EACTS expert consensus statement for surgical management of pleural empyema

Pleural infection is a frequent clinical condition. Prompt treatment has been shown to reduce hospital costs, morbidity and mortality. Recent advances in treatment have been variably implemented in clinical practice. This statement reviews the latest developments and concepts to improve clinical management and stimulate further research. The European Association for Cardio-Thoracic Surgery (EACTS) Thoracic Domain and the EACTS Pleural Diseases Working Group established a team of thoracic surgeons to produce a comprehensive review of available scientific evidence with the aim to cover all aspects of surgical practice related to its treatment, in particular focusing on: surgical treatment of empyema in adults; surgical treatment of empyema in children; and surgical treatment of post-pneumonectomy empyema (PPE). In the management of Stage 1 empyema, prompt pleural space chest tube drainage is required. In patients with Stage 2 or 3 empyema who are fit enough to undergo an operative procedure, there is a demonstrated benefit of surgical debridement or decortication [possibly by video-assisted thoracoscopic surgery (VATS)] over tube thoracostomy alone in terms of treatment success and reduction in hospital stay. In children, a primary operative approach is an effective management strategy, associated with a lower mortality rate and a reduction of tube thoracostomy duration, length of antibiotic therapy, reintervention rate and hospital stay. Intrapleural fibrinolytic therapy is a reasonable alternative to primary operative management. Uncomplicated PPE [without bronchopleural fistula (BPF)] can be effectively managed with minimally invasive techniques, including fenestration, pleural space irrigation and VATS debridement. PPE associated with BPF can be effectively managed with individualized open surgical techniques, including direct repair, myoplastic and thoracoplastic techniques. Intrathoracic vacuum-assisted closure may be considered as an adjunct to the standard treatment. The current literature cements the role of VATS in the management of pleural empyema, even if the choice of surgical approach relies on the individual surgeon's preference.

Refractory Hematuria in an Oliguric Patient After Pancreas Transplantation with Exocrine Pancreas Bladder Drainage

A 52-yr-old man presented with hematuria and clot retention. He had undergone simultaneous pancreas-kidney transplantation with exocrine pancreas bladder drainage 16 yr ago. The patient suffered from progressive transplant kidney failure with gradually decreasing urine output and needed hemodialysis every other day. Gross hematuria persisted after removal of all blood clots. Cystoscopy showed multiple small, flat ulcers of the bladder mucosa. Some bled discretely and were coagulated cautiously. However, hematuria was refractory to multiple urological interventions, which eventually necessitated an enteric diversion of the exocrine pancreas. Hematuria ceased following an uneventful postoperative course.

[The thoracoscopic talc pleurodesis with intraoperative pleural biopsy - a retrospective analysis in patients with malignant pleural effusion]

The thoracoscopic pleurodesis with talc is an established therapy in case of malignant pleural effusion. With the instillation of talc a -localised inflammation is induced. However, some-times it turns into a severe systemic reaction. In this study of the postoperative course, the -question is examined whether a pleural biopsy is an additional risk factor for morbidity and mortality after talc pleurodesis.

Putative cancer stem cells in malignant pleural mesothelioma show resistance to cisplatin and pemetrexed

Malignant pleural mesothelioma (MPM) is a lethal cancer of the mesothelium with high chemotherapeutic resistance via unknown mechanisms. A prevailing hypothesis states that cancer stem cells (CSCs) persist in tumors causing relapse after chemotherapy, thus, rendering these cells as critical targets responsible for tumor resistance and recurrence. We selected candidate CSC markers based on expansion under hypoxic conditions, a hallmark for the selection of chemoresistant cells; and investigated the expression of CSC markers: CD133, Bmi-1, uPAR and ABCG2 in three MPM cell lines and normal mesothelial cells by quantitative RT-PCR. Furthermore, we evaluated the chemotherapeutic resistance associated with each CSC marker by determining the change in CSC marker-mRNA levels as an index of drug-resistance following treatment with either cisplatin or pemetrexed. We demonstrate the expression of CSC markers: CD133, Bmi-1, uPAR and ABCG2 in both normal and MPM cell lines. Bmi-1+, uPAR+ and ABCG2+ cells show a distinct role in conferring chemoresistance to cisplatin and pemetrexed in the malignant setting. By contrast, these markers have no apparent participation in chemoresistance to drug treatments in normal mesothelial cells. Intriguingly, CD133 revealed chemoresistant properties in both normal mesothelial and malignant pleural mesothelioma cells. This study provides evidence of putative CSCs conferring drug-resistance to cisplatin and pemetrexed in MPM cell lines. Specific targeting of these drug-resistant cells, while considering the functional heterogeneity of the MPM subtypes, may contribute to more focused and effective chemotherapeutic regimens for malignant pleural mesothelioma.

Efficacy of silver-bearing external ventricular drainage catheters: a retrospective analysis

Catheter-related infection of CSF is a potentially life-threatening complication of external ventricular drainage (EVD). When using EVD catheters, contact between the ventricular system and skin surface occurs and CSF infection is possible. The aim of this analysis was to compare the efficacy of silver-bearing EVD catheters for reducing the incidence of infection with standard nonimpregnated EVD catheters in neurosurgical patients with acute hydrocephalus.

Long term survival after trimodal therapy in malignant pleural mesothelioma

Trimodal therapy results in long term survival in a small fraction of patients with malignant pleural mesothelioma, particularly in patients having epithelial histology, R0-resection and no nodal involvement. This study analyses the outcome after trimodal therapy including extrapleural pneumonectomy.

Is the use of antibiotic-impregnated external ventricular drainage beneficial in the management of iatrogenic ventriculitis?

Profound evidence substantiates significantly reduced risk of catheter-related infections with prophylactic use of rifampin- and clindamycin-impregnated silicone catheters (Bactiseal(®), Codman Johnson & Johnson, Raynham, MA, USA) for external ventricular drainage (EVD). However, whether Bactiseal(®)-EVD (B-EVD) influences the treatment of EVD-related ventriculitis remains controversial.

p53-induced apoptosis occurs in the absence of p14(ARF) in malignant pleural mesothelioma

Malignant pleural mesotheliomas (MPMs) are usually wild type for the p53 gene but contain homozygous deletions in the INK4A locus that encodes p14(ARF), an inhibitor of p53-MDM2 interaction. Previous findings suggest that lack of p14(ARF) expression and the presence of SV40 large T antigen (L-Tag) result in p53 inactivation in MPM. We did not detect SV40 L-Tag mRNA in either MPM cell lines or primary cultures, and treatment of p14(ARF)-deficient cells with cisplatin (CDDP) increased both total and phosphorylated p53 and enhanced p53 DNA-binding activity. On incubation with CDDP, levels of positively regulated p53 transcriptional targets p21(WAF), PIG3, MDM2, Bax, and PUMA increased in p14(ARF)-deficient cells, whereas negatively regulated survivin decreased. Significantly, p53-induced apoptosis was activated by CDDP in p14(ARF)-deficient cells, and treatment with p53-specific siRNA rendered them more CDDP-resistant. p53 was also activated by: 1) inhibition of MDM2 (using nutlin-3); 2) transient overexpression of p14(ARF); and 3) targeting of survivin using antisense oligonucleotides. However, it is noteworthy that only survivin downregulation sensitized cells to CDDP-induced apoptosis. These results suggest that p53 is functional in the absence of p14(ARF) in MPM and that targeting of the downstream apoptosis inhibitor survivin can sensitize to CDDP-induced apoptosis.

Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma

BACKGROUND: The aim of this multicenter trial was to prospectively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) and radiotherapy, including quality of life as outcome. PATIENTS AND METHODS: Eligible patients had malignant pleural mesothelioma of all histological types, World Health Organization performance status of zero to two and clinical stage T1-T3, N0-2, M0 disease considered completely resectable. Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP. Postoperative radiotherapy was considered for all patients. RESULTS: In all, 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy. Forty-five patients (74%) underwent EPP and in 37 patients (61%) the resection was complete. Postoperative radiotherapy was initiated in 36 patients. The median survival of all patients was 19.8 months [95% confidence interval (CI) 14.6-24.5]. For the 45 patients undergoing EPP, the median survival was 23 months (95% CI 16.6-32.9). Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82% (N = 36) at baseline and 76% (N = 26) at 3 months after surgery (P = 0.5). CONCLUSIONS: The observed rate of operability is promising. A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery. This approach was not associated with an increase in psychological distress.

[Hyperinsulinemia as a consequence of systemic venous drainage in patients with pancreas transplantation]

To evaluate the metabolic consequences of pancreatic transplantation with systemic venous drainage on beta cell function, we examined insulin and C-peptide responses to arginine and secretin in type I diabetic recipients of pancreas transplantation (n = 16), and normal controls (n = 28). Basal insulin levels were 24 +/- 3 microU/l in pancreas recipients, and 7 +/- 1 microU/l in controls (p less than 0.001). Stimulated insulin levels following arginine (MANOVA, p less than 0.001), and secretin (MANOVA, p less than 0.001) were 1.5 to 3 fold elevated compared to controls. In contrast, integrated C-peptide responses following stimulation with arginine or secretin did not differ significantly between the two groups. We conclude that recipients of pancreas allografts with systemic venous drainage have elevated basal and stimulated insulin levels and that these alterations are primarily due to alterations of first pass hepatic insulin clearance although insulin resistance secondary to immunosuppressive therapy (including prednisone) may also play a contributing role. To avoid hyperinsulinemia and its possible long term adverse consequences, transplantation of pancreas allografts in sites with portal rather than systemic venous drainage may be preferable.

Systemic venous drainage of pancreas allografts as independent cause of hyperinsulinemia in type I diabetic recipients

To evaluate the metabolic consequences of pancreas transplantation with systemic venous drainage on beta-cell function, we examined insulin and C-peptide responses to glucose and arginine in type I (insulin-dependent) diabetic pancreas recipients (n = 30), nondiabetic kidney recipients (n = 8), and nondiabetic control subjects (n = 28). Basal insulin levels were 66 +/- 5 pM in control subjects, 204 +/- 18 pM in pancreas recipients (P less than 0.0001 vs. control), and 77 +/- 17 pM in kidney recipients. Acute insulin responses to glucose were 416 +/- 44 pM in control subjects, 763 +/- 91 pM in pancreas recipients (P less than 0.01 vs. control), and 589 +/- 113 pM in kidney recipients (NS vs. control). Basal and stimulated insulin levels in two pancreas recipients with portal venous drainage were normal. Integrated acute C-peptide responses were not statistically different (25.3 +/- 4.3 nM/min in pancreas recipients, 34.2 +/- 5.5 nM/min in kidney recipients, and 23.7 +/- 2.1 nM/min in control subjects). Similar insulin and C-peptide results were obtained with arginine stimulation, and both basal and glucose-stimulated insulin-C-peptide ratios in pancreas recipients were significantly greater than in control subjects. We conclude that recipients of pancreas allografts with systemic venous drainage have elevated basal and stimulated insulin levels and that these alterations are primarily due to alterations of first-pass hepatic insulin clearance, although insulin resistance secondary to immunosuppressive therapy (including prednisone) probably plays a contributing role. To avoid hyperinsulinemia and its possible long-term adverse consequences, transplantation of pancreas allografts into sites with portal rather than systemic venous drainage should be considered.

Roux-en-Y drainage of the pancreatic stump decreases pancreatic fistula after distal pancreatic resection

Clinically relevant fistula after distal pancreatic resection occurs in 5-30% of patients, prolonging recovery and considerably increasing in-hospital stay and costs. We tested whether routine drainage of the pancreatic stump into a Roux-en-Y limb after distal pancreatic resection decreased the incidence of fistula. From October 2001, data of all patients undergoing pancreatic distal resection were entered in a prospective database. From June 2003 after resection, the main pancreatic duct and the pancreatic stump were oversewn, and in addition, anastomosed into a jejunal Roux-en-Y limb by a single-layer suture (n = 23). A drain was placed near the anastomosis, and all patients received octreotide for 5-7 days postoperatively. The volume of the drained fluid was registered daily, and concentration of amylase was measured and recorded every other day. Patient demographics, hospital stay, pancreatic fistula incidence (> or =30 ml amylase-rich fluid/day on/after postoperative day 10), perioperative morbidity, and follow-up after discharge were compared with our initial series of patients (treated October 2001-May 2003) who underwent oversewing only (n = 20). Indications, patient demographics, blood loss, and tolerance of an oral diet were similar. There were four (20%) pancreatic fistulas in the "oversewn" group and none in the anastomosis group (p < 0.05). Nonsurgical morbidity, in-hospital stay, and follow-up were comparable in both groups.