Variant hepatic arterial anatomy encountered during pancreatoduodenectomy does not influence postoperative outcomes or resection margin status: A matched pair analysis of 105 patients.

BACKGROUND/AIM: Anatomic vascular abnormalities of the hepatic arteries are frequent. The aim of the study was to analyze the influence of hepatic arterial variations on postoperative morbidity and resection margin status after pancreatoduodenectomy (PD). MATERIALS/METHODS: Patients who underwent PD over a 7-year period (2010-2017) were included in the study. Patients with variant hepatic arterial anatomy were matched 1:2 for age, sex, ASA score, and histology. RESULTS: A total of 232 patients underwent PD. Variant hepatic arterial anatomy was found in 35 (15.1% of the total patient population). The most common variation was an accessory right hepatic artery (8.19%) and a replaced right hepatic artery (5.60%) arising from the superior mesenteric artery. These 35 patients were compared with 70 patients with no hepatic artery variations. Postoperative surgical complications occurred in 12.1% and 26.5% (P = 0.08) and in-hospital mortality was 6% and 5.4% ( P = 0.99) between patients with and without variant hepatic arteries. There was no difference in positive resection margins (R1) (18.2% vs 20.5%, P = 0.99) between the two groups. CONCLUSIONS: An aberrant hepatic artery does not increase morbidity or R1 resection in patients undergoing PD.

Host's Endogenous Caveolin-1 Expression is Downregulated in the Lung During Sepsis to Promote Cytoprotection.

The present study focuses on the profile of "endogeneous" caveolin-1 protein in septic lung (CLP model).Caveolin-1, CD25, pP38, pAkt, and 14-3-3b protein expression profiles were studied using flow cytometry and immunohistochemistry 6, 12, 24, 36, and 48 h after sepsis induction. Cell viability was determined by 7-AAD staining and fibrosis by Masson trichrome stain. The effect of protein C zymogen concentrate (PC) on caveolin-1 expression was also investigated given that PC, once dissociated from caveolin-1, elicits a PAR-1-mediated protective signaling by forming a complex with endothelial protein C receptor (EPCR).CLP treatment increased lung inflammation and cell apoptosis. Fibrosis was apparent in vessels and alveoli. Caveolin-1+ cells presented reduced protein expression, especially 12 h post-CLP (P = 0.002). Immunohistochemistry revealed caveolin-1 positive expression mainly in regions with strong inflammatory reaction. Early induction of pP38+ cell population (P = 0.014) and gradual increase of CD25+ cells were also observed. Alternations in 14-3-3b expression related to apoptosis were apparent and accompanied by increased AKT phosphorylation activity late during sepsis progression.After PC administration, cell apoptosis was reduced (P = 0.004) and both the percentile and expression intensity of caveolin-1 positive cells were compromised (P = 0.009 and P = 0.027, respectively). 14-3-3b, CD25, and pP38 protein expression were decreased (P = 0.014, P = 0.004, and P = 0.007, respectively), whereas pAkt expression was induced (P = 0.032).The observed decline of endogenous caveolin-1 protein expression during sepsis implies its involvement in host's cytoprotective reaction either directly, by controlling caveolae population to decrease bacterial burden, or indirectly via regulating 14-3-3b-dependent apoptosis and EPCR-PAR-1-dependent protective signaling.

EXTENDED CYTOPROTECTIVE EFFECT OF AUTOPHAGY IN THE LATE STAGES OF SEPSIS AND FLUCTUATIONS IN SIGNAL TRANSDUCTION PATHWAYS IN A RAT EXPERIMENTAL MODEL OF KIDNEY INJURY.

The impact of a potential autophagy (LC3a/b) deregulation in hyper and in hypo stages during sepsis-induced kidney injury and the temporal profile of phosphorylated extracellular signal-related kinase, P38 (pP38), Akt (pAKT), and 13-3-3ß protein were investigated in the current study, using a rat cecal ligation and puncture (CLP) model, by means of flow cytometry and immunohistochemistry. Cell viability was assessed by protein C zymogen concentrate (PC), 7-aminoactinomycin D (7-AAD) staining and inflammation by S100 protein immunostaining. The impact of reduced kidney inflammation in autophagy was assessed by PC administration, an anti-inflammatory and cytoprotective substance. Sepsis induction increased LC3a/b expression, which presented two peaks at 6 and 36 h after CLP, both in the percentage of positive cells (P = 0.024, P = 0.025, respectively) and in fluorescence intensity. At 6 h when inflammation was already apparent, LC3a/b increase was escorted by phosphorylated extracellular signal-related kinase stimulation and high cell viability (65%), designating autophagy as a cytoprotective mechanism against microbial infection. The phosphorylation of P38 was delayed to 12 h after CLP, when autophagy was reduced. pAkt and 14-3-3ß expression was stimulated between 6 and 36 h after CLP, although a slight inhibition of pAkt within each cell was detected (lower MnIX value). During the second peak, inflammation was intensified, necrosis was significantly increased with LC3a/b+/7-AAD + cells to present a 1.5-fold increase. Protein C zymogen concentrate administration declined autophagy at 6 and 36 h after CLP and reduced necrosis, whereas double positive LC3a/b and 7-AAD cells were increased by 1.68 and 2.78-fold, respectively. These data open new prospectives in sepsis treatment, since they further support that autophagy represents a cytoprotective mechanism triggered by stress conditions, rather than an alternative cell death pathway.

Survival benefit with the combination of docetaxel, gemcitabine and erlotinib in advanced and/or metastatic pancreatic cancer patients.

BACKGROUND/AIMS: Although research on new effective treatments against pancreatic cancer is intense, limited therapeutic schemes are currently approved. The aim of the present study was to record the efficacy and safety of gemcitabine-erlotinib plus docetaxel combination therapy in patients with advanced and/or metastatic pancreatic cancer. METHODOLOGY: Twenty-five chemotherapy naive patients with histologically confirmed unresectable pancreatic cancer and documented extrapancreatic metastases, received biweekly gemcitabine 1,500mg/m2 during a 28-day long cycle; daily erlotinib 100mg per os; and docetaxel 80mg/m2 as intravenous infusion administered every 15 days. Patients were monitored every 4 cycles for survival, adverse events and tumour response with Computed Tomography scans. RESULTS: Patients received 153 cycles in total, with a median of 7.64 cycles (range, 1-24). The median overall survival was 10 months and 45% of the patients reached and surpassed 1-year survival. No grade IV toxicities were recorded. The only grade III recorded toxicities were thrombopenia (4 patients, 16%), anaemia (1 patient, 4%) and neutropenia (1 patient, 4%). Overall the most frequently experienced adverse events were grade I anaemia (18 patients, 72%) and grade II rash (13 patients, 52%). CONCLUSIONS: Biweekly gemcitabine with erlotinib plus docetaxel administration is a practical alternative to pancreatic cancer treatment, presenting comparable results to weekly gemcitabine administration.

Lymphocyte apoptosis after major abdominal surgery is not influenced by anesthetic technique: a comparative study of general anesthesia versus combined general and epidural analgesia.

STUDY OBJECTIVE: To examine the influence of abdominal colectomy with combined general anesthesia and epidural analgesia versus general anesthesia on apoptosis of circulating lymphocytes. DESIGN: Prospective, randomized, clinical comparison study. SETTING: Tertiary-care general hospital. PATIENTS: 40 ASA physical status I and II patients undergoing elective open colectomy for nonmetastatic colon carcinoma. INTERVENTIONS: Patients were randomly allocated to two groups to receiver either general anesthesia alone (Group G) or general anesthesia combined with epidural analgesia (Group C). Group C comprised 21 patients while 19 patients constituted Group G. All patients underwent median longitudinal laparotomy. MEASUREMENTS: Blood samples were collected preoperatively and 24 hours postoperatively for measurement of lymphocyte apoptosis, serum cortisol, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). MAIN RESULTS: There were no differences between the two groups in age, weight, or duration of surgery. No significant alterations in total lymphocyte counts, as well as in lymphocyte subpopulations (early apoptotic, late apoptotic, viable, and necrotic), were observed between the general and combined anesthesia groups. Cortisol, ESR, and CRP were significantly increased postoperatively in both groups. Group C presented with lower serum cortisol levels postoperatively than Group G (b = -5.38, CI95%: -8.72 to -2.05, P = 0.002). CONCLUSIONS: Epidural block could not suppress postoperative lymphocyte apoptosis, increases in cortisol, CRP, or ESR compared with general anesthesia.

Detection of epithelial cells by RT-PCR targeting CEA, CK20, and TEM-8 in colorectal carcinoma patients using OncoQuick density gradient centrifugation system.

BACKGROUND: The detection of epithelial-specific mRNA correlates well with the presence of cancer cells in the peripheral blood and provides a rational explanation for subsequent metastasis. MATERIAL AND METHODS: Forty-two, patients with colorectal cancer and 14 controls were included in our study. Peripheral blood samples were acquired at 24 h before and 48 h after laparotomy. Tissue samples were also acquired from the primary lesion. All samples were examined for the expression profile of CEA, CK20, and TEM-8. RESULTS: Tissue samples expressed CEA in every specimen, CK20 in 30, and TEM-8 in 41. CEA and CK20 were not identified in the control blood samples while TEM-8 was detected in 4. CEA was detected in 17, CK20 in 28 and TEM-8 in 23, of the preoperative blood samples. CEA mRNA expression in preoperative blood sample and TNM stage were found independently associated with increased tumor size. Positive CEA, CK20, and TEM-8 signals were found in 25, 25, and 23 of the postoperative blood samples respectively. CONCLUSIONS: CK20 and CEA are significantly more frequently detected in colon cancer patients than in healthy controls and can serve as markers. Cancer cell mRNA is commonly detected in the preoperative and postoperative peripheral blood samples. Tumor size was independently associated with the preoperative detection of CEA mRNA. Although TEM-8 mRNA detection in the peripheral blood showed no specificity for cancer patients or correlation with clinical stage, identification and validation of genes and proteins implicated in metastatic process needs to be further investigated.

Management of major bile duct injury after laparoscopic cholecystectomy: a case report.

INTRODUCTION: Bile duct injury is a severe and potentially life-threatening complication of laparoscopic cholecystectomy. Several series have described a 0.5% to 0.6% incidence of bile duct injury during laparoscopic cholecystectomy. The aim of this study was to analyze the presentation, characteristics, related investigation, and treatment results of major bile duct injuries after laparoscopic cholecystectomy. CASE PRESENTATION: A rare case of a 48-year-old Greek woman with a triple bile duct injury (right and left hepatic duct ligation and common bile duct cross-section) is presented. A Roux en Y hepaticojejunostomy was performed after repeated endoscopic retrograde cholangiopancreatographies, percutaneous transhepatic catheterization of the ducts and magnetic resonance cholangiographies to delineate the biliary anatomy and assess the level of injury. CONCLUSION: Early recognition and an adequate multidisciplinary approach are the cornerstones for the optimal final outcome. Suboptimal management of injuries often leads to more extensive damage to the biliary tree and its vasculature. Early referral to a tertiary care center with experienced hepatobiliary surgeons and skilled interventional radiologists would appear to be necessary to assure optimal results.

A misquoted mutation in exon16 of the BRCA2 gene.

A pathogenic mutation in the BRCA2 gene, nt7602del16, has been misquoted as a mutation, possibly due to the incorrect inclusion of the last 16 nucleotides of exon15 of the BRCA2 gene as part of the intron15-exon16 BRCA2 gene sequence in publicly available databases. This was concluded following mutational screening by sequencing and enzymatic mapping of the BRCA2 gene exon15-exon16 region in DNA from peripheral blood samples from a total of 74 breast cancer and non-breast cancer patients as well as healthy individuals and the cell line MCF7. Careful interpretation of genetic variants and direct feedback to the corresponding sequence databases prevent systemic errors by integrating updated data into broadly referenced sources.

Perioperative erythropoietin administration in patients with gastrointestinal tract cancer: prospective randomized double-blind study.

OBJECTIVE: To investigate the effect of recombinant human erythropoietin (r-HuEPO) administration on perioperative hemoglobin concentrations and on the number of blood transfusions in patients undergoing surgery for gastrointestinal tract malignancies. SUMMARY BACKGROUND DATA: Erythropoietin has been shown to improve the yield of autologously predonated blood and to reduce the subsequent requirements for homologous blood transfusions in cancer patients. METHODS: In this double-blind placebo-controlled study, 31 cancer patients received subcutaneous r-HuEPO in a dose of 300 IU/kg body weight plus 100 mg iron intravenously (study group) and 32 patients received placebo medication and iron (control group). All patients received the medications daily for at least 7 days before and 7 days after the operation. RESULTS: Patients who received erythropoietin received significantly fewer transfusions intraoperatively and postoperatively. Postoperatively, the study group had significantly higher hematocrit, hemoglobin, and reticulocyte count values compared to the control group. The use of erythropoietin was also associated with a reduced number of postoperative complications and improved 1-year survival. CONCLUSIONS: Patients with gastrointestinal tract cancer and mild anemia benefit from perioperative erythropoietin administration in terms of stimulated erythropoiesis, reduction in the number of blood transfusions, and a favorable outcome.

BRCA2 gene mutations in Greek patients with familial breast cancer.

Family history is a well-recognized risk factor for the development of breast cancer. The isolation of BRCA1 and BRCA2 genes, the two major predisposing genes in familial and to early onset breast and ovarian cancer, has resulted to the identification of a large number of families with mutations in these two genes. Despite the large number of distinct mutations detected in both genes, several mutations have been found to recur in unrelated families of diverse geographical origin. We have analyzed 27 Greek patients with familial breast cancer the majority of those having one first and one second degree relatives affected and 28 patients with sporadic breast cancer for BRCA2 germline mutations. The techniques used were single-strand conformation polymorphism analysis (SSCP) followed by sequencing. Furthermore, the clinical presentation and prognosis of BRCA2 associated breast cancer cases was compared to 20 adequately matched for age and date of diagnosis (within one year) sporadic breast cancer patients. We identified three novel BRCA2 mutations (3058delA, 6024delTA, and 4147delG) in the ovarian cancer cluster region (OCCR) and one already known (2024del5) germline BRCA2 gene mutation in five different breast cancer families. The 4147delG mutation was detected in two unrelated patients. BRCA2 germline mutations were correlated with early-onset breast cancer RR=4.77 (95% CI: 0.666-34.463). Although patients with BRCA2 germline mutations did not have a distinct histological phenotype they had an improved overall survival (100% vs 65%). Our findings suggest that there is a cluster of novel mutations in exons 10 and 11 in Greek patients with familial breast cancer. These mutations appear to have a milder clinical phenotype when compared to the rest of the study group.