International registry on the use of the CytoSorb® adsorber in ICU patients : Study protocol and preliminary results.

INTRODUCTION: The aim of this clinical registry is to record the use of CytoSorb® adsorber device in critically ill patients under real-life conditions. METHODS: The registry records all relevant information in the course of product use, e. g., diagnosis, comorbidities, course of the condition, treatment, concomitant medication, clinical laboratory parameters, and outcome (ClinicalTrials.gov Identifier: NCT02312024). Primary endpoint is in-hospital mortality as compared to the mortality predicted by the APACHE II and SAPS II score, respectively. RESULTS: As of January 30, 2017, 130 centers from 22 countries were participating. Data available from the start of the registry on May 18, 2015 to November 24, 2016 (122 centers; 22 countries) were analyzed, of whom 20 centers from four countries provided data for a total of 198 patients (mean age 60.3 ± 15.1 years, 135 men [68.2%]). In all, 192 (97.0%) had 1 to 5 Cytosorb® adsorber applications. Sepsis was the most common indication for CytoSorb® treatment (135 patients). Mean APACHE II score in this group was 33.1 ± 8.4 [range 15-52] with a predicted risk of death of 78%, whereas the observed mortality was 65%. There were no significant decreases in the SOFA scores after treatment (17.2 ± 4.8 [3-24]). However interleukin-6 levels were markedly reduced after treatment (median 5000 pg/ml before and 289 pg/ml after treatment, respectively). CONCLUSIONS: This third interim report demonstrates the feasibility of the registry with excellent data quality and completeness from 20 study centers. The results must be interpreted with caution, since the numbers are still small; however the disease severity is remarkably high and suggests that adsorber treatment might be used as an ultimate treatment in life-threatening situations. There were no device-associated side effects.

THE ROLE OF SURGERY IN A PATIENT WITH CARCINOID SYNDROME, COMPLICATED BY CARCINOID HEART DISEASE.

A 55-year-old female patient was admitted for flushing and abdominal pain in the right upper quadrant. Her past medical history revealed high blood pressure and a recent echocardiography showed thickened appearance of tricuspid valve with coaptation defect and grade II tricuspid regurgitation. Contrast enhanced abdominal CT scan and MRI were subsequently performed and revealed a large macronodular liver mass, as well as other micronodular lesions disseminated in the liver parenchyma. CT guided biopsy from the main liver mass revealed neuroendocrine tumor of unknown origin (probably GI) with Ki-67 of 8%. Surgical exploration was decided. During laparotomy, the primary tumor was found in the proximal ileum and the patient underwent segmental enterectomy. Non-anatomical hepatectomy was also performed to remove the bulk of the tumor burden (more than 90%). Postoperative course was uneventful and the carcinoid syndrome relieved. At present, 15 months postoperatively, the patient is under treatment with somatostatin analogue for its antiproliferative effect, with good clinical, biochemical and tumoral control and stable heart disease. In patients with neuroendocrine liver metastases from unknown primary, surgical exploration could allow detection (and resection) of the primary tumor and surgical debulking of liver metastases to control carcinoid syndrome and carcinoid heart disease.

PROGNOSTIC FACTORS IN PATIENTS WITH SURGICAL RESECTION OF PANCREATIC NEUROENDOCRINE TUMOURS.

CONTEXT: Pancreatic neuroendocrine tumours (PanNETs) are rare pancreatic neoplasms. PanNETs can be treated by multimodal approach including surgery, locoregional and systemic therapy. OBJECTIVE: The aim of the present study is to evaluate predictive factors of overall survival in patients with PanNETs surgically treated at a single center. SUBJECTS AND METHODS: The study group consisted of 120 patients with PanNETs who had undergone surgery at the Center of Digestive Diseases and Liver Transplantation of Fundeni Clinical Institute, Bucharest, Romania. Surgical resection of the primary tumor was performed in 110 patients. RESULTS: Tumor size > 2 cm (p=0.048) (90% CI) lymph node involvement (p=0.048), ENET grade (p<0.001), distant metastases (p<0.001), Ki 67 index (<2%, 2-5%, 5-10%, 10-20%, >20%) (p<0.001) were identified as significant prognostic factors for OS on univariate analysis. Using multivariate Cox proportional regression model we found that distant metastases and Ki 67 index were independent risk factors for the survival outcome. CONCLUSIONS: Surgery with curative intent should be considered in all cases if clinically appropriate and technically feasible. High grade (Ki67 index ≥10%) tumours were associated with a 2- fold increase in risk of death as compared to those with a Ki67 <10%.

Expression of interleukine-8 as an independent prognostic factor for sporadic colon cancer dissemination.

AIM: The aim of our study was to investigate the gene and serum protein expression profiles of IL-8 in colon cancer and associated hepatic metastasis and to correlate these results with clinicopathologic variables of the patients. MATERIALS AND METHODS: IL-8 was evaluated by qPCR and ELISA in a total number of 62 colon cancer patients (n=42 by qPCR and n=20 by ELISA) in normal and tumoral tissue specimens and serum samples respectively. Additionally synchronous metastasis from 5 of these patients were also collected at the time of surgery and analyzed by qPCR. RESULTS: IL-8 was up regulated in all analyzed tumoral samples compared with normal tissue (P-value = 0.01) and higher expressed in metastatic tissues compared with tumoral tissues (P -value= 0.03). The median expression of IL-8 in patients over 60 years old was found to be higher compared with the median expression of IL8 in patients less than 60 years old (3.89 compared with 14.69, P -value= 0.005). According to tumor grading, we found that IL-8 in tumors with well differentiated adenocarcinoma have a median mRNA expression of 9.78 compared with a median mRNA IL8 expression of 26.63 in moderate or poor differentiated adenocarcinoma. Levels of IL-8 determined in serum were statistically significant correlated with preoperative carcinoembryonic antigen level (P -value= 0.003, R=0.57) and with distant metastasis (P-value =0.008). Serum level of IL-8 increased proportionally along with TNM tumor stage and was found to be statistically significant correlated with C-reactive protein (P -value, R=0.64). Colon cancer patients had higher IL-8 levels as determined by ELISA (median value= 29.64 pg/ml) compared with healthy controls (median value= 4.86 pg/ml). DISCUSSIONS: Our results provide additional support for the role of inflammation in colon cancer and indicate that IL-8 could be further validated in association with other already used markers for prognostic and diagnostic of evolutional disease in colon cancer patients.

Technical aspects of biliary reconstruction correlated with biliary complications in 46 consecutive right lobe liver transplantations from living donors.

INTRODUCTION: Biliary complications contribute to a high morbidity rate in patients with right lobe liver transplant from a living donor. We retrospectively evaluated biliary reconstructions and complications in a number of recipients with liver transplant from a living donor, in a single center. PATIENTS AND METHODS: A number of 46 patients (23 males and 23 females aged 9-63) received a right lobe liver graft between 2009 and 2013, with the following types of biliary reconstruction:duct-to-duct choledochocholedochal anastomosis (n=24)or Roux-en-Y hepaticojejunoanastomosis, with or without an external transanastomotic biliary stent. RESULTS: The rate of biliary complications (leakage 15.21%,anastomotic stenosis 4.34%, overall 17.39%) was not statistically significantly influenced by the demographics of the studied lot, by the etiology of the liver disease or by the characteristics of the biliary reconstruction; the only risk factor which showed a statistically significant influence in terms of biliary complications was MELD. CONCLUSION: The type and technique of the biliary reconstruction in LDLT should be adapted depending on the anatomy of the biliary tree of both the donor and recipient, as well as the clinical and laboratory findings of the recipient.

Screening of hepatopulmonary syndrome (HPS) with CEUS and pulse-oximetry in liver cirrhosis patients eligible for liver transplant.

BACKGROUND AND AIM: The prevalence of hepatopulmonary syndrome (HPS) in the setting of cirrhosis ranges between 4%-47%. We aimed to detect a correlation between heart and lungs findings on contrast-enhanced ultrasound (CEUS)and pulse-oximetry, in order to early detect HPS and thus to improve patients referral to orthotopic liver transplantation(OLT). METHODS: We considered at risk for HPS all patients with delayed left ventricle (LV) enhancement of the contrast agent,at least 3 systolic beats after it appears in the right ventricle(RV). We correlated CEUS results with pulse-oximetry findings,considering to have a positive HPS diagnosis in all patients with both CEUS findings and SaO2 95%. RESULTS: From 186 patients diagnosed with liver cirrhosis, 56 patients (30.10%) had delayed LV enhancement of the contrast agent. Pulse-oximetry showed alterations, such as SaO2 95%and PaO2 70 mmHg in 62 patients (33.33%). Pearson index showed a good correlation between lung and heart CEUS findings and pulse-oximetry (r=0.99) in HPS diagnosis. CONCLUSIONS. Two non-invasive, simple and rapid methods such as CEUS and pulse-oximetry can easily diagnose HPS, a highly fatal complication of liver cirrhosis, and can also guide the future treatment by speeding up OLT recommendations.

Optimizing the indication for breast-conservative surgery (BCS) in patients with locally-advanced breast cancer.

BACKGROUND: The main benefit of neoadjuvant chemotherapy is a reduction in tumor size, which allows breast-conserving surgery (BCS) in patients who otherwise would have required a mastectomy. Breast magnetic resonance (MRI) has been proposed to evaluate tumor extent after neoadjuvant chemotherapy, to determine which patients have become eligible for BCS. AIM: The aim of our study was to determine how the association of breast MRI to routine clinical and radiologic assessment of the tumor at initial presentation, and after chemotherapy, affects the overall surgical decision process. MATERIAL AND METHODS: 54 women with stage IIB-IIIB breast cancer were prospectively enrolled in a study investigating the effects of MRI on the surgical decision. RESULTS: Surgical plan was changed from BCS to radical mastectomy in 6 cases (13.04%). As a result of using MRI in evaluating disease extent, 21.73% of valuable data were added by MRI (pectoralis major muscle and skin invasion, multifocal multicentric disease). Due to MRI examination 28 (60.86%) of the patients with operable breast cancer after neoadjuvant chemotherapy, were eligible for BCS. CONCLUSIONS: Our study demonstrates that MRI is the most accurate in determination of tumor size and extent, and in establishing eligibility for BCS.

Nutritional risk screening and prevalence of malnutrition on admission to gastroenterology departments: a multicentric study.

BACKGROUND AND AIMS: There is little awareness and a lack of data on the prevalence of hospital malnutrition in gastro-enterology departments. Since part of these patients are referred for surgical treatment and poor nutritional status is a known risk factor for perioperative morbidity, we conducted a prospective study aimed to screen for the nutritional risk and assess the prevalence and risk factors of malnutrition in gastro-enterology departments in Romania. METHODS: We included patients consecutively admitted to 8 gastroenterology units over a period of three months in our study. Nutritional risk was evaluated using NRS 2002. Malnutrition was defined using BMI ( 20 kg m2) or and 10% weight loss in the last six months. RESULTS: 3198 patients were evaluated, 51.6% males and 48.4% females, with the mean age of 54.5 Â+- 14.3 years. Overall percentage of patients at nutritional risk was 17.1%, with the highest risk for patients with advanced liver diseases (49.8%), oncologic (31.3%), inflammatory bowel diseases (20.2%), and pancreatic diseases (18.9%). The overall prevalence of malnutrition was of 20.4%, higher for advanced liver diseases (39.4%), inflammatory bowed diseases (30.6%), oncologic (26.8%) and pancreatic diseases (23%). Independent risk factors for malnutrition were younger age (p 0.0001), female gender (p 0.0001), a higher (A ≥ 3) NRS (p 0.0001), presence of neoplasm (p 0.0001), of advanced liver disease (p=0.0003) and a reduction of 25% of dietary intake (p 0.0001). CONCLUSIONS: One in five patients admitted to gastroenterology units could benefit from prompt nutritional intervention. Correction of nutritional status is mandatory before any surgical procedure. Emphasis on nutritional evaluation at admission and beginning of nutritional therapy where needed are particularly required in patients with advanced liver diseases, digestive neoplasms, inflammatory bowel diseases and pancreatic diseases. ABBREVIATIONS: NRS= nutritional risk score, BMI = body mass index, IBD = inflammatory bowel diseases.

The importance of early diagnosis of sepsis in severe burned patients: outcomes of 100 patients.

BACKGROUND/AIM: The burn-injured patient has a major potential to develop an infection because the wound itself, surgical treatment, mechanical ventilation and blood transfusions may potentially lead to a secondary immunodeficiency syndrome. PATIENTS AND METHODS: A total number of 100 consecutive burn-injured patients with sepsis were treated in the Clinical Emergency Hospital of Plastic Surgery and Burns, Bucharest,between 2009 and 2011. Their clinical and bioumoral data were analyzed. RESULTS: Flame was the main cause of burn injuries in the present series (78%). The mean body surface area burn wound was 49.7%. Most of the patients (97%) experienced the first septic episode within two weeks after burn injury.Sepsis was mainly due to Gram-positive (58%) and Gramnegative(26%) bacteria. Staphylococcus aureus (32%) and Pseudomonas aeruginosa (21%) were the most frequently encountered germs. The susceptibility for Gram-positive bacteria was the best for imipenem/cilastatin, followed byamikacin, ceftriaxone and ciprofloxacin. For Gram-negative bacteria, the susceptibility decreased from ciprofloxacin to imipenem/ cilastatin, amikacin and gentamicin. Mortality rate was 9%. CONCLUSIONS: The extensive knowledge of physiopathology,clinics, epidemiology, bioumoral and microbiology features of the sepsis in burn-injured patients allows an early and precise diagnosis and an adequate and efficient treatment.All these elements have been associated with a significant improvement of the survival rates. Every patient with burn injured sepsis must be treated as a different entity in order to obtain the best results.

[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.

Reconstructing gene networks: what are the limits?

To fully realize the benefits of high-throughput post-genomic technologies it is necessary to reconstruct and analyse the complicated network of interactions through which most genes operate. We briefly summarize the mathematical frameworks that can be used to model such networks, and the types of algorithms available for their reconstruction. We then focus on dynamic models, typically described using differential equations, and explain the two main reconstruction approaches in current use. We discuss the data requirements of these algorithms and ask how well they correspond to current microarray data.

Nucleotide excision repair gene XPD polymorphisms and genetic predisposition to melanoma.

The nucleotide excision repair pathway has evolved to deal with UV light-induced DNA damage. Individuals with the rare inherited nucleotide excision repair deficiency disease xeroderma pigmentosum have a 1000-fold increased incidence of skin cancer. We are interested in the possibility that more subtle changes in nucleotide excision repair genes, resulting in either a reduced capacity for repair or in altered interactions between repair proteins and components of the cell cycle control machinery, might constitute important genetic risk factors for the development of skin cancer in the general population. To investigate this hypothesis we have compared the frequency of polymorphisms in exons 6, 22 and 23 of the XPD gene in melanoma patients and a control group. For each of these two allele polymorphisms one of the alleles was over-represented in the melanoma group and there was a significant association with melanoma. Importantly, this association did not extend to markers immediately flanking the XPD gene, thus providing evidence that XPD gene polymorphisms might predispose to melanoma in the general population. There is a report that one of the polymorphic XPD alleles (exon 23 Lys), which is over-represented in the melanoma group, has reduced repair proficiency and we discuss the possibility that this is the causal change to the XPD gene that predisposes to melanoma.

[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.

[Primary exertion thrombophlebitis of the upper extremities: clinical and therapeutic aspects]. / Tromboflebita primitiva "de efort" a membrului toracic: aspecte clinice si terapeutice.

The authors present 4 cases of "effort" thrombophlebitis of the upper limb that were diagnosed both clinically and thrombophlebographically, and in whom classical therapy was applied: total rest, anticoagulants, elevation of the limb. All the cases had sequels of variable intensity, and in 2 of the patients Roos' transaxillary route was used which revealed a double anterior scalenus muscle insertion, and compressive fibro-sclerous tissue. The pathogeny of the affection makes mandatory the removal of extrinsic or intrinsic factors which may generate a new thrombosis or vascular and neurologic sequels.