Improved nationwide survival of sarcoma patients with a network of reference centers.

BACKGROUND: We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients' characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020. RESULTS: A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n = 9266 before 2013, n = 12 274 between 2013 and 2015, n = 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients >18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P < 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P < 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers. CONCLUSIONS: The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved.

Intraoperative motive for incomplete resection in primary retroperitoneal sarcoma.

INTRODUCTION: Surgical resection is the current standard of care for retroperitoneal sarcoma (RPS). Recent data suggests that up to 5% of patient have incomplete (R2) resection. The exact reason why patients scheduled for surgery with a curative intent to treat ended up with an R2 resection is largely unknown. AIM OF THE STUDY: To identify intraoperative findings responsible for incomplete (R2) resection in primary RPS. METHODS: All records of consecutive patients scheduled for a non-metastatic primary RPS surgery between 1995 and 2020 in a tertiary care sarcoma centre were retrospective analyzed. RESULTS: Among the 347 patients scheduled for surgery, 13 (3.7%) had an incomplete (R2) resection. The reasons for incomplete surgery were intraoperative finding of vascular involvement of great vessels in 5 patients, previously undetected peritoneal metastases in 5 patients, invasion of contralateral kidney/ureter in 2 patients and the need to preserve both kidneys in 1 patient because of his past medical history. Among these patients, 3 had a laparotomy without resection and 10 had a partial resection (i.e. debulking surgery). Severe postoperative complications occurred in 5 patients. The median length of stay in hospital was 19days. After a median follow-up of 12months, the median survival of patients after incomplete resection was 18months. The 1-y, 5-y and 8-y overall survival (OS) for these patients were 46%, 14%, and 7%, respectively. CONCLUSION: Incomplete (R2) resection for a primary RPS surgery is rare in specialized sarcoma center. The next steps should be to identify the preoperative criteria that lead to this accurate selection and to define the best practice in front of a peroperative discovery of an unresectable RPS. LEVEL OF EVIDENCE: III.

Lung carcinoids with high proliferative activity: Further support for the identification of a new tumor category in the classification of lung neuroendocrine neoplasms.

Highly proliferative lung carcinoids (HPLC) have been recently reported but information about this subset remains scarce. OBJECTIVES: Clinical and pathological data of 630 patients with lung carcinoids (LC) referred to Gustave Roussy Institute (GR) and European Institute of Oncology (IEO) were retrospectively reviewed to select HPLC and analyze their frequency, behavior and compare their outcome to conventional LC with Ki-67 ≤ 20 % and mitotic count (MC)≤10/2 mm2. MATERIALS AND METHODS: Selection criteria were: diagnosis of LC confirmed by local pathologist, and available clinical and follow-up data. Patients with Ki-67 > 20 % and/or MC > 10/ 2 mm2 in primary or metastatic specimens were identified as HPLC. RESULTS: 30/514 patients (6%) met the selection criteria of HPLC. Based on primary tumor evaluation, 22/25 (88 %) were classified as atypical carcinoids (AC). Median MC was 4.5/2 mm2 (1-11) 6/2 mm2 (3-15) in primary tumors and metastasis, respectively. Median Ki-67 was respectively 23 % (15-65) and 25 % (8-60). Recurrence rate was 66 % (12/18) in HPLC and 9 % (33/352) in conventional LC. Median RFS was 24 (10-NR) months in HPLC, 288 (141-NR) months in LC with Ki-67 index≤5 % and NR (148-NR) months in LC with Ki-67 6-20% (p < 001). Median OS was 203 (83-NR) months in LC with Ki-67 index≤5%, 101 (79-NR) months in LC with Ki-67 index 6-20 % and 53 (39-NR) months in HPLC (p = 002). Among 20 metastatic patients with HPLC, median PFS under platinum-based chemotherapy, everolimus, alkylating-based chemotherapy, FOLFOX and PRRT was 5.1 (95 % CI 0.7-9.4), 12.1(95 %CI 0.3-24), 6.8 (95 % CI 0-14.9), 10.2 (95 % CI 0.4-19.9) and 14.2 months (95 % CI 0-30) respectively. Best response was stable disease (SD) under platinum-based chemotherapy and partial response (PR) under alkylating-based chemotherapy and FOLFOX. CONCLUSION: This study confirms the existence and rarity of HPLC. Their characteristics and clinical behavior are more similar to LC rather than neuroendocrine carcinomas (NECs), suggesting that this entity could be managed accordingly.

Can we cure patients with abdominal Desmoplastic Small Round Cell Tumor? Results of a retrospective multicentric study on 100 patients.

BACKGROUND: Despite being associated with a very poor prognosis, long-term survivors across all series of Desmoplastic Small Round Cell Tumor (DSRCT) have been reported. AIM OF THE STUDY: To analyze patients 'characteristics associated with a prolonged survival after DSRCT diagnosis. METHODS: All consecutive patients treated for DSRCT in nine French expert centers between 1991 and 2018 were retrospectively analyzed. Patients with a follow-up of less than 2 years were excluded and cure defined as being disease-free at least 5 years. RESULTS: 100 pts were identified (median age 25 years, 89% male). 27 had distant metastases at diagnosis and 80 pts underwent upfront chemotherapy (CT). 71 pts were operated, 20 pts without prior CT). Surgery was macroscopically complete (CC0/1) in 50 pts. Hyperthermic intraperitoneal Chemotherapy (HIPEC) was administered during surgery in 15 pts 54 pts had postoperative CT and 26 pts had postoperative whole abdomino-pelvic RT (WAP-RT). After a median follow-up of 103 months (range 23-311), the median overall survival (OS) was 25 months. The 1- year, 3-year and 5-year OS rates were 90%, 35% and 4% respectively. 5 patients were considered cured after a median disease-free interval of 100 months (range 22-139). Predictive factors of cure were female sex (HR = 0.49, p = 0.014), median PCI<12 (HR = 0.32, p = 0.0004), MD Anderson stage I (HR = 0.25, p < 0.0001), CC0/1 (HR = 0.34, p < 0.0001), and WAP-RT (HR = 0.36, p = 0.00013). HIPEC did not statistically improve survival. CONCLUSION: Cure in DSRCT is possible in 5% of patients and is best achieved combining systemic chemotherapy, complete cytoreductive surgery and WAP-RT. Despite aggressive treatment, recurrence is common and targeted therapies are urgently needed.

Neoadjuvant isolated limb perfusion in newly diagnosed untreated patients with locally advanced soft tissue sarcomas of the extremities: the Gustave Roussy experience.

BACKGROUND: Limb-sparing surgery in locally advanced soft tissue sarcomas (LA STS) is challenging. The aim of this study is to evaluate upfront isolated limb perfusion (ILP) in untreated patients with LA STS. METHODS: All consecutive patients with LA STS of the limbs deemed borderline or unresectable and treated with upfront ILP as induction treatment between 2003 and 2016 were included. Demographic, clinical and long-term characteristics were obtained and retrospectively analyzed. RESULTS: 41 patients (pts), with a median age of 51 years [range 21-76], were identified (lower limb 68%, upper limb 32%). Liposarcoma and undifferentiated pleomorphic sarcoma were the most common subtypes (27% and 22%, respectively). Acute toxicities, using Wieberdink classification, were grade II (35 pts, 85%), grade III (2 pts, 5%) and no grade IV-V. Local control rate was 98%. 32 pts had limb-sparing surgery (78%). 1 pt had an early amputation due to progressive disease after ILP. 8 pts were not operated (four had RT alone, one had distant metastases, two had a complete response and one died 3 months after ILP of a pulmonary embolism). 36 pts (84%) received postoperative RT. After a median follow-up of 43 months, 18 pts (47%) relapsed. Median disease-free survival (DFS) was 6.7 years. The median overall survival (OS) was not reached. The 1-year, 5-year and 10-year DFS and OS rates were, respectively, 75%, 50% and 45%, and 90%, 63% and 55%. CONCLUSION: Upfront ILP is an efficient and well-tolerated limb-sparing procedure in borderline or unresectable LA STS without hampering OS.

Long-Term Outcome After Surgery for a Localized Retroperitoneal Soft Tissue Sarcoma in Elderly Patients: Results from a Retrospective, Single-Center Study.

BACKGROUND: To evaluate short- and long-term results after curative surgery for a retroperitoneal sarcoma (RPS) in elderly patients. METHODS: We retrospectively analyzed data of all patients operated in our single, tertiary care center for a nonmetastatic RPS and identified patients aged 70 years and older. RESULTS: Among 296 patients with an RPS treated between 1994 and 2015, 60 (20%) were aged 70 years and older (median age 74 years; range 70-85). The median tumor size was 24 cm (range 6-46). Forty-six patients (77%) had mass-related symptoms at the time of diagnosis. The most frequent histological subtypes were de-differentiated liposarcoma (53%, n = 32) and well-differentiated liposarcoma (35%, n = 21). Twenty-two patients (37%) had perioperative radiotherapy and/or chemotherapy. Fifty-eight patients (97%) had macroscopically complete resection. The postoperative mortality was 8% and severe morbidity (Dindo/Clavien ≥ 3) was 32%. A reoperation was required for ten patients (17%). After a median follow-up of 20 months (range 1-121), the 5-year overall survival (OS) rate was 90% (95% confidence interval [CI] 79-100%), and median OS was not reached. The cancer-specific death rate was 88%. No prognostic factor for disease-specific survival was detected. The 5-year disease-free survival (DFS) rate was 52% (95% CI 33-84%) and 5-year locoregional recurrence-free survival rate was 52% (95% CI 33-84%). Median DFS was 94 months (95% CI 35-NA). Reoperation after inappropriate surgery and postoperative morbidity were independent predictive factors of locoregional relapse. No predictive factors of distant metastasis were found. CONCLUSIONS: Curative surgery is feasible in selected elderly patients but with higher mortality and morbidity rates than in younger patients. It enables a prolonged survival. Future studies should focus on selection process to minimize postoperative mortality and morbidity.

Second-look surgery plus HIPEC for patients with colorectal cancer at high risk of peritoneal carcinomatosis: Should we resect the initial anastomosis? An observational study.

BACKGROUND: Cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improves the overall survival in selected cases of peritoneal carcinomatosis (PC) of colorectal origin. Second-look surgery in asymptomatic patients at high risk of developing PC has shown encouraging results. This study aims at identifying cases in which initial anastomosis should be resected. METHODS: Patients treated by second-look surgery and HIPEC were identified from a prospective database. High-risk was defined as synchronous resected and minimal PC, ovarian metastasis or perforated primary tumor. Patients were divided in two groups based on intra-operative evaluation of the anastomosis: possibly-invaded (PI) and unlikely-invaded (UI). PI was defined as 1) PC away from the anastomosis, 2) nodules resting on the anastomosis 3) anastomotic stenosis or anastomotic thickening. Anastomosis in the PI group were resected. RESULTS: Forty patients were included: 12 in the PI group and 28 in the UI group. Incidence of pathological anastomotic invasion was 42% (5 on 12 patients) in the PI group. In the UI group, 2 patients had anastomotic recurrence, both associated with peritoneal recurrence. Morbidity and mortality was not influenced by anastomosis resection. The presence of suspicious nodules on the anastomosis had a sensitivity of 100% and a specificity of 89% in predicting anastomotic invasion. CONCLUSION: In second-look surgery and HIPEC for colorectal cancer at high-risk of PC, anastomosis should be resected when overlying PC nodules are found. This attitude is supported by high sensitivity of this finding for anastomotic invasion and low morbidity related to anastomotic resection.

Mediastinitis due to Gram-negative bacteria is associated with increased mortality.

The aim of this study was to describe the features of a large cohort of patients with postoperative mediastinitis, with particular regard to Gram-negative bacteria (GNB), and assess their outcome. This bicentric retrospective cohort included all patients who were hospitalized in the Intensive Care Unit with mediastinitis after cardiac surgery during a 9-year period. Three hundred and nine patients developed a mediastinitis with a mean age of 65 years and a mean standard Euroscore of six points. Ninety-one patients (29.4%) developed a GNB mediastinitis (GNBm). Of the 364 pathogens involved, 103 GNB were identified. GNBm were more frequently polymicrobial (44% versus 3.2%; p <0.001). Being female was the sole independent risk factor of GNBm in multivariate analysis. Initial antimicrobial therapy was significantly more frequently inappropriate with GNBm compared with other microorganisms (24.6% versus 1.9%; p <0.001). Independent risk factors for inappropriateness of initial antimicrobial treatment were GNBm (OR = 8.58, 95%CI 2.53-29.02, p 0.0006), and polymicrobial mediastinitis (OR = 4.52, 95%CI 1.68-12.12, p 0.0028). GNBm were associated with more drainage failure, secondary infection, need for prolonged mechanical ventilation and/or use of vasopressors. Thirty-day hospital mortality was significantly higher with GNBm (31.9 % versus 17.0%; p 0.004). GNBm was identified as an independent risk factor of hospital mortality (OR = 2.31, 95%CI 1.16-4.61, p 0.0179).

[XPS Greenlight photoselective vaporization for benign prostatic hyperplasia: analysis of the learning curve and contribution of transrectal ultrasound monitoring]. / Traitement de l'hyperplasie bénigne de prostate par photovaporisation au laser Greenlight XPS: analyse de la courbe d'apprentissage et apport de l'échographie endorectale peropératoire.

INTRODUCTION: The aim of this study was to analyze the XPS laser learning curve of one single surgeon with no previous experience of PVP and the impact of the use of reel time transrectal ultrasound (TRUS) monitoring. MATERIALS AND METHODS: Retrospective analysis of the first 100 patients: group 1 (1st-49th patient without TRUS) and group 2 (50th-100th with TRUS). The learning curve was analyzed through technical variables: vaporization time/intervention time (VT/IT) (%), energy delivered (J)/prostate volume (J/mL) and delivered energy (J/s or Watt), peroperative conversion into monopolar transurethral resection, postoperative complication, duration of catheterization and hospitalization and evolution of International Prostate Symptom Score (IPSS), PSA level, prostate residual volume and Qmax. Relationships between variables were evaluated by analysing the covariance (R 2 software. 14.2). RESULTS: A significant increase in VT/IT (P=0.0001) and the energy delivered per mL prostate (P=0.043) was reported in group 1. The average energy delivered per second was significantly higher in group 2 (P=0.0016). No difference was observed in terms of intra- or postoperative complication and catheterization time. The duration of hospitalization was significantly shorter in group 2 (P=0.03). The use of TRUS was associated with a gain of energy delivered by prostate volume at the end of learning curve (P=0.018). Prostate residual volume was significantly lower in the group 2 (P=0.0004). CONCLUSION: In our experience, 50 procedures are required to achieve the learning curve of PVP. The use of reel time TRUS would increase the energy delivered by prostate volume.

[Objective evaluation and comparison of the scientific publication from the departments of the Assistance publique-Hôpitaux de Paris: analysis of the SIGAPS score]. / Évaluation comparative et objective de la production scientifique des services hospitaliers au sein de l'Assistance publique-Hôpitaux de Paris: analyse des scores SIGAPS.

PURPOSE: To analyze the results of the bibliometric system (SIGAPS score) of scientific publications in the Assistance publique-Hôpitaux de Paris (AP-HP) and to compare the scientific production among the various medical and surgical specialties of the academic hospitals of Paris. METHODS: All the publications imported from Pubmed between 2006 and 2008 were included. The following data were taken into account and analysed: the hospital department of origin, the number of articles published, the number of full-time physicians, the SIGAPS score. RESULTS: Thirty-eight thousand, seven hundred and nine publications were included. The departments were consisted of 747 full-time practitioners 5719 (1895 Professors [33.1%], 2772 Assistant Professors [48.4%] and 1052 fellows [18.4%]). The average number of full-time practitioner by department was 7.7±6.7 (range 1-69). The average total number of articles published in a department was 51.8±49.4 (range 1-453). The average SIGAPS score was more important in medicine than in surgery (621.2±670.1 vs. 401±382.2; P=0.01) but not the average number of article per practitioner (8.1±8.3 vs. 6.6±6.2; P=0.0797). The mean number of publication by full-time practitioner was 7.9±7.8 (1-45), or an average of 2.7±2.6 for each full-time practitioner each year. CONCLUSION: Academic hospitals in Paris have a reasonably scientific output but with a mean of 2.7 articles per full-time practitioner per year. No major differences between medical and surgical disciplines were observed.

Impact of primary tumour resection on survival of patients with colorectal cancer and synchronous metastases treated by chemotherapy: results from the multicenter, randomised trial Fédération Francophone de Cancérologie Digestive 9601.

OBJECTIVE: To assess the impact of primary tumour resection on overall survival (OS) of patients diagnosed with stage IV colorectal cancer (CRC). DESIGN: Among the 294 patients with non-resectable colorectal metastases enrolled in the Fédération Francophone de Cancérologie Digestive (FFCD) 9601 phase III trial, which compared different first-line single-agent chemotherapy regimens, 216 patients (73%) presented with synchronous metastases at study entry and constituted the present study population. Potential baseline prognostic variables including prior primary tumour resection were assessed by univariate and multivariate Cox analyses. Progression-free survival (PFS) and OS curves were compared with the logrank test. RESULTS: Among the 216 patients with stage IV CRC (median follow-up, 33 months), 156 patients (72%) had undergone resection of their primary tumour prior to study entry. The resection and non-resection groups did not differ for baseline characteristics except for primary tumour location (rectum, 14% versus 35%; p=0.0006). In multivariate analysis, resection of the primary was the strongest independent prognostic factor for PFS (hazard ratio (HR), 0.5; 95% confidence interval [CI], 0.4-0.8; p=0.0002) and OS (HR, 0.4; CI, 0.3-0.6; p<0.0001). Both median PFS (5.1 [4.6-5.6] versus 2.9 [2.2-4.1] months; p=0.001) and OS (16.3 [13.7-19.2] versus 9.6 [7.4-12.5]; p<0.0001) were significantly higher in the resection group. These differences in patient survival were maintained after exclusion of patients with rectal primary (n=43). CONCLUSION: Resection of the primary tumour may be associated with longer PFS and OS in patients with stage IV CRC starting first-line, single-agent chemotherapy.

[Analysis of the bibliometrics score of surgical department from the academic hospitals of Paris: what is the rank of urology?]. / Analyse des scores SIGAPS des services de chirurgie au sein des hôpitaux universitaires de l'Assistance publique-Hôpitaux de Paris : quelle est la place de l'urologie ?

OBJECTIVES: Analyze the results of the bibliometric system and analysis of scientific publications (SIGAPS) in the Assistance publique-Hôpitaux de Paris (AP-HP) and compare the scientific production among the various surgical disciplines of the academic hospitals of Paris and define the place of urology. METHODS: The publications from 115 surgical departments between 2006 and 2008 were included. Only surgical departments were considered in the current study. The following data were taken into account: the hospital department of origin, the number of articles published, the number of first place, last places, the number of full-time unit, the SIGAPS score. Statistical analysis focused on the quality and on the quantity of published articles per surgeons and per department. There were eight academic departments of urology identified within the AP-HP. RESULTS: The database contained information for 115 surgical departments. The mean number of articles published by department was 42.89±27.34 (13.2 to 110.75). The mean number of publications per full-time surgeon was 6.7±2.59 (3.77 to 12.84), or a mean of 2.25±0.86 released by full-time and by year. The median score SIGAPS of surgery was 304 with a wide interval (122 to 903.5). Urology was the specialty with the highest median score compared to other surgical specialties. The department, which published the most, was the center 1, in comparison with the center 6 which was publishing the most in A/B ranking journals. CONCLUSION: Urology was the absolute leader by far in terms of scientific publications in the AP-HP when compared to other surgical disciplines. The discipline is organized efficiently to juggle clinical work and research indicating a certain dynamism of the teams that invest there to fulfill the missions assigned to them in the University Hospital and the part of the autonomy of the universities.