Postoperative Outcomes After Laparoscopic Liver Resections in Low and High-Volume Centers: A Multicentric Case-Matched Comparative Study.

BACKGROUND: Laparoscopic liver resection (LLR) is the gold standard for liver resections. Despite its feasibility and safety in high-volume centers (HVC), its performance is controversial in low-volume centers (LVCs). We aimed to evaluate the results of LLR performed in LVC. METHODS: Patients who underwent LLR between 2013 and 2019 in three LVCs were compared after case-matching with those in an HVC using the Institut Mutualiste Montsouris LLR Difficulty Score (IMMLDS). RESULTS: Seventy-six patients treated in three LVCs were matched to 152 in HVCs for age, body mass index, and resection type. The incidence of LLR significantly increased in LVCs over time (2013-2016 vs. 2017-2019) (21.2% vs. 39.3%; p = 0.002 and) while abdominal drainage rate decreased (77.4% vs. 51.1%; p = 0.003). In IMMLDS group I (60 vs. 120 patients), higher Pringle maneuver (43.3% vs. 2.5%; p < 0.0001), median blood loss (175 ml vs. 50 ml; p < 0.0001), abdominal drainage (58.3% vs. 6.6%; p < 0.0001), and conversion rate (8.3% vs. 1.6%, p = 0.04) were observed in LVCs. The overall postoperative morbidity was comparable (Clavien I-II: p = 0.54; Clavien > II: p = 0.71). In IMMLDS groups II-III, Pringle maneuver (56.5% vs. 3.1%; p < 0.0001), blood loss (350 ml vs. 175 ml; p = 0.02), and abdominal drainage (75% vs. 28.3%; p = 0.004) were different; however, postoperative morbidity was not. The surgical difficulty notwithstanding, length of stay (group I: p = 0.13; group II-III: p = 0.93) and R0 surgical margin (group I: p = 0.3; group II-III p = 0.39) were not different between LVCs and HVCs. CONCLUSIONS: LLR performed at an LVC can be feasible and safe with acceptable morbidity.

Watch and Wait Approach for Re-excision After Unplanned Yet Macroscopically Complete Excision of Extremity and Superficial Truncal Soft Tissue Sarcoma is Safe and Does Not Affect Metastatic Risk or Amputation Rate.

BACKGROUND: The benefits of systematic re-excision (RE) after initial unplanned excision (UE) of soft tissue sarcoma (STS) are unknown. OBJECTIVE: The aim of this study was to evaluate the impact of delayed RE versus systematic RE after UE on overall survival (OS), metastatic relapse-free survival (MRFS), local relapse-free survival (LRFS), and rate of amputation. METHODS: Patients who underwent complete UE, without metastasis or residual disease, for primary extremity or superficial STS between 2007 and 2013 were analyzed. The amputation rate, LRFS, MRFS, and OS were assessed in cases of systematic RE in sarcoma referral centers (Group A), systematic RE outside of community centers (Group B), or without RE (Group C). RESULTS: Groups A, B, and C included 300 (48.2%), 71 (11.4%), and 251 (40.4%) patients, respectively. Median follow-up was 61 months and 5-year OS was 88.4%, 87.3%, and 88% in Groups A, B, and C, respectively (p = 0.22), while 5-year MFRS was 85.4%, 86.2%, and 84.9%, respectively (p = 0.938); RE (p = 0.55) did not influence MRFS. The 5-year LRFS was 83%, 73.5%, and 63.8% in Groups A, B and C, respectively (p = 0.00001). Of the 123 local recurrences observed, 0/28, 1/15, and 5/80 patients in Groups A, B, and C, respectively, required amputation (p = 0.41). Factors influencing LRFS were adjuvant radiotherapy [hazard ratio (HR) 0.21; p = 0.0001], initial R0 resection (HR 0.24, p = 0.0001), and Group A (HR 0.44; p = 0.01). CONCLUSION: Systematic RE in sarcoma centers offers best local control but does not impact OS. Delayed RE at the time of local relapse, if any, could be an option.

Long-term outcome and effect of maintenance therapy in patients with advanced sarcoma treated with trabectedin: an analysis of 181 patients of the French ATU compassionate use program.

BACKGROUND: The long term outcome of advanced sarcoma patients treated with trabectedin outside of clinical trials and the utility of maintenance treatment has not been reported. METHODS: Between 2003 and 2008, patients with advanced sarcoma failing doxorubicin could be treated within a compassionate use program (ATU, Temporary Use Authorization) of trabectedin in France using the standard 3-weekly regimen. Data from 181 patients (55%) were collected from 11 centres and analyzed. RESULTS: Trabectedin was given in first, second, third or fourth line in metastatic phase in 6%, 37%, 33% and 23% of patients respectively. With a median follow-up of 6 years, median PFS and OS were 3.6 months and 16.1 months respectively. The median number of cycles was 3 (range 1-19). Best response were partial response (PR, n = 18, 10%), stable disease (SD, n = 69, 39%) and progressive disease (PD, n = 83, 46%), non evaluable (NE, n = 9, 5%). Thirty patients (17%) had to be hospitalized for treatment- related side effects. Independent prognostic factors in multivariate analysis (Cox model) were myxoid LPS and line of trabectedin for PFS, and myxoid LPS and retroperitoneal sarcomas for OS. Patients in PR or SD after 6 cycles continuing treatment had a better PFS (median 5.3 vs 10.5 months, p = 0.001) and OS (median 13.9 vs 33.4 months, p = 0.009) as compared to patients who stopped after 6 cycles. CONCLUSIONS: In this compassionate use program, trabectedin yielded similar or better PFS and OS than in clinical trials. Maintenance treatment beyond 6 cycles was associated with an improved survival.

[Contribution of whole-body MRI to the initial assessment of myxoid liposarcoma]. / Apport de l'IRM corps entier au bilan initial du liposarcome myxoïde.

INTRODUCTION: Myxoid liposarcoma is a soft tissue sarcoma associated with multifocal metastases at diagnosis. These metastases are asymptomatic and occult on CT and FDG-PET and can alter the therapeutic management and prognosis. In this context, we evaluated the contribution of whole-body MRI to the initial workup of patients with myxoid liposarcoma. METHOD: This retrospective study was conducted between January 2015 and December 2020 at the Oscar Lambret Center. We enrolled 22 patients who were diagnosed with myxoid liposarcoma and underwent whole-body MRI at diagnosis. The number of metastases at diagnosis, their location, and the visibility of these lesions on CT were evaluated. Associations between clinical features, presence of metastasis, and their impact on management were assessed. RESULTS: Sixteen patients (72.7%) had non-metastatic disease at the initial diagnosis, and 15 of these patients were managed using local treatment. Six patients (27.3%) had metastases at multiple locations and received chemotherapy. The main locations were the bones (n=5) and lungs (n=3). In five patients with metastases, whole-body MRI demonstrated additional lesions that were not visible on CT (bone and soft tissue lesions). Only the presence of a round cell contingent (P=0.009) was found as a criterion associated with the presence of metastases. CONCLUSION: The patients' young age, absence of reliable prognostic factors at diagnosis, asymptomatic nature of the lesions, and the benefits of early and targeted therapeutic management encourage the use of whole-body MRI as part of the initial work-up as it seems to provide a better initial staging compared with conventional imaging.

Senescence Induced by UVB in Keratinocytes Impairs Amino Acids Balance.

Skin is one of the most exposed organs to external stress. Namely, UV rays are the most harmful stress that could induce important damage leading to skin aging and cancers. At the cellular level, senescence is observed in several skin cell types and contributes to skin aging. However, the origin of skin senescent cells is still unclear but is probably related to exposure to stresses. In this work, we developed an in vitro model of UVB-induced premature senescence in normal human epidermal keratinocytes. UVB-induced senescent keratinocytes display a common senescent phenotype resulting in an irreversible cell cycle arrest, an increase in the proportion of senescence-associated ß-galactosidase‒positive cells, unrepaired DNA damage, and a long-term DNA damage response activation. Moreover, UVB-induced senescent keratinocytes secrete senescence-associated secretory phenotype factors that influence cutaneous squamous cell carcinoma cell migration. Finally, a global transcriptomic study highlighted that senescent keratinocytes present a decrease in the expression of several amino acid transporters, which is associated with reduced intracellular levels of glycine, alanine, and leucine. Interestingly, the chemical inhibition of the glycine transporter SLC6A9/Glyt1 triggers senescence features.

Right hepatectomy with extra-hepatic vascular division prior to transection: intention-to-treat analysis of a standardized policy.

BACKGROUND: Right hepatectomy (RH) is the most common type of major hepatectomy and can be achieved without portal triad clamping (PTC) in non-cirrhotic liver. The present study reviews our standardized policy of performing RH without systematic PTC. METHODS: One hundred and eighty-one consecutive RH were performed in non-cirrhotic patients, with division of the right afferent and efferent blood vessels prior to transection, without systematically using PTC. Prospectively collected data were analysed, focusing on the following endpoints: need for salvage PTC, ischaemic time, blood loss and post-operative outcome. RESULTS: Extra-hepatic division of the right hepatic vessels was feasible in all patients, but was ineffective in 48 patients (26.5%) who required salvage PTC during transection. In those patients, the median ischaemic time was 20 min. The median blood loss was 500 ml (50-3000). Six patients (3.3%) experienced post-operative liver failure. Overall morbidity, severe morbidity and mortality were 42%, 12.1% and 1.6%, respectively, with peri-operative transfusion rate (16.6%) being the only factor associated with morbidity. DISCUSSION: By performing RH with extra-hepatic vascular division prior to transection, PTC can be safely avoided in the majority of patients.

Solitary fibrous tumors and so-called hemangiopericytoma.

We have reviewed the literature data regarding the spectrum of tumors including solitary fibrous tumor and hemangiopericytoma with special focus on definition of the disease, discussion of the criteria for malignancy, and the key elements of standard treatment of localized disease. We have discussed the emerging concepts on the tumor biology and the different systemic treatments (chemotherapy and molecular-targeted therapies).

Myositis ossificans circumscripta after surgery and radiotherapy and during sunitinib treatment: a case report.

BACKGROUND: Myositis ossificans circumscripta is a self-limiting, benign, ossifying lesion that can affect any type of soft tissue. It is most commonly found in muscles as a solitary lesion. A history of recent trauma has been reported in approximately 50% of cases. Clinically, MOC presents as a painful swelling, which rapidly increases in size. The pain and inflammatory symptoms spontaneously disappear after approximately 2-6 weeks, and the mass stabilizes or decreases. Radiologically, myositis ossificans circumscripta can be divided into two phases. The first is the acute phase, which is followed by the mature phase 2-6 weeks later. During the acute phase, the radiological aspect does not show any specific abnormality. In the mature phase, plain radiographs and computed tomography show blurred calcifications around a hypodense center. We describe here the first case of myositis ossificans circumscripta, with appropriate follow-up, occurring during sunitinib exposure. CASE PRESENTATION: We report a case of myositis ossificans circumscripta in a 34-year-old man (ethnicity unknown) receiving sunitinib for metastatic alveolar soft part sarcoma of the left thigh after surgery and radiotherapy. Four months after the first dose of sunitinib, the patient experienced painful swelling in the surgical scar area. Magnetic resonance imaging showed diffuse and marked edema of the anterior compartment of the thigh, without nodular lesions circumscribing a central core, and without bone signal abnormality. The increased visibility of the intermuscular fascia and convergence of normal muscle fibers (black hole effect), without the displacement seen in tumors, were suggestive of myositis. Therefore, antiangiogenic treatment was discontinued, and the symptoms rapidly resolved within a few days. Three weeks after the discontinuation of sunitinib, the inflammatory findings completely disappeared. Two months after the diagnosis of myositis ossificans circumscripta, plain radiographs and computed tomography showed an extensive calcified mass measuring > 12 cm. The continuation of favorable clinical outcomes was confirmed. CONCLUSIONS: To the best of our knowledge, this is the first case of myositis ossificans circumscripta with appropriate follow-up occurring during sunitinib exposure. Owing to multimodal treatment of sarcoma, we cannot rule out the radiotherapy and surgery causality.

No Geographical Inequalities in Survival for Sarcoma Patients in France: A Reference Networks' Outcome?

The national reference network NETSARC+ provides remote access to specialized diagnosis and the Multidisciplinary Tumour Board (MTB) to improve the management and survival of sarcoma patients in France. The IGéAS research program aims to assess the potential of this innovative organization to address geographical inequalities in cancer management. Using the IGéAS cohort built from the nationwide NETSARC+ database, the individual, clinical, and geographical determinants of the 3-year overall survival of sarcoma patients in France were analyzed. The survival analysis was focused on patients diagnosed in 2013 (n = 2281) to ensure sufficient hindsight to collect patient follow-up. Our study included patients with bone (16.8%), soft-tissue (69%), and visceral (14.2%) sarcomas, with a median age of 61.8 years. The overall survival was not associated with geographical variables after adjustment for individual and clinical factors. The lower survival in precarious population districts [HR 1.23, 95% CI 1.02 to 1.48] in comparison to wealthy metropolitan areas (HR = 1) found in univariable analysis was due to the worst clinical presentation at diagnosis of patients. The place of residence had no impact on sarcoma patients' survival, in the context of the national organization driven by the reference network. Following previous findings, this suggests the ability of this organization to go through geographical barriers usually impeding the optimal management of cancer patients.

[Dermatofibrosarcoma: Management]. / Dermatofibrosarcome : prise en charge.

Dematofibrosarcoma protuberans (DFSP) are very rare (1 to 4 incident cases per million of inhabitants). The local spreading of DFSP is underestimated. The histological diagnosis is challenging but we now know a specific marker (translocation t(17;22)(q22;q13) (COL1A1;PDGFB)). The risk of metastatic relapse is low (and related to fibrosarcoma component); the risk of local relapse depends on the quality of surgery. Management of localized DFSP is based on large resection with meticulous analysis of margins (with or without Mohs microsurgery). Advanced stages not amenable to surgery or metastatic DFSP (with presence of COL1A1;PDGFB) are best treated with imatinib. Locally advanced DFSP potentially amenable to curative intent surgery could be treated with imatinib as neo-adjuvant treatment. The management of these tumours requires multidisciplinary expertise.