Outcomes from the Delphi process of the Thoracic Robotic Curriculum Development Committee.

OBJECTIVES: As the adoption of robotic procedures becomes more widespread, additional risk related to the learning curve can be expected. This article reports the results of a Delphi process to define procedures to optimize robotic training of thoracic surgeons and to promote safe performance of established robotic interventions as, for example, lung cancer and thymoma surgery. METHODS: In June 2016, a working panel was spontaneously created by members of the European Society of Thoracic Surgeons (ESTS) and European Association for Cardio-Thoracic Surgery (EACTS) with a specialist interest in robotic thoracic surgery and/or surgical training. An e-consensus-finding exercise using the Delphi methodology was applied requiring 80% agreement to reach consensus on each question. Repeated iterations of anonymous voting continued over 3 rounds. RESULTS: Agreement was reached on many points: a standardized robotic training curriculum for robotic thoracic surgery should be divided into clearly defined sections as a staged learning pathway; the basic robotic curriculum should include a baseline evaluation, an e-learning module, a simulation-based training (including virtual reality simulation, Dry lab and Wet lab) and a robotic theatre (bedside) observation. Advanced robotic training should include e-learning on index procedures (right upper lobe) with video demonstration, access to video library of robotic procedures, simulation training, modular console training to index procedure, transition to full-procedure training with a proctor and final evaluation of the submitted video to certified independent examiners. CONCLUSIONS: Agreement was reached on a large number of questions to optimize and standardize training and education of thoracic surgeons in robotic activity. The production of the content of the learning material is ongoing.

Budesonide Inhibits Intracellular Infection with Non-Typeable Haemophilus influenzae Despite Its Anti-Inflammatory Effects in Respiratory Cells and Human Lung Tissue: A Role for p38 MAP Kinase.

BACKGROUND: Inhaled corticosteroids (ICS) are widely used in the treatment of obstructive lung diseases. Recent data suggest a higher pneumonia risk in chronic obstructive pulmonary disease (COPD) patients treated with ICS. OBJECTIVE: Since non-typeable Haemophilus influenzae (NTHi) is the most common pathogen associated with acute exacerbations of COPD, we investigated the effects of budesonide (BUD) on NTHi-induced inflammation and invasive infection. METHODS: The alveolar epithelial cell line A549 and specimens of human lung tissue (HLT) were used in our experiments. Intracellular infection was determined by a lysis/culture assay of infected cells. Activated p38 mitogen-associated protein kinase (MAPK) was assessed using Western blotting and immunohistochemistry, expression of toll-like receptor 2 (TLR2) was determined by PCR, and CXCL-8 levels were measured using ELISA. Immunohistochemistry was used for detection of CXCL-8, platelet-activating factor receptor (PAF-R) and NTHi. RESULTS: BUD significantly reduced CXCL-8 secretion in A549 cells and lung tissue infected with NTHi. Furthermore, BUD decreased the expression of PAF-R in HLT and A549 cells. In A549 cells and HLT, BUD inhibited intracellular infection and - synergistically with NTHi - increased the expression of TLR2 (in A549 cells). TLR2 stimulation did not influence the intracellular infection of A549 cells, but p38 MAPK inhibition resulted in a significant reduction of infection. CONCLUSION: The present study adds new insights into the effects of glucocorticoids on pulmonary host defence after NTHi infection. Although the inflammatory response to infection is suppressed by BUD, interestingly, the intracellular infection is also inhibited. This effect seems to depend on the inhibition of p38 MAPK - a key enzyme in many pro-inflammatory pathways - as well as of PAF-R expression.

Outcome and management of invasive candidiasis following oesophageal perforation.

The regular colonisation of the oesophagus with a Candida species can, after oesophageal perforation, result in a contamination of the mediastinum and the pleura with a Candida species. A patient cohort of 80 patients with oesophageal perforation between 1986 and 2010 was analysed retrospectively. The most common sources with positive results for Candida were mediastinal biopsies and broncho-alveolar secretions. Candida species were detected in 30% of the patients. The mortality rate was 41% in patients with positive microbiology results for Candida, whereas it was 23% in the remaining patient cohort. This difference did not reach statistical significance (P = 0.124). Mortality associated with oesophageal perforation was attributed mainly to septic complications, such as mediastinitis and severe pneumonia. During the study period we observed a shift towards non-albicans species that were less susceptible or resistant to fluconazole. In selected patients with risk factors as immunosuppression, granulocytopenia and long-term intensive-care treatment together with the finding of Candida, an antimycotic therapy should be started. A surgical approach offers the possibility to obtain deep tissue biopsies. The antimycotic therapy should start with an echinocandin, as the resistance to fluconazole is growing and to cover non-albicans Candida species, too.

Intrahepatic radiofrequency ablation versus electrochemical treatment in vivo.

BACKGROUND: Radiofrequency ablation (RFA) and electrochemical treatment (ECT) are two methods of local liver tumour ablation. The objective of this study was to compare these methods when applied in proximity to vessels in vivo. METHODS: In a total of ten laparotomised pigs, we used ECT (Group A, four animals) and RFA (Group B, four animals) to create four areas of ablation per animal under ultrasound guidance within 10 mm of a vessel. Group C consisted of two control animals. Chemical laboratory tests were performed immediately before and after each procedure and on days 1, 3 and 7 after surgery. Following the last tests, the livers were harvested for morphological evaluation. RESULTS: The mean duration of surgery was 5 h 40 min in Group A (ECT), 2 h 47 min in Group B (RFA), and 2 h 30 min in Group C (control animals). After ECT, the harvested livers showed a mean volume of necrosis of 1.84 cm(3) ± 0.88 at the anode and 2.59 cm(3) ± 1.06 at the cathode. The presence of vessels did not influence the formation of necrotic zones. Ablation time was 67 min when a charge of 200 coulombs was delivered. We measured pH values of 1.2 (range: 0.9-1.7) at the anode and 11.7 (range: 11.0-12.1) at the cathode. In one of the 16 RFA ablations (6%), the target temperature was not reached and the procedure was discontinued. After 14 of 16 RFA procedures (88%), morphological analysis showed incomplete ablation in perivascular sites. Both ECT and RFA were associated with a reversible increase in monocyte, C-reactive protein (CRP) and aspartate aminotransferase (AST) levels. There was no significant increase in interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α) and IL-6. CONCLUSION: In the majority of cases, intrahepatic RFA in vivo leads to incomplete necrosis in proximity to vessels and the presence of histologically intact perivascular cells. Without a reduction in liver perfusion, the central application of RFA should be considered problematic. ECT is a safe alternative. It is not associated with a heat sink effect but has the disadvantage of long treatment times.

The application of cold-plasma coagulation on the visceral pleura results in a predictable depth of necrosis without fistula generation.

A technique for the safe transfer of electric energy to the pulmonary surface for the potential evaporation of malignant tumours is non-existent to date. By conducting the current study, we wanted to generate data on the potential beneficiary effects and complications of using cold-plasma coagulation on the pulmonary surface. Cold-plasma coagulation was applied to the pulmonary surface in eight female mini-pigs via a thoracoscopic access. After 12 days, we performed a re-thoracoscopy on the contralateral side. After a further 12 days, we performed a median sternotomy and did cold-plasma coagulation on previously untreated areas of either lung. No pulmonary fistulas were detected. In two of the eight pigs, we found a localized chronic pneumonia. None of the pigs died during the course of the study. Morbidity was also low with two pigs refusing food intake, one pig with dyspnoea after difficult intubation and one pig coughing. All events were self-limited and occurred only on post-operative Day 1. The treatment effect was almost linear and correlated to the generator energy applied. The differences between the effects reached statistical significance (P < 0.05). The application of cold-plasma coagulation to the pulmonary surface is safe in pigs. A potential clinical application of this technique is treatment of malignant pleural mesothelioma.

Optimal management of pulmonary metastases from colorectal cancer.

The incidence of colorectal cancers is rising worldwide and pulmonary metastases were seen in approximately 10-15% of all patients. Surgical metastasectomy is a widely accepted procedure in selected patients and is considered as the only curative option in patients with secondary pulmonary malignancy. But surgical resection remains controversial due to the lack of randomized trials, comparing pulmonary metastasectomy to control, either medical therapy, or observation. This article will discuss the differentiated therapeutic strategies for patients with pulmonary metastases of colorectal cancer, focusing on surgical resection, patient evaluation, prognostic factors, interdisciplinary therapeutic approaches and current trials.

Emergency thoracic surgery in elderly patients.

OBJECTIVES: Emergency thoracic surgery in the elderly represents an extreme situation for both the surgeon and patient. The lack of an adequate patient history as well as the inability to optimize any co-morbidities, which are the result of the emergent situation, are the cause of increased morbidity and mortality. We evaluated the outcome and prognostic factors for this selected group of patients. DESIGN: Retrospective chart review. SETTING: Academic tertiary care referral center. PARTICIPANTS: Emergency patients treated at the Department of Thoracic Surgery, University Hospital of Luebeck, Germany. MAIN OUTCOME MEASURES: Co-morbidities, mortality, risk factors and hospital length of stay. RESULTS: A total of 124 thoracic procedures were performed on 114 patients. There were 79 men and 36 women (average age 72.5 ±6.4 years, range 65-94). The overall operative mortality was 25.4%. The most frequent indication was thoracic/mediastinal infection, followed by peri- or postoperative thoracic complications. Risk factors for hospital mortality were a high ASA score, pre-existing diabetes mellitus and renal insufficiency. CONCLUSIONS: Our study documents a perioperative mortality rate of 25% in patients over 65 who required emergency thoracic surgery. The main indication for a surgical intervention was sepsis with a thoracic/mediastinal focus. Co-morbidities and the resulting perioperative complications were found to have a significant effect on both inpatient length of stay and outcome. Long-term systemic co-morbidities such as diabetes mellitus are difficult to equalize with respect to certain organ dysfunctions and significantly increase mortality.

Sequential surgical resection of hepatic and pulmonary metastases from colorectal cancer.

BACKGROUND: Resection of isolated hepatic or pulmonary metastases from colorectal cancer is widely accepted and associated with a 5-year survival rate of 25-40%. The value of aggressive surgical management in patients with both hepatic and pulmonary metastases still remains a controversial area. MATERIALS AND METHODS: A retrospective review of 1,497 patients with colorectal carcinoma (CRC) was analysed. Of 73 patients identified with resection of CRC and, at some point in time, both liver and lung metastases, 17 patients underwent metastasectomy (resection group). The remaining 56 patients comprised the non-resection group. Primary tumour, hepatic and pulmonary metastases of all patients were surgically treated in our department of surgery, and the results are that of a single institution. RESULTS: The resection group had a 3-year survival of 77%, a 5-year survival of 55% and a 10-year survival of 18%; median survival was 98 months. The longest overall survival was 136 months; six patients are still alive. In the resection group, overall survival was significantly higher than in the non-resection group (p < 0.01). Independent from the chronology of metastasectomy, 5-year survival was 55% with respect to the primary resection, 28% with respect to the first metastasectomy and 14% with respect to the second metastasectomy. A disease-free interval (>18 months), stage III (UICC) and age (<70 years) were found to be significant prognostic factors for overall survival. CONCLUSION: Our report strongly supports aggressive surgical therapy in patients with both hepatic and pulmonary metastases from CRC. Overall survival for surgically treated selected patients with both hepatic and pulmonary metastases from CRC is comparable to hepatic or pulmonary metastasectomy. Simultaneous metastases tend to have a poorer outcome than metachronous metastases.

Cold-plasma coagulation in the treatment of malignant pleural mesothelioma: results of a combined approach.

Malignant pleural mesothelioma is on a continuous rise throughout the Western countries. It is associated with asbestos fibre exposition in the past. Surgical approaches include extrapleural pneumonectomy and pleurectomy/decortication (P/D). We investigated the feasability of the implementation of cold-plasma coagulation (CPC) on the pleura, pericardium and diaphragm into an established therapeutic algorithm consisting of P/D and hyperthermic intrathoracal chemoperfusion (HITHOC) therapy. The underlying rationale was the prevention of cardiotoxic effects during HITHOC as well as accidental translocation of malignant cells to the abdomen. CPC was done as part of a multimodal therapy in stage III mesothelioma patients. Histologic examinations of pleural excisates after CPC were done. The patients were followed up in three-month intervals. Neither parenchymal fistulas, nor cardiotoxic effects were observed. The histologic examination of the pleural excisates showed complete predictable necrosis. Moreover, until now (median time after operation 1 year) no relapse of the disease was observed. CPC proved to be a safe technique when used on the pleura, pericardium and diaphragm. We consider our trial as a pilot-study. To evaluate potential survival benefits using this technique larger trials are mandatory.

Giant thymoma in the anterior-inferior mediastinum.

Thymomas are usually found in the superior mediastinum and sternotomy is the standard approach for resection. We report a case of a male patient with a giant left-sided thymoma, nearly fulfilling the whole hemithorax. Due to the sheer size of the tumor and its location in the anterior-inferior mediastinum, we performed a lateral approach for thymectomy. On resection the specimen measured 18 x 16 x 12 cm. Histology revealed a mixed stage I thymoma. The patient is doing well 36 months after resection and has no signs of recurrence. In literature, a significant increase in the risk of recurrence for thymomas >8 cm is reported.

Fournier's gangrene: is the female gender a risk factor?

OBJECTIVE: Fournier's gangrene is a necrotizing fasciitis that affects the perineal, genital, or perianal regions. The objective of this study was to highlight this uncommon condition with a particular focus on the disease course in females. MATERIALS AND METHODS: From 1996 to 2008, we prospectively collected data from 38 patients with Fournier's gangrene (12 women, 26 men) and retrospectively analyzed relevant parameters. RESULTS: The mean age was 60.9 +/- 11.3 years for females (group I) and 56.2 +/- 11.7 years for males (group II). In both groups, the main predisposing factors were diabetes mellitus and obesity (body mass index of 30 or higher). Twelve men (46.2%), but no women, had chronic alcoholism. The most commonly isolated agents were Escherichia coli (n = 22), streptococcal species (n = 18), Pseudomonas aeruginosa (n = 9), and Staphylococcus aureus (n = 7). Mortality was significantly higher among females (50%) than males (7.7%; p = 0.011). Peritonitis was present in seven group I patients (58.3%) and in two group II patients (7.7%). The retroperitoneum was involved in seven female patients (58.3%) and four male patients (15.4%). CONCLUSION: The female gender is a risk factor for mortality in patients with Fournier's gangrene and is associated with a higher incidence of inflammation of the retroperitoneal space and abdominal cavity. Differences in male and female genital anatomy may be the reason for the rapid spread of infection to the retroperitoneum and the fatal outcome in women. Fournier's gangrene as a high-risk disease in females should attract exceeding attention.

Factors predicting the postoperative outcome of lower gastrointestinal hemorrhage.

PURPOSE: To examine the treatment outcome for patients with acute bleeding from the lower gastrointestinal tract requiring transfusion and acute surgical care as a function of various risk factors MATERIALS AND METHODS: Between 1999 and 2007, we collected data on 59 patients (39 male and 20 female patients) who received surgical intervention for acute lower intestinal hemorrhage requiring transfusion at our university clinic. Treatment complications and mortality were analyzed retrospectively. RESULTS: The average age of the patients in this study is 70.0 +/- 12.2 years (range, 39 to 97 years) with an overall mortality of 15.3%. Blood transfusions >10 U (p = 0.031), postoperative need for ventilation (p = 0.004), necessary reoperations (p = 0.016), and an initial hemoglobin level <80 g/L (p = 0.043) proved to be significant risk factors for death. Blood transfusions >10 U (p = 0.028), necessary reoperations (p = 0.001), and an initial hemoglobin level <80 g/L (p = 0.033) were found to be significant risk factors for postoperative complications. All other parameters have no significant impact. CONCLUSIONS: The decisive factors for the outcome of lower gastrointestinal hemorrhage requiring surgery are the severity of bleeding, beginning of treatment (initial hemoglobin level, need for packed red blood cells), and treatment efficiency (necessary reoperation).

Fournier's gangrene: vacuum-assisted closure versus conventional dressings.

BACKGROUND: Fournier's gangrene is a fulminant and destructive inflammation of the scrotum, penis, and perineum. The objective of this study was to compare 2 different approaches to wound management after aggressive surgical debridement. METHODS: Data from 35 patients with Fournier's gangrene were prospectively collected (1996-2007). Once the patients were stabilized following surgery, they were treated with either daily antiseptic (polyhexanide) dressings (group I, n = 16) or vacuum-assisted closure (VAC) therapy (group II, n = 19). RESULTS: The mean age of the patients was 58.2 years in group I and 57.2 years in group II. In both groups, the most common predisposing conditions were diabetes mellitus, chronic alcoholism, and obesity. Escherichia coli, streptococcal species, Pseudomonas aeruginosa, and Staphylococcus aureus were the most frequently isolated organisms. Length of hospital stay was 27.8 days +/- 27.6 days (mortality: 37.5%) in group I and 96.8 days +/- 77.2 days (mortality: 5.3%) in group II. Enterostomies were performed in 43.8% of group I patients and in 89.5% of group II patients. CONCLUSIONS: VAC was associated with significantly longer hospitalization and lower mortality. A partial explanation is that some patients with severe sepsis died within the first 3 days after admission and thus could not undergo vacuum therapy. Since our clinical experience has shown that vacuum dressings are particularly effective in the management of large wounds, we use VAC primarily for this indication despite the considerable material requirements involved.

Thoracic surgery in the elderly--co-morbidity is the limit.

A retrospective chart review was performed in 242 consecutive patients aged 65 years or older who were treated in an academic surgical centre between January 2004 and July 2007. A total of 249 thoracic procedures were performed in 242 patients, of whom 143 were men and 99 women with a mean age of 69.9 years (range 65-92). Overall operative mortality was 2.4%, rising to 26.4% in emergency patients. Negative predictors for perioperative mortality were: American Society of Anesthesiology (ASA) class 4, pre-existing kidney failure, leucocytosis, low haemoglobin, elevated C-reactive protein, diabetes mellitus and emergency surgery. In addition, the risk of major and minor complications resulting in a prolonged hospital stay was increased in emergency patients, patients with multiple co-morbidities and ASA class 3 or 4. Appropriate thoracic surgery can be offered to the elderly with an acceptable level of perioperative morbidity and mortality. Regardless of age, a high degree of co-morbidity or emergency surgery are the main risk factors for perioperative mortality and/or prolonged hospital stay.

Crohn's disease-a chameleon during pregnancy.

BACKGROUND: In the past, women with Crohn's disease (CD) as a risk factor in pregnancy were discouraged from becoming pregnant. Today, by contrast, gestation is medically acceptable in these patients despite several severe complications. MATERIALS AND METHODS: We present the course of five female patients with CD requiring surgery during pregnancy and giving birth at our institution between 1998 and 2008. These cases as well as our treatment recommendations for patients wishing to have children and our approaches to the management of complications during pregnancy are discussed in the light of the literature. RESULTS AND CONCLUSION: Three of five women had a preterm delivery (26 to 31 weeks' gestation) with a decreased neonatal weight. Generally, the diagnosis of CD is often delayed and diagnostic errors (four of five women) are not uncommon. The symptoms vary widely and include those typical of pregnancy. Three patients had to have a cesarean and only two patients were able to deliver vaginally. Especially in pregnant patients, the course of the disease is highly variable and difficult to predict. Our experience suggests that patients should be advised to conceive during remission. Indications for surgery in pregnant patients are the same as for nonpregnant women and include perforation, obstruction, hemorrhage, and abscess. The advantages of endoscopic surgery also apply to pregnant patients with acute manifestations. A stoma is not a contraindication to vaginal delivery.

Pulmonary lymphangioma.

We report on the very rare case of a 49-year-old man with a large solitary pulmonary lymphangioma. Rapid growth of the tumor led to dyspnea and pain. A chest roentgenogram and computed tomography scan revealed a large 18 x 12-cm space-occupying cystic lesion in the posterior mediastinum. The tumor was resected by lateral thoracotomy. Histopathology revealed a pulmonary cystic lymphangioma.

Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs.

RNA interference (RNAi) holds considerable promise as a therapeutic approach to silence disease-causing genes, particularly those that encode so-called 'non-druggable' targets that are not amenable to conventional therapeutics such as small molecules, proteins, or monoclonal antibodies. The main obstacle to achieving in vivo gene silencing by RNAi technologies is delivery. Here we show that chemically modified short interfering RNAs (siRNAs) can silence an endogenous gene encoding apolipoprotein B (apoB) after intravenous injection in mice. Administration of chemically modified siRNAs resulted in silencing of the apoB messenger RNA in liver and jejunum, decreased plasma levels of apoB protein, and reduced total cholesterol. We also show that these siRNAs can silence human apoB in a transgenic mouse model. In our in vivo study, the mechanism of action for the siRNAs was proven to occur through RNAi-mediated mRNA degradation, and we determined that cleavage of the apoB mRNA occurred specifically at the predicted site. These findings demonstrate the therapeutic potential of siRNAs for the treatment of disease.