Effect of laparoscopic liver resection versus the open technique on hepatocyte regenerating activity in the rat.

BACKGROUND: Laparoscopic liver resection offers a safe and feasible option primarily for the excision of hepatic neoplasms. Timely recovery of liver volume is a key factor for improving prognosis and post-operative mortality of patients undergone liver resection. The aim of the present study was to compare liver regeneration after laparoscopic over open partial hepatectomy. METHODS: Wistar rats were subjected to laparoscopic 70% hepatectomy (group LAP-HEP), open 70% hepatectomy (group HEP), sham operation (group Sham) or no intervention (group Control). At various timepoints following operation (1 h-2 weeks), the liver was excised to assess relative liver weight, thiobarbituric acid reactive substances (TBARS) levels, mitotic activity, tissue expression of Nuclear Factor-κB (NFκB), Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) and the histopathologic profile. RESULTS: No differences were seen in relative liver weight between hepatectomy groups. Mitotic index was increased in all operative study groups, being higher in group LAP-HEP than in group HEP. TBARS levels were higher in group LAP-HEP compared to group HEP. NFκB and VCAM-1 tissue expression scores were increased in all operative study groups with VCAM-1 being higher in group HEP, while ICAM-1 was overexpressed only in hepatectomy groups. Mild histopathologic lesions were noted in hepatectomy groups with the histopathologic score being higher in group HEP (24 h). CONCLUSIONS: Laparoscopic liver resection enhanced hepatocyte mitotic activity which was accompanied by mild oxidative stress and a less pronounced local inflammatory response and tissue injury to that of the open technique.

Survival, Intestinal Mucosa Adhesion, and Immunomodulatory Potential of Lactobacillus plantarum Strains.

Survival during transit through the gastrointestinal track, intestinal mucosa adhesion, and a potential immunomodulatory effect of Lactobacillus plantarum strains 2035 and ACA-DC 2640 were investigated in a rat model. According to microbiological and multiplex PCR analysis, both strains were detected in feces 24 h after either single-dose or daily administration for 7 days. Intestinal mucosa adhesion of L. plantarum 2035 was noted in the large intestine at 24 h after single-dose administration, while it was not detected at 48 h. Daily dosing, prolonged detection of the strain up to 48 h post-administration, and expanded adhesion to the small intestine. Adhesion of L. plantarum ACA-DC 2640 to the intestinal mucosa after single-dose administration was prolonged and more extended compared to L. plantarum 2035. Daily dosing increased both the levels and the rate of positive cultures of the strains compared to those of the single-dose scheme. In addition, both strains increased total IgG while decreased IgM and IgA serum levels. In conclusion, L. plantarum 2035 and L. plantarum ACA-DC 2640 survived transit through the gastrointestinal track, exhibited transient distinct adhesion to the intestinal mucosa and modulated the systemic immune response.

Tissue injury of the remnant liver following radiofrequency-assisted partial hepatectomy.

PURPOSE: To evaluate remnant liver tissue damage in a pig model of radiofrequency (RF)-assisted liver resection employing either the sequential coagulate cut (SCC) Belgrade technique using a monopolar RF electrode or the one using the bipolar Habib-4x device. METHODS: Sixteen pigs underwent either a) resection of part of the left lateral and left median hepatic lobes employing the SCC (SCC group), the Habib-4X (H group) or the "crushclamp" technique (CC group) or b) sham operation (Sham group). Forty-eight hours later, tissue specimens were excised from the right lateral hepatic lobe for histopathological examination and immunohistochemical assessment of tissue injury, mitosis and inflammation. RESULTS: Histopathologic lesions, apoptotic activity, HSP 40 and TNFα expression were more intense, while mitotic activity was less prominent in the SCC group technique compared to H group. Comparison between CC and H groups suggested the pivotal role of partial hepatectomy (PH) per se in the changes noted in H group. CONCLUSION: The Habib-4X liver resection technique proved to be less injurious in the remnant liver tissue after PH compared to the SCC technique.

HSPC280, a winged helix protein expressed in the subventricular zone of the developing ganglionic eminences, inhibits neuronal differentiation.

Winged helix proteins have critical roles in a variety of developmental processes. During a screening for genes expressed in the developing forebrain, we identified HSPC280, a non-typical winged helix protein, which shares similarity with a protein-protein interaction domain found in the proteins of the actin-binding Rho-activating protein family. In this work, we analyzed HSPC280 expression during mouse development as well as during neuronal differentiation of mouse Neuro2a cells. HSPC280 expression is tightly regulated; during mouse development, it was detected predominantly in the ganglionic eminences of the ventral telencephalon, from their appearance at E11.5 to P0, with the highest levels between E13.5 and E15.5, a period that correlates with the peak of neurogenesis in these structures. Comparative expression analysis of HSPC280 with Dlx2, cyclinD2 and Lhx6 revealed that, within the ganglionic eminences, HSPC280 was restricted in the proliferating cell population of the subventricular zone, in a pattern similar to that of cyclinD2. Finally, we showed that HSPC280 is a nuclear protein which, when overexpressed in Neuro2a cells, it inhibited neuronal differentiation in vitro, suggesting its involvement in the mechanisms controlling neural progenitor cells proliferation.

A laparoscopic technique of partial hepatectomy in the rat.

BACKGROUND: Laparoscopic partial hepatectomy is an increasingly applied technique in the treatment of liver tumors and in living donor transplantation. There is a need for establishing an animal model that would facilitate experimental research on the technique. The aim of the present study was to describe a safe and efficient laparoscopic technique of 70% partial hepatectomy in the rat. MATERIALS AND METHODS: Twenty-four male Wistar rats underwent either laparoscopic (group LAP-HEP) or open resection of the median and left lateral hepatic lobes (group HEP). In group LAP-HEP, a 5-mm Hg pneumoperitoneum was established. Three 5-mm trocars were introduced in the abdominal cavity. A self-made pretied ligature loop was used to ligate en bloc the pedicles of the hepatic lobes to be resected. A self-made sterile elastic specimen retrieval bag facilitated extraction of the resected liver tissue. In group HEP, the same liver lobes were resected by ligation of their pedicles after midline laparotomy. RESULTS: The percentage of resected liver parenchyma did not differ between groups. All animals returned to normal feeding activity by 48 h postoperation and had no complications. CONCLUSIONS: A simple, cost-effective, safe, and efficient laparoscopic technique for 70% partial hepatectomy in the rat was described.

Room air versus carbon dioxide pneumoperitoneum: effects on oxidative state, apoptosis and histology of splanchnic organs.

BACKGROUND: Although CO2 is the insufflation gas of choice in laparoscopic procedures, room air is usually used in natural orifice transluminal endoscopic surgery. The aim of the present study was to compare the safety of room air versus CO2 pneumoperitoneum in terms of their effect on the oxidative state, apoptosis and tissue injury of splanchnic organs. METHODS: Eighteen Wistar rats were assigned to three groups (n = 6 per group) and were subjected to 8 mm Hg room air (group Pne-Air) or CO2 pneumoperitoneum (group Pne-CO2) or sham operation for 60 min. Forty-five minutes postdeflation, tissue samples were excised from the liver, stomach, ileum and kidneys for reduced glutathione-to-glutathione disulfide (GSH/GSSG) ratio, caspase-8 and caspase-3 and hypoxia-inducible factor-1α (HIF-1α) immunohistochemical assessment and histopathologic examination. RESULTS: GSH/GSSG ratio substantially declined in both pneumoperitoneum groups. No change was noted in HIF-1α expression. Mild upregulation of caspase-8 and caspase-3 was noted in both pneumoperitoneum groups being less pronounced in group Pne-Air. Histopathologic score was increased in all organs studied, but the stomach, in both pneumoperitoneum groups. CONCLUSION: Pneumoperitoneum established by either room air or CO2 induced substantial oxidative stress, mild apoptosis and mild tissue injury in splanchnic organs. While air pneumoperitoneum conferred a less pronounced apoptotic effect, the oxidative state and histopathologic profile of splanchnic organs did not differ between insufflation gases.

Early hemodynamic effects after extended liver radiofrequency ablation.

BACKGROUND: The purpose of the present study was to assess early intestinal and systemic hemodynamic effects after extended radiofrequency ablation (RFA) of the liver in terms of investigating their potential contribution to gut barrier disruption. MATERIALS AND METHODS: Ten rabbits were assigned to two groups of five animals each and were subjected to either 30% liver RFA (group RFA-1) or sham operation (group sham-1). Blood flow rate at the superior mesenteric artery (SMA) was monitored for 90 min after operation. Ileal tissue was excised at 48 h for histomorphometric and histopathologic analysis. Eight pigs were assigned to two groups of four animals each and were also subjected to either 30% liver RFA (group RFA-2) or sham operation (group sham-2). A panel of systemic hemodynamic parameters was serially measured up to 90 min after operation. RESULTS: In group RFA-1, SMA blood flow rate was lower than that in group sham-1 throughout the study period. Intestinal mucosa atrophy and a deterioration of histopathologic profile were noted in group RFA-1. In group RFA-2, diastolic pulmonary artery pressure was lower (60-90 min), central venous pressure was gradually decreased, arterial pressure was higher (30-90 min), and systemic vascular resistance was higher (30-90 min) than those in group sham-2. No change was noted in the cardiac output. CONCLUSIONS: In conclusion, SMA blood flow was reduced during the early post-RFA period, justifying an ischemic insult at the intestine. In addition, a gradual decrease of the preload was counterbalanced by an increase of systemic vascular resistance leaving the cardiac output unaffected.

Oxidative stress in multi-port and single-port cholecystectomy.

BACKGROUND: This study was designed to analyze and compare plasma levels of 8-isoprostane (8-epiPGF2α), a biomarker of lipid peroxidation, and uric acid (UA), a marker of the antioxidant status, in standard laparoscopic (LC) and laparoendoscopic single-site cholecystectomy (LSSC). MATERIALS AND METHODS: Forty patients with noncomplicated cholelithiasis were randomized to undergo either LSSC (n = 20) or LC (n = 20). The patients had body mass index <30, American Society of Anesthesiologists score I or II, and no previous upper gastrointestinal surgery. Blood samples were taken preoperatively and 6 h and 24 h postoperatively. Levels of 8-epiPGF2α were determined using enzyme-linked immunosorbent assay, whereas levels of UA were calculated using automated analyzer. RESULTS: No significant differences were observed in operative data among the groups. Levels of 8-epiPGF2α were significantly higher in LSSC compared with LC at 6 h (P = 0.003) and 24 h (P < 0.001). 8-epiPGF2α levels showed significant changes over time in LC (LSSC: P = 0.720, LC: P < 0.001). UA levels were significantly higher in LC compared with LSSC, 24 h postoperatively (P = 0.021). No significant changes over time in the UA levels in both groups (LSSC: P = 0.056, LC: P = 0.205). CONCLUSIONS: LSSC is associated with increased oxidative stress compared with LC. Further studies are needed to confirm these results.

Coagulation and fibrinolysis activation after single-incision versus standard laparoscopic cholecystectomy: a single-center prospective case-controlled pilot study.

Laparoscopic cholecystectomy is associated with attenuated acute-phase response and hypercoagulable state compared with the open procedure. Single-incision laparoscopic cholecystectomy is a new technique aiming to minimize the invasiveness of the procedure. By comparing the degree of coagulation and fibrinolysis activation after conventional multiport (CLC) and single-incision (SILC) laparoscopic cholecystectomy, we aimed to determine whether the reduced incision size induces a lower thrombophilic tendency. Thirty-two adult patients with noncomplicated symptomatic cholelithiasis were nonrandomly assigned to CLC or SILC. Prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT), D-dimers, fibrinogen, and von Willebrand factor levels were measured at baseline, at 1st, and 24th hour, postoperatively. Twenty-six patients were finally included in the study. Fifteen patients underwent CLC (male/female: 5/10) and 11 underwent SILC (male/female: 1/10). There were no perioperative complications. An almost similar postoperative pattern and degree of activation of coagulation and fibrinolysis pathways was noted in both groups. No statistically significant differences were found between SILC and CLC for F1 + 2, TAT, D-dimers, fibrinogen, and von Willebrand factor levels, duration of surgery, length of hospital stay, and postoperative morbidity. A similar pattern and extent of coagulation and fibrinolysis activation is present in SILC and CLC, and therefore there is no difference in tendency for thrombosis. Thromboembolic prophylaxis should be considered in SILC as recommended for CLC, pharmacologic or mechanical, considering the hemorrhagic risk and the presence of additional thromboembolism risk factors. SILC appears to be a safe, feasible technique that can be recommended for its potential advantages in cosmesis and reduced incisional pain.

Long-term angiogenic activity of free grafts and pedicle flap in a rabbit urethroplasty model.

PURPOSE: We studied the late angiogenic activity of free grafts and a pedicle flap in a rabbit urethroplasty model to determine whether angiogenic activity plays a role in late outcomes of urethral reconstruction in rabbits. METHODS: Twenty-eight rabbits were randomly divided into five groups according to the method used to bridge a urethral defect as an onlay patch: Control, simple closure of urethral defect (Group O1); free penile skin graft (FPSG, Group A1); buccal mucosal graft (BuMG, Group B1); bladder mucosal graft (BlMG, Group C1); and pedicle penile skin flap (PPSF, Group D1). Angiogenic activity of the patch on postoperative day 84 was assessed by immunohistochemistry. RESULTS: The angiogenic activity in Groups O1, A1, B1, C1, and D1 was 23.33 ± 4.92 (means ± SD), 42.89 ± 6.52, 55.78 ± 3.46, 53.61 ± 6.17, and 24.11 ± 9.07 vessels per optical field, respectively. There were statistically significant differences (p < .001) between Group O1 and A1 B1, C1, Group A1 and B1, C1, D1, Groups B1 and D1 and Groups C1 and D1, but not between Groups O1 and D1 (p = 1.000) and Groups B1 and C1 (p = .872). The long-term angiogenic activity of all the groups was significantly lower (p < .001) than in the corresponding early groups. CONCLUSIONS: Although the angiogenic activity of all the groups decreased in the late assessment, the buccal mucosal graft continued to exhibit elevated angiogenesis above bladder or skin (free or pedicle) graft. Therefore, buccal mucosal patch graft might be preferable because of its easier harvesting.

The role of apigenin in an experimental model of acute pancreatitis.

AIM: The aim of the present study is to evaluate pathologic changes in the pancreatic parenchyma in an experimental model of acute pancreatitis (AP) following bilio-pancreatic duct ligation. An effort was made to clarify the role of apigenin, a substance that is well-known for its antioxidant and anti-inflammatory role and its likely beneficial activity to the pancreatic parenchyma following AP in rats. MATERIAL AND METHOD: One hundred twenty-six male Wistar rats 3-4 mo old and weighing 220-350 g were used. At time 0, the following groups were randomly assigned: group sham: rats were subjected to virtual surgery; group control: rats were subjected to surgery for induction of AP, by ligation of the bilio-pancreatic duct; group apigenin: rats were subjected to surgery for induction of AP and enteral feeding with apigenin. Pathologic changes of the pancreatic parenchymal and myeloperoxidase activity were measured at predetermined time intervals 6, 12, 24, 48, and 72 h. RESULT: From the pathologic reports, by comparing the control group with the apigenin group, an improvement of pancreatic tissue architecture following apigenin administration was observed. Inflammatory infiltration, edema, ductal dilation, and necrosis were reduced following apigenin administration over time (P = 0.049, P = 0.228, P = 0.387, P = 0.046). Treatment with apigenin significantly reduced the bilio-pancreatic duct ligation and evoked an increase in pancreatic myeloperoxidase activity (P = 0.030). CONCLUSION: Oral apigenin administration in rats, following experimentally induced pancreatitis, seems to protect the pancreatic tissue. Thus, apigenin administration to humans could potentially ameliorate the damages to the pancreas.

Effects of cigarette smoke exposure and its cessation on body weight, food intake and circulating leptin, and ghrelin levels in the rat.

INTRODUCTION: Smoking is associated with loss of body weight (BW) and reduced appetite, while smoking abstinence with the opposite effect. The role of peripheral signaling by appetite-controlling hormones leptin and ghrelin is not clear. In the present study, the relationship of circulating leptin and ghrelin with BW and food intake rate (FIR) changes was studied during cigarette smoke exposure (CSE) and after its cessation in the rat. METHODS: Male Wistar rats were subjected to CSE for 8 weeks by confinement to plexiglass chambers (Group S). Control animals were confined to identical chambers without smoke (Group C). During CSE and an equivalent follow-up period, BW and FIR was recorded and serum leptin and ghrelin levels were measured. RESULTS: A sharp decrease in BW was noted during the first 4 weeks of CSE, while FIR, after a substantial decrease noted at Week 1, returned to control levels. Thereafter, rats started to regain their BW until they reached control levels by the 1st week postCSE. BW regain was accompanied by a rebound increase of FIR, which plateaued during the first 4 weeks postCSE and then normalized. Serum leptin was decreased in Group S during both periods, normalizing at the 7th week postCSE. Ghrelin levels did not differ between groups. CONCLUSIONS: Circulating leptin could not explain by its own BW and FIR changes during the first few week of CSE in rats, in contrast to the rest of the CSE period as well as after its cessation. Serum ghrelin levels did not justify BW and FIR changes.

Soluble E-cadherin as a diagnostic and prognostic marker in gastric carcinoma.

OBJECTIVE: Modifications in E-cadherin (E-Cad) expression are associated with dedifferentiation, progression, metastases and poor prognosis in many types of tumors. The aim of the present study was to identify a potential association of the pre- and post-operative soluble E-Cad levels (sE-Cad) with the clinicopathological parameters of patients with gastric cancer. PATIENTS AND METHODS: Serum sE-Cad levels were determined in 99 gastric cancer patients and 78 healthy volunteers using ELISA. RESULTS: Levels of sE-Cad were significantly increased in gastric cancer patients compared with these levels in healthy controls (p < 0.001). For the evaluation of the diagnostic significance of sE-Cad the area under the receiver operating characteristic (ROC) curve (AUC) was 0.835, while the optimal cut-off point of 9.9 microg/mL was determined to classify gastric cancer patients, which yielded sensitivity of 72.7%, specificity of 80.8% and accuracy of 76.3%. Poor differentiation (p = 0.009) and the presence of distant metastases (p < 0.001) were the two significant independent prognostic determinants for high sE-Cad levels in multivariate linear regression analysis. The preoperative levels of sE-Cad also proved helpful in classifying patients according to the choice treatment (curative versus palliative) (AUC, 0.656); when the optimal cut-off point was set at 17.60 microg/mL, the sensitivity was 57%, the specificity was 83% and accuracy was 75%. Survival was shorter in patients with increased sE-Cad (median, 7 months vs 39 months, p = 0.0002), although multivariate Cox regression analysis demonstrated a marginal prognostic significance of sE-Cad for survival (adjusted HR = 1.68, 95% CI = 0.93 to 3.02, p = 0.072). CONCLUSIONS: Serum sE-Cad levels could be considered as a diagnostic and prognostic marker in gastric cancer patients as well as a tool to select a treatment approach. The prognostic value of sE-Cad on overall survival requires further study.

Distinct adhesion of probiotic strain Lactobacillus casei ATCC 393 to rat intestinal mucosa.

Adhesion to the intestine represents a critical parameter for probiotic action. In this study, the adhesion ability of Lactobacillus casei ATCC 393 to the gastrointestinal tract of Wistar rats was examined after single and daily administration of fermented milk containing either free or immobilized cells on apple pieces. The adhesion of the probiotic cells at the large intestine (cecum and colon) was recorded at levels ≥6 logCFU/g (suggested minimum levels for conferring a probiotic effect) following daily administration for 7 days by combining microbiological and strain-specific multiplex PCR analysis. Single dose administration resulted in slightly reduced counts (5 logCFU/g), while they were lower at the small intestine (duodenum, jejunum, ileum) (≤3 logCFU/g), indicating that adhesion was a targeted process. Of note, the levels of L. casei ATCC 393 were enhanced in the cecal and colon fluids both at single and daily administration of immobilized cells (6 and 7 logCFU/g, respectively). The adhesion of the GI tract was transient and thus daily consumption of probiotic products containing the specific strain is suggested as an important prerequisite for retaining its levels at an effective concentration.

Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine.

PURPOSE: The effect of ionizing irradiation on the autophagic response of normal tissues is largely unexplored. Abnormal autophagic function may interfere the protein quality control leading to cell degeneration and dysfunction. This study investigates its effect on the autophagic machinery of normal mouse lung. METHODS AND MATERIALS: Mice were exposed to 6 Gy of whole body γ-radiation and sacrificed at various time points. The expression of MAP1LC3A/LC3A/Atg8, beclin-1, p62/sequestosome-1 and of the Bnip3 proteins was analyzed. RESULTS: Following irradiation, the LC3A-I and LC3A-II protein levels increased significantly at 72 h and 7 days. Strikingly, LC3A-II protein was increased (5.6-fold at 7 days; p<0.001) only in the cytosolic fraction, but remained unchanged in the membrane fraction. The p62 protein, was significantly increased in both supernatant and pellet fraction (p<0.001), suggesting an autophagosome turnover deregulation. These findings contrast the patterns of starvation-induced autophagy up-regulation. Beclin-1 levels remained unchanged. The Bnip3 protein was significantly increased at 8 h, but it sharply decreased at 72 h (p<0.05). Administration of amifostine (200 mg/kg), 30 min before irradiation, reversed all the LC3A and p62 findings on blots, suggesting restoration of the normal autophagic function. The LC3A and Beclin1 mRNA levels significantly declined following irradiation (p<0.01), whereas Bnip3 levels increased. CONCLUSIONS: It is suggested that irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. Whether this is due to defective maturation or to aberrant degradation of the autophagosomes requires further investigation.

Increased prevalence of abdominal aortic aneurysm in patients undergoing inguinal hernia repair compared with patients without hernia receiving aneurysm screening.

BACKGROUND: The introduction of screening programs for abdominal aortic aneurysm (AAA) is being contemplated by health services in several countries. The correlation between aortic aneurysm and abdominal wall hernias is well reported, and inguinal hernia has been identified as a risk factor for aortic aneurysm. However, the prevalence of AAA in patients with inguinal hernia has not been adequately documented. This study evaluated whether patients with inguinal hernia are at increased risk of having an AAA compared with patients without hernia receiving aneurysm screening. METHODS: Men aged >55 undergoing primary inguinal hernia repair underwent ultrasound imaging of the abdominal aorta to screen for aneurysm. A reference group was selected from men without clinical evidence of inguinal hernia participating in an AAA screening program. Prevalence and odds ratios of AAA in the two groups were calculated. RESULTS: The study cohort comprised 235 patients with inguinal hernia and 203 controls. The mean ± SD aortic diameter was 22 ± 9 mm in patients with inguinal hernia vs 20 ± 6 mm for controls (P = .045). The prevalence of AAA was 8.1% in the hernia group and 3.9% in the control group (adjusted odds ratio, 3.9; 95% confidence interval, 1.6-9.5; P = .039). For aneurysms >4 cm, the prevalence was 5.1% in those with an inguinal hernia and 1.5% in those without an inguinal hernia (adjusted odds ratio, 4.7; 95% confidence interval, 1.2-18.5, P = .025). CONCLUSIONS: Inguinal hernia was a significant risk factor for AAA. Entry into a screening program of men aged >55 admitted for inguinal hernia repair should be considered.

Mesna preserves hepatocyte regenerating capacity following liver radiofrequency ablation under Pringle maneuver.

BACKGROUND: The objectives of the present study were to test the hypothesis that hepatocyte regenerating activity induced by radiofrequency ablation (RFA) of the liver is attenuated when performed under Pringle maneuver, and to investigate the potentially protective effect of mesna prophylactic administration. MATERIALS AND METHODS: Wistar rats were subjected to liver RFA (group RFA), RFA plus Pringle maneuver for 30 min (group RFA+P), RFA plus Pringle plus mesna (400mg/kg, per os, 3h prior to operation) (group RFA+P+M), Pringle only (group P), or sham operation (group S) after midline laparotomy. At 1h, liver oxidative state (glutathione to glutathione disulfide ratio-GSH/GSSG) and nuclear factor κB (NF-κB) activity were assessed in liver specimens. At 1, 3, and 6h, the levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured in blood serum. At 24h, 48 h, 1 wk, and 3 wk, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured in blood serum and the histopathologic profile and hepatocyte mitotic activity were assessed in liver specimens. RESULTS: Mitotic activity was low but sustained in groups RFA and RFA+P+M, more intense in group P, while suppressed in group RFA+P. Histopathologic profile was deteriorated with lesions being more intense in group RFA+P but significantly less severe in group RFA+P+M. Oxidative stress was equally induced in all experimental groups. NF-κB was activated in groups RFA, RFA+P, and P, but not in group RFA+P+M. IL-6 and TNF-α serum levels were increased; the levels were significantly higher in group RFA+P, while lower in group RFA+P+M. Serum transaminases levels were increased during the first 48 h. CONCLUSIONS: Hepatocyte regenerating activity is suppressed following liver RFA under Pringle maneuver. Prophylactic administration of mesna preserves hepatocyte regenerating capacity by attenuating acute inflammatory response and minimizing hepatic tissue injury in the non-ablated liver parenchyma.

Attenuation of propofol tolerance conferred by remifentanil co-administration does not reduce propofol toxicity in rabbits under prolonged mechanical ventilation.

BACKGROUND: Prolonged sedation with propofol at high doses may lead to fatal multi-organ dysfunction, know as propofol infusion syndrome. We tested the hypothesis that propofol plus remifentanil co-administration attenuates propofol tolerance to its sedative effect and assessed if such an effect has an impact on propofol toxicity in rabbits under prolonged mechanical ventilation. MATERIALS AND METHODS: Eighteen healthy male rabbits were mechanically ventilated and received propofol (group P, n = 6), propofol plus remifentanil (group PR, n = 6), or remifentanil plus sevoflurane (group RS, n = 6) in order to be kept under sedation (group P) or sedation/analgesia (groups PR and RS) for up to 48 h. Initial propofol and remifentanil infusion rates (IRs) were adjusted, if needed, to maintain the desired level of sedation and analgesia, respectively (groups P and PR). In group RS, remifentanil was infused at IRs equivalent to those of group PR. Propofol IRs were recorded, propofol concentrations were measured in the arterial plasma, and blood biochemical parameters and organ histopathology were assessed. RESULTS: Animals survived for 29-36 h in group P and 22-38 h in group PR (100% mortality rate). Tolerance was developed to propofol's sedative effect. The onset of tolerance was delayed and its magnitude was decreased in group PR compared with group P. Propofol was accumulated in the systemic circulation. Propofol clearance rate was gradually decreased. Arterial lactate, and serum aspartate aminotransferase (AST), lactate dehydrogenase (LDH), bilirubin, cholesterol, triglycerides, and creatine kinase (CK) levels were increased. The heart, lungs, liver, gallbladder, kidneys, urinary bladder, and skeletal muscles were seriously injured in groups P and PR. In group RS, mortality was 0%, while there was only mild injury of the lungs, liver, gallbladder, kidneys, and urinary bladder. CONCLUSIONS: Although propofol tolerance is attenuated in propofol plus remifentanil receiving rabbits under prolonged mechanical ventilation, fatal multi-organ injury occurs resembling human propofol infusion syndrome.

Pringle maneuver deteriorates gut barrier dysfunction induced by extended-liver radiofrequency ablation.

BACKGROUND: Large volume radiofrequency ablation (RFA) of the liver disrupts intestinal mucosa barrier with subsequent bacterial translocation. AIMS: To investigate the effect of the Pringle maneuver applied concurrently with extended liver RFA on gut barrier integrity and bacterial translocation. MATERIALS AND METHODS: Rats were subjected to 30% liver RFA following laparotomy (group RFA), RFA plus 30 min Pringle (group RFA + P), Pringle (group P) or sham operation (group S). Intestinal tissue specimens were excised for histopathological examination and assessment of mucosal morphometry, apoptotic activity, mitotic activity and oxidative state. Tissue specimens were collected from the mesenteric lymph nodes, non-ablated liver parenchyma, kidneys and lungs for bacterial culture. Blood samples were collected from the portal and systemic circulation for endotoxin level measurement. RESULTS: In group RFA + P, intestinal histopathologic lesions, mucosal atrophy and crypt cell apoptosis were more prominent compared to group RFA. Mitotic activity was suppressed. Oxidative stress was equally induced in all experimental groups. The incidence of positive bacterial cultures, bacterial counts and endotoxin levels were higher in group RFA + P compared to the other groups. CONCLUSION: The application of the Pringle maneuver concurrently with extended liver RFA aggravates gut barrier dysfunction with more aggressive translocation of endotoxins and intestinal bacteria.

Artificial Intelligence in Colorectal Cancer Screening, Diagnosis and Treatment. A New Era.

The development of artificial intelligence (AI) algorithms has permeated the medical field with great success. The widespread use of AI technology in diagnosing and treating several types of cancer, especially colorectal cancer (CRC), is now attracting substantial attention. CRC, which represents the third most commonly diagnosed malignancy in both men and women, is considered a leading cause of cancer-related deaths globally. Our review herein aims to provide in-depth knowledge and analysis of the AI applications in CRC screening, diagnosis, and treatment based on current literature. We also explore the role of recent advances in AI systems regarding medical diagnosis and therapy, with several promising results. CRC is a highly preventable disease, and AI-assisted techniques in routine screening represent a pivotal step in declining incidence rates of this malignancy. So far, computer-aided detection and characterization systems have been developed to increase the detection rate of adenomas. Furthermore, CRC treatment enters a new era with robotic surgery and novel computer-assisted drug delivery techniques. At the same time, healthcare is rapidly moving toward precision or personalized medicine. Machine learning models have the potential to contribute to individual-based cancer care and transform the future of medicine.