Prognostic nutritional index in predicting survival of patients with gastric or gastroesophageal junction adenocarcinoma: A systematic review.

BACKGROUND: Gastric cancer is the third most common cause of cancer related death worldwide. Surgery with or without chemotherapy is the most common approach with curative intent; however, the prognosis is poor as mortality rates remain high. Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy. The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed. The aim of this systematic review was to assess the role of the prognostic nutritional index (PNI) in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent. AIM: To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma. METHODS: A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival (OS) of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value. The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review. The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO). RESULTS: Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review. The patients were divided into high- and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study. The 5-year OS of patients in the low-PNI groups ranged between 39% and 70.6%, while in the high-PNI groups, it ranged between 54.9% and 95.8%. In most of the included studies, patients with high preoperative PNI showed statistically significant better OS than the low PNI groups. In multivariate analyses, low PNI was repeatedly recognised as an independent prognostic factor for poor survival. CONCLUSION: According to the present study, low preoperative PNI seems to be an indicator of poor OS of patients undergoing gastrectomy for gastric or gastroesophageal cancer.

Small Bowel Diverticulosis and COVID-19: Awareness Is the Key: A Case Series and Review of the Literature.

Small bowel non-Meckelian diverticulosis is a rare condition with only a few published cases despite being described over 200 years ago. In the midst of the COVID-19 pandemic, studies suggested that many patients may experience gastrointestinal manifestations. Intestinal symptoms could worsen the inflammation and infection associated with small bowel diverticulitis. Here we present three cases: one with inflammation and rupture in a COVID-19 patient and another as an asymptomatic detection. The third case involved recurrence after the first laparoscopic lavage approach. Furthermore, we provide a mini-review of the literature to emphasize the importance of considering this entity in the differential diagnosis of an acute abdomen. In the majority of cases involving small bowel diverticula, conservative management is the preferred approach. However, when complications arise, surgical intervention, including enteroctomy and primary anastomosis, may be necessary to achieve optimal outcomes.

Comparison between upfront surgery and neoadjuvant chemotherapy in patients with locally advanced gastric cancer: A systematic review.

BACKGROUND: Gastric cancer (GC) is a major health concern worldwide. Surgical resection and chemotherapy is the mainstay treatment for gastric carcinoma, however, the optimal approach remains unclear and should be different in each individual. Chemotherapy can be administered both pre- and postoperatively, but a multidisciplinary approach is preferred when possible. This is particularly relevant for locally advanced GC (LAGC), as neoadjuvant chemotherapy (NAT) could potentially lead to tumor downsizing thus allowing for a complete resection with curative intent. Even though the recent progress has been impressive, European and International guidelines are still controversial, thus attenuating the need for a more standardized approach in the management of locally advanced cancer. AIM: To investigate the effects of NAT on the overall survival (OS), the disease-free survival (DFS), the morbidity and the mortality of patients with LAGC in comparison to upfront surgery (US). METHODS: For this systematic review, a literature search was conducted between November and February 2023 in PubMed, Cochrane Library and clinicaltrials.gov for studies including patients with LAGC. Two independent reviewers conducted the research and extracted the data according to predetermined inclusion and exclusion criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to form the search strategy and the study protocol has been registered in the International Prospective Register of Systematic Reviews. RESULTS: Eighteen studies with 4839 patients with LAGC in total were included in our systematic review. Patients were separated into two groups; one receiving NAT before the gastrectomy (NAT group) and the other undergoing upfront surgery (US group). The OS ranged from 41.6% to 74.2% in the NAT group and from 30.9% to 74% in the US group. The DFS was also longer in the NAT group and reached up to 80% in certain patients. The complications related to the chemotherapy or the surgery ranged from 6.4% to 38.1% in the NAT group and from 5% to 40.5% in the US group. Even though in most of the studies the morbidity was lower in the NAT group, a general conclusion could not be drawn as it seems to depend on multiple factors. Finally, regarding the mortality, the reported rate was higher and up to 5.3% in the US group. CONCLUSION: NAT could be beneficial for patients with LAGC as it leads to better OS and DFS than the US approach with the same or even lower complication rates. However, patients with different clinicopathological features respond differently to chemotherapy, therefore currently the treatment plan should be individualized in order to achieve optimal results.

Median arcuate ligament syndrome often poses a diagnostic challenge: A literature review with a scope of our own experience.

The median arcuate ligament syndrome (MALS) is recognized as a rare clinical entity, characterized by chronic post-prandial abdominal pain, nausea, vomiting, and unintentional weight loss. Due to its vague symptomatology, it is mainly regarded as a diagnosis of exclusion. Patients can often be misdiagnosed for several years before a correct diagnosis is established, also due to a medical team's clinical suspicion. We present a case series of two patients who suffered from MALS and were treated successfully. The first patient is a 32-year-old woman, presenting with post-prandial abdominal pain and weight loss that have lasted for the past ten years. The second patient, a 50-year-old woman, presented with similar symptomatology, with the symptoms lasting for the last five years. Both cases were treated by laparoscopic division of the median arcuate ligament fibers, which alleviated extrinsic pressure from the celiac artery. Previous cases of MALS were retrieved from PubMed, to assemble a better diagnostic algorithm and propose a treatment method of choice. The literature review suggests an angiography with a respiratory variation protocol as the diagnostic modality of choice, along with the laparoscopic division of the median arcuate ligament fibers as the proposed treatment of choice.

Diagnostic work-up and advancement in the diagnosis of gastroenteropancreatic neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms ranging from well-differentiated, slowly growing tumors to poorly differentiated carcinomas. These tumors are generally characterized by indolent course and quite often absence of specific symptoms, thus eluding diagnosis until at an advanced stage. This underscores the importance of establishing a prompt and accurate diagnosis. The gold-standard remains histopathology. This should contain neuroendocrine-specific markers, such as chromogranin A; and also, an estimate of the proliferation by Ki-67 (or MIB-1), which is pivotal for treatment selection and prognostication. Initial work-up involves assessment of serum Chromogranin A and in selected patients gut peptide hormones. More recently, the measurement of multiple NEN-related transcripts, or the detection of circulating tumor cells enhanced our current diagnostic armamentarium and appears to supersede historical serum markers, such as Chromogranin A. Standard imaging procedures include cross-sectional imaging, either computed tomography or magnetic resonance, and are combined with somatostatin receptor scintigraphy. In particular, the advent of 111In-DTPA-octreotide and more recently PET/CT and 68Ga-DOTA-Octreotate scans revolutionized the diagnostic landscape of NENs. Likewise, FDG PET represents an invaluable asset in the management of high-grade neuroendocrine carcinomas. Lastly, endoscopy, either conventional, or more advanced modalities such as endoscopic ultrasound, capsule endoscopy and enteroscopy, are essential for the diagnosis and staging of gastroenteropancreatic neuroendocrine neoplasms and are routinely integrated in clinical practice. The complexity and variability of NENs necessitate the deep understanding of the current diagnostic strategies, which in turn assists in offering optimal patient-tailored treatment. The current review article presents the diagnostic work-up of GEP-NENs and all the recent advances in the field.

Inhibition of γδ-TcR or IL17a Reduces T-Cell and Neutrophil Infiltration after Ischemia/Reperfusion Injury in Mouse Liver.

Neutrophil and T-cell recruitment contribute to hepatic ischemia/reperfusion injury. The initial inflammatory response is orchestrated by Kupffer cells and liver sinusoid endothelial cells. However, other cell types, including γδ-Τ cells, seem to be key mediators in further inflammatory cell recruitment and proinflammatory cytokine release, including IL17a. In this study, we used an in vivo model of partial hepatic ischemia/reperfusion injury (IRI) to investigate the role of the γδ-Τ-cell receptor (γδTcR) and the role of IL17a in the pathogenesis of liver injury. Forty C57BL6 mice were subjected to 60 min of ischemia followed by 6 h of reperfusion (RN 6339/2/2016). Pretreatment with either anti-γδΤcR antibodies or anti-IL17a antibodies resulted in a reduction in histological and biochemical markers of liver injury as well as neutrophil and T-cell infiltration, inflammatory cytokine production and the downregulation of c-Jun and NF-κΒ. Overall, neutralizing either γδTcR or IL17a seems to have a protective role in liver IRI.

Neutrophil-to-lymphocyte ratio as a prognostic factor for survival in patients with colorectal liver metastases: A systematic review.

BACKGROUND: The inflammatory response to tumor has been proven to be closely related to the prognosis of colorectal cancer. Neutrophil to lymphocyte ratio (NLR) is a widely available inflammatory biomarker that may have prognostic value for patients with colorectal liver metastasis (CRLM). AIM: To assess the role of NLR as a prognostic factor of survival and tumor recurrence in patients with CRLM. METHODS: A systematic literature search of PubMed, Cochrane Library and clinicaltrials.gov was conducted by two independent researchers in order to minimize potential errors and bias. Conflicts were discussed and settled between three researchers. Studies including patients undergoing different types of medical interventions for the treatment of CRLM and evaluating the correlation between pretreatment NLR and disease-free survival (DFS) and overall survival (OS) were included in the review. Nineteen studies, involving 3283 patients matched our inclusion criteria. RESULTS: In the studies included, NLR was measured before the intervention and the NLR thresholds ranged between 1.9 and 7.26. Most studies used 5 as the cut-off value. Liver metastases were treated with hepatectomy with or without chemotherapy regimens in 13 studies and with radiofrequency ablation, radioembolization, chemoembolization or solely with chemotherapy in 6 studies. High NLR was associated with decreased OS and DFS after liver resection or other medical intervention. Moreover, high NLR was associated with poor chemosensitivity. On the contrary, CRLM patients with low pretreatment NLR demonstrated improved OS and DFS. NLR could potentially be used as a predictive factor of survival and tumor recurrence in patients with CRLM treated with interventions of any modality, including surgery, chemotherapy and ablative techniques. CONCLUSION: NLR is an inflammatory biomarker that demonstrates considerable prognostic value. Elevated pretreatment NLR is associated with poor OS and DFS in patients with CRLM who are submitted to different treatments.

Role of minimally invasive surgery in the treatment of gallbladder metastatic melanoma. A review of the literature and a case report.

BACKGROUND: Primary and secondary gallbladder melanomas are rare, and only 58 cases have been reported in scientific literature to date. This paper aimed to explore the role of minimally invasive surgery in the management of gallbladder metastatic melanomas. CASE: Herein, we present the case of a 68-year-old man with metastatic gallbladder melanoma who was treated with laparoscopic cholecystectomy. Our case management was then compared with that of other cases reported in the literature. CONCLUSION: Currently, metastatic melanomas can be considered as a potentially curable disease. Palliation of symptoms and fast recovery following minimally invasive procedures could be beneficial for these patients. Particularly, laparoscopic procedures appear to prolong the survival of gallbladder melanoma patients.

Radiofrequency-assisted liver resection: Technique and results.

BACKGROUND: Radiofrequency (RF)-assisted liver resection allows non-anatomical liver resection with reduced blood loss and offers the opportunity for a combination of resection and ablation. However, there are still concerns with regard to postoperative complications related to this technique. In the present study, we discuss the technical aspects of RF-assisted liver resections and analyse the rate of perioperative complications, focusing on post-hepatectomy liver failure (PLF), bile leak and abscess, and mortality. METHODS: Between 2001 and 2015, 857 consecutive open and laparoscopic elective RF-assisted liver resections for benign and malignant liver tumours were reviewed retrospectively to assess perioperative outcomes. RESULTS: Median intraoperative blood loss was 130 mL, with 9.8% of patients requiring blood transfusion. Intra-abdominal collections requiring percutaneous drainage developed in 8.7% of all patients, while bile leak at resection margin developed in 2.8% of the cases. Major liver resection was performed in 34% of patients and the incidence of PLF was 1.5% with one directly related mortality (0.1%). CONCLUSION: RF-assisted liver resection has evolved into a feasible and safe technique of liver resection with an acceptable incidence of perioperative morbidity and a low incidence of PLF and related mortality.

Identifying the role of neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio as prognostic markers in patients undergoing resection of pancreatic ductal adenocarcinoma.

BACKGROUNDS/AIMS: It is important to point out that the identification of inflammation is an essential component of the pathogenesis and the progression of cancer. In this study, we analysed the neutrophil-to-lymphocyte ratio (NLR) and the platelets-to-lymphocyte ratio (PLR), with an overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC), who were treated with a resection following or not following a procedure of neoadjuvant chemotherapy/chemoradiation. We intended to identify the significance of the role of NLR and PLR, as prognostic markers in patients undergoing surgery for PDAC. METHODS: There were 127 patients enrolled in the study. The NLR and PLR were calculated on the basis of the pre-treatment blood cell count. An NLR>4 and a PLR >120 were considered to be elevated as measured. OS was analysed in relation to the NLR and PLR values, by using both the Kaplan-Meier and multivariate Cox-regression methods. RESULTS: Both high the NLR and high PLR were associated with a decreased OS in the univariate analysis. In the multivariate analysis, the high NLR, but not the high PLR, was an independent predictor of a decreased OS. When we divided patients into three groups (group 1: normal both NLR and PLR, group 2: high NLR or high PLR, group 3: high both NLR and PLR), the three-years OS rates for these groups were 48%, 32%, 7% (p=0.001) respectively. CONCLUSIONS: It is noted that the pre-treatment NLR is an independent adverse prognostic factor, and considered to be superior to the PLR, in patients who undergo a resection for PDAC following or not neoadjuvant chemotherapy/chemoradiation.

Predicting complications in hepatic resection for colorectal liver metastasis: the lymphocyte-to-monocyte ratio.

BACKGROUND: Colorectal cancer is one of the most common malignancies worldwide; whilst approximately 20% of patients have hepatic disease at presentation. Hepatic resection remains the gold standard of care; however, it is associated with significant morbidity. We sought to establish whether the lymphocyte-to-monocyte ratio (LMR) could help predict post-operative complications, thus improving patient outcomes. METHODS: We performed a retrospective cohort study of patients undergoing hepatic resection at a single centre. Baseline demographics and complications within 30 days following surgery were recorded. White blood cell counts and C-reactive protein (CRP) were recorded pre-operatively, and until post-operative day 7. RESULTS: A total of 188 operations were included. About 47.3% of resections had a complicated recovery, of which 31.46% were major. The median LMR was 1.29 across the cohort, 1.60 for uncomplicated procedures, 1.14 for those with complications and 0.85 in major complications. For detecting major complications versus an uncomplicated recovery, median LMR was the best parameter (area under the curve 0.78), whilst it was the only parameter to accurately predict such complications within 48 hours of surgery (area under the curve 0.72 on day 1). It was consistently the most accurate parameter at detecting uncomplicated versus complicated recovery, minor versus major complications, and major complications versus an uncomplicated recovery, at numerous timepoints over the post-operative period. CONCLUSION: The LMR appears better at predicting complications following hepatic resection for colorectal liver metastases, as opposed to conventionally measured parameters.

Safety and feasibility of elective liver resection in adult Jehovah's Witnesses: the Henri Mondor Hospital experience.

BACKGROUND: Elective liver resection (LR) in Jehovah's Witness (JW) patients, for whom transfusion is not an option, involves complex ethical and medical issues and surgical difficulties. METHODS: Consecutive data from a LR program for liver tumors in JWs performed between 2014 and 2017 were retrospectively reviewed. A systematic review of the literature with a pooled analysis was performed. RESULTS: Ten patients were included (median age = 61 years). None needed preoperative erythropoietin. Tumor biopsy was not performed. Major hepatectomy was performed in 4 patients. The median estimated blood loss was 200 mL. A cell-saver was installed in 2 patients, none received saved blood. The median hemoglobin values before and at the end of surgery were 13.4 g/dL and 12.6 g/dL, respectively (p = 0.04). Nine complications occurred in 4 patients, but no postoperative hemorrhage occurred. In-hospital mortality was nil. Nine studies including 35 patients were identified in the literature; there was reported no mortality and low morbidity. None of the patients were transfused. CONCLUSIONS: By using a variety of blood conservation techniques, the risk/benefit ratio of elective liver resection for liver was maintained in selected adult JW patients. JW faith should not constitute an absolute exclusion from hepatectomy.

Neutrophil: Lymphocyte ratio as a method of predicting complications following hepatic resection for colorectal liver metastasis.

BACKGROUND AND OBJECTIVES: Approximately 30-50% of patients with colorectal cancer develop liver metastasis for which liver resection is the only hope for potential cure. However, hepatic resection is associated with considerable morbidity. The aim was to detect early complications by utilising the neutrophil: lymphocyte ratio (NLR). METHODS: We performed a retrospective cohort study of patients undergoing hepatic resection at a single institution between 2008 and 2016. Baseline demographics and complications within 30 days following surgery were recorded, with blood tests measured until day 7. Statistical analysis was performed using Mann Whitney and ROC analysis. RESULTS: One hundred eighty-eight operations were included. 47.3% had an associated complication, of which 31.46% were major. The median NLR was 6.31 across the cohort, 5.44 for uncomplicated procedures, 7.0 for complications and 10.65 in major complications. Median NLR was the best parameter for detecting major complications versus minor complications (AUC 0.74) as opposed to lymphocytes (AUC 0.65), neutrophils (AUC 0.60), and CRP (AUC 0.60). The diagnostic ability of NLR increased further when predicting major complications versus an uncomplicated recovery (AUC 0.78), and it was the only significant parameter in the early post-operative period on days 2, 3, and 4 (AUC 0.70, 0.72, and 0.75). CONCLUSIONS: The NLR may have a role in predicting complications following hepatic resection for CLM, and with earlier detection, potentially improving outcomes.

Preliminary qualification of a novel, hypoxic-based radiologic signature for trans-arterial chemoembolization in hepatocellular carcinoma.

BACKGROUND: Survival advantage following trans-arterial chemoembolization (TACE) is variable in patients with hepatocellular carcinoma (HCC). We combined pre-TACE radiologic features to derive a novel prognostic signature in HCC. METHODS: A multi-institutional dataset of 98 patients was generated from two retrospective cohorts from United Kingdom (65%) and Italy (36%). The prognostic impact of a number baseline imaging parameters was assessed and factors significant on univariate analysis were combined to create a novel radiologic signature on multivariable analyses predictive of overall survival (OS) following TACE. RESULTS: Median OS was 15.4 months. Tumour size > 7 cm (p < 0.001), intra-tumour necrosis (ITN) (p = 0.02) and arterial ectatic neovascularisation (AEN) (p = 0.03) emerged as individual prognostic factors together with radiologic response (p < 0.001) and elevated alpha-fetoprotein (AFP) (p = 0.01). Combination of tumour size > 7 cm, ITN and AEN identified patients with poor prognosis (p < 0.001). CONCLUSIONS: We identified a coherent signature based on commonly available imaging biomarkers likely to be reflective of differential patterns of relative hypoxia and neovascularisation. Large tumours displaying AEN and ITN are characterised by a shorter survival after TACE.

Increased carcinoembryonic antigen (CEA) following neoadjuvant chemotherapy predicts poor prognosis in patients that undergo hepatectomy for liver-only colorectal metastases.

BACKGROUND: The importance of preoperative chemotherapy in a multimodality management of patients with colorectal liver metastases (CRLM) has been demonstrated. We analyse the carcinoembryonic antigen (CEA) changes following neoadjuvant chemotherapy in patients with CRLM who underwent liver resection. METHODS: The final cohort included 107 eligible patients. Increased CEA levels following neoadjuvant chemotherapy were defined as the increase of baseline CEA level at diagnosis of CRLM compared with the CEA level after completion of neoadjuvant chemotherapy. Disease-free survival (DFS), post-recurrence survival (PRS) and overall survival (OS) were calculated using both Kaplan-Meier and multivariate Cox-regression methods. RESULTS: CEA increase was associated with decreased PRS and OS (HR 2.69; 95 % CI, 1.28-5.63; p = 0.009, and HR 2.50; 95 % CI, 1.12-5.56; p = 0.025, respectively) in multivariate analysis, but there was no association between CEA changes and DFS. CEA increase was only associated with disease progression during preoperative chemotherapy (p = 0.014). Interestingly, this association was not absolute, as only 5 of the 11 patients with disease progression demonstrated CEA increase. Regarding the remaining 12 patients with CEA increase, according to RECIST criteria, eight patients demonstrated partial response and four patients stable disease. CONCLUSION: In this study, we demonstrated the CEA increase following neoadjuvant chemotherapy as an adverse prognostic factor for PRS, and OS but not for DFS in patients undergoing liver resection for liver-only colorectal metastases.

Oncological Outcomes of Major Liver Resection Following Portal Vein Embolization: A Systematic Review and Meta-analysis.

BACKGROUND: Preoperative portal vein occlusion with either percutaneous portal vein embolization (PVE) or portal vein ligation is routinely used to induce liver hypertrophy prior to major liver resection in patients with hepatic malignancy. While this increases the future liver remnant, and hence the number of patients suitable for resection, recent evidence suggests that induction of liver hypertrophy preoperatively may promote tumor growth and increase recurrence rates. The aims of this current study were to evaluate the impact of PVE on hepatic recurrence rate and survival in patients with colorectal liver metastases (CRLM). METHODS: The MEDLINE, EMBASE and Web of Science databases were searched to identify studies assessing the oncological outcomes of patients undergoing major liver resection for CRLM following PVE. Studies comparing patients undergoing one-stage liver resection with or without preoperative PVE were included. The primary outcome was postoperative hepatic recurrence (PHR), while secondary outcomes were 3- and 5-year overall survival (OS). RESULTS: Of the 2131 studies identified, six non-randomized studies (n = 668) met the eligibility criteria, comparing outcomes of patients undergoing major liver resection with or without PVE (n = 182 and n = 486, respectively). No significant difference was observed in PHR (odds ratio [OR] 0.78; 95 % confidence interval [CI] 0.42-1.44), 3-year OS (OR 0.80; 95 % CI 0.56-1.14) or 5-year OS (OR 1.12; 95 % CI 0.40-3.11). CONCLUSIONS: PVE does not have any adverse effect on PHR or OS in patients undergoing major liver resection for CRLM. Further studies based on individual patient data are needed to provide definitive answers.

Two cases of gallbladder metastasis from renal cell carcinoma and review of literature.

BACKGROUND: Renal cell carcinoma accounts for 90% of renal neoplasms and metastatic disease is common. One third of newly diagnosed cases will have synchronous metastases at diagnosis and further 25-50 % will develop metachronous disease. CASE PRESENTATION: This study presents two new cases of gallbladder metastasis from renal cell carcinoma (RCC) from our institution and reviews the published literature. The final cohort included 52 evaluable patients. M/F ratio was 2:1 and median age was 62.5 years. Most patients were diagnosed incidentally after follow-up or staging imaging for RCC. Of the patients with available histology, all except one were clear cell type (n = 39) and 92% were polypoid. Thirty-six patients demonstrated metachronous gallbladder metastasis with median disease-free interval (DFI) from nephrectomy of 4 years. The most frequent site of metastasis was the contralateral kidney (46.7%) followed by the pancreas and lung. The median disease-free interval (DFS) after cholecystectomy was 37 months. Three- and five-year OS rates were 74 and 62%, respectively. Age younger than 45 years (p = 0.008) and DFI <24 months (p = 0.049) were associated with decreased OS. CONCLUSIONS: RCC metastasis to the gallbladder is associated with an unusual pattern of concomitant metastasis. Symptoms are not common. Simple cholecystectomy is associated with increased OS and nil local or port site recurrence. Young age and short DFI are associated with decreased OS.

Interleukin 18 binding protein ameliorates ischemia/reperfusion-induced hepatic injury in mice.

Inflammation-associated oxidative stress contributes to hepatic ischemia/reperfusion injury (IRI). Detrimental inflammatory event cascades largely depend on activated Kupffer cells (KCs) and neutrophils, as well as proinflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL) 18. The aim of our study was to evaluate the effects of IL 18 binding protein (IL 18Bp) in hepatic IRI of mice. Thirty C57BL/6 mice were allocated into 3 groups: sham operation, ischemia/reperfusion (I/R), and I/R with intravenous administration of IL 18Bp. Hepatic ischemia was induced for 30 minutes by Pringle's maneuver. After 120 minutes of reperfusion, mice were euthanized, and the liver and blood samples were collected for histological, immunohistochemical, molecular, and biochemical analyses. I/R injury induced the typical liver pathology and upregulated IL-18 expression in the liver of mice. Binding of IL 18 with IL 18Bp significantly reduced the histopathological indices of I/R liver injury and KC apoptosis. The I/R-induced increase of TNF-α, malondialdehyde, aspartate aminotransferase, and alanine aminotransferase levels was prevented in statistically significant levels because of the pretreatment with IL 18Bp. Likewise, blocking of IL 18 ablated the I/R-associated elevation of nuclear factor kappa B, c-Jun, myeloperoxidase, and IL 32 and the up-regulation of neutrophils and T-helper lymphocytes. Administration of IL 18Bp protects the mice liver from I/R injury by intervening in critical inflammation-associated pathways and KC apoptosis.

Aurora Kinases and Potential Medical Applications of Aurora Kinase Inhibitors: A Review.

Aurora kinases (AKs) represent a novel group of serine/threonine kinases. They were originally described in 1995 by David Glover in the course of studies of mutant alleles characterized with unusual spindle pole configuration in Drosophila melanogaster. Thus far, three AKs A, B, and C have been discovered in human healthy and neoplastic cells. Each one locates in different subcellular locations and they are all nuclear proteins. AKs are playing an essential role in mitotic events such as monitoring of the mitotic checkpoint, creation of bipolar mitotic spindle and alignment of centrosomes on it, also regulating centrosome separation, bio-orientation of chromosomes and cytokinesis. Any inactivation of them can have catastrophic consequences on mitotic events of spindle formation, alignment of centrosomes and cytokinesis, resulting in apoptosis. Overexpression of AKs has been detected in diverse solid and hematological cancers and has been linked with a dismal prognosis. After discovery and identification of the first aurora kinase inhibitor (AKI) ZM447439 as a potential drug for targeted therapy in cancer treatment, approximately 30 AKIs have been introduced in cancer treatment.