Intraoperative Contrast-Enhanced Ultrasonography (Io-CEUS) in Minimally Invasive Thoracic Surgery for Characterization of Pulmonary Tumours: A Clinical Feasibility Study.

BACKGROUND: The intraoperative detection of solitary pulmonary nodules (SPNs) continues to be a major challenge, especially in minimally invasive video-assisted thoracic surgery (VATS). The location, size, and intraoperative frozen section result of SPNs are decisive regarding the extent of lung resection. This feasibility study investigates the technical applicability of intraoperative contrast-enhanced ultrasonography (Io-CEUS) in minimally invasive thoracic surgery. METHODS: In this prospective, monocentric clinical feasibility study, n = 30 patients who underwent Io-CEUS during elective minimally invasive lung resection for SPNs between October 2021 and February 2023. The primary endpoint was the technical feasibility of Io-CEUS during VATS. Secondary endpoints were defined as the detection and characterization of SPNs. RESULTS: In all patients (female, n = 13; mean age, 63 ± 8.6 years) Io-CEUS could be performed without problems during VATS. All SPNs were detected by Io-CEUS (100%). SPNs had a mean size of 2.2 cm (0.5-4.5 cm) and a mean distance to the lung surface of 2.0 cm (0-6.4 cm). B-mode, colour-coded Doppler sonography, and contrast-enhanced ultrasound were used to characterize all tumours intraoperatively. Significant differences were found, especially in vascularization as well as in contrast agent behaviour, depending on the tumour entity. After successful lung resection, a pathologic examination confirmed the presence of lung carcinomas (n = 17), lung metastases (n = 10), and benign lung tumours (n = 3). CONCLUSIONS: The technical feasibility of Io-CEUS was confirmed in VATS before resection regarding the detection of suspicious SPNs. In particular, the use of Doppler sonography and contrast agent kinetics revealed intraoperative specific aspects depending on the tumour entity. Further studies on Io-CEUS and the application of an endoscopic probe for VATS will follow.

[Rare cause of necrotizing pneumonia : A case report]. / Seltene Ursache einer einschmelzenden Pneumonie : Ein Fallbericht.

A 29-year-old Indian patient was admitted to the authors' pulmonary clinic with cough and fever. Community-acquired pneumonia was initially suspected. Various antibiotic therapies were administered, which did not lead to any clinical improvement. Despite detailed diagnostics, no pathogen was found. Computed tomography showed rapidly progressive pneumonia in the left upper lobe. Since the infection could not be managed conservatively, upper lobe resection was performed. Histologically, an amoebic abscess was found to be the cause of the infection. Since cerebral and hepatic abscesses were also found, hematogenous dissemination may be assumed.

EpCAM-positive disseminated cancer cells in bone marrow impact on survival of early-stage NSCLC patients.

INTRODUCTION: Detection of disseminated cancer cells (DCC) in bone marrow (BM) of patients with early-stage NSCLC has been associated with poor outcome. However, the phenotype, and hence relevant therapy targets, of DCCs in BM are unknown. We therefore compared a classical pan-Cytokeratin (CK) antibody for DCC detection with an anti-EpCAM antibody that may also detect more stem-like cells and tested whether assay positivity impacts on the survival of NSCLC patients. MATERIALS AND METHODS: We prospectively collected BM aspirates from 104 non-metastasized NSCLC patients that underwent potentially curative tumor resection from 2011 to 2016 at the Department of Thoracic Surgery of the University Hospital and Hospital Barmherzige Brüder in Regensburg. DCCs were detected by staining with the pan anti-CK antibody A45-B/B3 and the anti-EpCAM antibody HEA-125. We analyzed the association between detection of DCCs and clinicopathological characteristic and patient outcome. RESULTS: CK + and EpCAM + DCCs were detected in 45.2% and 52.9% of patients, respectively. Correlation between the two markers was low and neither of them was associated with sex, age, histology, T or N classification, resection status, grading or smoking habit. No significant association with tumor specific survival (TSS) and progression-free survival (PFS) was observed in patients with CK + DCCs. In contrast, detection of EpCAM + DCCs significantly correlated with reduced PFS (P = 0.017) and TSS (P = 0.017) and remained an independent prognostic variable for PFS and TSS upon multivariate testing (hazard ratio: 7.506 and 3.551, respectively). Detection of EpCAM + DCCs was the only prognostic marker for PFS. CONCLUSIONS: EpCAM+, but not CK + DCCs in BM predict reduced PFS and TSS. This finding suggests that EpCAM + DCCs in the BM comprise metastatic founder cells necessitating their in-depth molecular analysis for detection of novel therapy targets.

Evaluation of Surgical Therapy in Advanced Thymic Tumors.

A complete resection of thymic tumors is known to be the most important prognostic factor, but it is often difficult to perform, especially in advanced stages. In this study, 73 patients with advanced thymic tumors of UICC stages III and IV who underwent radical resection were examined retrospectively. The primary endpoint was defined as the postoperative resection status. Secondary endpoints included postoperative morbidity, mortality, recurrence/progression-free, and overall survival. In total, 31.5% of patients were assigned to stage IIIa, 9.6% to stage IIIb, 47.9% to stage IVa, and 11% to stage IVb. In stages III a R0 resection was achieved in 53.3% of patients. In stages IV a R0/R1 resection was documented in 76.7% of patients. Surgical revision was necessary in 17.8% of patients. In-hospital mortality was 2.7%. Median recurrence/progression-free interval was 43 months (p = 0.19) with an overall survival of 79 months. The 5-year survival rate was 61.3%, respectively. Median survival after R2 resection was 25 months, significantly shorter than after R0 or R1 resection (115 months; p = 0.004). Advanced thymic tumors can be resected with an acceptable risk of complications and low mortality. In stage III as well as in stage IV the promising survival rates are dependent on the resection-status.

Evaluation of treatment options for postoperative and spontaneous chylothorax in adults.

OBJECTIVES: Both postoperative and spontaneous chylothorax remain therapeutic challenges without recommendations for a standardized treatment approach. Regardless of its aetiology, patients with chylothorax experience prolonged hospitalization and suffer from the associated complications or the invasive therapy administered. METHODS: We conducted a retrospective, observational review of adult patients with chylothorax treated between January 2010 and September 2019. The primary end point was successful management with sustained cessation and/or controlled chylous output. Therapy duration, inpatient stay and the incidence of complications were evaluated as secondary end points. RESULTS: Of the 36 patients included (22 men; median age 63 years), 24 patients (67%) suffered from a postoperative accumulation of chylous fluid in the pleural space; in the remaining 12 (33%) patients, chylothoraces occurred spontaneously. Initial conservative treatment was successful in 42% (n = 15); in the other 20 cases (56%) additional invasive therapeutic strategies were followed. A complicated course requiring more than 1 treatment was seen in 54% (n = 13) of the postoperative and in 58% (n = 7) of the spontaneous cases. The median length of hospitalization was significantly longer in the postoperative group (37.5 vs 15.5 days; P = 0.016). Serious complications were observed only in the postoperative group (P = 0.28). There were no in-hospital deaths. CONCLUSIONS: Basic treatment of both postoperative and spontaneous chylothorax should include dietary measures in all patients. Additional sclerosing radiotherapy and interventional or surgical therapy are often necessary. The choice of therapeutic approach should be indicated, depending on the aetiology and development of the chylothorax. Early, multimodal treatment is recommended.

Recurrent necrotizing cellulitis, multi-organ autoimmune disease and humoral immunodeficiency due to a novel NFKB1 frameshift mutation.

BACKGROUND: Mutations in NFKB1(nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) are associated with a variety of clinical symptoms, including lymphadenopathy, splenomegaly, hepatomegaly, autoimmune haemolytic anaemia, arthralgia, recurrent respiratory tract infections and post-operative necrotizing cellulitis. CASE PRESENTATION: We describe a case of a 47-year-old man, who presented with deep necrotizing cellulitis after incision of a submucous abscess by a dentist. Surgical intervention led to a massive progress. Pyoderma gangraenosum (PG) was diagnosed clinically and confirmed histopathologically. High dose corticosteroids and intravenous immunoglobulins (IVIG) improved wound healing dramatically. Until now, immune mediated inflammation events not only affected the skin, but also multiple inner organs, i.e. the heart, lungs and gut. Sequencing of all coding exons of NFKB1 revealed a heterozygous 1bp deletion in exon 23 predicting a frameshift starting at codon Ala891 and resulting in a subsequent stop codon at position 6 in the new reading frame: NM_003998.4: c.2671del; p.(Ala891Glnfs*6) Acute episodes were always successfully treated with corticosteroids, IVIG and concomitant antibiotics. To prevent further exacerbations, the patient receives IVIG once a month, low-dose corticosteroids and methotrexate. CONCLUSION: This is the first case of a patient with recurrent necrotizing cellulitis and immune mediated multi-organ involvement (heart, lungs, intestine) carrying the novel frameshift mutation c.2671del (p.Ala891Glnfs*6) in NFKB1 effectively treated with IVIG, low-dose corticosteroids and methotrexate.

Surgical Cytoreduction and HITOC for Thymic Malignancies with Pleural Dissemination.

BACKGROUND: Objective of this study was to assess postoperative morbidity and mortality as well as recurrence-free and overall survival in patients with thymic malignancies and pleural dissemination undergoing surgical cytoreduction and hyperthermic intrathoracic chemotherapy (HITOC). METHODS: Retrospective study between September 2008 and December 2017 with follow-up analysis in May 2018. RESULTS: A total of 29 patients (male: n = 17) with thymic malignancies and pleural spread (primary stage IVa: n = 11; pleural recurrence: n = 18) were included. Surgical cytoreduction was performed via pleurectomy/decortication (P/D; n = 11), extended P/D (n = 15), and extrapleural pneumonectomy (EPP; n = 3). These procedures resulted in 25 (86%) patients with macroscopically complete (R0/R1) resection. Intraoperative HITOC was performed for 60 minutes at 42°C either with cisplatin (100 mg/m2 body surface area [BSA] n = 8; 150 mg/m2 BSA n = 6; 175 mg/m2 BSA n = 1) or with a combination of cisplatin (175 mg/m2 BSA)/doxorubicin (65 mg; n = 14). Postoperative complications occurred in nine patients (31%). Cytoprotective therapy resulted in lower postoperative creatinine levels (p = 0.036), and there was no need for temporary dialysis in these patients. The 90-day mortality rate was 3.4%, as one patient developed multiple organ failure. While recurrence-free 5-year survival was 54%, an overall 5-year survival rate of 80.1% was observed. Survival depended on histological subtype (p = 0.01). CONCLUSION: Surgical cytoreduction with HITOC is feasible in selected patients and offers encouraging survival rates. The application of cytoprotective agents appears to be effective for the prevention of postoperative renal insufficiency.

[Surgical Treatment of Lung Cancer: How Has the Introduction of the 8th Edition of the TNM Classification Affected Guideline-Based Therapy?] / Ergeben sich durch die Einführung der 8. Auflage der TNM-Klassifikation Änderungen für eine leitliniengerechte, chirurgische Therapiestrategie des Lungenkarzinoms?

STUDY AIM: The 8th edition of the TNM classification combined with the latest update of the S3-guideline (by AWMF/Scientific Medical Societies in Germany) on prevention, diagnosis, therapy and follow-up of lung cancer led to several changes in staging and treatment of lung cancer. The aim of this study was to identify differences in the distribution of patients due to changes from the 7th to the 8th edition that affected staging. The influence on surgical therapy will be discussed by using the recommendations of the latest S3 guideline. METHODS: Prospective analysis of all primary cases at two thoracic surgical centres in the year 2016 and follow-up in March 2019. Comparison of the 7th edition of tumour classification for lung cancer with the 8th edition, focused on changes in tumour staging and its effects on the appropriate surgical therapy according to the latest S3 guideline. RESULTS: A total of 432 primary cases comprised the study population. According to the 8th edition, 82 patients (7th edition: n = 85) in stage I, 43 (n = 49) patients in stage II, 100 (n = 91) patients in stage III and 207 (n = 207) patients are assigned to stage IV. 81 changes (18.7%) were detected (77 upgrades vs. 4 downgrades). 63 patients (14.6%) exhibited a different graduation within the stages. 18 patients (4.1%) were classified in different tumour stages. As a result, fewer patients (n = 12; 2.8%) should have surgery according to the latest S3 guidelines. 290 patients (67.1%) were classified to new subgroups (IA1-3, IIIC and IVA/B). Two-year survival was significantly higher in IVA (25.2%) vs. IVB (13.0%) patients (p < 0.05). CONCLUSION: The 8th edition of the TNM-classification affords a higher level of differentiation. In this study, the new TNM classification led to a shift in the distribution, with a tendency to increase the tumour stage. This is mainly caused by changes in the T-descriptor and stage grouping. As a result, fewer patients in stage I - IIIA should have surgery according to the latest S3 guidelines. A significantly higher two-year survival rate was detected in stage IVA (M1a and M1b) compared to IVB and justifies the new differentiation due to the metastatic pattern.

[Minimum volumes in surgical treatment of lung cancer : A survey of thoracic surgeons in Germany on the introduction of a minimum volume regulation for surgical treatment of lung cancer]. / Mindestmengen in der chirurgischen Behandlung des Lungenkarzinoms : Ein Meinungsbild von in Deutschland aktiven Thoraxchirurgen zur Einführung einer Mindestmengenregelung für die chirurgische Therapie des Lungenkarzinoms.

BACKGROUND: The Federal Joint Committee (G­BA) is currently discussing the introduction of new minimum volume regulations (MVR) in Germany. The present study examined the current opinions of active thoracic surgeons regarding minimum volumes (MV) for the surgical treatment of lung cancer. METHODS: The participating centers for the online survey were identified on the basis of the thoracic surgery departments in the 2017 hospital directory (Federal Statistical Office), lung cancer centers (German Cancer Society), certified centers of excellence for thoracic surgery (German Society for Thoracic Surgery), hospitals with a focus on lung surgery and German university hospitals. They were asked about the potential effects of MVR on the quality of results and quality of care, economic aspects and the structure of care. Furthermore, a recommendation for MV was requested and possible provisions for exemption were evaluated. RESULTS: A total of 145 hospitals (response rate 85%) with 454 thoracic surgeons (response rate 54%) were surveyed. The results showed a high degree of approval for MV to improve the quality of results and 78.4% of the surgeons surveyed expected it to result in centralization of surgical care, although this would not lead to a deterioration in care according to 70.1% of the participants. Approximately 46.1% of the participants expected care to become more economical and 83.3% supported the introduction of an MVR, with the average recommended MV being 67 anatomical lung resections per center per year. CONCLUSION: An MVR for the surgical treatment of lung cancer met with a high degree of approval among active thoracic surgeons. The MV that was called for (n = 67) was slightly below the prerequisite for primary surgical cases at a certified lung cancer center.

Adequate nephroprotection reduces renal complications after hyperthermic intrathoracic chemotherapy.

BACKGROUND AND OBJECTIVES: Hyperthermic intrathoracic chemotherapy (HITOC) is used for the treatment of malignant pleural tumors. Although HITOC proved to be safe, postoperative renal failure due to nephrotoxicity of intrapleural cisplatin remains a concern. METHODS: This single-center study was performed retrospectively in patients who underwent pleural tumor resection and HITOC between September 2008 and December 2018. RESULTS: A total of 84 patients (female n = 33; 39.3%) with malignant pleural tumors underwent surgical cytoreduction with subsequent HITOC (60 minutes; 42°C). During the study period, we gradually increased the dosage of cisplatin (100-150 mg/m2 BSA n = 36; 175 mg/m2 BSA n = 2) and finally added doxorubicin (cisplatin 175 mg/m2 BSA/doxorubicin 65 mg; n = 46). All patients had perioperative fluid balancing. The last 54 (64.3%) patients also received perioperative cytoprotection. Overall 29 patients (34.5%) experienced renal insufficiency. Despite higher cisplatin concentrations, patients with cytoprotection showed significantly lower postoperative serum creatinine levels after 1 week (P = .006) and at discharge (P = .020). Also, they showed less intermediate and severe renal insufficiencies (5.6% vs 13.3%). CONCLUSIONS: Adequate perioperative fluid management and cytoprotection seem to be effective in protecting renal function. This allows the administration of higher intracavitary cisplatin doses without raising the rate of renal insufficiencies.

[Comparison of the Masaoka-Koga Classification with the New TNM Staging of the IASLC/ITMIG for Thymoma and Thymic Carcinoma]. / Vergleich der Masaoka-Koga-Klassifikation mit der neuen TNM-Klassifikation der IASLC/ITMIG für Thymome und Thymuskarzinome.

BACKGROUND: The Masaoka-Koga classification describes the extent and spread of thymic epithelial malignancies. The objective of this study was to evaluate the Masaoka-Koga and the new TNM-staging system regarding differences in stage distributions, clinical implementation and therapeutic consequences. METHODS: Retrospective analysis of all patients who underwent surgery between January 2005 and December 2015 for thymoma/thymic carcinoma in two centres for thoracic surgery. The final tumour stages were determined on the basis of preoperative imaging, surgical reports and histological findings. RESULTS: A total of 118 patients (male 51%) with a mean age of 56 ± 14.8 years were included. Indications for surgery were primary mediastinal tumour (n = 97), pleura dissemination (n = 15) or mediastinal recurrence (n = 7). Radical tumour resection was performed in 92% of patients (n = 109) within one operation, whereas 8% of patients (n = 9) underwent two operations. Surgical revision was necessary in 12 patients (10.1%) and in-hospital mortality was 1.7% (n = 2). Early Masaoka-Koga stages I (n = 34) and II (n = 16) shifted to the new UICC stage I (T1: n = 58). Locally advanced stages (Masaoka-Koga stage III n = 22 vs. UICC stage IIIA + IIIB n = 20) and metastasised stages (Masaoka-Koga stage IV n = 36 vs. UICC stage IV n = 39) remained very similar. CONCLUSIONS: The new TNM staging system gave rise to changes, especially in early stages (downstaging), but these had no therapeutic implications. Although advanced stages were very similar, the new TNM staging provides more clinically relevant differentiation.

Burden between Undersupply and Overtreatment in the Care of Primary Spontaneous Pneumothorax.

BACKGROUND: The optimal treatment of primary spontaneous pneumothorax (PSP) is still controversial. The purpose of this study was to analyze the incidence of recurrence, the recurrence-free time, and to identify risk factors for recurrence after PSP. METHODS: We performed a retrospective analysis of 135 patients with PSP who were treated either conservatively with a chest tube (n = 87) or surgically with video-assisted thoracoscopic surgery (VATS; n = 48) from January 2008 through December 2012. RESULTS: In this study, 101 (74.8%) male and 34 (25.2%) female patients were included with a mean age of 35.7 years. The indications for surgery included blebs/bullae in the radiological images (n = 20), persistent air leaks (n = 15), or the occupations/wishes of the patients (n = 13). A first ipsilateral recurrent pneumothorax (true recurrence) was observed in 31.1% of all patients (VATS: 6.25%, conservative: 44.8%). Including contralateral recurrence, the overall first recurrence rate was 41.3% (VATS: 14.6%, conservative: 57.5%). The recurrence-free time did not differ significantly between the treatment groups (p = 0.51), and most recurrences were observed within the first 6 months after PSP. Independent risk factors identified for the first recurrence were conservative therapy (p = 0.0001), the size of the PSP (conservative; p = 0.016), and a body mass index <17 (VATS; 0.022). The risk for second and third recurrences of PSP was 17.5 and 70%, respectively, for both treatment groups, but it was 100% after conservative therapy. CONCLUSION: Surgery for PSP should be selected based on the risk factors and the patient's wishes to prevent first recurrences but also to avoid overtreatment. The treatment of first and subsequent PSP recurrences should be with surgery since conservative treatment is associated with a 100% recurrence rate.

[Surgical Treatment of Pseudotumours of the Lung]. / Chirurgische Therapie von Pseudotumoren der Lunge.

INTRODUCTION: Pseudotumour of the lung is a collective term for various subentities. Some subgroups are considered to be intermediary malignant tumours. A pseudotumour is a rare condition, which makes it difficult to estimate its incidence and prevalence. METHODS: Retrospective analysis of all surgically treated patients between 2008 and 2015 diagnosed with a pseudotumour of the lung. The primary endpoint of this study was to estimate the rates of local recurrence and metastasis. Secondary endpoints were to determine the nomenclature, medical history, treatment, and the perioperative course. RESULTS: Out of 27 patients (10 females and 17 males) with a median age of 58 years, 19 patients (70%) had an inflammatory pseudotumour (IPT), and four patients (15%) had an inflammatory myofibroblastoma (IMT). Two patients had a pneumocytoma/histiocytoma. A preoperative pulmonary infection was present in 12 (44%) patients. The average tumour size was 2.1 cm (0.8 - 5.3 cm), with the lower pulmonary lobes being mostly affected (52%). One enucleation, 20 atypical wedge resections and six anatomical resections were performed. This was done in a minimally invasive procedure (VATS) in 48% of cases (13/27). R0 resection was achieved in 93% of cases (25/27). Complications occurred in seven (26%) patients. The difference between the duration of hospital stay (mean duration 8 days) after open resection and VATS was minimal (8.8 vs. 7.2 days). Patients were followed up over a period of 4 years, during which time only one patient developed a tumour recurrence, which led to the patient's death, although she had had a R0 resection of an IMT. CONCLUSIONS: The treatment of choice for pseudotumours of the lung is R0 resection, preferably with VATS. Most patients have a benign course of disease, although relapses are possible in some cases, especially in IMT. Follow-up monitoring is necessary for IMT. The application of a uniform nomenclature and classification would be a sensible approach.

High mortality in patients with tracheoarterial fistulas: clinical experience and treatment recommendations.

OBJECTIVES: A tracheoarterial fistula (TAF) is an uncommon but a critical complication of tracheostomy and represents a surgical emergency. Surgical therapy with ligation of the brachiocephalic trunk can be considered as the first choice of treatment to control massive and life-threatening haemorrhage. METHODS: We describe 3 cases of TAF in patients who had long-term placement of a tracheostomy tube and the occurrence of a severe massive haemorrhage caused by an injured brachiocephalic trunk. All cases required emergent surgical revision. Different surgical techniques were used. In addition to the 3 case reports, we present a review of the literature of published TAF cases, summarize the different measures to control bleeding and compare the operative procedures used in the treatment of TAF. RESULTS: The occurrence of TAF is rare and constitutes a surgical emergency. The mortality rate of tracheoarterial erosion is 100% without surgical intervention for active bleeding into the airway. Therefore, rapid control of bleeding (via digital compression and an overinflated cuff) is the most important and first step of therapy. Subsequent emergency surgery with ligation and resection of the TAF and covering of the trachea should be considered to finally control the massive haemorrhage. In addition, cardiopulmonary bypass and circulatory arrest can be useful for surgical treatment of cases with uncontrollable bleeding. CONCLUSIONS: The mortality rate after resection of the fistula remains high. Finally, the most important factors for patient survival and outcomes are quick diagnosis of the TAF and immediate surgical control of bleeding.

Evaluation of the new TNM-staging system for thymic malignancies: impact on indication and survival.

BACKGROUND: The objective of this study is the evaluation of the Masaoka-Koga and the International Association for the Study of Lung Cancer (IASLC)/International Thymic Malignancy Interest Group (ITMIG) proposal for the new TNM-staging system on clinical implementation and prognosis of thymic malignancies. METHODS: A retrospective study of 76 patients who underwent surgery between January 2005 and December 2015 for thymoma. Kaplan-Meier survival analysis was used to determine overall and recurrence-free survival rates. RESULTS: Indication for surgery was primary mediastinal tumor (n = 55), pleural manifestation (n = 17), or mediastinal recurrence (n = 4) after surgery for thymoma. Early Masaoka-Koga stages I (n = 9) and II (n = 14) shifted to the new stage I (n = 23). Advanced stages III (Masaoka-Koga: n = 20; ITMIG/IASLC: n = 17) and IV (Masaoka-Koga: n = 33; ITMIG/IASLC: n = 35) remained nearly similar and were associated with higher levels of WHO stages. Within each staging system, the survival curves differed significantly with the best 5-year survival in early stages I and II (91%). Survival for stage IV (70 to 77%) was significantly better compared to stage III (49 to 54%). Early stages had a significant longer recurrence-free survival (86 to 90%) than advanced stages III and IV (55 to 56%). CONCLUSIONS: The proportion of patients with IASLC/ITMIG stage I increased remarkably, whereas the distribution in advanced stages III and IV was nearly similar. The new TNM-staging system presents a clinically useful and applicable system, which can be used for indication, stage-adapted therapy, and prediction of prognosis for overall and recurrence-free survival.

Superior vasodilation of human pulmonary vessels by vardenafil compared with tadalafil and sildenafil: additive effects of bosentan.

OBJECTIVES: Pulmonary arterial hypertension is characterized by pulmonary vascular proliferation and remodelling, leading to a progressive increase in pulmonary arterial resistance. Vasodilator properties of 3 different phosphodiesterase (PDE)-5 inhibitors alone and in combination with an endothelin (ET) receptor antagonist were compared in an ex vivo model. METHODS: Segments of human pulmonary arteries (PAs) and pulmonary veins (PVs) were harvested from lobectomy specimens. Contractile forces were determined in an organ bath. Vessels were constricted with norepinephrine (NE) to determine the effects of sildenafil, tadalafil and vardenafil and with ET-1 to assess the effects of bosentan. RESULTS: All 3 PDE-5 inhibitors had no relevant effect on the basal tone of the vessels. Both sildenafil and vardenafil significantly (P < 0.0001) reduced the responses of the vessels to NE, whereas tadalafil was effective only in PA (P = 0.0009) but not in PV (P = 0.097). Sildenafil relaxed NE-preconstricted PV (P < 0.0001) but not PA (P = 0.143). Both tadalafil and vardenafil relaxed PA and PV significantly. Vardenafil appears to be the most potent of the PDE-5 inhibitors tested. Furthermore, we analysed the combination of bosentan and vardenafil in PA. Bosentan and vardenafil reduced ET-1 and NE induced vasoconstriction stronger than vardenafil alone (P ≤ 0.049). CONCLUSIONS: Vardenafil caused the most consistent antihypertensive response in this ex vivo model. However, ET receptor antagonism appears to be an even more potent mechanism. A combination therapy using vardenafil and bosentan turned out to be an effective combination to lower vessel tension in PA.

Impact of Surgical Evaluation of Additional Cine Magnetic Resonance Imaging for Advanced Thymoma with Infiltration of Adjacent Structures: The Thoracic Surgeon's View.

Background Preoperative radiological assessment is important for clarification of surgical operability for advanced thymic tumors. Objective was to determine the feasibility of magnetic resonance imaging (MRI) with cine sequences for evaluation of cardiovascular tumor invasion. Patients and Methods This prospective study included patients with advanced thymoma, who underwent surgical resection. All patients received preoperative computed tomography (CT) scan and cine MRI. Results Tumor infiltration was surgically confirmed in the pericardium (n = 12), myocardium (n = 1), superior caval vein (SCV; n = 3), and aorta (n = 2). A macroscopic complete resection was possible in 10 patients, whereas 2 patients with aortic or myocardial tumor invasion had R2 resection. The positive predictive value (PPV) was 50% for cine MRI compared with 0% for CT scan regarding myocardial tumor infiltration. The PPV for tumor infiltration of the aorta was 50%, with a higher sensitivity for the CT scan (100 vs. 50%). Infiltration of the SCV could be detected slightly better with cine MRI (PPV 75 vs. 66.7%). Conclusion Cine MRI seems to improve the accuracy of preoperative staging of advanced thymoma regarding infiltration of cardiovascular structures and supports the surgical approach.

Octreotide LAR and Prednisone as Neoadjuvant Treatment in Patients with Primary or Locally Recurrent Unresectable Thymic Tumors: A Phase II Study.

Therapeutic options to cure advanced, recurrent, and unresectable thymomas are limited. The most important factor for long-term survival of thymoma patients is complete resection (R0) of the tumor. We therefore evaluated the response to and the induction of resectability of primarily or locally recurrent unresectable thymomas and thymic carcinomas by octreotide Long-Acting Release (LAR) plus prednisone therapy in patients with positive octreotide scans. In this open label, single-arm phase II study, 17 patients with thymomas considered unresectable or locally recurrent thymoma (n = 15) and thymic carcinoma (n = 2) at Masaoka stage III were enrolled. Octreotide LAR (30 mg once every 2 weeks) was administered in combination with prednisone (0.6 mg/kg per day) for a maximum of 24 weeks (study design according to Fleming´s one sample multiple testing procedure for phase II clinical trials). Tumor size was evaluated by volumetric CT measurements, and a decrease in tumor volume of at least 20% at week 12 compared to baseline was considered as a response. We found that octreotide LAR plus prednisone elicited response in 15 of 17 patients (88%). Median reduction of tumor volume after 12 weeks of treatment was 51% (range 20%-86%). Subsequently, complete surgical resection was achieved in five (29%) and four patients (23%) after 12 and 24 weeks, respectively. Octreotide LAR plus prednisone treatment was discontinued in two patients before week 12 due to unsatisfactory therapeutic effects or adverse events. The most frequent adverse events were gastrointestinal (71%), infectious (65%), and hematological (41%) complications. In conclusion, octreotide LAR plus prednisone is efficacious in patients with primary or recurrent unresectable thymoma with respect to tumor regression. Octreotide LAR plus prednisone was well tolerated and adverse events were in line with the known safety profile of both agents.

Short-term and long-term outcomes of intrathoracic vacuum therapy of empyema in debilitated patients.

BACKGROUND: This retrospective study analyzed the effectiveness of intrathoracic negative pressure therapy for debilitated patients with empyema and compared the short-term and long-term outcomes of three different intrapleural vacuum-assisted closure (VAC) techniques. METHODS: We investigated 43 consecutive (pre)septic patients with poor general condition (Karnofsky index ≤ 50 %) and multimorbidity (≥ 3 organ diseases) or immunosuppression, who had been treated for primary, postoperative, or recurrent pleural empyema with VAC in combination with open window thoracostomy (OWT-VAC) with minimally invasive technique (Mini-VAC), and instillation (Mini-VAC-Instill). RESULTS: The overall duration of intrathoracic vacuum therapy was 14 days (5-48 days). Vacuum duration in the Mini-VAC and Mini-VAC-Instill groups (12.4 ± 5.7 and 10.4 ± 5.4 days) was significantly shorter (p = 0.001) than in the group treated with open window thoracostomy (OWT)-VAC (20.3 ± 9.4 days). No major complication was related to intrathoracic VAC therapy. Chest wall closure rates were significantly higher in the Mini-VAC and Mini-VAC-Instill groups than in the OWT-VAC group (p = 0.034 and p = 0.026). Overall, the mean postoperative length of stay in hospital (LOS) was 21 days (median 18, 6-51 days). LOS was significantly shorter (p = 0.027) in the Mini-VAC-Instill group (15.1 ± 4.8) than in the other two groups (23.8 ± 12.3 and 22.7 ± 1.5). Overall, the 30-day and 60-day mortality rates were 4.7 % (2/43) and 9.3 % (4/43), and none of the deaths was related to infection. CONCLUSIONS: For debilitated patients, immediate minimally invasive intrathoracic vacuum therapy is a safe and viable alternative to OWT. Mini-VAC-Instill may have the fastest clearance and healing rates of empyema.

Radical surgical resection of advanced thymoma and thymic carcinoma infiltrating the heart or great vessels with cardiopulmonary bypass support.

BACKGROUND: Radical surgical resection of advanced thymic tumors invading either the heart or great vessels facing towards the heart is uncommonly performed because of the potential morbidity and mortality. To achieve a complete tumor resection, the use of cardiolpulmonary bypass (CPB) support might be necessary. METHODS: Retrospective analysis of the results in six patients, who underwent radical tumor resection with CBP support. RESULTS: Mean age was 46 years (27 to 66 years) and five patients were male. Tumor infiltration of the heart or the great vessels was evident in all patients. Five patients underwent induction therapy. Two patients were operated in complete cardioplegic arrest (antegrade cerebral perfusion: n = 1). Arterial cannulation of the ascending aorta (n = 5) or the femoral artery (n = 1) and venous cannulation of the right atrium (n = 4) or the femoral vein (n = 2) were performed. Resection of the left brachiocephalic vein (n = 6), resection of the superior caval vein (n = 2), the ascending aorta (n = 1) and the complete aortic arch with outgoing branches (n = 1) were performed. A macroscopic complete resection (R0/R1) was achieved in five patients, whereas one patient was resected incompletely (R2). In-hospital mortality was 0 %. Three (50 %) patients needed operative revision (hematothorax: n = 2, chylothorax: n = 1). All patients had a complicated postoperative course and developed respiratory insufficiency. CONCLUSIONS: Locally advanced thymoma/thymic carcinoma invading the heart or great vessels can be treated with radical surgical resection alongside with increased perioperative morbidity. The usage of CBP improves the chance of complete tumor resection in selected patients and might lead to a prolonged survival.