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Introduction Multivisceral resections (MVRs) in gastric cancer are potentially curable in selected patients in whom clear resection margins are possible. However, there are still uncertain data on their feasibility and safety considering short- and long-term results. The study compares survival, morbidity, mortality, and other secondary outcomes between standard and MVRs for gastric cancer. Materials and Methods A monocentric retrospective study in patients with gastric adenocarcinoma, covering 2004 to 2020. Of the 336 operable cases, 101 patients underwent MVRs. The remaining 235 underwent standard gastric resections (SGRs), of which 173 patients were in stage T3/T4. To compare survival, a control group of 101 patients with palliative procedures was used-bypass anastomosis or exploration. Results MVR had a lower survival rate than the SGR but significantly higher than the palliative procedures. The predominant gender in MVR was male (72.3%), with a mean age of 61 years. The perioperative mortality was 3.96% ( n = 4), and the overall median survival was 28.1 months. The most frequently resected organs were the spleen (67.3%), followed by the pancreas (32.7%) and the liver (20.8%). In 56.4% of the cases two organs were resected, in 28.7% three organs, and in 13.9% four organs. The main complication was bleeding (9.9%). The major postoperative complications in the MVR were 14.85%, and in the SGR 6.4% ( p < 0.05). Better long-term results were observed in patients who underwent R0 resections compared with R1. Conclusion Multiorgan resections are characterized by poorer survival and a higher complication rate than gastrectomies. On the other hand, they have better long-term outcomes than palliative procedures. However, MVRs are admissible when performed by an experienced surgical team in high-volume centers.

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Background: We present a comparative analysis of survival, complications and major risk factors in patients who underwent surgery for pancreatic head carcinoma. Methods: This is a single-centre retrospective study aimed to evaluate clinical, surgical and pathoanatomical features of 467 patients who underwent radical surgery for pancreatic head carcinoma between September 2004 and October 2019. The series includes 88 patients (18.8%) with venous resections for borderline resectable pancreatic adenocarcinoma. Results: The estimated median survival rates were statistically significant with 19.3 months in pancreatoduodenal venous resections (VR) and 26.9 months in pancreatoduodenal resections (PDR), respectively (p=0.047). On the other hand, one, three, and five-year survival rates of 46.6%, 17.6% and 8.3% in VR, and 53.6%, 20.8%, 14.9% in PDR were not statistically significant (p=0.13, 0.5 and 0.11 respectively). Survival rates comparison in PDR, VR, and palliative procedures (PP) between the three groups showed statistical significance (p 0.05). The clinically relevant postoperative complications in venous resections (13.6%) vs. 14.8% in PDR were not statistically significant (p=0.77). Postoperative bleeding and reoperation (p 0.05) are independent prognostic factors for worse outcomes. There was no statistically significant relationship between survival and presence of vascular invasion (p=0.581). Conclusions: When performed by experienced surgeons at specialized high-volume centres, pancreatoduodenal resections combined with venous resection and reconstruction are reliable and safe surgical procedures.

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BACKGROUND: Tumours involving the supra-renal segment of IVC have dismal prognosis if left untreated. Currently, aggressive surgical management is the only potentially curative treatment but is associated with relatively high morbidity and mortality. This study aims to evaluate perioperative factors, associated with adverse postoperative outcomes, based on the perioperative characteristics and type of IVC reconstruction. METHODS: We identified 44 consecutive patients, who underwent supra-renal IVC resection with a mean age of 57.3 years. Isolated resection of IVC was performed in four patients, concomitant liver resection was performed in 27 patients and other associated resection in 13 patients. Total vascular exclusion was applied in 21 patients, isolated IVC occlusion in 11 patients. Neither venovenous bypass (VVB) nor hypothermic perfusion was used in any of the cases. RESULTS: The mean operative time was 205 min (150-324 min) and the mean estimated blood loss was 755 ml (230-4500 ml). Overall morbidity was 59% and major complications (Dindo-Clavien ≥ III) occurred in 11 patients (25%). The 90-day mortality was 11% (5pts). Intraoperative haemotransfusion was significantly associated with postoperative general complications (p < 0,001). With a mean follow-up of 26.2 months, the actuarial 1-, 3- and 5-year survival is 69%, 34%, and 16%, respectively. CONCLUSIONS: IVC resection and reconstruction in the aspect of aggressive surgical management of malignant disease confers a survival advantage in patients, often considered unresectable. When performed in experienced centres it is associated with acceptable morbidity and mortality.

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AIM: To evaluate the results of an aggressive surgical approach of resection and reconstruction of the inferior vena cava (IVC). METHODS: The approach to caval resection depends on the extent and location of tumor involvement. The supra- and infra-hepatic portion of the IVC was dissected and taped. Left and right renal veins were also taped to control the bleeding. In 12 of the cases with partial tangential resection of the IVC, the flow was reduced to less than 40% so that the vein was primarily closed with a running suture. In 3 of the cases, the lumen of the vein was significantly reduced, requiring the use of a polytetrafluoroethylene (PTFE) patch. In 2 of the cases with segmental resection of the IVC, a PTFE prosthesis was used and in 1 case, the IVC was resected without reconstruction due to shunting the blood through the azygos and hemiazygos veins. RESULTS: The mean operation time was 266 min (230-310 min) with an average intraoperative blood loss of 300 mL (200-2000 mL). The patients stayed in intensive care unit for 1.8 d (1-3 d). Mean hospital stay was 9 d (7-15 d). Twelve patients (66.7%) had no complications and 6 patients (33.3%) had the following complications: acute bleeding in 2 patients; bile leak in 2 patients; intra abdominal abscess in 1 patient; pulmonary embolism in 2 patients; and partial thrombosis of the patch in 1 patient. General complications such as pneumonia, pleural effusion and cardiac arrest were observed in the same group of patients. In all but 1 case, the complications were transient and successfully controlled. The mortality rate was 11.1% (n = 2). One patient died due to cardiac arrest and pulmonary embolism in the operation room and the second one died 2 d after surgery due to coagulopathy. With a median follow-up of 24 mo, 5 (27.8%) patients died of tumor recurrence and 11 (61.1%) are still alive, but three of them have a recurrence on computed tomography. CONCLUSION: There are a variety of options for reconstruction after resection of the IVC that offers a higher resectable rate and better prognosis in selected cases.

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Activation of G protein-coupled receptors (GPCRs) leads to the dissociation of heterotrimeric G-proteins into Gα and Gßγ subunits, which go on to regulate various effectors involved in a panoply of cellular responses. During chemotaxis, Gßγ subunits regulate actin assembly and migration, but the protein(s) linking Gßγ to the actin cytoskeleton remains unknown. Here, we identified a Gßγ effector, ElmoE in Dictyostelium, and demonstrated that it is required for GPCR-mediated chemotaxis. Remarkably, ElmoE associates with Gßγ and Dock-like proteins to activate the small GTPase Rac, in a GPCR-dependent manner, and also associates with Arp2/3 complex and F-actin. Thus, ElmoE serves as a link between chemoattractant GPCRs, G-proteins and the actin cytoskeleton. The pathway, consisting of GPCR, Gßγ, Elmo/Dock, Rac, and Arp2/3, spatially guides the growth of dendritic actin networks in pseudopods of eukaryotic cells during chemotaxis.

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The ability of cells to sense external chemical cues and respond by directionally migrating towards them is a fundamental process called chemotaxis. This phenomenon is essential for many biological responses in the human body, including the invasion of neutrophils to sites of inflammation. Remarkably, many of the molecular mechanisms involved in controlling neutrophils chemotaxis arose millions of years ago in the simple eukaryotic organism Dictyostelium discoideum. Both neutrophils and Dictyostelium use G protein-coupled signaling cascades to mediate chemotactic responses, which are responsible for transducing external cues into highly organized cytoskeletal rearrangements that ultimately lead to directed migration. By using the genetically and biochemically tractable organism Dictyostelium as a model system, it has been possible to decipher many of the signal transduction events that are involved in chemotaxis.

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Familial hypercholesterolemia (FH) is a common, autosomal dominant disorder of lipid metabolism, caused by defects in the receptor-mediated uptake of LDL (low-density lipoproteins) due to mutations in the LDL receptor gene ( LDLR). Mutations underlying FH in Bulgaria are largely unknown. The aim of the present study was to provide information about the spectrum of point mutations in LDLR in a sample of 45 Bulgarian patients with severe hypercholesterolemia. Exons 3, 4, 6, 8, 9, and 14, previously shown to be mutational hot spots in LDLR, were screened using PCR-single-strand conformation polymorphism (SSCP). Samples with abnormal SSCP patterns were sequenced. Three different, hitherto undescribed point mutations (367T>A, 377T>A, 917C>A) and two previously described mutations (858C>A and 1301C>T) in eight unrelated patients were identified; four of the detected point mutations being missense mutations and one, a nonsense mutation. One of the newly described point mutations (917C>A) is a base substitution at a nucleotide position, at which two other different base substitutions have already been reported. Thus, all three possible base substitutions at this nucleotide position have been detected, making it a hot spot for point mutations causing FH. This is the first such mutational hot spot described in exon 6 of LDLR.

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