Multimodal Treatment of Pleural Mesothelioma with Cytoreductive Surgery and Hyperthermic Intrathoracic Chemotherapy: Impact of Additive Chemotherapy.

Cytoreductive surgery (CRS) combined with hyperthermic intrathoracic chemoperfusion (HITOC) is a promising treatment strategy for pleural mesothelioma (PM). The aim of this study was to evaluate the impacts of this multimodal approach in combination with systemic treatment on disease-free survival (DFS) and overall survival (OS). In this retrospective multicenter study, clinical data from patients after CRS and HITOC for PM at four high-volume thoracic surgery departments in Germany were analyzed. A total of 260 patients with MPM (220 epithelioid, 40 non-epithelioid) underwent CRS and HITOC as part of a multimodal treatment approach. HITOC was administered with cisplatin alone (58.5%) or cisplatin and doxorubicin (41.5%). In addition, 52.1% of patients received neoadjuvant and/or adjuvant chemotherapy. The median follow-up was 48 months (IQR = 38 to 58 months). In-hospital mortality was 3.5%. Both the resection status (macroscopic complete vs. incomplete resection) and histologic subtype (epithelioid vs. non-epithelioid) had significant impacts on DFS and OS. In addition, adjuvant chemotherapy (neoadjuvant/adjuvant) significantly increased DFS (p = 0.003). CRS and HITOC within a multimodal treatment approach had positive impacts on the survival of patients with epithelioid PM after macroscopic complete resection. The addition of chemotherapy significantly prolonged the time to tumor recurrence or progression.

Outcome after cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy in patients with secondary pleural metastases.

Background: The role of cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy (CRS+HITOC) for patients with secondary pleural metastases has scarcely been investigated. Patients and Methods: We conducted a retrospective, multicentre study investigating the outcome of CRS+HITOC for 31 patients with pleural metastases from different primary tumours in four high-volume departments of thoracic surgery in Germany. The primary endpoint was overall survival (OS). Secondary endpoints included postoperative complications and recurrence/progression-free survival (RFS/PFS). Results: The primary tumour was non-small cell lung cancer in 12 (39%), ovarian cancer in 5 (16%), sarcoma in 3 (10%), pseudomyxoma peritonei in 3 (10%), and others in 8 (26%) patients. A macroscopic complete resection (R/1) could be achieved in 28 (90%) patients. Major postoperative complications as classified by Clavien-Dindo (III-V) were observed in 11 (35%) patients. The postoperative mortality rate was 10% (n=3). A total of 13 patients received additive chemotherapy (42%). The median time of follow up was 30 months (95% CI = 17- 43). The median OS was 39 months (95% CI: 34-44 months) with 1-month, 3-month, 1-, 3-, and 5-year survival estimates of 97%, 89%, 77%, 66%, and 41%. There was a significantly prolonged OS in patients who received additive chemotherapy compared to patients with only CRS+HITOC (median OS 69 vs 38 months; p= 0.048). The median RFS was 14 months (95% CI: 7-21 months). Conclusions: We observed that CRS+HITOC is a feasible approach with reasonable complications and prolonged survival as a part of multimodal concept for highly selected patients with secondary pleural metastases.

The Excretion of Cisplatin after Hyperthermic Intrathoracic Chemotherapy.

Hyperthermic intrathoracic chemotherapy (HITOC) is an additional intraoperative treatment option within the multimodality therapy of pleural malignancies. A chemotherapy perfusion with high-dose cisplatin is performed over a period of 60 min after surgical cytoreduction to improve local tumour control through the eradication of residual tumour cells. Although HITOC is increasingly used, there is only little scientific evidence about the necessary safety measures after HITOC. Therefore, the objective of this study was an analysis of cisplatin excretion via various body fluids after HITOC, with the aim of providing recommendations on occupational health and safety. Five patients undergoing HITOC were included. Before and after the HITOC, as well as during the following days, serum, urine, and bronchial secretion, as well as pleural effusion, were sampled. The platinum levels in the samples were measured using ICP-MS (inductively coupled plasma-mass spectrometry). Immediately after the HITOC, the mean levels of cisplatin increased dramatically in the serum (from 0.79 to 1349 µg/L), urine (from 3.48 to 10,528 µg/g creatinine), and bronchial secretion (from 0.11 to 156 µg/L). Thereafter, the cisplatin levels dropped to 133 µg/L in the serum and 994 µg/g creatinine in the urine within nine days after the HITOC. The AUC ratio shows 59% of the cisplatin being excreted via the urine after 48 h. The sampling of pleural effusion started 24 h after the HITOC, and the cisplatin levels decreased from 618 to 93 µg/L within nine days. Although the cisplatin levels in the body fluids of HITOC patients are much lower compared to patients receiving intravenous chemotherapy, a significant amount of cisplatin is excreted via these body fluids. Consequently, safety precautions must be implemented in the post-HITOC care of patients to avoid occupational exposure to cisplatin.

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.

Surgical cytoreduction and hyperthermic intrathoracic chemotherapy for thymic tumours with pleural spread is effective on survival: results from the multicentre German hyperthermic intrathoracic chemotherapy study.

OBJECTIVES: Cytoreductive surgery and hyperthermic intrathoracic chemotherapy (HITOC) is effective on survival for patients with pleural metastatic thymic tumours. METHODS: Multicentre, retrospective analysis of patients with stage IVa thymic tumours treated with surgical resection and HITOC. Primary end point was overall survival, secondary end points were recurrence-/progression-free survival and morbidity/mortality. RESULTS: A total of n = 58 patients (thymoma, n = 42; thymic carcinoma, n = 15; atypical carcinoid of the thymus, n = 1) were included, who had primary pleural metastases (n = 50; 86%) or pleural recurrence (n = 8; 14%). Lung-preserving resection (n = 56; 97%) was the preferred approach. Macroscopically complete tumour resection was achieved in n = 49 patients (85%). HITOC was performed with cisplatin alone (n = 38; 66%) or in combination with doxorubicin (n = 20; 34%). Almost half of the patients (n = 28; 48%) received high-dose cisplatin > 125 mg/m2 body surface area. Surgical revision was required in 8 (14%) patients. In-hospital mortality rate was 2%. During follow-up, tumour recurrence/progression was evident in n = 31 (53%) patients. Median follow-up time was 59 months. The 1-, 3- and 5-year survival rates were 95%, 83% and 77%, respectively. Recurrence/progression-free survival rates were 89%, 54% and 44%, respectively. Patients with thymoma had significantly better survival compared to patients with thymic carcinoma (P-value ≤0.001). CONCLUSIONS: Promising survival rates in patients with pleural metastatic stage IVa in thymoma (94%) and even in thymic carcinoma (41%) were achieved. Surgical resection and HITOC is safe and effective for treatment of patients with pleural metastatic thymic tumours stage IVa.

[Mediastinal tumors : Diagnosis and treatment of the most common tumor entities]. / Mediastinaltumoren : Übersicht zu Diagnostik und Therapie der häufigsten Entitäten.

The mediastinum is defined as the space formed ventrally by the sternum, dorsally by the spine, and laterally by the mediastinal pleura. A mediastinal mass is frequently an incidental finding. The wide spectrum of underlying diseases and the anatomic proximity to central structures makes diagnosis and treatment challenging. In many cases, the combination of anamnesis, physical examination, imaging and laboratory tests already provides valuable information about the tumor entity. In addition to diagnostic procedures for histological examination of an unclear mediastinal tumor, radical resection is very important for the prognosis of the patients, especially in the case of tumors of the thymus. Multimodal treatment of advanced tumors that involve adjacent structures is best performed in designated centers.

Postoperative outcome after palliative treatment of malignant pleural effusion.

BACKGROUND: The objective of this nationwide, registry-based study was to compare the two most frequently used procedures for the palliative treatment of a malignant pleural effusion (MPE) and to evaluate differentiated indications for these two procedures. METHODS: This was a retrospective observational study based on data of the "PLEURATUMOR" registry of the German Society for Thoracic Surgery. Patients who were documented in the period from January 2015 to November 2021 and had video-assisted thoracic surgery (VATS) talc pleurodesis or implantation of an indwelling pleural catheter (IPC) were included. RESULTS: A total of 543 patients were evaluated. The majority suffered from secondary pleural carcinomatosis (n = 402; 74%). VATS talc pleurodesis (n = 361; 66.5%) was performed about twice as often as IPC implantation (n = 182; 33.5%). The duration of surgery was significantly shorter in IPC-patients with 30 min compared to VATS talc pleurodesis (38 min; p = 0.000). Postoperative complication rate was 11.8% overall and slightly higher after VATS talc pleurodesis (n = 49; 13.6%) than after IPC implantation (n = 15; 8.2%). After VATS talc pleurodesis patients were hospitalized significantly longer compared to the IPC group (6 vs. 3.5 days; p = 0.000). There was no significant difference in postoperative wound infections between the groups (p = 0.10). The 30-day mortality was 7.9% (n = 41). CONCLUSION: The implantation of an IPC can significantly shorten the duration of surgery and the hospital stay. For this reason, the procedure should be matched with the patient's expectations preoperatively and the use of an IPC should be considered not only in the case of a trapped lung.

The Treatment of Malignant Pleural Effusion With Permanent Indwelling Pleural Catheters.

BACKGROUND: 40 000 to 60 000 people develop malignant pleural effusion (MPE) in Germany each year. The most common causes are lung cancer and breast cancer. Patients with pleural carcinomatosis have a median survival time of four months. METHODS: We investigated the current health services situation regarding treatment with indwelling pleural catheters (IPC) versus talc pleurodesis (TP) in Germany based on registry data from the Federal Statistical Office, the Pleural Tumor Registry of the German Society for Thoracic Surgery, and the IPC registry of the ewimed GmbH company. In addition, we conducted a selective literature review on IPC and TP. RESULTS: The symptoms of dyspnea and thoracic pressure determine the need for therapy in MPE. Both TP and IPC are effective treatment options for MPE. Both therapeutic procedures are considered equally effective with respect to the relief of dyspnea, post-interventional quality of life, and complication rates. TP yields a higher rate of successful pleurodesis than IPC (relative risk: 1.56; 95% confidence interval: [1.26; 1.92]; p < 0.0001), while patients who receive an IPC stay in the hospital for a shorter time than those who undergo TP (a difference of slightly more than two days). The survival of patients with MPE is not affected by which of the two local therapeutic procedures is chosen. CONCLUSION: The indication for either IPC or TP needs to be determined individually for each patient on the basis of his or her general condition, symptoms, clinical situation ("trapped lung"), and prognosis.

Exposure to cisplatin in the operating room during hyperthermic intrathoracic chemotherapy.

PURPOSE: Hyperthermic intrathoracic chemotherapy (HITOC) is an additive, intraoperative treatment for selected malignant pleural tumors. To improve local tumor control, the thoracic cavity is perfused with a cisplatin-containing solution after surgical cytoreduction. Since cisplatin is probably carcinogenic to humans, potential contamination of surfaces and pathways of exposure should be systematically investigated to enable risk assessments for medical staff and thus derive specific recommendations for occupational safety. METHODS: Wipe sampling was performed at pre-selected locations during and after ten HITOC procedures, including on the surgeon's gloves, for the quantitation of surface contaminations with cisplatin. After extraction of the samples with hydrochloric acid, platinum was determined as a marker for cisplatin by voltammetry. RESULTS: High median concentrations of cytostatic drugs were detected on the surgeons' (1.73 pg Cis-Pt/cm2, IQR: 9.36 pg Cis-Pt/cm2) and perfusionists' (0.69 pg Cis-Pt/cm2, IQR: 1.73 pg Cis-Pt/cm2) gloves. The display of the perfusion device showed partially elevated levels of cisplatin up to 4.92 pg Cis-Pt/cm2 and thus could represent an origin of cross-contamination. In contrast, cisplatin levels on the floor surfaces in the area of the surgeon and the perfusion device or in the endobronchial tube were relatively low. CONCLUSION: With a correct use of personal protective equipment and careful handling, intraoperative HITOC appears to be safe to perform with a low risk of occupational exposure to cisplatin.

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.

Hyperthermic Intrathoracic Chemotherapy (HITOC) after Cytoreductive Surgery for Pleural Malignancies-A Retrospective, Multicentre Study.

In the context of quality assurance, the objectives were to describe the surgical treatment and postoperative morbidity (particularly renal insufficiency). A retrospective, multicentre study of patients who underwent cytoreductive surgery (CRS) with cisplatin-based HITOC was performed. The study was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation (GZ: RI 2905/3-1)). Patients (n = 350) with malignant pleural mesothelioma (n = 261; 75%) and thymic tumours with pleural spread (n = 58; 17%) or pleural metastases (n = 31; 9%) were analyzed. CRS was accomplished by pleurectomy/decortication (P/D: n = 77; 22%), extended P/D (eP/D: n = 263; 75%) or extrapleural pneumonectomy (EPP: n = 10; 3%). Patients received cisplatin alone (n = 212; 61%) or cisplatin plus doxorubicin (n = 138; 39%). Low-dose cisplatin (≤125 mg/m2 BSA) was given in 67% of patients (n = 234), and high-dose cisplatin (>125 mg/m2 BSA) was given in 33% of patients (n = 116). Postoperative renal insufficiency appeared in 12% of the patients (n = 41), and 1.4% (n = 5) required temporary dialysis. Surgical revision was necessary in 51 patients (15%). In-hospital mortality was 3.7% (n = 13). Patients receiving high-dose cisplatin were 2.7 times more likely to suffer from renal insufficiency than patients receiving low-dose cisplatin (p = 0.006). The risk for postoperative renal failure is dependent on the intrathoracic cisplatin dosage but was within an acceptable range.

Assessment of concentration and penetration depth of cisplatin in human lung tissue after decortication and hyperthermic exposure.

BACKGROUND: Hyperthermic perfusion of the pleural cavity with cisplatin after pleurectomy/decortication is an additional therapeutic option to reduce local relapse of malignant pleural tumours. Although there are data on the clinical effect, only little is known about the local impact on human lung tissue by cisplatin. The objective of this experimental study is to evaluate both the concentration and the penetration depth of cisplatin in human lung tissue after normothermic and hyperthermic exposure under ex-vivo-in-vitro conditions. METHODS: This study was approved by the local ethics committee. In total, 46 patients underwent elective lobectomy and wedge resections were taken from the resected lobes. A decortication of the visceral pleura was performed under ex-vivo conditions, and the tissue samples were incubated with cisplatin (c =0.05 mg/mL) at 37, 42 or 45 °C for 60 minutes. Then the mass concentration of platinum was measured with flameless atomic absorption spectroscopy and then converted into cisplatin concentration. In addition, the current data were compared with previous data of our working group (42 °C, without decortication). RESULTS: The overall maximum penetration depth was 7.5 mm due to limitations of our methods. The functional maximum penetration depth did not vary with temperature (P=0.243) but by decortication (P<0.001). The cisplatin concentration decreased with increasing penetration depth (P<0.001). An increase of temperature showed no effect on the cisplatin concentration in decorticated tissue samples (P=0.985). However, decortication at 42 °C significantly increased the cisplatin concentration in comparison to not decorticated tissue samples (P=0.005). CONCLUSIONS: Decortication of the visceral pleura increases the cisplatin concentration in the lung tissue. Therefore, it possibly reduces the likelihood of a local relapse. An increase of temperature did not show any effect.

Hyperthermic intrathoracic chemotherapy (HITHOC): narrative review of the current literature, recommendations and future studies.

Although the method of hyperthermic intrathoracic chemotherapy (HITHOC) after cytoreductive surgery is known for more than 20 years now, the interest of the scientific community has been growing especially in recent years with annually increasing numbers of publications. The feasibility and safety of HITHOC has already been demonstrated. The primary objective now is to reach a consent about the optimal implementation and standardization of the procedure. In the international clinical practice of HITHOC the parameters of temperature, duration, type and number of chemotherapeutic agents vary, making a comparison of the short- and long-term results difficult. For about ten years, the combination of surgical cytoreduction and HITHOC has been performed more routinely in several departments of thoracic surgery in Germany, especially in university hospitals. Recently, a group of experts for thoracic surgery of five departments of thoracic surgery elaborated recommendations for the HITHOC procedure in Germany. These recommendations represent a standardized and consistent implementation of HITHOC. Through this, postoperative complications associated to HITHOC should be reduced and a better comparison of the results should be enabled. This article is intended to give a brief overview of the literature, current recommendations in the implementation of HITHOC and also aims to show future perspectives of this procedure.

Video-assisted pulmonary metastectomy is equivalent to thoracotomy regarding resection status and survival.

BACKGROUND: Surgical resection of pulmonary metastases leads to prolonged survival if strictly indicated. Usually, thoracotomy with manual palpation of the entire lung with lymph node dissection or sampling is performed. The aim of this study was to evaluate the role of video-assisted thoracoscopic surgery (VATS) in pulmonary metastectomy with curative intent. METHODS: In this study, all patients with suspected pulmonary metastasis (n = 483) who visited the Center for Thoracic Surgery in Regensburg, between January 2009 and December 2017 were analysed retrospectively. RESULTS: A total of 251 patients underwent metastectomy with curative intent. VATS was performed in 63 (25.1%) patients, 54 (85.7%) of whom had a solitary metastasis. Wedge resection was the most performed procedure in patients treated with VATS (82.5%, n = 52) and thoracotomy (72.3%, n = 136). Postoperative revisions were necessary in nine patients (4.8%), and one patient died of pulmonary embolism after thoracotomy (0.5%). Patients were discharged significantly faster after VATS than after thoracotomy (p < 0.001). Complete (R0) resection was achieved in 89% of patients. The median recurrence-free survival was 11 months (95% confidence interval 7.9-14.1). During follow-up, eight (12.7%) patients in the VATS group and 42 (22.3%) patients in the thoracotomy group experienced recurrence (p = 0.98). The median overall survival was 61 months (95% confidence interval 46.1-75.9), and there was no significant difference with regard to the surgical method used (p = 0.34). CONCLUSIONS: VATS metastasectomy can be considered in patients with a solitary lung metastasis. An open surgical approach with palpation of the lung showed no advantage in terms of surgical outcome or survival.

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.

[Five Years PLEURATUMOR Register of the German Society of Thoracic Surgery]. / Fünf Jahre PLEURATUMOR-Register der Deutschen Gesellschaft für Thoraxchirurgie.

BACKGROUND: Since 01.01.2015, the nationwide "PLEURATUMOR Register of the German Society of Thoracic Surgery (DGT)" has documented the most relevant parameters of patients with primary and secondary malignant pleural diseases receiving thoracic surgery in Germany. This online database is intended to record both primary and recurrent diseases. In particular, the registry focuses on the documentation of patients with pleural carcinosis, malignant pleural mesothelioma and tumours of the thymus with pleural dissemination. METHODS: A structured evaluation of all patients documented up to and including December 2019 was carried out. RESULTS: At this time, 33 departments participated in the PLEURATUMOR Register and 670 patients have been recorded. Of these patients, 522 data sets were complete and 516 patients received surgical treatment. Most patients were documented in 2017 (n = 135; 26.2%), and in 2019 (n = 72; 14%). With 317 listed patients (61.4%), pleural carcinosis was the most frequently reported pleural tumour, followed by malignant pleural mesothelioma (n = 175; 33.9%) and thymoma/thymic carcinoma with pleural metastases (n = 11; 2.1%). The majority of patients (n = 499; 96.7%) were treated because of an initial manifestation. The most frequently documented procedure was VATS-talcum pleurodesis (n = 204; 39.5%). In 69 patients (13.4%) hyperthermic intrathoracic chemotherapy was performed after cytoreductive surgery. Postoperative complications occurred in 107 patients (20.7%); in 35 cases (6.8%) surgical revision was necessary. The overall 30-day mortality was 8.3% (n = 43). CONCLUSION: Due to the consistent data entry of the participating clinics, a representative dataset of pleural tumour diseases could be recorded. In the future, we hope for consistent continuation of data entry and the initiation of register-based studies.

[Extended Resection of Locally Advanced Thymic Tumours in Stage III]. / Erweiterte Resektionsverfahren bei lokal fortgeschrittenen Tumoren des Thymus im Stadium III.

In the treatment of locally advanced thymic tumours, specific diagnostic testing is required, with a multimodal therapeutic approach consisting of surgery, radio- and/or chemotherapy. The complete resection of the tumour represents the most important prognostic factor with regard to recurrence-free and long-term survival. Local invasive growth of malignant thymic tumours into neighbouring mediastinal structures is classified as Masaoka-Koga stage III. Surgical resection can be performed primarily or after induction therapy, depending on the extent of the tumour. However, in some cases these tumours must be classified as non-resectable, so that only palliative radio-/chemotherapy remains as therapeutic option. TNM classification for malignant thymic tumours has been recently introduced. This resembles the established Masaoka-Koga classification in many aspects, but also includes some therapy-relevant changes. A differentiation is made between stages IIIA and IIIB, with the aim of assessing the resectability of advanced thymic tumours in a more differentiated manner and consequent planning of the therapy concept. Besides the thymus, thymoma, perithymic tissue, mediastinal pleura (stage I) or pericardium (stage II), all infiltrated structures should be removed "en bloc", if possible in stage III tumours. While the lung, brachiocephalic vessels or extrapericardial pulmonary vessels can still be resected and reconstructed if necessary, infiltration of the aorta or intrapericardial pulmonary vessels often limits macroscopically complete resection.

Protocol of a retrospective, multicentre observational study on hyperthermic intrathoracic chemotherapy in Germany.

INTRODUCTION: Objective of the 'German hyperthermic intrathoracic chemotherapy (HITOC) study' is to evaluate the HITOC as additional treatment after surgical cytoreduction for malignant pleural tumours. Even though HITOC is applied with increasing frequency, there is no standardised therapy protocol concerning the technique of HITOC, the selection as well as dosage of chemotherapeutic agents and perioperative management in order to provide a safe and comparable, standardised treatment regime. METHODS AND ANALYSIS: This trial is a retrospective, multicentre observational study, which is funded by the German Research Foundation. Approximately 300 patients will be included. Four departments of thoracic surgery, which are performing the most HITOC procedures in Germany, are contributing to this study: Center for Thoracic Surgery at the University Hospital Regensburg, Thoracic Clinic Heidelberg of the University of Heidelberg, Center for Thoracic Surgery of the Hospital University of Munich and the Department of Thoracic Surgery at the University Hospital Freiburg. All patients who underwent surgical cytoreduction and subsequent HITOC at one of the four centres between starting the HITOC programme in 2008 and December 2019 will be included. Information on the performed HITOC will be obtained, focusing on the technique as well as the applied perfusion solution including the chemotherapeutic agent. Furthermore, parameters of the patient's postoperative recovery will be analysed to determine 30-day morbidity and mortality. ETHICS AND DISSEMINATION: The approvals by the local ethics committee of the respective clinic and the three participating clinics have been obtained. The results will be presented in conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: German Clinical Trials Registry (DRKS00015012; Pre-results).

Classification and staging of thymoma.

The appropriate therapy and prognosis of patients with thymic malignancies is decisively influenced by the local extent and dissemination of the tumor. For this reason, a staging system that reflects these factors is essential. Mainly the Masaoka-Koga classification, which was introduced in 1994, has been applied for this purpose. The rarity of thymic malignancies makes it difficult not only to establish internationally standardized diagnostics and treatment, but also to progress staging. Besides, efforts were made to adapt the classification into a tumor-node-metastasis-based (TNM) system for standardization with the staging of other tumor entities. The 2017 published 8th edition of the TNM Classification of Malignant Tumors introduced several adjustments based on a proposal of the International Association for the Study of Lung Cancer (IASLC) and the International Thymic Malignancy Interest Group (ITMIG). Compared to the Masaoka-Koga classification, surgically good resectable tumor involvements like pericardium, mediastinal fat or mediastinal pleura have been shifted to lower stages. Thus, even more than in Masaoka-Koga classification, tumors are basically divided into completely resectable and thus surgically treatable tumors (stage I, II, IIIA) and advanced stages (stage IIIB, IVA and IVB) that require multimodal therapy.

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.