Surgical site infections after sarcoma resections in the peripelvic region: do we need perioperative antibiotic prophylaxis?

Introduction: Surgical site infections (SSI) are one of the most common complications after extensive sarcoma resections and represent a daily challenge. SSI occur in up to 50% of cases particularly in the peripelvic area. One possible approach to reduce infection rate is perioperative antibiotic prophylaxis. The aim of this study therefore was to investigate the influence of perioperative antibiotic prophylaxis on the infection rate and the possible influence of location-specific antibiotic prophylaxis with ampicillin/sulbactam. Methods: This monocentric retrospective study included 366 patients who underwent sarcoma resections in the groin, proximal thigh, or gluteal region. All patients were operated on by 2 surgeons after neoadjuvant pretreatment if necessary. 3 groups of patients were defined. Group 1: In 60.4% of all cases, antibiotic prophylaxis was administered with cephalosporins (also clindamycin in case of penicillin allergy). Group2: In 9.8% of cases, ampicillin/sulbactam was used. Group 3: 29.8% of patients did not receive any antibiotic prophylaxis. Results: In 31.1% of treated cases, antibiotic therapy was prolonged due to extended tumor resections. Postoperative infections occurred in 23.2% (85 cases), in 77 cases within the first 90 days (on average after 20 days). The median operating time, blood loss was higher, and tumor size were significantly larger in cases with infections, compared to patients without infection. In group 1 and 2 with perioperative single-shot prophylaxis, infection occurred in 24.1% of cases, compared to 13.5% of cases without prophylaxis (group 3) (p= 0.032). In the patients with prolonged antibiotic therapy, infection occurred in 31.6% of cases, compared to 16.3% of cases without prolongation (p< 0.001). In the group 2, infection occurred in 19.4% of cases compared to 24.9% of cases in the group 1 (p= 0.479). In the multivariate analysis, surgery time longer 80 min, blood substitution, neoadjuvant radio- and chemotherapy proved to be a risk factor for SSI. Discussion: Region adapted perioperative antibiotic prophylaxis may reduce the risk of infection after extended sarcoma resection in the peripelvic area. However, the particular bacterial spectrum of this anatomic region should be taken into account when deciding which antibiotics to use.

Spectrum of Pathogens in Surgical Site Infections after Sarcoma Resection in the Peri-Pelvic and Pelvic Region. Distinct Location, Distinct Infection?

Background: Soft tissue sarcomas (STS) often occur in the peri-pelvic region (proximal thigh, groin, gluteal region). A common complication following resection of STS is surgical site infection (SSI). The peri-pelvic site appears to be particularly problematic. Surgical site infections are associated with a high proportion of gram-negative and anaerobic micro-organisms. To date, there are no published recommendations for peri-operative antibiotic prophylaxis in pelvic STS resection. Therefore, the aim of this study was to determine the rate of SSI and the spectrum of micro-organisms detected in this region. Methods: In this monocentric study, 366 patients were retrospectively evaluated. All of these patients had undergone surgery for STS in the peri-pelvic and pelvic regions. Surgical site infections were recorded, and the microbial spectrum was analyzed. Results: There were 85 (23.2%) patients with SSI, and 188 revisions were required in these patients (2.21 per case). Swabs were sterile in 20% of clinically infected cases. In total, 36.5% of infections were polymicrobial. The most common bacteria were coagulase-negative staphylococci in 31.5%, followed by Enterococcus species in 13.3% and Escherichia coli in 7.7%. In total, 30.8% of the bacteria were gram-negative and 25.9% were anaerobic. Conclusions: Our results demonstrate the uniqueness of the bacterial spectrum of SSI after STS resection in the peri-pelvic region. In the authors' opinion, recommendations regarding the peri-operative antibiotic prophylaxis need to be adapted for the typical microbial spectrum at this site.

Unraveling the role of local ablative therapies for patients with metastatic soft tissue sarcoma - A retrospective multicenter study of the Bavarian university hospitals.

BACKGROUND: Local ablative therapies (LAT) are increasingly used in patients with metastatic soft tissue sarcoma (STS), yet evidence-based standards are lacking. This study aimed to assess the impact of LAT on survival of metastatic STS patients and to identify prognostic factors. METHODS: In this retrospective multicenter study, 246 STS patients with metastatic disease who underwent LAT on tumor board recommendation between 2017 and 2021 were analyzed. A mixed effects model was applied to evaluate multiple survival events per patient. RESULTS: Median overall survival (OS) after first metastasis was 5.4 years with 1-, 2- and 5-year survival rates of 93.7, 81.7, and 53.1 %, respectively. A treatment-free interval ≥12 months and treatment of liver metastases were positively correlated with progression-free survival (PFS) after LAT (HR = 0.61, p = 0.00032 and HR = 0.52, p = 0.0081, respectively). A treatment-free interval ≥12 months and treatment of metastatic lesions in a single organ site other than lung and liver were positive prognostic factors for OS after first LAT (HR = 0.50, p = 0.028 and HR = 0.40, p = 0.026, respectively) while rare histotypes and LAT other than surgery and radiotherapy were negatively associated with OS after first LAT (HR = 2.56, p = 0.020 and HR = 3.87, p = 0.025). Additional systemic therapy was independently associated with a PFS benefit in patients ≤60 years with ≥4 metastatic lesions (for max. diameter of treated lesions ≤2 cm: HR = 0.32, p = 0.02 and >2 cm: HR = 0.20, p = 0.0011, respectively). CONCLUSION: This multicenter study conducted at six German university hospitals underlines the value of LAT in metastatic STS. The exceptionally high survival rates are likely to be associated with patient selection and treatment in specialized sarcoma centers.

Unplanned Resections of Soft Tissue Sarcomas-Necessity of Re-Resection?

BACKGROUND: In soft tissue sarcomas, unplanned resections, or so-called Whoops procedures, do occur quite frequently, thus primarily owing to the abundant presence of benign lesions. Whether re-resection reduces local recurrence or improves overall survival remains a topic of ongoing debate. The principle objective of this study was to analyze the outcomes of patients with soft tissue sarcomas of the extremities or trunk wall after an incidental marginal resection by comparing re-resections to individuals who declined the procedure. METHODS: A total of 185 patients who underwent unplanned resection were included. These patients were stratified into two groups: Group A (n = 156) underwent re-excision, while Group B (n = 29) was treated conservatively. Depending on the clinical scenario, radio- or chemotherapy was either administered in a neoadjuvant or an adjuvant setting. The presence of residual tumor and metastatic disease was documented. Clinical outcomes, specifically local recurrence (LR), local recurrence-free survival (LRFS) and overall survival (OS), were utilized for evaluation. RESULTS: Group B exhibited significantly larger tumors (p < 0.0001) and a higher mean age than Group A. Among the patients in Group A, 11 (5.9%) had contaminated resection margins (R1), and residual disease (RD) was observed in 93 (59.6%) of the resected specimens. In group B, 10 patients received adjuvant radiotherapy alone, 5 received chemotherapy alone, and 13 underwent a combined approach consisting of both radio- and chemotherapy. In Group A, 8% (n = 12) of the patients developed local recurrence (LR) during the observation period. Conversely, in Group B, this amount was 14% (n = 4) (n.s.). Of the 12 LR in Group A, 10 were found in the subgroup with residual disease. Overall survival and local recurrence-free survival were not significantly different between the groups. A total of 15% (n = 24) of the patients in Group A developed metastatic disease, while 10% (n = 3) in Group B developed metastatic disease (n.s.). CONCLUSIONS: Following the reresection of unplanned resected STS, there was no statistically significant difference observed in overall survival or LR compared to patients who did not undergo re-resection. However, within the subgroup of patients with residual disease in the re-resected specimen, the OS was compromised, and the LR rate was higher. Particularly for low-grade lesions, adopting a more conservative approach seems to be justified.

The Effect of chemo- and radiotherapy on tumor necrosis in soft tissue sarcoma- does it influence prognosis?

BACKGROUND: Soft tissue sarcomas (STSs) are a heterogeneous group of tumors. Wide surgical resection is standard, often combined with neoadjuvant chemotherapy, radiotherapy, or both. Studies have shown the predictive value of tumor necrosis in bone sarcoma (BS); however, the role of necrosis in STS after neoadjuvant therapies is still unclear. This study aimed to investigate the role of chemo- and radiotherapy in the formation of tumor necrosis and to evaluate the influence of tumor necrosis on overall survival and local recurrence-free survival. Data from BS patients and patients who did not receive neoadjuvant therapy were compared. METHODS: A total of 779 patients with STS or BS were treated surgically. In all patients, tumor-specific factors such as type, size, or grading and the type of adjuvant therapy were documented. Local recurrence (LR), the diagnosis of metastatic disease, and survival during follow-up were evaluated. RESULTS: A total of 565 patients with STS and 214 with BS were investigated. In STS, 24.1% G1 lesions, 34.1% G2 lesions, and 41.8% G3 lesions were observed. Two hundred twenty-four of the patients with STS and neoadjuvant therapy had either radiotherapy (RTx) (n = 80), chemotherapy (CTx) (n = 93), or both (n = 51). Three hundred forty-one had no neoadjuvant therapy at all. In STS, tumor necrosis after neoadjuvant treatment was significantly higher (53.5%) than in patients without neoadjuvant therapy (15.7%) (p < 0.001). Patients with combined neoadjuvant chemo-/radiotherapy had substantially higher tumor necrosis than those with radiotherapy alone (p = 0.032). There was no difference in tumor necrosis in patients with combined chemo-/radiotherapy and chemotherapy alone (p = 0.4). The mean overall survival for patients with STS was 34.7 months. Tumor necrosis did not influence survival in a subgroup of G2/3 patients. In STS with no neoadjuvant therapy and grading of G2/3, the correlation between necrosis and overall survival was significant (p = 0.0248). There was no significant correlation between local recurrence (LR) and necrosis. CONCLUSION: STS shows a broad spectrum of necrosis even without neoadjuvant chemo- or radiotherapy. After CTx or/and RTx necrosis is enhanced and is significantly pronounced with a combination of both. There is a trend toward higher necrosis with CTx than with RTx. Grading substantially influences the necrosis rate, but necrosis in soft-tissue sarcoma following neoadjuvant therapy does not correlate with better survival or a lower local recurrence rate, as in bone sarcomas.

Differentiation of benign and metastatic lymph nodes in soft tissue sarcoma.

Lymph node metastasis (LNM) occurs in less than 5% of soft tissue sarcoma (STS) patients and indicates an aggressive course of disease. Suspicious lymph nodes (LN) in staging imaging are a frequent topic of discussion in multidisciplinary tumor boards. Predictive markers are needed to facilitate stratification and improve treatment of STS patients. In this study, 56 STS patients with radiologically suspicious and subsequently histologically examined LN were reviewed. Patients with benign (n = 26) and metastatic (n = 30) LN were analyzed with regard to clinical, laboratory and imaging parameters. Patients with LNM exhibited significantly larger short axis diameter (SAD) and long axis diameter (LAD) vs. patients with benign LN (median 22.5 vs. 14 mm, p < 0.001 and median 29.5 vs. 21 mm, p = 0.003, respectively). Furthermore, the presence of central necrosis and high maximal standardized uptake value (SUVmax) in FDG-PET-CT scans were significantly associated with LNM (60 vs. 11.5% of patients, p < 0.001 and median 8.59 vs. 3.96, p = 0.013, respectively). With systemic therapy, a slight median size regression over time was observed in both metastatic and benign LN. Serum LDH and CRP levels were significantly higher in patients with LNM (median 247 vs. 187.5U/L, p = 0.005 and 1.5 vs. 0.55 mg/dL, p = 0.039, respectively). This study shows significant associations between LNM and imaging features as well as laboratory parameters of STS patients. The largest SAD, SUVmax in FDG-PET-CT scan, the presence of central necrosis, and high serum LDH level are the most important parameters to distinguish benign from metastatic LNs.

Refusal of Adjuvant Therapies and Its Impact on Local Control and Survival in Patients with Bone and Soft Tissue Sarcomas of the Extremities and Trunk.

BACKGROUND: In soft tissue or bone sarcomas, multimodal therapeutic concepts represent the standard of care. Some patients reject the therapeutic recommendations due to several reasons. The aim of this study was to assess the impact of that rejection on both prognosis and local recurrence. METHODS: Between 2012 and 2019, a total of 828 sarcoma patients were surgically treated. Chemotherapy was scheduled as a neoadjuvant, and adjuvant multi-agent therapy was performed following recommendations from an interdisciplinary tumor board. Radiotherapy, if deemed appropriate, was administered either in a neoadjuvant or an adjuvant manner. The recommended type of therapy, patient compliance, and the reasons for refusal were documented. Follow-ups included local recurrences, diagnosis of metastatic disease, and patient mortality. RESULTS: Radiotherapy was recommended in 407 (49%) patients. A total of 40 (10%) individuals did not receive radiation. A reduction in overall survival and local recurrence-free survival was evident in those patients who declined radiotherapy. Chemotherapy was advised for 334 (40%) patients, 250 (75%) of whom did receive all recommended cycles. A total of 25 (7%) individuals did receive a partial course while 59 (18%) did not receive any recommended chemotherapy. Overall survival and local recurrence-free survival were reduced in patients refusing chemotherapy. Overall survival was worst for the group of patients who received no chemotherapy due to medical reasons. Refusing chemotherapy for non-medical reasons was seen in 8.8% of patients, and refusal of radiotherapy for non-medical reasons was seen in 4.7% of patients. CONCLUSIONS: Divergence from the advised treatment modalities significantly impacted overall survival and local recurrence-free survival across both treatment modalities. There is an imperative need for enhanced physician-patient communication. Reducing treatment times, as achieved with hypofractionated radiotherapy and with therapy in a high-volume sarcoma center, might also have a positive effect on complying with the treatment recommendations.

Ten recommendations for sarcoma surgery: consensus of the surgical societies based on the German S3 guideline "Adult Soft Tissue Sarcomas".

PURPOSE: The evidence-based (S3) guideline "Adult Soft Tissue Sarcomas" (AWMF Registry No. 032/044OL) published by the German Guideline Program in Oncology (GGPO) covers all aspects of sarcoma treatment with 229 recommendations. Representatives of all medical specialties involved in sarcoma treatment contributed to the guideline. This paper compiles the most important recommendations for surgeons selected by delegates from the surgical societies. METHODS: A Delphi process was used. Delegates from the surgical societies involved in guideline process selected the 15 recommendations that were most important to them. Votes for similar recommendations were tallied. From the resulting ranked list, the 10 most frequently voted recommendations were selected and confirmed by consensus in the next step. RESULTS: The statement "Resection of primary soft tissue sarcomas of the extremities should be performed as a wide resection. The goal is an R0 resection" was selected as the most important term. The next highest ranked recommendations were the need for a preoperative biopsy, performing preoperative MRI imaging with contrast, and discussing all cases before surgery in a multidisciplinary sarcoma committee. CONCLUSION: The evidence-based guideline "Adult Soft Tissue Sarcomas" is a milestone to improve the care of sarcoma patients in Germany. The selection of the top ten recommendations by surgeons for surgeons has the potential to improve the dissemination and acceptance of the guideline and thus improve the overall outcome of sarcoma patients.

TIM-3 Qualifies as a Potential Immunotherapeutic Target in Specific Subsets of Patients with High-Risk Soft Tissue Sarcomas (HR-STS).

(1) Background: The expression of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), an immune checkpoint receptor on T cells, has been associated with dismal outcomes and advanced tumor stages in various solid tumors. The blockade of TIM-3 is currently under examination in several clinical trials. This study examines TIM-3 expression in high-risk soft tissue sarcomas (HR-STS). (2) Methods: Tumor cell expression of TIM-3 on protein level was analyzed in pre-treatment biopsies of patients with HR-STS. TIM-3 expression was correlated with clinicopathological parameters including tumor-infiltrating lymphocyte (TIL) counts, programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PDL-1) expression in patients with HR-STS. Survival dependent on the expression of TIM-3 was analyzed. (3) Results: TIM-3 expression was observed in 101 (56%) out of 179 pre-treatment biopsies of patients with HR-STS. TIM-3 expression was significantly more often observed in undifferentiated pleomorphic sarcomas (UPS) compared to other histological subtypes (p < 0.001), high TIL counts (p < 0.001), and high PD-1 (p < 0.001) and PD-L1 expression (p < 0.001). TIM-3 expression did not have a prognostic impact on survival in patients with HR-STS. (4) Conclusions: This is the first study to demonstrate a significant tumor cell expression of TIM-3 in specific subsets of patients with HR-STS. TIM-3 qualifies as a potential immunotherapeutic target in HR-STS.

Impact of postoperative baseline MRI on diagnostic confidence and performance in detecting local recurrence of soft-tissue sarcoma of the limb.

OBJECTIVE: To evaluate the impact of a postoperative baseline (PB) MRI on diagnostic confidence and performance in detecting local recurrence (LR) of soft-tissue sarcoma (STS) of the limb. MATERIALS AND METHODS: A total of 72 patients (8 with LR, 64 without LR) with primary STS of the limb were included. Routine follow-up MRI (1.5 T) at 6 and approximately 36 months (meanLR: 39.7 months; meanno LR: 34.9 months) after multimodal therapy or at time of LR were assessed by three independent readers using a 5-point Likert scale. Furthermore, the following imaging parameters were evaluated: presence of a mass, signal characteristics at T2- and T1-weighted imaging, contrast enhancement (CE), and in some of the cases signal intensity on the apparent diffusion coefficient (ADC). U-test, McNemar test, and ROC-analysis were applied. Interobserver reliability was calculated using Fleiss kappa statistics. A p value of 0.05 was considered statistically significant. RESULTS: The presence of a PB MRI significantly improved diagnostic confidence in detecting LR of STS (p < 0.001) and slightly increased specificity (mean specificity without PE 74.1% and with presence of PB MRI 81.2%); however, not to a significant level. The presence of a mass showed highest diagnostic performance and highest interreader agreement (AUC [%]; κ: 73.1-83.6; 0.34) followed by T2-hyperintensity (50.8-66.7; 0.08), CE (52.4-62.5; 0.13), and T1-hypointensity (54.7-77.3; 0.23). ADC showed an AUC of 65.6-96.6% and a κ of 0.55. CONCLUSION: The presence of a PB MRI increases diagnostic confidence in detecting LR of STS of the limb.

Finger Pain as an Uncommon Primary Manifestation of Lung Carcinoma.

A 54-year-old patient presented with progressive pain for one month in the second finger of the right hand with an emphasis on the proximal interphalangeal (PIP) joint. Subsequent magnetic resonance imaging (MRI) showed a diffuse intraosseous lesion at the base of the middle phalanx with destruction of the cortical bone and extraosseous soft tissue. An expansively growing chondromatous bone tumor, e.g., a chondrosarcoma, was suspected. After incisional biopsy, the pathologic findings finally revealed, surprisingly, a metastasis of a poorly differentiated non-small cell adenocarcinoma of the lung. This case illustrates a rare but important differential diagnosis for painful finger lesions.

Best clinical management of tenosynovial giant cell tumour (TGCT): A consensus paper from the community of experts.

Tenosynovial giant cell tumour (TGCT) is a rare, locally aggressive, mesenchymal tumor arising from the joints, bursa and tendon sheaths. TGCT comprises a nodular- and a diffuse-type, with the former exhibiting mostly indolent course and the latter a locally aggressive behavior. Although usually not life-threatening, TGCT may cause chronic pain and adversely impact function and quality of life (QoL). CSFR1 inhibitors are effective with benefit on symptoms and QoL but are not available in most countries. The degree of uncertainty in selecting the most appropriate therapy and the lack of guidelines on the clinical management of TGCT make the adoption of new treatments inconsistent across the world, with suboptimal outcomes for patients. A global consensus meeting was organized in June 2022, involving experts from several disciplines and patient representatives from SPAGN to define the best evidence-based practice for the optimal approach to TGCT and generate the recommendations presented herein.

Are Postoperative Infections in the First 12 Months after Wide Resection and Megaprosthetic Replacement Associated with the Survival of Osteosarcoma Patients? Results of a Multicenter Study.

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.

Hematopoietic islands mimicking osteoblastic metastases within the axial skeleton.

BACKGROUND: Hyperplasia of the hematopoietic bone marrow in the appendicular skeleton is common. In contrast, focal hematopoietic islands within the axial skeleton are a rare entity and can confuse with osteoblastic metastases. This study aimed to characterize typical MRI and CT findings of hematopoietic islands in distinction from osteoblastic metastases to help both radiologists and clinicians, on the one hand, not to overdiagnose this entity and, on the other hand, to decide on a reasonable work-up. METHODS: We retrospectively analyzed the imaging findings of 14 hematopoietic islands of the axial skeleton in ten patients (nine females, median age = 65.5 years [range, 49-74]) who received both MRI and CT at initial diagnosis between 2006 and 2020. CT-guided biopsy was performed in five cases to confirm the diagnosis, while the other five patients received long-term MRI follow-up (median follow-up = 28 months [range, 6-96 months]). Diffusion-weighted imaging was available in three, chemical shift imaging respectively 18F- fluorodeoxyglucose PET/CT in two, and Technetium 99 m skeletal scintigraphy in one of the patients. RESULTS: All lesions were small (mean size = 1.72 cm2) and showed moderate hypointense signals on T1- and T2-weighted MRI sequences. They appeared isointense to slightly hyperintense on STIR images and slightly enhanced after gadolinium administration. To differentiate this entity from osteoblastic metastases, CT provides important additional information, as hematopoietic islands do not show sclerosis. CONCLUSIONS: Hematopoietic islands within the axial skeleton can occur and mimic osteoblastic metastases. However, the combination of MRI and CT allows for making the correct diagnosis in most cases.

Defect Coverage after Forequarter Amputation-A Systematic Review Assessing Different Surgical Approaches.

Autologous fillet flaps are a common reconstructive option for large defects after forequarter amputation (FQA) due to advanced local malignancy or trauma. The inclusion of osseous structures into these has several advantages. This article therefore systematically reviews reconstructive options after FQA, using osteomusculocutaneous fillet flaps, with emphasis on personalized surgical technique and outcome. Additionally, we report on a case with an alternative surgical technique, which included targeted muscle reinnervation (TMR) of the flap. Our literature search was conducted in the PubMed and Cochrane databases. Studies that were identified were thoroughly scrutinized with regard to relevance, resulting in the inclusion of four studies (10 cases). FQA was predominantly a consequence of local malignancy. For vascular supply, the brachial artery was predominantly anastomosed to the subclavian artery and the brachial or cephalic vein to the subclavian or external jugular vein. Furthermore, we report on a case of a large osteosarcoma of the humerus. Extended FQA required the use of the forearm for defect coverage and shoulder contour reconstruction. Moreover, we performed TMR. Follow-up showed a satisfactory result and no phantom limb pain. In case of the need for free flap reconstruction after FQA, this review demonstrates the safety and advantage of osteomusculocutaneous fillet flaps. If the inclusion of the elbow joint into the flap is not possible, we recommend the use of the forearm, as described. Additionally, we advocate for the additional implementation of TMR, as it can be performed quickly and is likely to reduce phantom limb and neuroma pain.

VISTA in Soft Tissue Sarcomas: A Perspective for Immunotherapy?

(1) Background: V domain immunoglobulin suppressor of T cell activation (VISTA) plays a critical role in antitumor immunity and may be a valuable target in cancer immunotherapy. To date, it has never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: Using immunohistochemistry, we examined VISTA expression in tumour tissues of 213 high-risk STS. We then analysed whether VISTA was associated with other clinicopathological parameters, including tumour-infiltrating lymphocyte (TIL) counts, programmed death receptor-1 (PD1), programmed death ligand-1 (PDL1), CD3, grading, and long-term survival. (3) Results: We observed VISTA expression in 96 (45%) of 213 specimens with distinct patterns ranging from 26 to 63% for histological subtypes. VISTA was associated with higher grade (G3 vs. G2, p = 0.019), higher TIL counts (p = 0.033), expression of PD1 (p = 0.046), PDL1 (p = 0.031), and CD3+ (p = 0.023). In patients without CD3+ TILs, 10-year survival was higher when VISTA was expressed compared to when there was no VISTA expression (p = 0.013). In a multivariate analysis, VISTA expression was independently associated with prolonged survival (p = 0.043). (4) Conclusions: VISTA is expressed in different STS subtypes and is associated with increased TILs, PD-1, PD-L1, and CD3 expression. Patients with VISTA+ tumours show improved survival. These results may help define future immunotherapeutic approaches in STS.

Sarcomas of the extremities and the pelvis: comparing local recurrence after incisional and after core-needle biopsy.

BACKGROUND: The degree of contamination of healthy tissue with tumor cells during a biopsy in bone or soft tissue sarcomas is clearly dependant on the type of biopsy. Some studies have confirmed a clinically relevant contamination of the biopsy tract after incisional biopsies, as opposed to core-needle biopsies. The aim of our prospective study was to evaluate the risk of local recurrence depending on the biopsy type in extremity and pelvis sarcomas. METHODS: We included 162 patients with a minimum follow-up of 6 months after wide resection of extremity sarcomas. All diagnostic and therapeutic procedures were performed at a single, dedicated sarcoma center. The excision of the biopsy tract after an incisional biopsy was performed as a standard with all tumor resections. All patients received their follow-up after the conclusion of therapy at our center by means of regional MRI studies and, at a minimum, CT of the thorax to rule out pulmonary metastatic disease. The aim of the study was the evaluation of the influence of the biopsy type and of several other clinical factors on the rate of local recurrence and on the time of local recurrence-free survival. RESULTS: One hundred sixty-two patients with bone or soft tissue tumors of the extremities and the pelvis underwent either an incisional or a core-needle biopsy of their tumor, with 70 sarcomas (43.2%) being located in the bone. 84.6% of all biopsies were performed as core-needle biopsies. The median follow-up time was 55.6 months, and 22 patients (13.6%) developed a local recurrence after a median time of 22.4 months. There were no significant differences between incisional and core-needle biopsy regarding the risk of local recurrence in our subgroup analysis with differentiation by kind of tissue, grading of the sarcoma, and perioperative multimodal therapy. CONCLUSIONS: In a large and homogenous cohort of extremity and pelvic sarcomas, we did not find significant differences between the groups of incisional and core-needle biopsy regarding the risk of local recurrence. The excision of the biopsy tract after incisional biopsy in the context of the definitive tumor resection seems to be the decisive factor for this result.

Functional results after oncological scapula resections.

INTRODUCTION: Tumors of the scapula are rare representing only 1.6%-2.8% of all skeletal tumor localizations. Wide resection of these tumors is often necessary, and their anatomic location is the most decisive factor for the extent of the resection. Because of the importance of the shoulder girdle for all daily activities, such resections can have major functional consequences. However, only few reports with small numbers of cases are found in the literature. PATIENTS AND METHODS: We retrospectively evaluated 31 consecutive patients with scapular tumors treated surgically for aggressive benign or malignant tumors of the scapula. Patients who had received curettage only were excluded. Four of these 31 patients were lost to follow-up. In 7 of the remaining 27 patients, a total scapulectomy had to be performed, whereas all others received a partial resection. In 1 case, a partial resection and replantation after irradiation was performed. Musculoskeletal Tumor Society Scoring System (MSTS) and Toronto Extremity Salvage Score (TESS) scores were evaluated postoperatively at the time of their follow-up. RESULTS: In 16 men and 11 women, the median age was 46.2 years and the tumor entities were heterogeneous. The median follow-up time was 71 months. Three patients died during follow-up due to their tumor and 1 due to cardiac disease. We found significantly better functional results in the group with incomplete scapula resections as opposed to the scapulectomy group. We did not see a significant functional difference between the patients with benign and those with malignant lesions. Both the MSTS score with median 83.3% (range between 23% and 100%) and the TESS score with 81.6% (ranging from 20.4% to 100%) were at a satisfactory level. The preservation of the supraspinatus muscle was shown to be advantageous for better shoulder function, and younger patients also tended to have better postoperative results. CONCLUSION: The resection of scapular tumors may lead to a significant functional disability of the shoulder girdle and the affected arm in many cases. However, this is represented neither in the MSTS or TESS score nor in the overall acceptance of the patients. Only 1 patient, an artisan, had to change his job. In total, the clinical results are quite good in short- and long-term follow-up. The score results were comparable to other studies.

Expression Patterns of TOP2A and SIRT1 Are Predictive of Survival in Patients with High-Risk Soft Tissue Sarcomas Treated with a Neoadjuvant Anthracycline-Based Chemotherapy.

Molecular predictors of response to chemotherapy and survival have not been put into clinical practice in high-risk soft tissue sarcomas (HR-STS) by now. The expression of TOP2A and SIRT1 has implications for the mechanism of action of doxorubicin, which is the backbone of chemotherapy in HR-STS. Pre-treatment samples of 167 patients with HR-STS were collected. Protein expression levels of TOP2A and SIRT1 were evaluated with tissue microarrays and immunohistochemistry and correlated with clinicopathological parameters, including overall survival (OS). The expression of TOP2A and SIRT1 was seen in 47% and 60% of patients with HR-STS, respectively. TOP2A expression was associated with higher tumor grading and shorter 5-year OS. The expression of SIRT1 was correlated with a better 5- and 10-year OS. The combination of high SIRT1 and low TOP2A ("Top survivors") significantly predicted a better OS compared to other biomarker combinations. A multivariate analysis confirmed the expression of SIRT1 and the "Top survivor" biomarker combination as independent predictive factors of OS. This is the first study to associate SIRT1 overexpression with a statistically significant prolongation of OS in HR-STS. Both individual markers and their combination can be used as predictive indicators for HR-STS patients scheduled for neoadjuvant anthracycline-based chemotherapy.