Primary leiomyosarcoma of bone (LMSoB) is extremely rare, comprising only <0.7% of primary malignant bone tumors, and is therefore considered an ultra-rare tumor entity. There is currently no consensus as to whether therapeutic strategies should be based on the biological characteristics of soft tissue leiomyosarcoma or on primary tumor localization in the bone. The use of perioperative chemotherapy and its effectiveness in this rare tumor entity remains unclear. We aimed to evaluate the impact of different treatment approaches in a multicenter setting with a total of 35 patients included. The 5-year overall survival (OS) was 74%. Patients with localized disease undergoing surgery had a significantly higher 5-year OS compared to patients who did not undergo surgical treatment (82% vs. 0%, p = 0.0015). Axial tumor localization was associated with worse event-free survival (EFS) probability (p < 0.001) and OS (p = 0.0082). A high proportion of our patients developed secondary metastases. Furthermore, the perioperative chemotherapy protocols applied to our patients were not associated with an improved EFS or OS. Therefore, the benefit of perioperative chemotherapy in LMSoB needs to be further investigated, and the choice of agents still needs to be clarified.
BACKGROUND: Isolated limb perfusion (ILP) is a well-established surgical procedure for the administration of high dose chemotherapy to a limb for the treatment of advanced extremity malignancy. Although the technique of ILP was first described over 60 years ago, ILP is utilised in relatively few specialist centres, co-located with tertiary or quaternary cancer centres. The combination of high dose cytotoxic chemotherapy and the cytokine tumour necrosis factor alpha (TNFα), mandates leakage monitoring to prevent potentially serious systemic toxicity. Since the procedure is performed at relatively few specialist centres, an ILP working group was formed with the aim of producing technical consensus guidelines for the procedure to streamline practice and to provide guidance for new centres commencing the technique. METHODS: Between October 2021 and October 2023 a series of face to face online and hybrid meetings were held in which a modified Delphi process was used to develop a unified consensus document. After each meeting the document was modified and recirculated and then rediscussed at subsequent meeting until a greater than 90% consensus was achieved in all recommendations. RESULTS: The completed consensus document comprised 23 topics in which greater than 90% consensus was achieved, with 83% of recommendations having 100% consensus across all members of the working group. The consensus recommendations covered all areas of the surgical procedure including pre-operative assessment, drug dosing and administration, perfusion parameters, hyperthermia, leakage monitoring and theatre logistics, practical surgical strategies and also post-operative care, response evaluation and staff training. CONCLUSION: We present the first joint expert-based consensus statement with respect to the technical aspects of ILP that can serve as a reference point for both existing and new centres in providing ILP.
If thoracic surgery is to remain an attractive career path for young physicians, it is essential to provide opportunities to balance work, residency, and family time. With an increasing proportion of women in thoracic surgery, it has become increasingly important to create a work environment that allows safe employment during pregnancy and breast feeding becomes an important concern.Based on the legal requirements of the German Maternity Protection Act (Mutterschutzgesetz), this interdisciplinary consensus paper was developed by representatives of thoracic surgery, anaesthesiology, and occupational medicine.The vast majority of thoracic operations can be performed by pregnant or breast-feeding surgeons. We established a risk-stratified list of operations with potentially acceptable risk, and a list of operations that pregnant or breast-feeding surgeons should not perform. A checklist aims to aid the individual implementation of thoracic surgery during pregnancy and breast feeding.Thoracic surgery can be performed by pregnant or breast-feeding surgeons when certain protective measures are observed. The prerequisite is the voluntary and independent decision of the surgeon, and the implementation of safety precautions by the employer.
Thoracic Surgery , Thoracic Surgical Procedures , Female , Pregnancy , Humans , Breast Feeding , Consensus , Employment
BACKGROUND: Primary therapy of localized myxofibrosarcoma (MFS) remains controversial. Primary resection is complicated by a high rate of local recurrence, and the refractoriness to non-surgical treatment results in a higher risk of metastasis. The aim of the present study was to contribute the findings of a single sarcoma-specialized center and encourage investigating new treatment options. PATIENTS AND METHODS: We analyzed 134 patients treated with localized MFS in our center regarding prognostic factors defining overall survival, local recurrence, and metastasis. We focused on multimodal treatment of localized MFS: surgery, radiation, chemotherapy, hyperthermia, and isolated limb perfusion. RESULTS: The 5-year OS was 74.9%. From a total of 134 patients: 74 (55.2%) stayed disease free, 48 (35.8%) had a local recurrence (LR), and 23 (17.2%) developed a distant metastasis (DM). The 5-year LR-free survival (LRFS) and DM-free survival (DMFS) were 66.1% and 80.8%, respectively. Older age, tumor size (cT) cTâ ≥â 2, non-extremity localization, and distant metastasis were adverse predictive factors for OS. Performing an incision biopsy, surgery in a sarcoma-center, wide local excision or compartment-oriented excision, negative margins, and radiotherapy were positive predictive factors for LR. Tumor size cTâ ≥â 3 was a negative predictive factor for DM. Grading was a negative predictive factor for LR (Gâ ≥â 2) and for DM (G3) in the multivariable analysis. CONCLUSION: Adjuvant radiation had a positive impact on LRFS in all localized tumor stages, even in cT1 tumors. Chemotherapy did not have a significant impact on DMFS, regardless of tumor stage. Our findings indicate that myxofibrosarcoma may be a chemotherapy-resistant entity and a much closer monitoring is required, in case of neoadjuvant treatment.
Sarcoma , Soft Tissue Neoplasms , Adult , Humans , Retrospective Studies , Prognosis , Sarcoma/pathology , Treatment Outcome , Combined Modality Therapy , Soft Tissue Neoplasms/pathology , Neoplasm Recurrence, Local/pathology
BACKGROUND: Isolated limb perfusion (ILP) for soft tissue sarcomas (STS) is usually performed with tumor necrosis factor alpha (TNF-α) and melphalan. ILP regularly leads to a total blood loss (BLt) of 1.5-2 L/patient. Blood inflow from the central blood circulation to the limb is influenced by unstable pressure gradients and pain reactions after the administration of melphalan. With perioperative regional anesthesia (RA), pain levels can be reduced, and the pressure gradient stabilized resulting in a reduced BLt. The aim of this study was to compare the BLt with and without RA in patients with ILP during circulation of drugs. METHODS: Patients were treated according to the following protocol: After the establishment of limb circulation, ILP was started with the administration of TNF-α. Half the dose of melphalan was given as a bolus after 30 min, and the remaining dose was continuously administered in the following 30 min. The extremity was washed out after 90 min. ILP with perioperative RA (supraclavicular plexus block/peridural catheter) was performed prospectively in 17 patients and compared to a matched retrospective control group of 17 patients without RA. BLt was documented and perioperative anesthesiological data were analyzed for response rates after the application of melphalan (RaM). RESULTS: BLt and RaM tended to be lower for the intervention group with RA if compared to the control group without RA in all analyses. The trend of lower BLt and RaM in ILP with RA was more pronounced for the upper extremity compared to the lower extremity. Results were not statistically significant. CONCLUSION: These findings indicate that the use of RA can help to stabilize hemodynamic anesthetic management and reduce the BLt in ILP, especially during perfusion of the upper extremities.
OBJECTIVE: The aim of this study was to investigate the response rates of different extremity soft-tissue sarcoma subtypes (eSTS) after isolated limb perfusion (ILP), based on an international multi-centre study. MATERIALS AND METHODS: The retrospective cohort comprised eSTS patients from 17 specialised ILP centres that underwent melphalan-based ILP, with or without recombinant human tumour necrosis factor (rhTNFα) (TM-ILP and M-ILP, respectively). Response was measured on imaging (magnetic resonance imaging) and/or clinical response, for which M-ILPs were excluded. RESULTS: A total of 1109 eSTS patients were included. The three most common histological subtypes were undifferentiated pleomorphic sarcoma (17%, n = 184), synovial sarcoma (16%, n = 175) and myxofibrosarcoma (8%, n = 87). rhTNFα was used in 93% (TM-ILP) and resulted in a significantly better overall response rate (ORR, p = 0.031) and complete responses (CR, p < 0.001) in comparison to M-ILP, without significant differences among histological subgroups. The ORR of TM-ILP was 68%, including 17% CR. Also, 80% showed progressive disease. Significantly higher response rates were shown for Kaposi sarcoma (KS) with 42% CR and 96% ORR (both p < 0.001), and significantly higher CR rates for angiosarcoma (AS, 45%, p < 0.001) and clear cell sarcoma (CCS, 31%, p = 0.049). ILP was followed by resection ≤ 6 months in 80% of the patients. The overall limb salvage rate was 88%, without significant differences among histological subgroups, but was significantly higher for ILP responders compared to non-responders (93% versus 76%, p < 0.001). CONCLUSION: ILP resulted in high response and LRS among all eSTS subtypes, however, with significant differences between subtypes with most promising results for KS, AS and CCS.
Sarcoma, Kaposi , Sarcoma , Soft Tissue Neoplasms , Adult , Humans , Retrospective Studies , Chemotherapy, Cancer, Regional Perfusion/methods , Sarcoma/pathology , Melphalan/therapeutic use , Extremities/pathology , Soft Tissue Neoplasms/pathology , Perfusion , Tumor Necrosis Factor-alpha , Antineoplastic Agents, Alkylating/therapeutic use
Although Ewing's sarcoma (ES) is a rare, but very aggressive tumor disease affecting the musculoskeletal system, especially in children, it is very aggressive and difficult to treat. Although medical advances and the establishment of chemotherapy represent a turning point in the treatment of ES, resistance to chemotherapy, and its side effects, continue to be problems. New treatment methods such as the application of cold physical plasma (CPP) are considered potential supporting tools since CPP is an exogenous source of reactive oxygen and nitrogen species, which have similar mechanisms of action in the tumor cells as chemotherapy. This study aims to investigate the synergistic effects of CPP and commonly used cytostatic chemotherapeutics on ES cells. The chemotherapy drugs doxorubicin and vincristine, the most commonly used in the treatment of ES, were applied to two different ES cell lines (RD-ES and A673) and their IC20 and IC50 were determined. In addition, individual chemotherapeutics in combination with CPP were applied to the ES cells and the effects on cell growth, cell viability, and apoptosis processes were examined. A single CPP treatment resulted in the dose-dependent growth inhibition of ES cells. The combination of different cytostatics and CPP led to significant growth inhibition, a reduction in cell viability, and higher rates of apoptosis compared to cells not additionally exposed to CPP. The combination of CPP treatment and the application of cytostatic drugs to ES cells showed promising results, significantly enhancing the cytotoxic effects of chemotherapeutic agents. These preclinical in vitro data indicate that the use of CPP can enhance the efficacy of common cytostatic chemotherapeutics, and thus support the translation of CPP as an anti-tumor therapy in clinical routine.
Antineoplastic Agents , Bone Neoplasms , Cytostatic Agents , Sarcoma, Ewing , Child , Humans , Sarcoma, Ewing/pathology , Cytostatic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Vincristine/pharmacology , Vincristine/therapeutic use , Doxorubicin/therapeutic use , Bone Neoplasms/metabolism , Cell Line, Tumor
BACKGROUND: To achieve clear margins in rare malignant clavicular neoplasms, claviculectomy may become necessary. This study aimed to review clinical, functional, and oncologic outcomes following partial or total claviculectomy without reconstruction. METHODS: This study retrospectively included 15 patients from 2 tertiary sarcoma centers (mean age, 42.6 ± 20.3 years; 66.7% male patients). The median length of clinical and oncologic follow-up was 48.0 months (interquartile range [IQR], 24.0-83.5 months). Functional follow-up (Musculoskeletal Tumor Society score and QuickDASH score [short version of the Disabilities of the Arm, Shoulder and Hand questionnaire]) was available in 9 patients at a median of 36.0 months (IQR, 20.0-100.0 months). RESULTS: Of the 15 patients, 7 underwent total claviculectomy; 5, partial lateral claviculectomy; and 3, partial medial claviculectomy. No postoperative complications emerged. The median Musculoskeletal Tumor Society and QuickDASH scores at latest follow-up amounted to 26.0 points (IQR, 24.0-29.0 points) and 18.0 points (IQR, 11.0-22.0 points), respectively. Notably, scores tended to be lower in patients who underwent total claviculectomy (n = 2) in comparison to partial claviculectomy (n = 7). CONCLUSION: Satisfactory clinical and functional results can be achieved following partial or total claviculectomy without reconstruction, with a low complication rate and acceptable mid- to long-term function.
Bone Neoplasms , Clavicle , Humans , Male , Young Adult , Adult , Middle Aged , Female , Retrospective Studies , Treatment Outcome , Clavicle/pathology , Shoulder/pathology , Scapula/pathology , Bone Neoplasms/pathology , Syndrome
BACKGROUND: The use of cold atmospheric plasma (CAP) in oncology has been intensively investigated over the past 15 years as it inhibits the growth of many tumor cells. It is known that reactive oxidative species (ROS) produced in CAP are responsible for this effect. However, to translate the use of CAP into medical practice, it is essential to know how CAP treatment affects non-malignant cells. Thus, the current in vitro study deals with the effect of CAP on human bone cancer cells and human osteoblasts. Here, identical CAP treatment regimens were applied to the malignant and non-malignant bone cells and their impact was compared. METHODS: Two different human bone cancer cell types, U2-OS (osteosarcoma) and A673 (Ewing's sarcoma), and non-malignant primary osteoblasts (HOB) were used. The CAP treatment was performed with the clinically approved kINPen MED. After CAP treatment, growth kinetics and a viability assay were performed. For detecting apoptosis, a caspase-3/7 assay and a TUNEL assay were used. Accumulated ROS was measured in cell culture medium and intracellular. To investigate the influence of CAP on cell motility, a scratch assay was carried out. RESULTS: The CAP treatment showed strong inhibition of cell growth and viability in bone cancer cells. Apoptotic processes were enhanced in the malignant cells. Osteoblasts showed a higher potential for ROS resistance in comparison to malignant cells. There was no difference in cell motility between benign and malignant cells following CAP treatment. CONCLUSIONS: Osteoblasts show better tolerance to CAP treatment, indicated by less affected viability compared to CAP-treated bone cancer cells. This points toward the selective effect of CAP on sarcoma cells and represents a further step toward the clinical application of CAP.
Recent retrospective studies suggested that early postoperative infections might be associated with a survival benefit for extremity osteosarcoma patients, but the reported results have been conflicting. The files of 437 patients with a newly diagnosed, high-grade osteosarcoma of the extremities treated at 5 referral centers in Germany and Austria between 1989 and 2016 were retrospectively evaluated. All patients underwent multi-agent chemotherapy and limb-sparing tumor excision, followed by endoprothetic replacement. We used the Kaplan-Meier method to calculate survival curves, which we compared with the log-rank test. With a median follow-up of 100 months (interquartile range, 49-155 months), local recurrence (LR) probability, event-free survival (EFS), and disease-specific survival (DSS) after 5 years in this selected patient cohort amounted to 5%, 67%, and 79%, respectively, and 46 patients (10.5%) developed an early postoperative infection. We found no significant differences in LR, EFS, or DSS between patients with and without early infections, and there were no differences in known prognostic factors between the two groups. However, in subgroup analyses patients with a poor response to neoadjuvant chemotherapy and an early infection had a better DSS compared to patients without early infections (93% vs. 62% after 5 years, p = 0.044). Provided that our findings can be validated in separate patient cohorts, we believe that patient outcome after adjuvant immunomodulatory treatments in osteosarcoma patients should be evaluated and reported separately for good and poor responders to neoadjuvant chemotherapy in future studies.
BACKGROUND: The updated 8th version of the AJCC-staging system for soft tissue sarcomas (STS) has been criticised for omitting tumour depth as category-defining variable and eventually not improving prognostic accuracy in comparison to the 7th version. This study aimed at investigating the prognostic accuracy of both AJCC-versions in STS-patients treated at European tertiary sarcoma centres. METHODS: 1032 patients (mean age: 60.7 ± 16.3 years; 46.0% [n = 475] females; median follow-up: 38.6 months), treated at five tertiary sarcoma centres for localised, intermediate or high-grade STS of extremities and trunk were retrospectively included. Uni- and multivariate Cox-regression models and Harrell's C-indices were calculated to analyse prognostic factors for overall survival (OS) and assess prognostic accuracy. RESULTS: In univariate analysis, prognostic accuracy for OS was comparable for both AJCC-versions (C-index: 0.620 [8th] vs. 0.614 [7th]). By adding margins, age, gender, and histology to the multivariate models, prognostic accuracy of both versions could be likewise improved (C-index: 0.714 [8th] vs. 0.705 [7th]). Moreover, tumour depth did not significantly contribute to prognostic accuracy of the 8th version's multivariate model (C-index for both models: 0.714). Stratification into four main T-stages based on tumour size only, as implemented in the 8th version, significantly improved prognostic accuracy between each category. However, T-stages as defined in the 7th version had poorer discriminatory power (C-index: 0.625 [8th] vs. 0.582 [7th]). CONCLUSION: Both AJCC-versions perform equally well regarding prognostic accuracy. Yet, simplification of the 8 th version by omitting tumour depth as T-stage-defining parameter, whilst emphasizing the importance of tumour size, should be considered advantageous.
Neoplasm Staging , Practice Guidelines as Topic , Sarcoma/pathology , Soft Tissue Neoplasms/pathology , Survival Rate , Adult , Aged , Chemotherapy, Adjuvant , Europe , Extremities/pathology , Extremities/surgery , Female , Humans , Leiomyosarcoma/pathology , Leiomyosarcoma/therapy , Liposarcoma, Myxoid/pathology , Liposarcoma, Myxoid/therapy , Male , Margins of Excision , Middle Aged , Multivariate Analysis , Neoadjuvant Therapy , Neoplasm Grading , Neurofibrosarcoma/pathology , Neurofibrosarcoma/therapy , Prognosis , Proportional Hazards Models , Radiotherapy, Adjuvant , Sarcoma/therapy , Sarcoma, Synovial/pathology , Sarcoma, Synovial/therapy , Soft Tissue Neoplasms/therapy , Tertiary Care Centers , Torso/pathology , Torso/surgery
BACKGROUND AND OBJECTIVES: Abdominal metastases (AM) from soft tissue sarcoma (STS) are rare and prognosis is poor. The aims of the study were to (a) identify risk factors for the development of AM and to (b) investigate the outcome of AM-patients. METHODS: Seven-hundred-sixty-nine STS-patients with localised disease at diagnosis treated at three tumour centres (2000-2016) were retrospectively included (409 males; mean age, 55.6 years [range, 8-96 years]; median follow-up, 4.1 years [interquartile-range, 2.5-6.6 years]). RESULTS: Two-hundred-two patients (26.3%) developed secondary metastases, and 24 of them AM (3.1%). Ten patients developed first AM (FAM) after a mean of 2.4 years and 14 patients late AM (LAM, after being diagnosed with metastases to other sites) after a mean of 2.0 years. Patients with liposarcoma had a significantly higher risk of developing AM (P = .007), irrespective of grading. There was no difference in post-metastasis-survival (PMS) between patients with AM at any time point and those with metastases to other sites (P = .585). Patients with LAM or FAM showed no difference in post-abdominal-metastasis-survival (P = .884). CONCLUSIONS: Survival in patients with AM is poor, irrespective of whether they develop secondarily to other metastases or not. Patients at high-risk of AM (ie, liposarcoma) may be followed-up regularly by abdominal-ultrasound/CT.
Abdominal Neoplasms/secondary , Abdominal Neoplasms/therapy , Extremities/pathology , Sarcoma/pathology , Sarcoma/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk Factors , Young Adult
OBJECTIVES: Worldwide, not only the number of female medical students, but also of female surgeons increases. Simultaneously, younger generations take a closer look to their work-life balance. With this in mind, it seems necessary to evaluate the expectations of female surgeons in particular with respect to pregnancy during their surgical career. METHODS: Therefore, a nationwide survey was conducted in Germany from July to December 2016 under the auspices of the German Society of Surgery as well as the Professional Board of German Surgeons. The questionnaire involved 2,294 female surgeons and 1,843 complete records were evaluated. RESULTS: Of the analyzed answers, 62% of the women (n=781) were operating during pregnancy. The joy of surgery (91.6%), followed by team spirit (57.1%), were the main motivations to perform operations while pregnant. Operative activity decreased from 30.8% in the first 3 months of pregnancy to 21.5% during the last three months. Regarding the possible complaints, e.g., leg edema, back pain, premature labor and vaginal bleeding, there were no significant differences between the women with or without activity in the operating room. Sick leave due to pregnancy (1-10 days) was stated by 40.4% of respondents. CONCLUSION: Despite strong legal regulations for pregnant surgeons, the survey showed that most female surgeons are eager to operate despite their pregnancy. The results also demonstrate no significant differences regarding complications during pregnancy- or pregnant-dependent absence from work. Hospitals and surgical departments are asked to establish proper working conditions for pregnant surgeons and pregnancy should not be an obstacle for a career in surgery.
Due to the marked increase in the numbers of women in medicine, professional and political discussions on equality among doctors are gaining increasing attention. One such issue is "operating during pregnancy". As a result of existing legislation and federal regulations, it has been virtually impossible for pregnant surgeons to continue their surgical work. After approval by the Federal Council or Bundesrat, the revised Maternity Protection Act will come into force on 01.01.2018. It will thereafter be easier for surgeons to operate during pregnancy. The focus will now be on the transformation of workplace practices, in which individual risk assessments of the participating surgeons will be carried out in order to achieve a risk-adapted operation, and thus to prevent premature and unwanted restrictions on the employment of pregnant female surgeons.
National Health Programs/legislation & jurisprudence , Physicians, Women/legislation & jurisprudence , Pregnancy , Public Policy , Surgical Procedures, Operative/legislation & jurisprudence , Female , Germany , Humans , Parental Leave/legislation & jurisprudence , Postpartum Period , Women's Rights/legislation & jurisprudence , Work Schedule Tolerance , Workload/legislation & jurisprudence
Background. Surgical treatment of malignant pelvic bone tumors can be very challenging. The objective of this retrospective study was to evaluate the oncological as well as the clinical and functional outcome after limb salvage surgery and biological reconstruction. Methods. The files of 27 patients with malignant pelvic bone tumors, who underwent surgical resection at our department between 2000 and 2011, were retrospectively analyzed (9 Ewing's sarcoma, 8 chondrosarcoma, 4 osteosarcoma, 1 synovial sarcoma, 1 malignant fibrous histiocytoma, and 4 carcinoma metastases). Results. After internal hemipelvectomy reconstruction was performed by hip transposition (n = 16), using autologous nonvascularised fibular graft (n = 5) or autologous iliac crest bone graft (n = 2). In one patient a proximal femor prothetis and in three patients a total hip prosthesis was implanted at the time of resection. The median follow-up was 33 months. Two- and five-year disease-specific survival rates of all patients were 86.1% and 57.7%, respectively. The mean functional MSTS score was 16.5 (~55%) for all patients. Conclusion. On the basis of the oncological as well as the clinical and functional outcome, biological reconstruction after internal hemipelvectomy seems to be a reliable technique for treating patients with a malignant pelvic bone tumor.
This paper deals with bilateral vascularized fibular grafts (BVFG) as a method for reconstruction of metadiaphyseal defects of the femur and tibia in young patients suffering from malignant bone tumors of the lower limb. This reconstructional technique was used in 11 patients undergoing metadiaphyseal resection of lower limb malignant bone tumors. All patients with Ewing's sarcoma and osteosarcoma had multimodal treatment according to the EURO-E.W.I.N.G 99 or COSS-96 protocol. Median FU was 63 months. None of the patients experienced local recurrence during FU. 2 patients died due to distant disease during FU. Full weight- bearing was permitted after a mean of 8 months. The median MSTS score was 87%. Complications occurred in five patients. None of the complications led to failure of the biological reconstruction or to amputation. Biological reconstruction of osseous defects is always desirable when possible and aims at a permanent solution. Good functional and durable results can be obtained by using BVFG for the reconstruction of metadiaphyseal defects of the femur and tibia. Radiotherapy in the multimodal setting increases the risk for graft or fixation failure.
