Effectiveness and safety of 1-L PEG-ASC versus other bowel preparations for colonoscopy: A meta-analysis of nine randomized clinical trials.

BACKGROUND AND AIMS: A 1-L polyethylene glycol plus ascorbate (PEG-ASC) preparation has been recently developed to improve patients' experience in colonoscopy. This meta-analysis aimed to evaluate the effectiveness and safety of 1-L PEG-ASC compared with those of other bowel preparations for colonoscopy. METHODS: MEDLINE, Embase, Scopus, and the Cochrane Library were systematically searched for randomized controlled trials comparing 1-L PEG-ASC with other bowel preparations published through July 2022. A random-effects model was applied for pooling the results; heterogeneity was expressed as I2. RESULTS: Nine studies met the inclusion criteria and were included. The analysis showed significantly higher cleansing success (CS) (OR = 1.50; 95% CI = 1.25-1.81; p < 0.01, I2 = 0%) and right-colon high-quality cleansing (HQC) (OR = 1.67; 95% CI = 1.21-2.31; p < 0.01, I2 = 43%) with 1-L PEG-ASC compared to the other preparations. The pooled estimate of the adenoma detection rate (ADR) did not significantly differ between the two groups either in the overall (OR = 1.02; 95% CI = 0.87-1.20; p = 0.79, I2 = 0%) or split-dosing regimen subgroup analysis (OR = 0.99; 95% CI = 0.84-1.18; p = 0.94, I2 = 0%). A significantly higher pooled estimate of the number of patients with adverse events (AEs) (OR = 1.51; 95% CI = 1.23-1.84; p<0.01, I2 = 0%) and incidence of AEs (IRR=1.33; 95% CI = 1.11-1.58; p<0.01, I2 = 71%) was observed with 1-L PEG-ASC than with the other preparations. No serious AEs or deaths occurred. CONCLUSIONS: Compared to other preparations, 1-L PEG-ASC yielded higher overall CS, higher right-colon HQC rates, and similar ADR. The number of patients with AEs and incidence of the total AEs were significantly higher with 1-L PEG-ASC in the absence of serious AEs.

Primary tumour resection may improve survival in functional well-differentiated neuroendocrine tumours metastatic to the liver.

BACKGROUND: Functional well-differentiated neuroendocrine tumours (NET) with liver metastases represent a therapeutic challenge with few alternative options in guidelines. In these patients, the role of surgical resection of the primary tumour is controversial. PATIENTS AND METHODS: From a regional registry collecting somatostatin analogue (SSA)-treated tumours from 1979 to 2005, a series of 139 patients presenting with symptomatic, liver-metastatic, well-differentiated NET (G1-G2, mitoses: ≤20, Ki-67: ≤20%) was prospectively collected and retrospectively analysed. Surgery on either the primary tumour or liver metastases was chosen: 1) when low perioperative risk was predictable; 2) in presence of an impending risk of obstruction, bleeding, or perforation; or 3) if liver metastases were suitable of curative or subtotal (>90%) tumour removal. Impact of the most relevant clinico-pathological parameters on survival was studied. RESULTS: Median follow-up was 127 months and median survival was 94 months, with 138 vs. 37 months in resected vs. non-resected primary NET (p < 0.001), respectively. In the univariate analysis, prolonged survival was significantly associated with primary tumour resection (p < 0.001), resection of liver metastases (p = 0.002), site of primary (carcinoid vs. pancreatic, p = 0.018), basal chromogranin-A (CgA) <200 ng/mL (p = 0.001), and absence of diarrhea (p = 0.012). Multivariate analysis showed that primary tumour resection was an independent positive prognostic factor (HR = 3.17; 95% CI: 1.77-5.69, p < 0.001), whereas diarrhea, basal CgA ≥200 ng/mL, and high tumour load were independent negative prognostic factors. Also, in 103 patients with non-resectable liver metastases, primary tumour resection was significantly associated with prolonged survival (median 137 vs. 32 months, p < 0.0001). CONCLUSIONS: Primary tumour resection may improve survival in functional well-differentiated NET with liver metastases.

Propensity score analysis of outcomes following laparoscopic or open liver resection for hepatocellular carcinoma.

BACKGROUND: Liver resection is a potentially curative approach for hepatocellular carcinoma (HCC). Laparoscopic liver resections may reduce complication rates, especially in patients with cirrhosis. The aim of this study was to compare the results of laparoscopic liver resection with those of open liver resection for HCC. METHODS: Patients with cirrhosis who underwent minor liver resections for HCC from 2006 to 2013 were identified retrospectively from a prospective database according to the technique adopted (laparoscopic or open). Short- and long-term outcomes were compared between the two groups before and after 1 : 1 propensity score matching. RESULTS: A total of 269 patients were considered: 226 who underwent open liver resection and 43 who had a laparoscopic procedure. The two groups differed at baseline in terms of median age, sex, performance status, tumour location and type of resection. After propensity score matching, two comparable groups of 43 patients each were obtained. Intraoperative bleeding, margin clearance and operative mortality were similar in the two groups, whereas complication rates were lower (49 versus 19 per cent in open versus laparoscopic groups respectively; P = 0·004) and median hospital stay was shorter (8 versus 5 days; P < 0·001) in the laparoscopic group. On multivariable logistic regression analysis, the only independent factor that reduced the risk of postoperative complications was the use of laparoscopy (odds ratio 0·12, 95 per cent c.i. 0·03 to 0·55; P = 0·006). Median overall survival was 57·8 months in the open group and 48·8 months in the laparoscopic group (P = 0·802). Median disease-free survival was 31·7 and 25·5 months respectively (P = 0·990). CONCLUSION: In comparison with the open approach, laparoscopic minor liver resections for HCC improved short-term outcomes, with similar survival results.

A comparison of the nutritional status between adult celiac patients on a long-term, strictly gluten-free diet and healthy subjects.

BACKGROUND/OBJECTIVES: There are conflicting data on the effect of a gluten-free diet (GFD) on the nutritional status of celiac patients. In the present study, we evaluated, in adult celiac patients, the influence of a long-term, strictly GFD on their nutritional status and compared it with matched healthy volunteers. SUBJECTS/METHODS: Our study included 39 celiac patients and 39 healthy volunteers. The body mass index (BMI) of patients and controls was evaluated at enrollment, while the patients' BMI before the GFD was retrieved from clinical records. In addition, at enrollment, in both groups, we compared BMI, fat mass (FM), bone mineral density (BMD), as well as their dietary intake, recorded on a 7-day diary. RESULTS: At the time of diagnosis, the majority of celiac patients (82.0%) had a normal BMI or were overweight, while 10.3% were malnourished. After the GFD, patients with a normal BMI showed a significant weight increase (P=0.002), but none of them switched in the overweight or obese category. Two (50%) of the four malnourished patients achieved a normal BMI. Controls and patients on a GFD had a similar BMI, FM, BMD and total calorie intake, but the amount of lipids and fiber intake was significantly different in the two groups (P=0.003 and P<0.0001, respectively). CONCLUSIONS: Our study demonstrates that a GFD is able to improve the nutritional status of celiac patients without inducing overweight or obesity. Our findings are related to a celiac population adopting a GFD based on a Mediterranean-type diet.

Radioembolization of hepatocarcinoma with (90)Y glass microspheres: development of an individualized treatment planning strategy based on dosimetry and radiobiology.

PURPOSE: The aim of this study was to optimize the dosimetric approach and to review the absorbed doses delivered, taking into account radiobiology, in order to identify the optimal methodology for an individualized treatment planning strategy based on (99m)Tc-macroaggregated albumin (MAA) single photon emission computed tomography (SPECT) images. METHODS: We performed retrospective dosimetry of the standard TheraSphere® treatment on 52 intermediate (n = 17) and advanced (i.e. portal vein thrombosis, n = 35) hepatocarcinoma patients with tumour burden < 50% and without obstruction of the main portal vein trunk. Response was monitored with the densitometric radiological criterion (European Association for the Study of the Liver) and treatment-related liver decompensation was defined ad hoc with a time cut-off of 6 months. Adverse events clearly attributable to disease progression or other causes were not attributed to treatment. Voxel dosimetry was performed with the local deposition method on (99m)Tc-MAA SPECT images. The reconstruction protocol was optimized. Concordance of (99m)Tc-MAA and (90)Y bremsstrahlung microsphere biodistributions was studied in 35 sequential patients. Two segmentation methods were used, based on SPECT alone (home-made code) or on coregistered SPECT/CT images (IMALYTICS™ by Philips). STRATOS™ absorbed dose calculation was validated for (90)Y with a single time point. Radiobiology was used introducing other dosimetric variables besides the mean absorbed dose D: equivalent uniform dose (EUD), biologically effective dose averaged over voxel values (BEDave) and equivalent uniform biologically effective dose (EUBED). Two sets of radiobiological parameters, the first derived from microsphere irradiation and the second from external beam radiotherapy (EBRT), were used. A total of 16 possible methodologies were compared. Tumour control probability (TCP) and normal tissue complication probability (NTCP) were derived. The area under the curve (AUC) of the receiver-operating characteristic (ROC) curve was used as a figure of merit to identify the methodology which gave the best separation in terms of dosimetry between responding and non-responding lesions and liver decompensated vs non-decompensated liver treatment. RESULTS: MAA and (90)Y biodistributions were not different (71% of cases), different in 23% and uncertain in 6%. Response correlated with absorbed dose (Spearman's r from 0.48 to 0.69). Responding vs non-responding lesion absorbed doses were well separated, regardless of the methodology adopted (p = 0.0001, AUC from 0.75 to 0.87). EUBED gave significantly better separation with respect to mean dose (AUC = 0.87 vs 0.80, z = 2.07). Segmentation on SPECT gave better separation than on SPECT/CT. TCP(50%) was at 250 Gy for small lesion volumes (<10 cc) and higher than 1,000 Gy for large lesions (>10 cc). Apparent radiosensitivity values from TCP were around 0.003/Gy, a factor of 3-5 lower than in EBRT, as found by other authors. The dose-rate effect was negligible: a purely linear model can be applied. Toxicity incidence was significantly larger for Child B7 patients (89 vs 14%, p < 0.0001), who were therefore excluded from dose-toxicity analysis. Child A toxic vs non-toxic treatments were significantly separated in terms of dose averaged on whole non-tumoural parenchyma (including non-irradiated regions) with AUC from 0.73 to 0.94. TD50 was ≈ 100 Gy. No methodology was superior to parenchyma mean dose, which therefore can be used for planning, with a limit of TD15 ≈ 75 Gy. CONCLUSION: A dosimetric treatment planning criterion for Child A patients without complete obstruction of the portal vein was developed.

Pathways and gene expression profiles in hepatocellular carcinoma.

Hepatocarcinogenesis is a process attributed to progressive genomic changes which alter the hepatocellular phenotype producing cellular intermediates evolving into clearly neoplastic cells (hepatocellular carcinoma, HCC). During the preneoplastic phase, the liver is often the site of chronic hepatitis and/or cirrhosis, and this process leads to the production of monoclonal populations of aberrant and dysplastic hepatocytes that develop genetic and chromosomal alterations. At the moment three main molecular pathways of liver carcinogenesis have been described and several attempts of genetic classification of HCC have been proposed. The definition of genomic and molecular changes which occur during the development of HCC should improve the classification and prognostis of liver tumors. The development of sorafenib and other new targeted developing therapies were rendered possible by the discovery and understanding of the molecular and genetic pathogenesis of hepatocellular carcinoma. Besides viruses, such as Hepatitis B virus (HBV) and Hepatitis C virus (HCV), may contribute to cancer development by several ways; however, additional factors, such as host immunity and chronic inflammation and host cellular mutations also play a role in the transformation process. The understanding of these pathways will in the future enable the clinician to focus the treatment patients with HCC and customize single or combination therapy.

Salivary markers of work stress in an emergency team of urban police (1 degree step).

INTRODUCTION: Stress is usually defined as the experience of negative events or the perceptions of distress and negative affect that are associated with the inability to cope with them. The parameter most suitable for large-scale field studies is the determination of endocrine activity by measurement of salivary cortisol. The aim of the present study is to identify the presence of sources of stress in an emergency team of urban police and to objective such stress using the PSS (Professional Stress Scale) test and bioumoral markers as salivary cortisol and interleukin 1 /f (IL-IB). MATERIALS AND METHODS: We studied 30 policemen who belonged to an emergency team. Salivary samples were collected at the start and at the end of the work-shift. As control we used the same subjects during the holiday. T test was performed to evaluate the differences between the means, the Chi Square's Test was performed to determine the statistically significant association between PSS subscales and salivary cortisol and ILl-B concentrations. RESULTS: Thirty policeman were evaluated, their mean age was 44,5 years, their mean work experience was 17,1 years. The PSS test indicated high scores in three subscales, they were work load, organizational structure and processes and lack of resources. SALIVARY CORTISOL: The mean concentration at the start of work-shift was higher than at the end of shift-work (p<0,05). T test indicated a statistically significant difference between mean cortisol concentrations at the same hour during the work (start and end) and during the holiday (P<0,05). A statistically significant negative association was noted between the PERC1 and PSS subscale called "work load" (p<0,05). SALIVARY IL-1B: the mean concentration of ILl-B at the start of the work-shift resulted higher than at the end, such reduction was statistically significant (P<0.05). We verified a positive association between the subclass of PSS Test called "conflict with other professionals" and salivary IL-1B concentration at the start of shift-work (p<0,05). DISCUSSION. Several precedent studies agree with our results. Our study has suggested a work related stress in urban police employed in an emergency team. We might conclude that salivary IL-1B and cortisol are useful markers of stress. We think that our findings, surely preliminary, have be corroborated by the study of vegetative parameters (heart rate, heart rate variability) that is still current. It might be useful to evaluate again the cortisol and IL-1B variations after some structure organizational modifications and after training that will teach the workers coping strategies. We might conclude that the stress discovered in this study is not hazardous for the health, if the workers have adequate holidays.

[Assessment of heart rate variability (HRV) as a stress index in an emergency team of urban police]. / Valutazione della variabilità della frequenza cardiaca (HRV) come indice di stress in addetti al pronto intervento nella polizia urbana.

Stress is usually defined as the experience of negative events or the perceptions of distress and negative affect that are associated with the inability to cope with them. The parameter most suitable for large-scale field studies is the determination of endocrine activity by measurement of salivary cortisol. The aim of the present study is to identify the presence of sources of stress in an emergency team of urban police and to objective such stress using the PSS (Professional Stress Scale) test and bioumoral markers as salivary cortisol and interleukin 1 beta (IL1-B). Moreover it will be determined the Heart Rate Variability (HRV) that is able to mirror the sympathetic-parasympathetic balance. We studied 30 policemen who belonged to an emergency team. Thirty policemen made cardiologic exams as ECG, Heart Eco-doppler and Holter Ecg during the work and during the holiday. Particularly we studied HRV using frequency-domain based HRV measures. The results were evidenced as the differences of the spectral power. As control we used the same subjects during the holiday. T test was performed to evaluate the differences between the means, the Chi Square's Test was performed to determine the statistically significant association between PSS subscales, HRV, salivary cortisol and IL1-B concentrations. The study of HRV demonstrated a statistically significant association between HRV parameters during the holiday, salivary cortisol concentrations and PSS test. IL1-B, instead, was not associated with HRV parameters. Several precedent studies agree with our results. Our study has suggested a work related stress in urban police employed in an emergency team. We might conclude that salivary IL1-B and cortisol are useful markers of stress. The study of HRV parameters gave evidence that LF/HF during the holiday is a useful marker of work stress, because it correlated with cortisol difference during the work. Conclusively we can believe that the HRV parameters evaluated during the work are useful as confront, instead the HRV parameters during the holiday are surest indexes of work stress. Probably the effect of stress on the heart aren't present during the work because the work experience reduces these effects, they appear during the holiday when the imagination could make the conflicts or the problems more complex than they are. It might be useful to repeat this study after some structure organizational modifications and after training that will teach the workers coping strategies. If we consider only the bioumoral and PSS results, we might conclude that the stress discovered in this study is not hazardous for the health when the workers have adequate holidays, but if we evaluate the HRV parameters, we have believe that, for a heart health, it's necessary either to increment the holidays or, it can appear paradoxical, to work again.