Cellular and Kaposi's sarcoma-associated herpes virus microRNAs in sepsis and surgical trauma.

Once a patient is in septic shock, survival rates drop by 7.6% for every hour of delay in antibiotic therapy. Biomarkers based on the molecular mechanism of sepsis are important for timely diagnosis and triage. Here, we study the potential roles of a panel of cellular and viral miRNAs as sepsis biomarkers. We performed genome-wide microRNA (miRNA) expression profiling in leukocytes from septic patients and nonseptic controls, combined with quantitative RT-PCR in plasmas from two cohorts of septic patients, two cohorts of nonseptic surgical patients and healthy volunteers. Enzyme-linked immunosorbent assay, miRNA transfection and chromatin immunoprecipitation were used to study the effects of Kaposi sarcoma herpes virus (KSHV) miRNAs on interleukin's secretion. Differences related to sepsis etiology were noted for plasma levels of 10 cellular and 2 KSHV miRNAs (miR-K-10b and miR-K-12-12*) between septic and nonseptic patients. All the sepsis groups had high KSHV miRNAs levels compared with controls; Afro-American patients had higher levels of KSHV-miR-K12-12* than non-Afro-American patients. Both KSHV miRNAs were increased on postoperative day 1, but returned to baseline on day 7; they acted as direct agonists of Toll-like receptor 8 (TLR8), which might explain the increased secretion of the IL-6 and IL-10. Cellular and KSHV miRNAs are differentially expressed in sepsis and early postsurgical patients and may be exploited for diagnostic and therapeutic purposes. Increased miR-K-10b and miR-K12-12* are functionally involved in sepsis as agonists of TLR8, forming a positive feedback that may lead to cytokine dysregulation.

Pre-liver transplantation, cardiac assessment.

Liver transplantation (LT) is a stressful condition for the cardiovascular system of patients with advanced hepatic disease. The underlying hemodynamic and cardiac status of patients with cirrhosis is crucial to determine which patients should became recipients. In addition to advanced age and the presence of comorbidities, there are specific cardiovascular responses in cirrhosis that can be detrimental to the LT candidate. Patients with cirrhosis requiring LT usually demonstrate increased cardiac output, a compromised ventricular response to stress, low systemic vascular resistance and bradycardia. Post-transplant reperfusion may result in cardiac death due to a multitude of causes, including arrhythmia, acute heart failure and myocardial infarction. This review examines screening strategies for transplant candidates and details the prognostic value of common test used to identify ischemic heart disease, heart failure, portopulmonary hypertension. There are discused evidence-based recommendations for their evaluation and management.

[Liver transplantation--indications, surgical technique, results--the analysis of a clinical series of 200 cases]. / Transplantul hepatic--indicati, tehnica, rezultate-analiza unei serii clinice de 200 de cazuri.

INTRODUCTION: Initially considered experimental, liver transplantation (LT) has become the treatment of choice for the patients with end-stage liver diseases. MATERIAL AND METHODS: Between April 2000 and October 2009, 200 LTs (10 reLTs) were performed in 190 patients, this study being retrospective. There were transplanted 110 men and 80 women, 159 adults and 31 children with the age between 1 and 64 years old (mean age--39.9). The main indication in the adult group was represented by viral cirrhosis, while the pediatric series the etiology was mainly glycogenosis and biliary atresia. There were performed 143 whole graft LTs, 46 living donor LTs, 6 split LTs, 4 reduced LTs and one domino LT RESULTS: The postoperative survival was 90% (170 patients). The patient and graft one-year and five-year survivals were 76.9%, 73.6% and 71%, 68.2%, respectively. The early complications occurred in 127 patients (67%). The late complications were recorded in 71 patients (37.3%). The intraoperative and early postoperative mortality rate was 9.5% (18 patients). CONCLUSIONS: The Romanian liver transplantation program from Fundeni includes all types of current surgical techniques and the results are comparable with those from other international centers.

[Anesthesia for experimental surgery in swine]. / Anestezia pentru chirurgia experimentala la porci.

New surgical techniques cannot be safely and widely performed in human subjects unless they are first applied to large animal models. Experimental model using swine as surgical practice subject is one of the most reliable and widely practiced, taking into consideration the similarity between human and swine anatomy. Based on our large experience (around 100 pigs) we hereby present important aspects of handling and anesthesia procedures for pigs. Our goal is to share our experience with young surgical and anesthesia investigators who are planning investigations using pig as an experimental animal.

[Liver rupture of a subcapsular haematoma after pharmacologic revascularization (Streptokinase) for acute myocardial infarction--case report]. / Ruptura de ficat post revascularizare farmacologica (streptokinaza) pentru infarct miocardic acut.

We report the case of a 56 years old male patient, smoker, obese, with untreated arterial hypertension, hospitalized on 16.02.07 with the diagnosis of inferior acute myocardial infarction, for which he received thrombolysis with streptokinase, followed by anticoagulation with non fractioned heparin. Two days later he started to complain of acute abdominal pain, and laboratory findings showed a low hemoglobin level. Imaging findings (ultrasonography and CT scan) showed evidence of subcapsular liver haematoma, caused by bleeding at hepatic and splenic level. He received red blood packed cells, fresh frozen plasma, cryoprecipitate, activated factor VII and was transferred by helicopter to Fundeni Clinical Institute--Intensive care unit (ICU). On admission, the patient was conscious, anxious, dyspneic, with mild hypoxia, with no signs of low cardiac output and with a painful abdomen. ECG, echocardiography and elevated myocardial necrosis enzymes confirmed myocardial infarction. Shortly after admission there was a worsening of his clinical condition, with a decrease in hemoglobin level despite red blood packed cells administration (Hb=7.8 g/dl) and thrombocytopenia (82000/mmc), with normal coagulation tests, thus suggesting active intraabdominal bleeding. Echography and CT scan confirmed bleeding. Emergency surgery was performed, showing massive haemoperitoneum (approx 4.5 L of blood), due to spontaneous rupture of a subcapsular hematoma in the liver. The surgical hemostasis was performed on the liver parenchyma laceration. Duration of surgery was 4 hours. There were no significant cardiac events during surgery (no signs of ischemia on ECG, no ST elevation), despite the need for inotropic agent. After surgery, the patient was referred to the ICU, intubated and ventilated, with inotropic support - dobutamine. Sequential ECG's, enzymatic trend and echocardiographies were performed to monitor myocardial ischemia. The outcome was favourable, no further bleeding and no postoperative myocardial infarction occurred. Secondary prevention was started early (thromboprophylaxis, selective beta-blocker, angiotensin inhibitors and statins). The patient had a favorable outcome and was discharged from the ICU the fourth day after surgery. He had a total length of stay in hospital of seven days, with a follow-up in the cardiology department.

Combined liver and islet transplantation using steroid-free immunosuppression.

Due to a vicious circle in which HCV favors insulin resistance and, alternatively, insulin resistance facilitates the persistence of HCV, HCV patients have often diabetes associated with liver cirrhosis. We present the case of combined liver and pancreatic islets transplantation performed in a patient with HCV liver cirrhosis associated with insulin-dependent diabetes. This is also the first case of islet allotransplantation in Romania. A 40-year-old male diagnosed with liver cirrhosis due to HCV infection and insulin dependent diabetes underwent combined liver and islet transplantation. Our therapeutic design was based on data provided by both the use of Edmonton immunosuppressive steroid-free protocol in islets cell transplantation and the findings of international studies on the effects of this protocol in liver transplantation for patients with HCV infection. Good metabolic control of the diabetes was obtained. The absence of anti beta cell autoimmunity could explain also the good tolerance for the transplanted islets, proved by the rapid and durable decrease of the insulin need, from 64 U/day to 20 U/day at one month post-transplantation, dose that was maintained for 16 months when the patient died due to recurrent HCV hepatitis. Islet transplantation can be associated to liver transplantation in order to improve the associated diabetes in cirrhotic patients.

[Hemodynamic changes induced by positive pressure capnothorax during thoracoscopic thymectomy]. / Consecintele hemodinamice ale aplicarii capnotoraxului cu presiuni pozitive în timectomia toracoscopica.

Low-flow insufflation of CO2 into the thorax helps the surgeon by increasing the surgical field during thoracoscopy, but older studies performed on animals (pigs and dogs) showed that positive pressure capnothorax had negative hemodynamic impact on animals and strongly recommended against using it on humans. We included in our study 24 ASA I-II myasthenic patients (20 females and 4 males) age 29 yo (+/- 10.2) weight 62.8 kg (+/- 10.6) whose thymuses were surgically removed by thoracoscopy. Using thoracic electrical bioimpedance (TEB) we assessed noninvasively cardiac index (CI) stroke index (SI) systemic stroke vascular resistance index (SSVRI) and end diastolic index (EDI). Well known for its hemodynamic stability we chose sevoflurane for induction and maintenance of anesthesia (VIMA). According to Copenhagen scale, adding minimal iv dose of fentanyl (3 mcg/kg) to sevoflurane induction, allowed us to endobronchial intubate in good and excellent conditions. During anesthesia almost all measured parameters (CI, SI, MAP, EDI) recorded statistically significant decrease but with minimal clinical significance. Thus, the maximal drop was measured during application of 10 mm Hg capnothorax: CI and SI dropped by 1.16 1/min/m2 (19%) (p = 0.02) and respectively 16.58 ml/m2 (21%) (p = 0.001). Thereby we are applying low-flow positive pressure insufflation of CO2 into the thorax, to almost all thoracoscopies performed in our clinic.

[Total pelvic exenteration in the treatment of advanced pelvic cancer]. / Exenteratia pelvina totala in tratamentul cancerului pelvin avansat.

Total pelvic exenteration (TPE) is a radical and aggressive procedure performed in the local advanced pelvic cancer started from any pelvic organ. The experience of 73 TPE performed for local invasive cancer and centro-pelvic recurrences with initial malignancy at the cervix (45 cases), rectum (19 cases), vagina (5 cases), endometrial (3 cases) and urinary bladder (1 case), in 61 females and 12 males with age range 27-78 years, are analysed. The procedures were performed for advanced pelvic cancer in 24 cases and also for invasive centro-pelvic recurrences in 49 cases (67.5%). In 5 cases, TPE was extended laterally. In 42 patients reconstructive procedures were added. All patients survived to surgery but 5 postoperative deaths (6.8%) were recorded. Complications occurred in 52% of cases, 38 from 73 patients had one or more than one complication with an average of 1.5 per patient. 22 among these patients (30%) requiring operative treatment. The average survival was 49.07 months, the median survival of 55 months and the estimated survival at 11 and 78 months was 66%, respectively 50%. The procedure is indicated in the absence of pelvic wall invasion and secondary distant dissemination and lengthens significantly the life span and increase the quality of life.

[Disease-related malnutrition and its influence on perioperative outcome]. / Malnutritia si impactul sau asupra prognosticului pacientului chirurgical.

Disease-related malnutrition is highly prevalent among surgical patients and has important deleterious effects on postoperative outcome: increased complications rate, length of hospital stay, mortality and costs. Malnutrition (equivalent with undernutrition in the surgical patients) can be present already on admission, could rapidly develop or aggravate during hospital stay. The determination of malnutrition in this high-risk group of patients in multifactorial: decreased intake (anorexia, gastrointestinal symptoms, prolonged perioperative fasting) and increased demands (hyper-catabolism due to underlying disease, surgical stress, eventual postoperative complications). The identification of patients at nutritional risk by screening on admission and whenever the patient situation changes throughout hospitalization is the first, mandatory step for developing an accurate nutritional care plan in these patients, in order to positively influence postoperative outcome.

[Activated recombinant factor VII (Novoseven) in multiple trauma patients: an outcome analysis]. / Utilizarea factorului VII activat recombinat (Novoseven) la pacientii politraumatizati: analiza evolutiei si prognosticului.

BACKGROUND AND OBJECTIVE: In multiple trauma patient the bleeding is a major cause of death and it is caused by vascular injury or post-traumatic coagulopathy. Regardless of etiology, management of massive bleeding requires immediate surgery to stop bleeding with simultaneous stabilization of hemostasis and maintenance of normovolemia. The objective was to evaluate the efficacity and safety of recombinant activated factor VII in patients with massive posttraumatic hemorrhage after failure of conventional methods to control bleeding (surgical haemostasis, volemic resuscitation, transfusions, rewarming). METHODS: 34 multiple trauma patients with severe hemorrhage requiring > 10 transfusion units of packed red cells received recombinant activated factor VII. Postdrug transfusion requirements were assessed (red packed cells, fresh frozen plasma, platelet concentrations and cryoprecipitate), and mortality was compared with predicted outcomes, using Injury Severity Score, Revised Trauma Score and Trauma Score-Injury Severity Score. We also noted the incidence of adverse effects, mostly thromboembolic events. We use a special design chart to follow the patients who received rFVIIa. RESULTS: We have the following results: the mortality rate was reduced (without statistical relevance), the coagulation times also reduced--aPTT decreases from 76 s to 38.5 (p = 0.000), PT from 23 s to 18 s (p = 0.000), transfusion requirements decrease- RPCs from 11.5 units to 3 units (p = 0.000), FFP from 7.5 units to 2 units (p = 0.000). We analysed the cases with adverse effects but we didn't find a direct cause- effect explication. CONCLUSIONS: The rFVIIa is efficient in post-trauma-tic bleeding (decrease transfusion requirements, normalized coagulation times), reduce mortality rate.

[Orthotopic liver transplantation in adult patients with cadaveric grafts. Experience of the Fundeni Center of General Surgery and Liver Transplantation]. / Transplantul hepatic ortotopic de la donator cadavru la adult. Experienta Centrului de Chirurgie Generalai si Transplant Hepatic Fundeni.

We analyze the experience of the Center of General Surgery and Liver Transplantation from the Fundeni Clinical Institute (Bucharest, Romania) regarding orthotopic liver transplantation (OLT) in adult recipients, with whole liver grafts from cadaveric donors, between April 2000 (when the first successful LT was performed in Romania) and December 2004. This series includes 37 OLTs in adult recipients (16 women and 21 men, aged between 29-57 years--average 46 years). Other two LT with whole liver cadaveric grafts and two reduced-size LT were performed in children; also, in the same period, due to the acute organ shortage, other methods of LT were performed in 28 patients (21 living donor LT, 6 split LT and one "do mino" LT), that were not included in the present series. The indications for OLT were HBV cirrhosis--10, HBV+HDV cirrhosis--4, HCV cirrhosis--11, HBV+HCV cirrhosis--2, biliary cirrhosis--5, Wilson disease--2, alcoholic cirrhosis--1, non-alcoholic liver disease--1, autoimmune cirrhosis--1. With three exceptions, in which the classical transplantation technique was used, the liver was grafted following the technique described by Belghiti. Local postoperative complications occurred in 15 patients (41%) and general complications in 17 (46%); late complications were registered in 18 patients (49%) and recurrence of the initial disease in 6 patients (16%). Intrao- and postoperative mortality was 8% (3/37). There were two patients (5%) who died because of immunosuppressive drug neurotoxicity at more than 30 days following LT. Four patients (11%) died lately because of PTLD, liver venoocclusive disease, recurrent autoimmune hepatitis and liver venoocclusive disease, myocardial infarction, respectively. Thirty-four patients survived the postoperative period (92%); according to Kaplan-Meier analysis, actuarial patient-survival rate at month 31 was 75%.

Thymectomy by thoracoscopic approach in myasthenia gravis.

BACKGROUND: A series of 25 thoracoscopic thymectomies performed in the Department of General Surgery and Liver Transplantation of the Fundeni Clinical Institute between April 1999 and April 2000 is analyzed. METHODS: Thoroscopic thymectomies were performed on 4 male patients (16%) and 21 female patients (84%), aged between 8 and 60 years. RESULTS: The mean operative time was 90 (+/-15) min. There were no conversions to open thymectomy. Mortality was nil, and morbidity consisted of one minor postoperative right pneumothorax probably related to a injury to right mediastinal pleura that was not observed intraoperatively. Hospital stay ranged from 2 to 4 days, with a mean of 2.28 days. The patients were transferred to the neurological department and they were usually discharged after 1 more day. CONCLUSIONS: Postoperatively, all patients had clinical improvement of their disease both in symptoms and medication requirements, but a longer follow-up is necessary. The results are edifying regarding the very low morbidity, the lack of mortality, the acceptance of the patients, and the short hospitalization.

Liver hemangioma revisited: current surgical indications, technical aspects, results.

BACKGROUND/AIMS: New developments regarding the diagnosis of liver hemangiomas, surgical indication and therapeutic options emerged recently. We reviewed our experience from the point of view of these modern developments. METHODOLOGY: Fifty-seven patients with liver hemangiomas were retrospectively studied. The relationship between size, symptoms and treatment was assessed. RESULTS: Indication for surgery was the size of the lesion in 5 patients, symptomatology in 48 and uncertain diagnosis in 4. Increase in size was noted in four patients. Six patients had associated intraabdominal benign or malignant pathology. The treatment of choice was enucleation. Postoperative complications were noted in 6 patients and mortality was nil. In 3 patients the hemangiomas recurred and were reresected in 2. CONCLUSIONS: Hemangiomas should be resected when larger than 10 cm and when they become symptomatic. With the modern diagnostic work-up, uncertainty of diagnosis as an indication for surgery should be rare. Surgery remains the main treatment, with a low morbidity and mortality if performed in a specialized hepatobiliary unit. Enucleation is the surgical option of choice. In selected cases laparoscopic enucleation can be performed with good results.

[Liver transplantation--considerations over 8 cases operated in the year 2000]. / Transplantul hepatic--consideratii asupra a 8 cazuri operate în anul 2000.

In the year 2000, at the Department for General Surgery and Liver Transplantation from The Fundeni Clinical Institute Bucharest, seven OLTs and one living-related transplantation were performed in 6 adults and 2 children. Postoperative complications were: bile leakage, hemoperitoneum, lower gastrointestinal hemorrhage, parietoabdominal hematoma. There was only one postoperative death due to septic complications in the 18th p.o.d. and one late death due to pneumonia of unknown origin. After the results in the year 2000 there was an increased number of donors and referrals. We consider that now in Romania this is an established program that will continue depending on the number of donors and financing.

[Video-assisted thoracoscopic thymectomy--preliminary results]. / Timectomia pe cale toracoscopica--rezultate preliminare.

Video-assisted thoracoscopic surgery (VATS) provides a new approach to thymectomy. From April 1999 to December 1999, we performed a total of 10 video-assisted thoracoscopic thymectomies for myasthenia gravis (MG). There were one male and nine female patients with ages ranging from 8 to 59 years. Thymoma was present in one of the ten patients. We considered that complete thymectomy was accomplished in all cases by examination of the thymic bed and of the resected specimen. There was no mortality or intraoperative complications. The median postoperative hospital stay was 4 days. Clinical improvement was observed in all patients after this short follow-up. Compared with a similar historical group of patients with MG who underwent transsternal thymectomy, the VATS group was associated with significantly less analgesic requirement and shortened hospital stay. We conclude that VAT thymectomy is technically feasible and is associated with a favorable postoperative course compared with the transsternal approach. We believe that complete thymectomy can be achieved by this approach. Further investigation with long-term follow-up is needed to further clarify the role of VAT thymectomy in thoracic surgery.

[Repeat hepatic resections]. / Rezectiile hepatice iterative.

Five cases of iterative liver resections are presented, out of a total of 150 hepatectomies performed between 1.01.1995-1.01.1998. The resections were carried out for recurrent adenoma (one case), cholangiocarcinoma (two cases), hepatocellular carcinoma (one case), colo-rectal cancer metastasis (one case). Only cases with at least one major hepatic resection were included. Re-resections were more difficult than the primary resection due, first of all, to the modified vascular anatomy. Intraoperative ultrasound permitted localization of intrahepatic recurrences. Iterative liver resection appears to be the best therapeutical choice for patients with recurrent liver tumors.

[Scheduled reinterventions in the treatment of acute peritonitis]. / Reinterventiile programate în tratamentul peritonitelor acute.

UNLABELLED: This is a clinical series of 83 cases, admitted in the Surgical Department of Fundeni Hospital between 1988-1996 of severe acute peritonitis in which scheduled reoperations (at least one planned reoperation at 24-48 hours after the first operation) were performed. The main criteria for scheduled reoperations were; unresolved source of contamination, acute peritonitis older than 48 hours and the presence of multiple system organ failures. 63 cases (76%) were postoperative peritonitis. 203 planned reoperations were performed (minimum: 1, maximum: 10, mean: 2,4 reoperations per patient). In 12 cases (14,4%) a laparotomy "on demand" was necessary after the scheduled reoperations were stopped. The source of peritonitis was resolved in 61 cases (73,5%) and unresolved in 22 cases (26,5%). In 9 cases (10%) specific complications of the method (hemorrhages, fistulas) were encountered. The global mortality was 65,06%, with 55,73% mortality when the source of peritonitis was resolved and 90,9% mortality when the source was not resolved. CONCLUSION: scheduled reoperations have to be reserved for the most severe cases of acute peritonitis in which the mortality after the "classical" methods of treatment is extremely high.

[Total vascular exclusion in liver surgery]. / Excluderea vasculara totalâ în chirurgia hepatica.

II cases of major hepatic resections under total vascular isolation (TVA) are presented: 4 women and 7 men, age between 17 and 70 years (mean 39.6 years). In another 2 cases the method was abandoned because the patients did not tolerate the vena cava clamping. The main indication for TVA were large tumors located near the suprahepatic veins opening into the vena cava. The diagnosis in the 11 cases was: hepatocellular carcinoma--3 cases, cholangiocarcinoma--1 case, colo-rectal metastasis--1 case, hemangioma--3 cases, hamartoma--2 cases, diffuse suppuration of the right lobe--1 case. The warm ischemia time was between 25 and 50 min (mean: 36.8 min). There were no intraoperative complications. The mean quantity of transfused blood was 450 ml. Postoperatively two patients bled and were reoperated. Both subsequently developed liver failure and died and in both cases microscopy found histologic lesions of chronic hepatitis. The mortality was then 18.1%. Six patients (54.5%) developed postoperative complications. Worth noting are 2 cases of transient liver failure, both in patients with cancer. The ICU stay was between 2 and 14 days (mean 7.1) and the whole postoperative hospitalization was between 11 and 46 days (mean: 16).

[Amputation of the rectum via laparoscopy]. / Amputatie de rect pe cale laparoscopica.

We report the case of a 66-year-old woman with a bleeding adenocarcinoma of the lower thirty of the rectum. The laparoscopic procedure was initiated with mobilization of the sigmoid colon. The left ureter was identified as it crosses the left iliac vessels. The peritoneum along the right side of the rectosigmoid mesentery was transected. The superior rectal artery was divided utilizing extracorporeal ligatures. The anterior rectum was separated from the uterus, the pararectal tissue was mobilized, the middle rectal arteries were ligated and the posterior rectum was dissected from the presacral tissue. The perineal component of the procedure was simultaneously performed. The sigmoid loop was extracorporeally transected with a linear stapler. The proximal sigmoid end was exteriorized through the colostomy site (site of the left superior port). The distal sigmoid end was replaced in the abdominal cavity and was grasped through the perineal wound; the anus, rectum and sigmoid were removed through the perineal wound. The feasibility of this procedure has been well established. However, it seems to be an alternative for the classical abdominoperineal resection as treatment for adenocarcinoma of the lower rectum. His superiority has yet to be confirmed by future studies.

[Changes in cellular and humoral immunologic mechanisms in the postoperative period]. / Modificari ale mecanismelor imunologice celulare si umorale în perioada postoperatorie.

The study attempted to evaluate the effects of anesthesia and of surgical interventions on certain humoral and cellular components of the mechanism of specific immunity. A total of 64 patients suffering with benign and malignant affections of the stomach and of the colon that had underwent resections under general anesthesia of the hypnoanalgesia type were followed at three stages of their evolution--before surgery, at 24 hours after surgery, and 7 days after surgery. Blood samples were obtained for performing the following tests: count of lymphocytes, blastic transformations test, stimulated control (with PHA and PWM), rosetting test, total number of eosinophils, high affinity eosinophils, and other tests. Electrophoretic fractions, total serum proteins, and dosage of IgG, IgM, and IgA immunoglobulins were also measured. A total of 24 tests have been performed. The patients were investigated both globally and according to sex, type of affection (malignant, or other), and by age. The results indicated a depression of the majority of the results of tests excepting those which detect precursor B, and T-helper cells, which showed a stimulation. Differentiated behaviours were also noted in the various groups with regard to the intensity of the reaction, although not with its direction.