bowel cancer, 27 patients with lung cancer, 4 patients with duodenal cancer, and 3 patients with gastric cancer, while the surgical cohort comprised patients with R0 (
n
= 102) and R1 and R2 (
n
= 51) resection. The mean follow-up time was 14 months (range 3–68). The NETest was positive in 153/153 (100%) samples preoperatively (mean levels of 68 ± 28). In the R0 cohort, POD30 levels decreased from 62 ± 28 to 22 ± 20 (
p <
0.0001), but remained elevated in 30% (31/102) of patients: 28% lung, 29% pancreas, 27% small bowel, and 33% gastric. By 18 months, 25/31 (81%) patients with a POD30 NETest >20 had image-identifiable recurrence. An NETest score of >20 predicted recurrence with 100% sensitivity and correlated with residual disease (Chi-square 17.1,
p <
0.0001). AUROC analysis identified an AUC of 0.97 (
p <
0.0001) for recurrence-prediction. In the R1 (
n
= 29) and R2 (
n
= 22) cohorts, the score decreased (R1: 74 ± 28 to 45 ± 24,
p =
0.0012; R2: 72 ± 24 to 60 ± 28,
p =
non-significant). At POD30, 100% of NETest scores were elevated despite surgery (
p <
0.0001).
Conclusion
The preoperative NETest accurately identified all NETs (100%). All resections decreased NETest levels and a POD30 NETest score >20 predicted radiologically recurrent disease with 94% accuracy and 100% sensitivity. R0 resection appears to be ineffective in approximately 30% of patients. NET mRNA blood levels provide early objective genomic identification of residual disease and may facilitate management.
Background
Decision-making in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas depends on scaling the risk of malignancy with the surgical burden of a pancreatectomy. This study aimed ...to develop a preoperative, disease-specific tool to predict surgical morbidity for IPMNs.
Methods
Based on preoperative variables of resected IPMNs at two high-volume institutions, classification tree analysis was applied to derive a predictive model identifying the risk factors for major morbidity (Clavien–Dindo ≥3) and postoperative pancreatic insufficiency.
Results
Among 524 patients, 289 (55.2%) underwent pancreaticoduodenectomy (PD), 144 (27.5%) underwent distal pancreatectomy (DP), and 91 (17.4%) underwent total pancreatectomy (TP) for main-duct (18.7%), branch-duct (12.6%), or mixed-type (68.7%) IPMN. For 98 (18.7%) of the patients, major morbidity developed. The classification tree distinguished different probabilities of major complications based on the type of surgery (area under the surve AUC 0.70; 95% confidence interval CI, 0.63–0.77). Among the DP patients, the presence of preoperative diabetes identified two risk classes with respective probabilities of 5% and 25% for the development of major morbidity, whereas among the PD/TP patients, three different classes with respective probabilities of 15%, 20%, and 36% were identified according to age and body mass index (BMI). Overall, history of diabetes, age, and cyst size segregated three different risk classes for new-onset/worsening diabetes.
Conclusions
In presumed IPMNs, the disease-specific risk of major morbidity and pancreatic insufficiency can be determined in the preoperative setting and used to personalize the possible surgical indication. Age and overweight status in case of PD/TP and diabetes in case of DP tip the scale toward less aggressive clinical management in the absence of features suggestive for malignancy.
Background
Surgery remains the only treatment for the cure of pancreatic neuroendocrine tumors (PanNETs). Biomarkers to identify the completeness of resection and predict recurrence are lacking.
...Objective
The aims of this study were to evaluate if the blood measurement of neuroendocrine gene transcripts (NETest) was diagnostic of PanNETs, and whether NETest blood levels could identify complete resection. We compared transcript analysis with the biomarker chromogranin A (CgA).
Methods
This was a prospective, longitudinal, single-center study including 30 patients with a postoperative histological confirmation of PanNET. Blood for NETest and CgA was collected preoperatively and on postoperative day (POD) 1, POD5, and POD30. Transcripts were measured by real-time quantitative reverse transcription polymerase chain reaction and multianalyte algorithmic analysis (NETest; normal < 20), and CgA was measured by enzyme-linked immunosorbent assay (ELISA; normal < 109 ng/mL). Data are expressed as mean ± standard deviation (SD).
Results
Pancreatic surgical resections (
n
= 30) were
R
0, 26;
R
1, 2; and
R
2, 2. Preoperatively, NETest score was elevated in all 30 patients (44.7 ± 27), but postoperatively, NETest scores significantly decreased (
p
= 0.006) to POD30 (24.7 ± 24). The proportion of patients (15/30) with an elevated score significantly decreased by POD30 (
p
< 0.0001). CgA levels were elevated preoperatively (184 ± 360 ng/mL) in only 9/30 patients, but did not decrease significantly postoperatively at POD30 (260 ± 589 ng/mL,
p
= 0.398). The number of patients with elevated CgA levels remained unchanged (9/30).
Conclusions
The NETest is an accurate diagnostic biomarker for PanNETs (100%). A decrease in NETest levels after radical resection suggests this blood test provides early assessment of surgical efficacy. CgA had no clinical utility.
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