Manousos M. Konstadoulakis

Real-time ultrasound-guided catheterisation of the internal jugular vein: a prospective comparison with the landmark technique in critical care patients

IntroductionCentral venous cannulation is crucial in the management of the critical care patient. This study was designed to evaluate whether real-time ultrasound-guided cannulation of the internal jugular vein is superior to the standard landmark method.MethodsIn this randomised study, 450 critical care patients who underwent real-time ultrasound-guided cannulation of the internal jugular vein were prospectively compared with 450 critical care patients in whom the landmark technique was used. Randomisation was performed by means of a computer-generated random-numbers table, and patients were stratified with regard to age, gender, and body mass index.ResultsThere were no significant differences in gender, age, body mass index, or side of cannulation (left or right) or in the presence of risk factors for difficult venous cannulation such as prior catheterisation, limited sites for access attempts, previous difficulties during catheterisation, previous mechanical complication, known vascular abnormality, untreated coagulopathy, skeletal deformity, and cannulation during cardiac arrest between the two groups of patients. Furthermore, the physicians who performed the procedures had comparable experience in the placement of central venous catheters (p = non-significant). Cannulation of the internal jugular vein was achieved in all patients by using ultrasound and in 425 of the patients (94.4%) by using the landmark technique (p < 0.001). Average access time (skin to vein) and number of attempts were significantly reduced in the ultrasound group of patients compared with the landmark group (p < 0.001). In the landmark group, puncture of the carotid artery occurred in 10.6% of patients, haematoma in 8.4%, haemothorax in 1.7%, pneumothorax in 2.4%, and central venous catheter-associated blood stream infection in 16%, which were all significantly increased compared with the ultrasound group (p < 0.001).ConclusionThe present data suggest that ultrasound-guided catheterisation of the internal jugular vein in critical care patients is superior to the landmark technique and therefore should be the method of choice in these patients.

Strategies for the management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) generally develops as a consequence of underlying liver disease, most commonly viral hepatitis. The development of HCC follows an orderly progression from cirrhosis to dysplastic nodules to early cancer development, which can be reliably cured if discovered before the development of vascular invasion (typically occurring at a tumor diameter of approximately 2 cm). The identifiable population at risk makes screening a realistic possibility, and liver imaging is recommended every 6 months for patients with cirrhosis. For patients with preserved liver function and no portal hypertension who develop HCC that is confined to one region of the liver, resection is the preferred treatment. If resection is not possible because of poor liver function, and the HCC is within the Milan criteria (1 nodule ≥5 cm, 2–3 nodules ≥3 cm), liver transplantation is the treatment of choice. To prevent tumor progression while waiting, nonsurgical treatments including percutaneous ethanol injection, radiofrequency ablation, and transarterial chemoembolization are employed, but drop-out from the waiting list remains a problem. Living donor transplantation is an alternative that can eliminate drop-out and enable liver transplantation for patients with HCC whose disease does not fall within the Milan criteria. There is a need for more effective adjuvant therapies after resection and liver transplantation; newer antiangiogenic agents offer hope for improved outcomes in the future.

Time-dependent mitochondrial-mediated programmed neuronal cell death prolongs survival in sepsis.

Objective:To investigate whether apoptosis is a possible mechanism of brain dysfunction occurring in septic syndrome. Design:Experimental prospective study. Setting:Laboratory of Surgical Research at the University of Athens. Subjects:Male pathogen-free Wistar rats. Interventions:Rats (n = 112) were subjected to sepsis by cecal ligation and puncture. Sham-operated animals (n = 40) underwent the same procedure but without ligation or puncture. Septic animals were either randomly divided (n = 62) in six groups and studied at 6, 12, 24, 36, 48, and 60 hrs after the operation or monitored (n = 50) for 48 hrs as a survival study group. Sham-operated animals were killed at 6, 12, 24, 36, 48, and 60 hrs after the procedure. Brain and cecum were then removed and postfixed in paraffin sections. Apoptosis was evaluated by light microscopy in hematoxylin and eosin-stained specimens and by transmission electron microscopy. In paraffin-embedded sections, immunostaining for bax, bcl-2, cytochrome c, and caspase-8 was done. Measurements and Main Results:In septic rats, increased apoptosis was detected in neurons of the CA1 region of the hippocampus, in choroid plexus, and in Purkinje cells of the cerebellum. Bax immunopositivity was found decreased after the septic insult (p = .03). Bax immunoreactivity was altered as the septic syndrome evolved; it was up-regulated in the early stages (6–12 hrs) and progressively decreased in the late phases (p = .001). Cytochrome c presented a similar regional pattern of expression and was found to be the sole gene marker carrying an independent prognostic role (p = .03). Both bcl-2 and caspase-8 expression remained at constant levels at all times evaluated. Conclusions:There is evidence that more neurons undergo apoptosis during sepsis than in normal brain tissue in certain sites where the blood-brain barrier is compromised. In this phenomenon, mitochondrial gene regulators such as bax and products such as cytochrome c seem to play important regulating and prognostic roles, respectively.

Aggressive surgical resection for hilar cholangiocarcinoma: is it justified? Audit of a single center's experience

BACKGROUND The current study presents our experience with resectional surgery for patients with hilar cholangiocarcinoma (HC). METHODS Medical records of 73 HC patients who were referred to our department between 1988 and 2006 were reviewed. Resectability rate, surgical mortality, and factors contributing to survival were investigated. RESULTS Resectional surgery was performed in 59 patients (80.8%), 51 of whom (86.4%) underwent major hepatic resection. Negative margins were obtained in 35 of 51 patients (68.6%) and were associated with right-sided hepatectomy (80% vs 20%, P = .049). In-hospital mortality and morbidity were 6.8% and 25.4%, respectively. One-, 3- and 5-year survival rates after liver resection were 86%, 48.9%, and 34.9%, respectively. Histologic differentiation, left-sided hepatectomy, and inferior vena cava resection independently predicted survival. Patients undergoing R1 hepatectomy had significantly improved 5-year survival rates compared with patients who were unresectable (P <.01). CONCLUSIONS Major hepatic resections with concomitant vascular resection and reconstruction, when needed, are justified for patients with Bismuth type III and IV hilar cholangiocarcinoma with negative nodes. Reluctance to incorporate segments V and/or VIII into a left lobectomy often results in tumor-positive margins and unfavorable prognosis. Resections for hilar lesions less than stage IVB, even when resulting in microscopically positive margins, confer prolonged survival compared with untreated patients. The results are further improved for patients with well-differentiated HC.

Somatostatin versus octreotide in the treatment of patients with gastrointestinal and pancreatic fistulas.

BACKGROUND AND PURPOSE Gastrointestinal and pancreatic fistulas are characterized as serious complications following abdominal surgery, with a reported incidence of up to 27% and 46%, respectively. Fistula formation results in prolonged hospitalization, increased morbidity/mortality and increased treatment costs. Conservative and surgical approaches are both employed in the management of these fistulas. The purpose of the present study was to assess, evaluate and compare the potential clinical benefit and cost effectiveness of pharmacotherapy (somatostatin versus its analogue octreotide) versus conventional therapy. PATIENTS AND METHODS Fifty-one patients with gastrointestinal or pancreatic fistulas were randomized to three treatment groups: 19 patients received 6000 IU/day of somatostatin intravenously, 17 received 100 microg of octreotide three times daily subcutaneously and 15 patients received only standard medical treatment. RESULTS The fistula closure rate was 84% in the somatostatin group, 65% in the octreotide group and 27% in the control group. These differences were of statistical significance (P=0.007). Overall mortality rate was less than 5% and statistically significant differences in mortality among the three groups could not be established. Overall, treatment with somatostatin and octreotide was more cost effective than conventional therapy (control group), and somatostatin was more cost effective than octreotide. The average hospital stay was 21.6 days, 27.0 and 31.5 days for the somatostatin, octreotide and control groups, respectively. CONCLUSIONS Data suggest that pharmacotherapy reduces the costs involved in fistula management (by reducing hospitalization) and also offers increased spontaneous closure rate. Further prospective studies focusing on the above parameters are needed to demonstrate the clinicoeconomic benefits.

Apoptosis in cells of bronchoalveolar lavage: a cellular reaction in patients who die with sepsis and respiratory failure.

Objective Apoptosis represents a physiologic clearance mechanism in human tissues. The role of apoptosis has not been examined in lung cell populations, such as alveolar macrophages of septic patients, an organ frequently insulted in these patients. This study was designed to examine the effect of sepsis on the apoptosis of alveolar macrophages. Design Prospective study. Setting Intensive care unit and surgical intensive care and trauma unit of a large university hospital in Athens, Greece. Patients Bronchoalveolar lavage was obtained from 20 consecutive patients who met the criteria for sepsis, admitted to two intensive care units. Bronchoalveolar lavage was obtained from nine volunteers without lung disease who served as controls. Interventions None. Measurements and Main Results The specimens were analyzed by using annexin V binding, terminal deoxynucleotidyl transfer-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL), DNA laddering, light microscopy, and immunohistochemistry. Spontaneous apoptosis of bronchoalveolar lavage cells and particularly of alveolar macrophages was significantly decreased in septic patients compared with nonseptic controls. This finding was confirmed by using morphologic criteria and the TUNEL method. Furthermore, gel electrophoresis of DNA obtained from bronchoalveolar cells revealed that DNA fragmentation was not necessarily associated with apoptotic cell death. The bcl-2 gene was minimally expressed in the control group. An inverse correlation was found between the percentage of apoptotic alveolar macrophages and the severity of sepsis. Conclusions The prolonged survival of lung cells in septic patients and especially of alveolar macrophages may be attributable to the inhibition of apoptosis. This seems to represent an initial attempt of the host to increase the defense capacity to kill the invading microorganism, resulting in an unbalanced tissue load of cells and an uncontrolled release of toxic metabolites. Furthermore, the inhibition of apoptosis in septic patients may explain why lung function is impaired, leading to sepsis-induced acute respiratory distress syndrome and death.

Administration of human protein C improves survival in an experimental model of sepsis

Objective:Study the effect of human protein C (PC) concentrate administration on organ damage and survival in septic rats. Design:Animal study. Setting:University laboratory. Subjects:Male Wistar rats. Interventions:Cecal ligation and puncture (CLP) was performed in 210 rats. Rats were randomly assigned to receive either human protein C (PC) IV 1, 7, and 13 hrs after CLP (CLP+PC) or placebo (CLP). Septic animals were again randomized in a survival group (CLP: n = 50 and CLP+PC: n = 40) that was monitored for 60 hrs and time groups (CLP: n = 60 and CLP+PC: n = 60) that were killed at 6, 12, 24, 36, 48, and 60 hrs after CLP. Brain, heart, lung, liver, kidney, gastric, and colon tissue were removed and postfixed in paraffin sections. Measurements and Main Results:PC infusion increased PC serum levels in early sepsis (median 7.25) compared with late sepsis (median 2, p = .001). Activated protein C/a1-antitrypsin complex levels in the CLP+PC group were significantly increased in late sepsis (60 hrs after CLP) compared with early sepsis (6, 12, and 24 hrs after CLP, p = .009, p = .004, and p = .008, respectively) and to late septic CLP and normal rats (p = .005 and p = .007, respectively). Their IL-6 and tumor necrosis factor a plasma levels were decreased (by 27% and 25%, respectively) at 6 hrs compared with placebo (p = .008 and p = .016). Their serum PC levels were also decreased in CLP+PC survivors compared with nonsurvivors of the same group (median = 1.5 vs. median = 7, p = .001). Apoptosis was reduced in brain (10% vs. 77.8%, p < .001), stomach (66.7% vs. 100%, p < .002) and intestine (33.3% vs. 85.2%, p < .001) compared with placebo. Finally, the survival of septic rats treated with human PC was significantly increased compared with placebo (75% vs. 54%, p = .033). Conclusions:Human Protein C administration increased survival in septic rats, decreased plasma inflammatory cytokines levels and tissue injury in vital organs.

Long-term primary cultures of human adult atrial cardiac myocytes: cell viability, structural properties and BNP secretion in vitro.

BACKGROUND Human adult cardiomyocytes (CM) have been used in short-term cultures for in vitro studies of the adult myocardium. However, little information is available regarding human adult CMs cultured for long term (>2 weeks). METHODS Human adult CMs were isolated from atrial specimens of 43 patients undergoing cardiopulmonary bypass surgery. Cell viability, cytoskeletal properties, intercellular junctional mediators and responsiveness to extracellular stimuli were monitored in CM cultures for 8 weeks. RESULTS Absolute numbers of CMs decreased through the first 2 weeks, with substantially lower rates of cell loss thereafter. Apoptosis predominated over necrosis as the principal mode of cell death, affecting 4.1+/-1.6% of freshly dissociated cells, that declined in culture (3.6+/-1.0% week 1, 1.3+/-0.5% week 2). CMs maintained rod-shaped morphology and cross-striated expression pattern of sarcomeric proteins desmin and beta-myosin heavy chain for the first 4 weeks. Levels of desmin remained stable on first 3 weeks, but declined thereafter. CMs expressed cardiac-specific adherence molecule N-cadherin throughout the culture duration, indicating conserved contractile potential. CMs remained functional early in culture, as indicated by BNP secretion, with maximal levels on 1st week that declined gradually by week 4. Cell responsiveness to metabolic stresses (serum deprivation) was detected, inducing an early (6 h) 1.8-fold increase in levels of BNP. CONCLUSION Long-term cultured human adult CMs maintain morphological integrity, adult-type cytoskeletal protein expression, cell-cell communication potential and functionality for 3-4 weeks in vitro.

Bilateral synchronous breast carcinomas followed by a metastasis to the gallbladder: a case report.

BackgroundBreast cancer is usually associated with metastases to lungs, bones and liver. Breast carcinoma metastasizing to the gallbladder is very rare.Case presentationA 59-year-old woman presented with bilateral synchronous breast lesions. A palpable, retroareolar solid lesion of diameter equal to 5 cm was present in the right breast, and a newly developed, non-palpable lesion with microcalcifications (diameter equal to 0.7 cm) was present in the upper outer quadrant of the left breast. Modified radical mastectomy was performed on the right breast and lumpectomy after hook-wire localization was performed on the left breast, combined with lymph node dissection in both sides. The pathological examination revealed invasive lobular carcinoma grade II in the right breast and invasive ductal carcinoma grade I in the left breast. Chemotherapy, radiation therapy, trastuzumab and letrozole were appropriately administered. At her 18-month follow-up, the patient was free of symptoms; the imaging tests (chest CT, abdominal U/S, bone scan), biochemical tests, blood cell count and tumor markers were also normal. At the 20th month after surgery however, the patient developed symptoms of cholecystitis and underwent cholecystectomy. The histopathological examination revealed metastasis of the lobular carcinoma to the gallbladder.ConclusionThis extremely rare case confirms on a single patient the results of large series having demonstrated the preferential metastasis of lobular breast cancer to the gallbladder. Symptoms of cholecystitis should not be neglected in such patients, as they might indicate metastasis to the gallbladder.

Complications of percutaneous stereotactic vacuum assisted breast biopsy system utilizing radio frequency

OBJECTIVE The Breast Lesion Excision System (BLES) is a novel, automatic breast biopsy device that utilizes radiofrequency to excise suspicious non-palpable mammographic lesions. The purpose of the present prospective study is to report and evaluate the complications of this new technique. MATERIALS AND METHODS In a two year period, we used the BLES device in 132 consecutive patients (134 procedures) with non-palpable mammographic lesions. The inclusion criteria consisted of suspicious microcalcifications, solid lesions and asymmetric density. In order to retrieve an intact biopsy specimen, we used the 12mm, 15mm or 20mm tissue basket under local anesthesia, depending on the size of the lesion. Complications were recorded and classified as immediate if occurring during or shortly after the procedure, or late, if occurring in the post-procedure days. RESULTS The procedure was considered successful in all cases, with mammographic confirmation of appropriate excision of the targeted lesion. Although, in a single case the basket initially failed to deploy. Immediate complications were encountered in 11 patients, with minor hemorrhage being the most common (n=6). 17 patients suffered late complications, in seven of whom delayed wound healing was observed. Overall, 27 patients suffered Grade 1 complications (20.14%), one patient experienced a Grade 2 complication while no patients encountered Grade 3-5 complications. CONCLUSIONS According to our experience, the BLES device is an efficient and safe breast biopsy method, with low complication rates, which are minor in their majority. It appears to be a very promising alternative to other, minimally invasive, breast biopsy techniques.