Lifestyle intervention with diet modification and increase in physical activity is effective for reducing hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD). However, for a ...similar weight loss, there is a large variability in the change in liver fat. We hypothesised that cardiorespiratory fitness may predict the response to the intervention.
Longitudinal study with increase in physical activity and diet modification.
University teaching hospital.
50 adults with NAFLD and 120 controls at risk for metabolic diseases.
Total-, subcutaneous abdominal- and visceral adipose tissue by magnetic resonance tomography, liver fat by 1HMR spectroscopy and cardiorespiratory fitness (VO(2,max)) by a maximal cycle exercise test at baseline and after 9 months of follow-up.
In all subjects total-, subcutaneous abdominal- and visceral adipose tissue decreased and fitness increased (all p<0.0001) during the intervention. The most pronounced changes were found for liver fat (-31%, p<0.0001). Among the parameters predicting the change in liver fat, fitness at baseline emerged as the strongest factor, independently of total- and visceral adipose tissue as well as exercise intensity (p = 0.005). In the group of subjects with NAFLD at baseline, a resolution of NAFLD was found in 20 individuals. For 1 standard deviation increase in VO(2,max) at baseline the odds ratio for resolution of NAFLD was 2.79 (95% confidence interval, 1.43-6.33).
Cardiorespiratory fitness, independently of total adiposity, body fat distribution and exercise intensity, determines liver fat content in humans, suggesting that fitness and liver fat are causally related to each other. Moreover, measurement of fitness at baseline predicts the effectiveness of a lifestyle intervention in reducing hepatic steatosis in patients with NAFLD.
The ALPSS procedure has been recently introduced as an alternative to PVE for liver volume augmentation in cases of planned right trisectionectomy with small future RLV and high risk of PHLF. We ...retrospectively analysed our single centre experience with 15 ALPPS procedures in order to better assess the limits and indications of the procedure.
The following volumetric parameters were evaluated: total liver volume (TLV), remnant liver volume (RLV), remnant liver volume to total liver volume ratio (RLV/TLV), remnant liver volume to body weight ratio (RLV/BWR) and median volume gain. The ALPPS procedure was usually considered when RLV/TLV < 25 % or RLV/BWR < 0.5. The ALPPS procedure consisted of phase 1 (in situ splitting of the liver), interphase (waiting for liver regeneration) and phase 2 (completion of right trisectionectomy). Postoperative complications were reported according to the Dindo-Clavien classification. Patient survival, late complications and tumour recurrence were analysed.
Between November 2010 and September 2013, we performed 15 ALPPS procedures in 10 patients with primary liver tumours (5 h-CCA, 4 i-CCA and 1 HCC) and in 5 with CRLM. The preoperative RLV/TLV ratio was 22.6 % (15.7 - 29.2) and the RLV/BWR 0.46 (0.22 - 0.66). After 10 days (range 8 - 16) the RLV/TLV ratio and RLV/BWR increased up to 36.3 % (30 - 59.2 %) and 0.67 (0.5 - 1.2) respectively, with a median volume gain of 87.2 % (23.8 - 161 %). The time interval between phases 1 and 2 was 13 days (9 - 18). An R0 status was reached in 13 patients and R1 in 2. The overall postoperative morbidity was 66.7 %. After phase 1, 8 patients experienced 19 complications and 7 none. After phase 2, 11 patients experienced 36 complications and 4 none. Four patients died postoperatively after 22 days (9 - 36 days) resulting in a postoperative mortality of 28.7 %. After a median follow-up of 17 months (1 - 33), 10 out of 15 patients are still alive (survival rate 66.6 %). Four patients (2 i-CCA, 1 CRLM, 1 HCC) developed tumour recurrences (2 intrahepatic and 2 extrahepatic). One patient with i-CCA died at POM 4 secondary to peritoneal carcinosis.
The actual high morbidity and mortality rates related to the ALPPS procedure should lead us to a more cautious selection of the candidates for this operation and restriction of the indications through an accurate work-up based on interdisciplinary cooperation among hepatologists, oncologists, radiologists and surgeons.
Background
Laparoscopic appendectomy is now the treatment of choice in uncomplicated appendicitis. To date its importance in the treatment of complicated appendicitis is not clearly defined.
Methods
...From January 2005 to June 2013 a total of 1762 patients underwent appendectomy for the suspected diagnosis of appendicitis at our institution. Of these patients 1516 suffered from complicated appendicitis and were enrolled. In total 926 (61 %) underwent open appendectomy (OA) and 590 (39 %) underwent laparoscopic appendectomy (LA). The following parameters were retrospectively analyzed: age, sex, operative times, histology, length of hospital stay, 30-day morbidity focusing on occurrence of surgical site infections, intraabdominal abscess formation, postoperative ileus and appendiceal stump insufficiency, conversion rate, use of endoloops and endostapler.
Results
A statistically significant difference in operative time was observed between the laparoscopic and the open group (64.5 vs. 60 min;
p
= 0.002). Median length of hospitalization was significantly shorter in the laparoscopic group (
p
< 0.000). Surgical site infections occurred exclusively after OA (38 vs. 0 patients). Intraabdominal abscess formation occurred statistically significantly more often after LA (2 vs. 10 patients;
p
= 0.002). There were no statistical significances concerning the occurrence of postoperative ileus (
p
= 0.261) or appendiceal stump insufficiencies (
p
= 0.076).
Conclusions
The laparoscopic approach for complicated appendicitis is a safe and feasible procedure. Surgeons should be aware of a potentially higher incidence of intraabdominal abscess formation following LA. Use of endobags , inversion of the appendiceal stump and carefully conducted local irrigation of the abdomen in a supine position may reduce the incidence of abscess formation.
Sensing of nutrients in the stomach is of crucial importance for the regulation of ingestive behavior especially in the context of metabolic dysfunctions such as obesity. Cells in the gastric mucosa ...with taste-signaling elements are considered as candidates for sensing the composition of ingested food and consequently modulate gastrointestinal processes. To assess whether obesity might have an impact on gastric chemosensory cells, gastric tissue samples from morbidly obese patients and normal-weight subjects were compared using a reverse transcriptase (RT)-PCR, qPCR and immunohistochemical approach.
Analysis of biopsy tissue samples from human stomach revealed that transcripts for the taste-signaling elements, including the receptor T1R3 involved in the reception of amino acids and carbohydrates, the fatty acid receptor GPR120, the G protein gustducin, the effector enzyme PLCβ2 and the ion channel TRPM5 are present in the human gastric mucosa and led to the visualization of candidate chemosensory cells in the stomach expressing gustatory marker molecules. RT-PCR and qPCR analyses indicated striking differences in the expression profiles of specimens from obese subjects compared with controls. For GPR120, gustducin, PLCβ2 and TRPM5 the expression levels were increased, whereas for T1R3 the level decreased. Using TRPM5 as an example, we found that the higher expression level was associated with a higher number of TRPM5 cells in gastric tissue samples from obese patients. This remarkable change was accompanied by an increased number of ghrelin-positive cells.
Our findings argue for a relationship between the amount of food intake and/or the energy status and the number of candidate chemosensory cells in the gastric mucosa.
Background
Optimized drug delivery systems are needed for intraperitoneal chemotherapy. The aim of this study was to develop a technology for applying pressurized intraperitoneal aerosol chemotherapy ...(PIPAC) under hyperthermic conditions (hPIPAC).
Methods
This is an ex-vivo study in an inverted bovine urinary bladder (IBUB). Hyperthermia was established using a modified industry-standard device (Humigard). Two entry and one exit ports were placed. Warm-humid CO
2
was insufflated in the IBUB placed in a normothermic bath to simulate body thermal inertia. The temperature of the aerosol, tissue, and water bath was measured in real-time.
Results
Therapeutic hyperthermia (target tissue temperature 41–43 °C) could be established and maintained over 30 min. In the first phase (insufflation phase), tissue hyperthermia was created by insufflating continuously warm-humid CO
2
. In the second phase (aerosolization phase), chemotherapeutic drugs were heated up and aerosolized into the IBUB. In a third phase (application phase), hyperthermia was maintained within the therapeutic range using an endoscopic infrared heating device. In a fourth phase, the toxic aerosol was discarded using a closed aerosol waste system (CAWS).
Discussion
We introduce a simple and effective technology for hPIPAC. hPIPAC is feasible in an ex-vivo model by using a combination of industry-standard medical devices after modification. Potential pharmacological and biological advantages of hPIPAC over PIPAC should now be evaluated.
Hepatic recurrence of liver malignancies is a leading problem in patients after liver resection with curative intention. Thermoablation is a promising treatment approach for patients after hepatic ...resection, especially in liver-limited conditions. This study aimed to investigate safety, survival, and local tumor control rates of MRI-guided percutaneous thermoablation of recurrent hepatic malignancies following hepatic resection.
Data from patients with primary or secondary hepatic malignancies treated between 2004 and 2018 with MRI-guided percutaneous thermoablation of hepatic recurrence after prior hepatic resection were retrospectively analyzed. Disease-free survival and overall survival rates were calculated using the Kaplan-Meier method.
A total of 57 patients with hepatic recurrence (mean tumor size = 18.9 ± 9.1 mm) of colorectal cancer liver metastases (n = 27), hepatocellular carcinoma (n = 17), intrahepatic recurrence of cholangiocellular carcinoma (n = 9), or other primary malignant tumor entities (n = 4) were treated once or several times with MR-guided percutaneous radiofrequency (n = 52) or microwave ablation (n = 5) (range: 1-4 times). Disease progression occurred due to local recurrence at the ablation site in nine patients (15.8%), non-local hepatic recurrence in 33 patients (57.9%), and distant malignancy in 18 patients (31.6%). The median overall survival for the total cohort was 40 months and 49 months for the colorectal cancer group, with a 5-year overall survival rate of 40.7 and 42.5%, respectively. The median disease-free survival was 10 months for both the total cohort and the colorectal cancer group with a 5-year disease-free survival rate of 15.1 and 14.8%, respectively. The mean follow-up time was 39.6 ± 35.7 months.
MR-guided thermoablation is an effective and safe approach in the treatment of hepatic recurrences in liver-limited conditions and can achieve long-term survival.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Occurrence of abdominal wall hernias during and before peritoneal dialysis constitutes a pivotal role in treatment discontinuation, failure, and exclusion from this dialysis method. We ...herein present a single-center experience regarding a one-stage surgical strategy, including hernia repair and simultaneous peritoneal dialysis catheter implantation.
Patients and methods
Over a 4-year period, 123 patients underwent peritoneal dialysis catheter implantation and 23 patients (19%) had concomitant abdominal wall hernias and were enrolled in this monocentric prospective study. Data collection included recurrent and new-onset hernias, surgical site infection, 1-year and 2-year catheter survival.
Results
In 23 patients, 27 hernia repairs combined with peritoneal dialysis catheter implantation were performed. Median age was 52 years (range, 30–85 years) and 18/23 (78%) patients were male. There were no recurrent hernias and no early surgical site infections. Daily flushing was regularly started on the 1st to 3rd postoperative day. Five patients (22%) developed hernias on other anatomical sites, which required hernia repair and perioperative discontinuation of peritoneal dialysis. After a median follow-up of 37 months (range, 28–87 months), 96% of all implanted catheters were still working.
Conclusion
Hernia repair and simultaneous peritoneal dialysis catheter implantation are associated with no recurrent hernias, an early start of peritoneal dialysis, a very low postoperative morbidity and very high 1-year and 2-year catheter survival.
Renal sinus fat (RSF) is a perivascular fat compartment located around renal arteries. In this in vitro and in vivo study we hypothesized that the hepatokine fetuin-A may impair renal function in ...non alcoholic fatty liver disease (NAFLD) by altering inflammatory signalling in RSF. To study effects of the crosstalk between fetuin-A, RSF and kidney, human renal sinus fat cells (RSFC) were isolated and cocultured with human endothelial cells (EC) or podocytes (PO). RSFC caused downregulation of proinflammatory and upregulation of regenerative factors in cocultured EC and PO, indicating a protective influence of RFSC. However, fetuin-A inverted these benign effects of RSFC from an anti- to a proinflammatory status. RSF was quantified by magnetic resonance imaging and liver fat content by
H-MR spectroscopy in 449 individuals at risk for type 2 diabetes. Impaired renal function was determined via urinary albumin/creatinine-ratio (uACR). RSF did not correlate with uACR in subjects without NAFLD (n = 212, p = 0.94), but correlated positively in subjects with NAFLD (n = 105, p = 0.0005). Estimated glomerular filtration rate (eGRF) was inversely correlated with RSF, suggesting lower eGFR for subjects with higher RSF (r = 0.24, p < 0.0001). In conclusion, our data suggest that in the presence of NAFLD elevated fetuin-A levels may impair renal function by RSF-induced proinflammatory signalling in glomerular cells.
Purpose
Completion pancreatectomy for grade-C pancreatic fistula is associated with unacceptably high mortality and therefore this strategy should be reassessed. This study presents an update of our ...experience with a pancreas-preserving technique in the course of salvage re-laparotomy in terms of closure of the open jejunum via segmental resection and external drainage of the pancreas.
Methods
Between April 2004 and January 2015, 292 pancreaticoduodenectomies (PD) with pancreaticojejunostomy (PJ) were performed. Thirteen patients (5 %) underwent salvage re-laparotomy for symptomatic grade-C fistulas, and clinical data were retrospectively analyzed.
Results
In all patients, the preservation of the pancreas remnant and external drainage of the pancreatic juice was feasible. Median hospital stay was 58 days (range, 21–142 days). In 4/13 patients (31 %), further reoperations were necessary. In-hospital mortality was 15 % (2/13). 3/13 patients (23 %) were readmitted and two received inpatient non-surgical treatment. To date re-pancreaticojejunostomy was performed in seven of the remaining 11 patients (63 %) after 168 days in median. In 1/7 patients (14 %), a re-operation after re-PJ was necessary. In one patient, externalization of the pancreas juice was chosen as a definite option. In another patient, secretion ceased spontaneously without stasis and normal endocrine function. Neither before nor after re-anastomosis impairment of endocrine function was observed.
Conclusions
Closure of the intestinum and preservation of the pancreas remnant in grade-C pancreatic fistula is easy to perform and can be categorized as a life-saving procedure. Prevention of total pancreatectomy associated with high morbidity and mortality was achieved in all cases.
It has not been solved whether subjects carrying the minor alleles of the -455T>C or -482C>T single nucleotide polymorphisms (SNPs) in the apolipoprotein-C3-gene (APOC3) have an increased risk for ...developing fatty liver and insulin resistance. We investigated the relationships of the SNPs with hepatic APOC3 expression and hypothesized that visceral obesity may modulate the effects of these SNPs on liver fat and insulin sensitivity (IS).
APOC3 mRNA expression and triglyceride content were determined in liver biopsies from 50 subjects. In a separate group (N=330) liver fat was measured by (1)H-magnetic resonance spectroscopy. IS was estimated during an oral glucose tolerance test (OGTT) and the euglycemic, hyperinsulinemic clamp (N=222).
APOC3 mRNA correlated positively with triglyceride content in liver biopsies (r=0.29, P=0.036). Carriers of the minor alleles (-455C and -482T) tended to have higher hepatic APOC3 mRNA expression (1.80 (0.45-3.56) vs 0.77 (0.40-1.64), P=0.09), but not higher triglyceride content (P=0.76). In 330 subjects the genotype did not correlate with liver fat (P=0.97) or IS (OGTT: P=0.41; clamp: P=0.99). However, a significant interaction of the genotype with waist circumference in determining liver fat was detected (P=0.02) in which minor allele carriers had higher liver fat only in the lowest tertile of waist circumference (P=0.01). In agreement, during a 9-month lifestyle intervention the minor allele carriers of the SNP -482C>T in the lowest tertile also had less decrease in liver fat (P=0.04).
APOC3 mRNA expression is increased in fatty liver and is regulated by SNPs in APOC3. The impact of the APOC3 SNPs on fatty liver is small and depends on visceral obesity.
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