The Expression Patterns and Implications of MALAT1, MANCR, PSMA3-AS1 and miR-101 in Esophageal Adenocarcinoma.

Esophageal adenocarcinoma (EAC) is a malignant tumor with poorly understood molecular mechanisms. This study endeavors to elucidate how the long non-coding RNAs (lncRNAs) MALAT1, MANCR and PSMA3-AS1, as well as the microRNA miR-101, exhibit specific expression patterns in the pathogenesis and prognosis of EAC. A total of 50 EAC tissue samples (tumors and lymph nodes) and a control group comprising 26 healthy individuals were recruited. The samples underwent quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses. The relative expression levels of MALAT1, MANCR, PSMA3-AS1, and miR-101 were ascertained and correlated with various clinicopathological parameters including TNM staging, tumor characteristics (size and grade of the tumor) lymphatic invasion, disease-free (DFS) and overall survival (OS) of EAC patients. Quantitative analyses revealed that MALAT1 and MANCR were significantly upregulated in EAC tumors and positive lymph nodes when compared to control tissues (p < 0.05). Such dysregulations correlated positively with advanced lymphatic metastases and a higher N stage. DFS in the subgroup of patients with negative lymph nodes was higher in the setting of low-MANCR-expression patients compared to patients with high MANCR expression (p = 0.02). Conversely, miR-101 displayed a significant downregulation in EAC tumors and positive lymph nodes (p < 0.05), and correlated negatively with advanced tumor stage, lymphatic invasion and the grade of the tumor (p = 0.006). Also, patients with low miR-101 expression showed a tendency towards inferior overall survival. PSMA3-AS1 did not demonstrate statistically significant alterations (p > 0.05). This study reveals MALAT1, MANCR, and miR-101 as putative molecular markers for prognostic evaluation in EAC and suggests their involvement in EAC progression.

KLF4 Upregulation in Atherosclerotic Thoracic Aortas: Exploring the Protective Effect of Colchicine-based Regimens in a Hyperlipidemic Rabbit Model.

BACKGROUND: Inflammatory dysregulation of KLF4 is related to atheromatosis. In the present study, we explored the impact of colchicine-based regimens on the development of thoracic aortic atheromatosis and KLF4 expression. METHODS: Twenty-eight New Zealand White rabbits were divided to 4 groups. The control group (n = 6) was fed standard chow, group A (n = 6) was fed chow enriched with 1% w/w cholesterol, group B (n = 8) was fed the same cholesterol-enriched diet plus 2 mg/kg body weight/day colchicine and 250 mg/kg body weight/day fenofibrate, while group C (n = 8) was also fed the same diet plus 2 mg/kg body weight/day colchicine and 15 mg/kg body weight/day N-acetylcysteine. After 7 weeks, all animals were euthanized, and their thoracic aortas were isolated. Atherosclerotic plaque area was estimated with morphometric analysis. KLF4 expression was quantified with quantitative RT-PCR. RESULTS: Group A developed significantly more atherosclerosis compared to group B (MD: 13.67, 95% CI: 7.49-19.84) and C (MD: 20.29, 95% CI: 14.12-26.47). Colchicine with N-acetylcysteine resulted in more pronounced reduction in the extent of atherosclerotic plaques compared to colchicine/fibrate (MD: 6.62, 95% CI: 0.90-12.34). Group A exhibited significantly greater KLF4 expression compared to group B (MD: 4.94, 95% CI: 1.11-8.77) and C (MD: 9.94, 95% CI: 6.11-13.77). Combining colchicine with N-acetylcysteine instead of fenofibrate (MD: 5.00, 95% CI: 1.45-8.54) led to a more robust reduction in KLF4 expression. CONCLUSIONS: In the present hyperlipidemic animal model, colchicine-based regimens curtailed de novo atherogenesis and KLF4 overexpression in thoracic aortas.

Alterations in Toll-Like Receptor 7 and -9 mRNA Levels in Lungs after Ovariohysterectomy in a Pyometra Mouse Model.

BACKGROUND: Pyometra (P) leads to sepsis and multiple organ dysfunction syndrome. Toll-like receptors (TLRs) recognize pathogens which can cause P. The aim of this study was to investigate TLR-7 and -9 via the MYD88 pathway and the nuclear factor kappa B (NFκB) response in the uterus of a P mouse model before and after ovariohysterectomy (RP) as well as potential lung injury. MATERIALS AND METHODS: 200 female C57BL/6J mice were randomly divided into groups (N = 10/subgroup; sham 1, 2, 3, 7; P1, 2, 3, 7; 1RP1, 2, 3, 7; 2RP1, 2, 3, 7; 3RP1, 2, 3, 7) according to the day of euthanasia. Pathogens were administrated in the groups P and RP in order to induce P. RESULTS: Alterations in blood chemistry, histopathology, and RT-qPCT analysis before (P) and after RP were observed. Significant correlations were also found between MYD88, NFκB, and TLR9 in P and RP groups in the lungs and in RP groups in the uterus, suggesting that the immune system responded via the TLR9-MYD88 pathway. CONCLUSIONS: This is the first report of immunohistochemical TLR-7 and -9 localization and of TLR-7, -9, MYD88, and NFκB mRNA expression in the uterus causing lung injury in a P mouse model.

Gastrectomy for Cancer: A 15-Year Analysis of Real-World Data from the University of Athens.

Background and Objectives: Encouraging data have been reported from referral centers following gastrointestinal cancer surgery. Our goal was to retrospectively review patient outcomes following gastrectomy for gastric or gastroesophageal junction (GEJ) cancer at a high-volume unit of the University of Athens. Methods: The enrollment period was from June 2003 to September 2018. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazard models were constructed to identify variables independently associated with time-to-event outcomes. Results: A total of 205 patients were analyzed. R0 resection was achieved in 183 (89.3%) patients and was more likely to occur following neoadjuvant chemotherapy (p = 0.008). Recurrence developed in 46.6% of our cohort and the median disease-free survival was 31.2 months. On multivariate analysis, only staging (HR = 2.15; 95% CI: 1.06-4.36) was independently associated with increased risk of recurrence. All-cause mortality was 57.2% and the median time of death was 40.9 months. On multivariate regression, staging (HR: 1.35; 95% CI: 1.11-1.65) and recurrence (HR: 2.87; 95% CI: 1.32-6.22) predicted inferior prognosis. Conclusions: Gastrectomy at the University of Athens has yielded favorable outcomes for patients with GEJ cancer.

GNRI as a Prognostic Factor for Outcomes in Cancer Patients: A Systematic Review of the Literature.

Oncologic patients often suffer from malnutrition which in turn, might have negative impact on treatment outcomes. The Geriatric Nutritional Risk Index (GNRI), as an index of impaired nutritional status, has emerged as a significant prognostic factor for short-and long-term outcomes in cancer patients. The aim of the current systematic review is to determine whether the GNRI is an independent prognostic factor of postoperative complications and survival in cancer patients. A systematic search was conducted to identify studies, published from 2005 to 2019, which assessed associations between GNRI and short- and long-term outcomes in cancer patients. Eighteen studies fulfilled the eligibility criteria and were included in the analysis. Low scores of GNRI were associated with increased risk for developing postoperative complications and impaired survival of cancer patients in most studies. Our findings support the use of the GNRI in the clinical practice, since it is a simple and reliable tool for assessing nutritional status in oncologic patients. More prospective, multi-centered studies are warranted to confirm the current results, as well as the role of nutritional support in improving the prognosis of cancer patients.

Experimental Devices Versus Hand-Sewn Anastomosis of the Aorta: A Systematic Review and Meta-Analysis.

BACKGROUND: To minimize complications associated with the construction of the hand-sewn aortic anastomosis, alternative experimental methods have been pursued. This study aimed to evaluate the efficacy of experimental anastomotic devices in relation to time and point of rupture of the anastomosis in comparison to the conventional technique. MATERIALS AND METHODS: An electronic search was performed using MEDLINE, Scopus, Science Direct, and Cochrane Library databases by two independent authors. Our exclusion criteria referred to studies reporting results solely from end-to-side anastomosis, results on vessels other than the aorta, studies that did not involve animal experiments, and non-English publications. The last search date was January 1, 2020. RESULTS: The meta-analysis included 22 studies with 34 anastomosis samples and a total of 316 animals. The pooled mean automated anastomosis time was 10.38 min, and the mean point of rupture was 32.7 N. In the subgroup analysis of automated anastomosis time by device category, the anastomotic stenting technique reported significantly lower anastomosis time but also showed significantly lower point of rupture. Comparing the efficacy of experimental devices and the hand-sewn technique, our pooled analysis showed that automated devices significantly decrease the time needed to perform the anastomosis (weighted mean difference -7.24 min). On the other hand, the automated anastomosis is also associated with decreased tensile strength (weighted mean difference -20.68 N). CONCLUSIONS: Although experimental devices seem to offer a faster anastomosis, they lack endurance when compared with the hand-sewn technique. Further research is needed for the development of an "ideal" anastomotic technique.

Esophageal cancer surgery in Greece during the era of the financial crisis.

The aim of this study is to describe outcomes of esophageal cancer surgery in a quaternary upper gastrointestinal (GI) center in Athens during the era of the Greek financial crisis. We performed a retrospective analysis of patients that underwent esophagectomy for esophageal or gastroesophageal junction (GEJ) cancer at an upper GI unit of the University of Athens, during the period January 2004-June 2019. Time-to-event analyses were performed to explore trends in survival and recurrence. A total of 146 patients were identified. Nearly half of the patients (49.3%) underwent surgery during the last 4 years of the financial crisis (2015-2018). Mean age at the time of surgery was 62.3 ± 10.3 years, and patients did not present at older ages during the recession (P = 0.50). Most patients were stage III at the time of surgery both prior to the recession (35%) and during the financial crisis (39.8%, P = 0.17). Ivor-Lewis was the most commonly performed procedure (67.1%) across all eras (P = 0.06). Gastric conduit was the most common form of GI reconstruction (95.9%) following all types of surgery (P < 0.001). Pre-recession anastomoses were usually performed using a circular stapler (65%). Both during (88.1%) and following the recession (100%), the vast majority of anastomoses were hand-sewn. R0 resection was achieved in 142 (97.9%) patients. Anastomosis technique did not affect postoperative leak (P = 0.3) or morbidity rates (P = 0.1). Morbidity rates were not significantly different prior to (25%), during (46.9%), and after (62.5%) the financial crisis, P = 0.16. Utilization of neoadjuvant chemotherapy (26.9%, P = 0.90) or radiation (8.4%, P = 0.44) as well as adjuvant chemotherapy (54.8%, P = 0.85) and irradiation (13.7%, P = 0.49) was the same across all eras. Disease-free survival (DFS) and all-cause mortality rates were 41.2 and 47.3%, respectively. Median DFS and observed survival (OS) were 11.3 and 22.7 months, respectively. The financial crisis did not influence relapse (P = 0.17) and survival rates (P = 0.91). The establishment of capital controls also had no impact on recurrence (P = 0.18) and survival (P = 0.94). Austerity measures during the Greek financial crisis did not influence long-term esophageal cancer outcomes. Therefore, achieving international standards in esophagectomy may be possible in resource-limited countries when centralizing care.

Oral Nutritional Supplementation Following Upper Gastrointestinal Cancer Surgery: A Prospective Analysis Exploring Potential Barriers to Compliance.

Objective: Malnutrition is common in patients who underwent upper gastrointestinal cancer surgery. Our goal was to explore postoperative compliance with oral nutritional supplementation and define barriers to consumption in patients with esophageal, gastroesophageal junction, and gastric cancer.Methods: Participants were prospectively recruited from September 2015 to November 2018. Preoperative nutritional status was assessed using the Patient Generated Subjective Global Assessment. Malnourished patients and patients at risk for malnutrition were offered oral nutritional supplementation at the time of hospital discharge. Compliance was evaluated 1 month after hospital discharge.Results: A total of 78 patients were analyzed. Mean patient age was 62.8 ± 10.7 years and 83.3% were males. Εsophagectomy and gastrectomy were performed in 60.3% and 39.7% of the patients respectively. Twenty-eight (35.9%) participants reported consuming all prescribed supplements, whereas 50 (64.1%) patients were noncompliant with their prescribed oral nutritional supplementation regimen. The main barriers to oral nutritional supplementation compliance were bloating (compliant vs. noncompliant patients: 17.9% vs. 58%, p < 0.001), early satiety (compliant vs. noncompliant patients: 25% vs. 52.32%, p < 0.001), flavor or texture dislike (compliant vs. noncompliant patients: 7.1% vs. 34%, p < 0.001), and diarrhea (compliant vs. noncompliant patients: 10.7% vs. 24%, p < 0.001). No other statistically significant differences were identified between the two groups.Conclusions: Postoperative compliance to oral nutritional supplementation is low in patients who underwent upper gastrointestinal cancer surgery. Patient education and support as well as providing a range of oral nutrition supplement flavors, texture, and compositions may be useful in increasing adherence to oral nutritional supplementation regimens.

Increased Serum KLF4 in Severe Atheromatosis and Extensive Aneurysmal Disease.

BACKGROUND: Krüppel-like factor 4 (KLF4) is known to preserve vascular homeostasis. In the present study, we sought to correlate serum KLF4 levels with arterial aneurysm size and their clinical presentation. We also explored the association between serum KLF4 levels and the severity of extracranial carotid and peripheral arterial disease. METHODS: Patients undergoing surgery for various forms of atheromatosis (ATH group) or for arterial aneurysm repair (AA group) were eligible for inclusion. KLF4 levels were measured via enzyme-linked immunosorbent assay. RESULTS: Patients in the atheromatic and aneurysmal groups had significantly higher serum KLF4 levels compared with controls. Patients with permanent end-organ damage (ATH3) had higher serum KLF4 (6.96 ± 0.75 pg/mL) compared with patients with asymptomatic internal carotid stenosis >70% or claudication (ATH1) (2.76 ± 0.68 pg/mL; mean difference [MD], -4.20; 95% confidence interval [95% CI], -5.35 to -3.04; P < 0.01) and those with transient ischemic attack or rest pain (ATH2) (4.47 ± 1.08 pg/mL; MD, -2.48; 95% CI, -3.76 to -1.21). Furthermore, patients with an asymptomatic aneurysm of a diameter 250-300% of that of the normal artery (AA1, 5.01 ± 1.08 pg/mL) had considerably lower serum KLF4 compared with those suffering from either a symptomatic aneurysm or an asymptomatic aneurysm of a diameter >350% of that of normal artery (AA3, 6.63 ± 1.92 pg/mL; MD, -2.61; 95% CI, -5.04 to -0.18; P < 0.01). CONCLUSIONS: Serum KLF4 levels are significantly increased in patients with end-organ damage related to atheromatosis as well as those with extensive aneurysmal disease.

Staged esophagectomy: surgical legacy or a bailout option?

Staged esophagectomy was developed in the mid-twentieth century in an attempt to reduce high rates of postoperative morbidity and mortality. Nowadays, the operation has almost been abandoned due to its significant disadvantages, especially the need for multiple surgeries, inability of patients to feed between operations, and morbidity of esophageal stoma. However, staged esophagectomy is still occasionally useful for very high-risk patients and in particular cases, for example multiple cancers of the aerodigestive tract and emergent esophagectomy. Staged esophagectomy is based on the division of surgical stress into two operations, which gives the patient time to recover before final restoration. Gastric tube ischemic preparation may be a more important mechanism in staged esophagectomy. This approach may survive and expand with the application of ischemic gastric pre-conditioning through embolization or laparoscopic ligation of the gastric arteries, which is a less explored and promising technique.

Α systematic review and meta-analysis of the efficacy of aortic anastomotic devices.

OBJECTIVE: One of the factors contributing to complications related to open repair of the aorta is the construction of a hand-sewn anastomosis. Aortic anastomotic devices (AADs), such as the intraluminal ringed graft (IRG), and the anastomotic stenting technique have been developed to perform a sutureless and less complicated anastomosis. This study performed a systematic review and meta-analysis of the literature reporting clinical use of AADs and aimed to assess, primarily, the effect of each device on 30-day overall and operation-related mortality and aortic cross-clamping time and, secondarily, the rate of successful two-sided application of the IRG device and the operation-related morbidity for each device. METHODS: An electronic search was performed using MEDLINE, Scopus, ScienceDirect, and Cochrane Library by two independent authors. Our exclusion criteria included studies incorporating fewer than three patients and studies reporting results solely from animals or in vitro testing, results solely from end-to-side anastomosis, and results solely from endarterectomy procedures. The last search date was February 1, 2018. RESULTS: A total of 41 studies were identified that reported outcomes for the use of three different device types: IRG, anastomotic stenting technique, and surgical staplers. The last two types were classified together as the non-IRG group. The meta-analysis included 27 studies with 50 cohorts incorporating 1260 patients. The median age of the incorporated patients was 61.4 years (range, 51-73 years), and 68.9% were male. The operations were performed for the treatment of acute aortic dissection in 82.3%. The pooled overall 30-day mortality rate varied by device type; IRG devices had a mean rate of all-cause mortality of 9.71%, whereas non-IRG devices were associated with a significantly (I2 = 15.78%; P for Cochrane Q test < .19) lower rate of death (1.47%). The pooled mean aortic cross-clamping time was 35.83 minutes. Metaregression showed that the performance of two-sided anastomosis with the IRG device significantly decreased the aortic cross-clamping time. However, a successful two-sided ringed anastomosis was performed in approximately half of the cases. CONCLUSIONS: Taking into account that the majority of operations were performed for the treatment of acute aortic dissection, AADs had a relatively low rate of 30-day mortality. Despite the observed heterogeneity in study protocols and the small sample size in the non-IRG group, the non-IRG group presented with the lowest 30-day mortality rate. Specific device-related complications between the different device types need further investigation.

Apolipoprotein J as a predictive biomarker for restenosis after carotid endarterectomy: a retrospective study.

Carotid endarterectomy (CEA) is an effective surgical option for stroke prophylaxis in most patients. Restenosis after CEA can lead to re-intervention and adverse events, but the factors predicting restenosis are poorly understood. Apolipoprotein J (ApoJ) is considered to be a novel predictive factor of vascular restenosis and is associated with a large number of processes related to atherosclerosis and cell-cycle phases. The aim of this study was to elucidate the predictive value of Apo J in internal carotid artery (ICA) restenosis following CEA. This retrospective study examined all prospectively collected data for patients who underwent CEA at our surgical department over a 2-year period. The serum ApoJ levels of 100 patients were examined; 56 patients who underwent CEA comprised the vascular group (VG), and 44 patients who underwent minor surgery comprised the control group (CG). ApoJ samples were obtained preoperatively, 24 h after the surgical procedure and at 1, 6 and 12 months thereafter during the follow-up. The preoperative difference in ApoJ levels between the CG and VG was statistically signifcant; the mean values were 39.11±14.16 and 83.03±35.35 µg/mL, respectively. In the VG, the serum ApoJ levels were 112.09±54.40, 71.20±23.70, 69.92±25.76 and 62.25±19.17 µg/mL at postoperative day 1 and at 1, 6 and 12 months post-operatively, respectively, while the ApoJ concentrations of patients in the CG remained unchanged. Further subdivision of the VG into patients with or without restenosis revealed that restenosis patients presented signifcantly higher mean ApoJ values than non-restenosis VG patients. In summary, ApoJ seems to be an important predictor for carotid restenosis at 6 and 12 months postoperatively.

Remote Ischemic Preconditioning Decreases the Magnitude of Hepatic Ischemia-Reperfusion Injury on a Swine Model of Supraceliac Aortic Cross-Clamping.

BACKGROUND: Temporary hepatic ischemia is inevitable during open aortic surgery when supraceliac clamping is necessary, as in thoracoabdominal or pararenal aneurysms. Remote ischemic preconditioning (RIPC) has been described as a potential protective means against ischemia-reperfusion injury (IRI) in various tissues including the liver. The aim of this experimental study was to detect the effect of RIPC on liver IRI in a model of supraceliac aortic cross-clamping. METHODS: An animal study was performed. Four groups of 6 swines each were examined: the control (sham) group, the ischemia-reperfusion (IR) group, and 2 remote ischemic preconditioning groups (RIPC I and RIPC II group). In the IR group, the animals underwent a complete cessation of the splanchnic arterial circulation for 30 min by a concomitant occlusion of the supraceliac and the infrarenal aorta. In the RIPC groups, a remote preconditioning was applied before the splanchnic ischemia. This consisted of a temporary occlusion of the infrarenal aorta for 15 min followed by 15 min of reperfusion (RIPC I group), and 3 cycles of 5 min similar ischemia, followed by 5 min of reperfusion each (RIPC II group). All animals were followed for 24 hr after the ischemia (reperfusion period). The liver ischemia-reperfusion injury was assessed by examining specific serum biomarkers indicating the magnitude of metabolic injury from selective blood samples of the hepatic circulation. In particular, the following parameters were examined: C-reactive protein, interleukin 6, tumor necrosis factor a, ferritin, and L-arginine. RESULTS: All parameters were affected in the IR group as compared to the sham group. Both RIPC groups developed a less serious change as compared to the IR group, in all examined parameters. CONCLUSIONS: In an animal study of splanchnic ischemia produced in a way to this produced during a supraceliac aortic aneurysm open repair, the remote ischemic preconditioning seemed to attenuate the effect of hepatic ischemia-reperfusion injury. CLINICAL RELEVANCE: Remote ischemic preconditioning produced with short bouts of ischemia of the lower body by temporary clamping of the infrarenal aorta might be used as a means of decreasing the detrimental effects of hepatic ischemia-reperfusion injury after supraceliac aortic cross-clamping. This was found in a swine model of suprarenal AAA open repair by studying the variance of certain biological biomarkers in selective blood samples retrieved from the hepatic vein.

Stenting of Subclavian Artery True and False Aneurysms: A Systematic Review.

BACKGROUND: Aneurysms of the subclavian artery are usually the result of trauma, atherosclerosis, or thoracic outlet syndrome. Until the 90s, open surgical repair was considered the only therapeutic choice, exhibiting high complication rates. Since the first report of endovascular repair of subclavian aneurysms in 1991, promising results have been published. The aim of this review was to summarize all available data on subclavian artery (SA) true and false aneurysm stenting to reach conclusions regarding morbidity, mortality, and other procedure-related characteristics. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Eligible studies were sought in the Medline (PubMed), ClinicalTrials.gov, and Cochrane library-Cochrane Central Register of Controlled Trials (CENTRAL) databases through February 2017 using the following MeSH terms: "endovascular", "hybrid", "aneurysm", "pseudo-aneurysm", "pseudo-aneurysm", "false aneurysm", "arterial injury", "subclavian artery", "axillo-subclavian," and "axillosubclavian artery". The reference lists of eligible articles and pertinent reviews were screened for potential relevant studies. RESULTS: Seventy-three studies encompassing data on 142 patients who underwent endovascular or hybrid SA aneurysm repair were deemed eligible. One hundred forty-seven stents and stent grafts were used. Median age of all patients was 56 years, and males comprised 46% of the study sample. Trauma was the most common mechanism of injury. Pulsatile mass or hematoma was the most frequent presenting sign. Pseudoaneurysms were the most frequent type of aneurysms, followed by true aneurysms. Most authors used self-expanding polytetrafluoroethylene-covered stents. Access was obtained by either brachial, femoral, or both arteries. Through-and-through technique was also used in angulated vessels. All-cause mortality was 10.6%, slightly higher to that already reported in literature and lower to the respective rate of the open repair. Reintervention rate was 8.5% despite the high 15.5% complication rate. CONCLUSIONS: Endovascular SA aneurysm repair is a technically feasible technique, useful in both elective and emergency cases. Although preliminary results quote its safety and efficacy, larger cohort studies are warranted to elucidate its benefit in treating SA aneurysms.

The beneficial role of simultaneous splenectomy after extended hepatectomy: experimental study in pigs.

BACKGROUND: The role of hepatic hemodynamic modulation in the development of "small-for-size" syndrome (SFSS) after extended hepatectomy (EH) or living-donor liver transplantation is still controversial. We have designed an experimental study to investigate the effect of hemodynamic parameters of the liver circulation on the development of SFSS after EH in a porcine model. METHODS: Eighteen pigs were randomly divided into two groups: group A has received EH (75%-80%) without splenectomy, and group B with EH and simultaneous splenectomy was carried out. Portal hemodynamics, liver function tests, histologic findings, injury and survival rates were compared between groups A and B. RESULTS: The 7-d survival rate in the splenectomy group was significantly improved compared with group A (88.9% versus 44.4%, P < 0.05). Portal vein pressure, portal vein flow, and liver function tests in the splenectomy group were significantly lower than in group A immediately after splenectomy and postoperatively until the day of sacrifice. Histologic findings in group A clearly illustrate severe inflammation, bridging necrosis, ischemic cholangitis, and severe congestion, while in group B there were less serious histologic changes. CONCLUSIONS: Our experimental study indicates that perioperative portal modulation can successfully prevent the manifestation of SFSS after EH. Therefore, by focusing on "flow" rather than on "size," researchers may understand better the pathophysiology of this syndrome.

Neoaortoiliac System Procedure to Treat Infected Aortic Grafts.

BACKGROUND: The aim of this case series is to report the results of our center in the surgical treatment of infected abdominal aortic grafts using the neoaortoiliac system (NAIS) procedure. METHODS: Four male and 2 female patients underwent an NAIS repair after endovascular (n = 3), open (n = 2), or combined surgery (n = 1) in our center. Mean age was 73 ± 5.2 years. Graft infection was diagnosed by computed tomography angiography (CTA), and only in 2 cases further imaging was necessary. The diagnosis was set at average 6.2 years after the initial procedure. RESULTS: Four patients underwent a standard pantaloon NAIS procedure, 1 patient with a small aortic diameter received 1 femoral vein as aortoaortic interposition graft, and 1 patient received a unilateral aortoiliac bypass; all patients received autologous femoral veins grafts. Thirty-day mortality was zero, with in-hospital mortality of 1 patient (16.7%). Mean hospital stay was 27 ± 4.9 days, with mean intensive care unit stay of 2.2 days (range: 1-3). During follow-up (mean: 6.17 months, range: 1-24 months), 2 patients presented with thigh wound complications, one of which required surgical revision. One patient was readmitted due to upper gastrointestinal (GI) bleeding as a side effect of anticoagulation, without the presence of ulcer or other GI pathology. CONCLUSIONS: In our early experience, NAIS showed to be a demanding procedure for both the patient and the surgical team. It avoids however the disadvantages of extra-anatomic bypass and other methods used to treat aortic graft infection. Larger study groups are necessary to support these findings.

From Clinical Standards to Translating Next-Generation Sequencing Research into Patient Care Improvement for Hepatobiliary and Pancreatic Cancers.

Hepatobiliary and pancreatic (HBP) cancers are associated with high cancer-related death rates. Surgery aiming for complete tumor resection (R0) remains the cornerstone of the treatment for HBP cancers. The current progress in the adjuvant treatment is quite slow, with gemcitabine chemotherapy available only for pancreatic ductal adenocarcinoma (PDA). In the advanced and metastatic setting, only two targeted drugs have been approved by the Food & Drug Administration (FDA), which are sorafenib for hepatocellular carcinoma and erlotinib for PDA. It is a pity that multiple Phase III randomized control trials testing the efficacy of targeted agents have negative results. Failure in the development of effective drugs probably reflects the poor understanding of genome-wide alterations and molecular mechanisms orchestrating therapeutic resistance and recurrence. In the post-ENCODE (Encyclopedia of DNA Elements) era, cancer is referred to as a highly heterogeneous and systemic disease of the genome. The unprecedented potential of next-generation sequencing (NGS) technologies to accurately identify genetic and genomic variations has attracted major research and clinical interest. The applications of NGS include targeted NGS with potential clinical implications, while whole-exome and whole-genome sequencing focus on the discovery of both novel cancer driver genes and therapeutic targets. These advances dictate new designs for clinical trials to validate biomarkers and drugs. This review discusses the findings of available NGS studies on HBP cancers and the limitations of genome sequencing analysis to translate genome-based biomarkers and drugs into patient care in the clinic.

FAK, Src and p-Paxillin expression is decreased in liver metastasis of colorectal carcinoma patients.

PURPOSE: The FAK/Src/Paxillin (PXN) axis has been implicated in malignant transformation, tumor growth, progression and metastasis. The present study aimed to assess FAK/Src/PXN protein expression in both primary and liver metastatic sites of colorectal adenocarcinoma (CRC). METHODS: FAK, Src and p-PXN expression was assessed immunohistochemically on 32 primary CRCs and their corresponding liver metastases, being also analyzed in relation with clinicopathological characteristics and patient survival. RESULTS: FAK, Src and p-PXN expression was significantly decreased in liver metastasis compared to matched paired primary CRCs (p<0.01). Increased FAK expression in primary CRCs was significantly associated with poor histological grade and advanced disease stage (p=0.0330 and p=0.0204, respectively). Increased Src expression in primary colorectal tumors was significantly associated with the presence of lymph node metastasis (p=0.0325), while elevated p-PXN expression with poor histological grade (p=0.0284). CONCLUSIONS: FAK, Src and p-PXN appear to play a role in the pathophysiological aspects of CRC. The lower expression of these proteins in liver metastasis compared to the primary CRC could significantly impact the choice of a novel therapeutic agent according to the disease stage.

E-cadherin in gastric carcinomas: Relations with histological parameters and its prognostic value.

PURPOSE: Gastric cancer (GC) is still one of the most common malignancies with the majority of the tumors being diagnosed at advanced stage. The need for identification of prognostic and early detection biomarkers is thus compulsory. E-cadherin is one of the emerging biomarkers that is currently evaluated in the literature in the frame of epithelial-mesenchymal transition (EMT). Our aim was to study the expression of E-cadherin in the various histological subtypes of GC and to evaluate its prognostic value. METHODS: This historical cohort survey was performed on gastric tumors obtained from 66 (46 men and 20 women) patients with documented gastric adenocarcinoma who underwent total or partial gastrectomy and regional lymphadenectomy from 2003 till 2011. Features such as tumor size, depth of invasion, grade and histological subtype, lymphovascular space invasion and regional lymph nodes involvement were also evaluated. Immunohistochemistry (IHC) was used for assessing the expression of E-cadherin with a semi-quantitative model. RESULTS: The correlation of E-cadherin tissue expression with patient overall survival (OS) or disease-free survival (DFS) was not statistically significant, as well as with gender, T stage, N stage, TNM stage, grade, positive lymph nodes ratio or lymphovascular invasion. CONCLUSIONS: 73.0% of the evaluated tumors showed abnormal E-cadherin expression in IHC, but the correlation of E-cadherin tissue expression with patient OS or DFS was not statistically significant. Literature stands equivocal about the association between E-cadherin gene mutation, and histopathology and tumor invasiveness. Our results further strengthen the need of larger studies to fully elucidate the predictive role of E-cadherin in the natural history of GC.

The expression of Claudin-4 in gastric cancer tissue: A single center experience.

PURPOSE: Gastric cancer (GC) is still one of the most common malignancies with the majority of the tumors diagnosed at advanced stage. The need for identification of prognostic and early detection biomarkers is thus compulsory. Claudins are biomarkers that are currently evaluated in the literature in the frame of epithelial-mesenchymal transition. The purpose of this investigation was to study the expression of claudin-4 in the various histological subtypes of GC and to evaluate its prognostic value. METHODS: This investigation was performed on gastric tumors obtained from 66 (46 men and 20 women) patients with documented gastric adenocarcinoma who underwent total or partial gastrectomy and regional lymphadenectomy from 2003 till 2011. Features such as tumor size, depth of invasion, grade and histological subtype, lymphovascular space invasion and regional lymph nodes involvement were also evaluated. Immunohistochemistry (IHC) was used for assessing the expression of claudin-4 with a semi-quantitative model. RESULTS: 66.7% of our cases showed abnormal claudin-4 expression in IHC. Claudin-4 was significantly correlated with tumor T stage and with intestinal type classification. The correlation of claudin-4 tissue expression with patient overall survival survival (OS) or disease-free survival (DFS) was not statistically significant, as well as with age, gender, tumor N stage, grade, TNM stage, positive lymph node ratio or lymphovascular invasion. CONCLUSIONS: Literature stands equivocal about the exact role and prognostic value of claudin-4 and histopathology and tumor invasiveness in patients with GC. Our results further strengthen the need of larger studies to fully elucidate the predictive role of claudin-4 in the natural history of GC.