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.

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.

Minimally Invasive Vacuum-Assisted Closure Therapy With Instillation (Mini-VAC-Instill) for Pleural Empyema.

Enthusiasm for minimally invasive thoracic surgery is increasing. Thoracoscopy plays a significant therapeutic role in the fibrinopurulent stage (stage II) of empyema, in which loculated fluid cannot often be adequately drained by chest tube alone. For some debilitated and septic patients, further procedures such as open-window thoracostomy (OWT) with daily wound care or vacuum-assisted closure (VAC) therapy are necessary. In the present article, we propose a new option of minimally invasive VAC therapy including a topical solution of the empyema without open-window thoracostomy (Mini-VAC-instill). Three patients who underwent surgery using this technique are also presented. The discussion is focused on the advantages and disadvantages of the approach.

Combination of sildenafil and bosentan for pulmonary hypertension in a human ex vivo model.

PURPOSE: Both sildenafil and bosentan have been used clinically to treat pulmonary arterial hypertension. As these substances target different pathways to modulate vasoconstriction, we investigated the combined effects of both drug classes in isolated human pulmonary vessels. METHODS: Segments of pulmonary arteries (PA) and veins (PV) were harvested from 51 patients undergoing lobectomy. Contractile force was determined isometrically in an organ bath. Vessels were constricted with norepinephrine (NE) to determine effects of sildenafil. They were constricted with ET-1 to assess effects of bosentan, and with NE and ET-1 to evaluate the combination of both substances. RESULTS: Sildenafil (1E-5 M) significantly reduced maximum constriction by NE of both PA (13.0 ± 11.1 vs. 34.9 ± 7.6% relative to KCl induced constriction; n = 6; p < 0.001) and PV (81.2 ± 34.2 vs 121.6 ± 20.8%; n = 6; p < 0.01) but did not affect basal tones. Bosentan (1E-5 M) significantly reduced maximum constriction of PV (56.6 ± 21.5 vs. 172.1 ± 30.0%; n = 6; p < 0.01) by ET-1 and led to a small but insignificant decrease of basal tone (p = 0.07). Bosentan almost completely abolished constriction of PA (1.0 ± 0.9 vs. 74.7 ± 25.7 %; n = 6; p < 0.001) by ET-1, but did not affect basal tone. Bosentan (1E-7 M) significantly attenuated combined ET-1/NE dose-response curves in PA (93.1 ± 47.4 vs. 125.3 ± 41.0%; n = 12; p < 0.001) whereas the effect of sildenafil (1E-5 M) was less pronounced (103.6 ± 20.2%; p < 0.05). Simultaneous administration of both substances showed a significantly greater reduction of maximum constriction in PA compared to individual administration (64.6 ± 26.3 %; p < 0.001). CONCLUSIONS: Sildenafil only at its highest concentration was effective in suppressing NE induced pulmonary vessel contraction. Bosentan was able to completely suppress ET-1 induced contraction of PA and strongly attenuated contraction of PV. The present data suggest a benefit of sildenafil/bosentan combination therapy as they affect different pathways and may allow lower dosages.

Extended surgical resections of advanced thymoma Masaoka stages III and IVa facilitate outcome.

OBJECTIVE: Extended thymoma resections including adjacent structures and pleurectomy/decortication (P/D) with hyperthermic intrathoracic chemotherapy (HITHOC) perfusion were performed in a multidisciplinary treatment regime. PATIENTS AND METHODS: Between July 2000 and February 2012, 22 patients with Masaoka stage III (n = 9; 41%) and Masaoka stage IVa (n = 13; 59%) thymic tumors were included. RESULTS: Mean age was 55 years (25-84 years) and 50% (11 out of 22) of patients were female. World Health Organization histological classification was as follows: B2 (n = 15), A (n = 1), B1 (n = 1), B3 (n = 2), and thymic carcinoma (C; n = 3). Radical thymectomy and partial resection of the mediastinal pleura and pericardium were performed. Of the 13, 9 patients with pleural involvement (stage IVa) received radical P/D followed by HITHOC (cisplatin). Macroscopic complete resection (R0/R1) was achieved in 19 (86%) patients. All patients received multimodality treatment depending on tumor stage, histology, and completeness of resection. Thirty-day mortality was 0% and three (13.6%) patients needed operative revision. Recurrence of thymoma was documented in five (22.7%) patients (stage III, n = 1; stage IVa, n = 4). Mean disease-free interval of patients with complete resection (n = 14 out of 22) was 30.2 months. After a mean follow-up of 29 months, 18 out of the 22 (82%) patients are alive. After P/D and HITHOC, 89% (8 out of 9 patients) are alive (current median survival is 25 months) without recurrence. CONCLUSIONS: Extended surgical resection of advanced thymic tumors infiltrating adjacent structures (stage III) or with pleural metastases (stage IVa) is safe and feasible. It provides a low recurrence rate and an acceptable survival. Additional HITHOC in patients with pleural thymoma spread seems to offer a better local tumor control.

Prospective, comparative study of the On-Q® PainBuster® postoperative pain relief system and thoracic epidural analgesia after thoracic surgery.

OBJECTIVE: Pain after thoracotomy is associated with intense discomfort leading to impaired pulmonary function. DESIGN: Prospective, non-randomized trial from April 2009 to September 2011. SETTING: Department of Thoracic Surgery, single-center. PARTICIPANTS: Thoracic surgical patients. INTERVENTIONS: Comparison of thoracic epidural analgesia (TEA) with the On-Q® PainBuster® system after thoracotomy. MEASUREMENTS AND MAIN RESULTS: The TEA group (n=30) received TEA with continuous 0.2% ropivacaine at 4 mL-to-8 mL/h, whereas Painbuster® patients (n=32) received 0.75% ropivacaine at 5 mL/h until postoperative day 4 (POD4). Basic and on-demand analgesia were identical in both groups. Pain was measured daily on a numeric analog scale from 0 (no pain) to 10 (worst pain) at rest and at exercise. There were no significant differences regarding demographic and preoperative data between the groups, but PainBuster® patients had a slightly lower relative forced expiratory volume in 1 second (FEV1) (71±20% versus 86±21%; p=0.01). Most common surgical procedures were lobectomies (38.8%) and atypical resections (28.3%) via anterolateral thoracotomy. Most common primary diagnoses were lung cancer (48.3%) and tumor of unknown origin (30%). At POD1, median postoperative pain at rest was 2.1 (1; 2.8) in the TEA group and 2 (1.5; 3.8; p=0.62) in the PainBuster® group. At exercise, median pain was 4.3 (3.5; 3.8) in the TEA group compared to 5.0 (4.0; 6.5; p=0.07). Until POD 5 there were decreases in pain at rest and exercise but without significant differences between the groups. CONCLUSIONS: Sufficient analgesia after thoracotomy can be achieved with the intercostal PainBuster® system in patients, who cannot receive TEA.

Acute renal dysfunction does not develop more frequently among octogenarians compared to septuagenarians after cardiac surgery.

BACKGROUND: We tested the hypothesis that octogenarians develop more frequently renal dysfunction compared with septuagenarians after cardiac surgery. METHODS: A retrospective, observational study on an age-, gender- and operation-matched cohort of 598 patients, (299 octogenarians vs. 299 septuagenarians) who underwent cardiac surgery between January 2006 and August 2009, was performed. Kidney function was estimated with the abbreviated Modification in Renal Disease equation and acute kidney injury was defined as a decrease of glomerular filtration rate ≥50%. RESULTS: Operations included 246 coronary, 198 isolated valve, and 154 combined coronary and valve procedures. Mean logistic EuroSCORE was 8.5% in septuagenarians and 13.2% in octogenarians. Octogenarians had significantly more frequent and estimated GFR < 60 mL/min/1.73 m² (44 vs. 34.4%, p = 0.02). The incidence of dialysis-dependent acute kidney failure did not differ between both groups (6.7 vs. 5.4%, p = 0.60). Postoperative decline of glomerular filtration rate <25% occurred significantly more often in septuagenarians (40 vs. 30%, p = 0.02). Septuagenarians with a preoperative GFR < 60 mL/min/1.73 m² had a higher 30-day mortality compared with patients with a GFR > 60 mL/min/1.73 m² (10.9 vs. 3.1%, p = 0.02). Overall, 30-day mortality in octogenarians was 7.7% without significant differences with respect to preoperative GFR. CONCLUSIONS: Octogenarians do not develop acute kidney failure more frequently than their matched septuagenarian counterparts. They can be operated on at an acceptable risk for morbidity and mortality. Preoperative impaired renal function is associated with higher risk for mortality in septuagenarians.

Cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion for malignant pleural tumours: perioperative management and clinical experience.

OBJECTIVES: A combination of cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion (HITHOC) was performed for the treatment of primary and secondary pleural malignancies. We describe the perioperative management and our clinical experience. METHODS: Between September 2008 and August 2011, eight patients with pleural manifestation of thymoma (Masaoka stage IVa) and eight patients with malignant pleural mesothelioma (MPM) were prospectively enrolled. Postoperative morbidity, recurrence and survival rates were analysed. RESULTS: All the patients received multimodality therapy, including chemotherapy, radiation and surgical resection (pleurectomy/decortication) followed by the HITHOC procedure. Chemotherapy perfusion was performed with cisplatin (100-150 mg/m(2)) at 42°C for 1 h. Severe chemotherapy-related complications were not observed. Reoperation was necessary in two patients. There was no 30-day mortality. The median stay on the intensive care unit was 1 day, and the median duration of hospitalization was 15 days. Pleural recurrence of thymoma was evident in one thymoma patient 6 months after HITHOC. At mean follow-up of 22 months, seven thymoma patients (7/8; 88%) are alive without recurrence. Tumour progression was present in six mesothelioma patients (6/8; 75%). Four patients (50%) with MPM are alive, including two with no evidence of mesothelioma, and the median survival is 18 months. CONCLUSIONS: Cytoreductive surgery in combination with HITHOC can be performed with acceptable morbidity and mortality rates in selected patients. Patients should be evaluated by an interdisciplinary team to determine their eligibility for this therapeutic alternative. Early clinical results may encourage the use of this surgical option to provide better local tumour control in a multimodality treatment setting.