Nationwide Audit of Postoperative Mortality and Complications After Digestive Cancer Surgery: Will New Legal Thresholds be Sufficient?

BACKGROUND: French policymakers recently chose to regulate high-risk digestive cancer surgery (DCS). A minimum of five cases per year should be performed for each of the following types of curative cancer surgery: esophagus/esogastric junction (ECS), stomach (GCS), liver (LCS, metastasis included), pancreas (PCS), and rectum (RCS). This study aimed to evaluate the hypothetical beneficial effects of the new legal minimal volume thresholds on the rates of 90-day postoperative mortality (90POM) for each high-risk DCS. METHODS: This nationwide observational population-based cohort study used data extracted from the French National Health Insurance Database from 1 January 2015-31 December 2017. Mixed-effects logistic regression models were performed to estimate the independent effect of hospital volume. RESULTS: During the study period, 61,169 patients (57.1 % male, age 69.7 ±12.2 years) underwent high-risk DCS including ECS (n = 4060), GCS (n = 5572), PCS (n = 8598), LCS (n = 10,988), and RCS (n = 31,951), with 90POM of 6.6 %, 6.9 %, 6.0 %, 5.2 %, and 2.9 %, respectively. For hospitals fulfilling the new criteria, 90POM was lower after adjustment only for LCS (odds ratio [OR],15.2; 95 % confidence interval [CI], 9.5-23.2) vs OR, 7.6; 95 % CI, 5.2-11.0; p < 0.0001) and PCS (OR, 3.6; 95 % CI, 1.7-7.6 vs OR, 2.1; 95 % CI, 1.0-4.4; p<0.0001). With higher thresholds, all DCSs showed a lower adjusted risk of 90POM (e.g., OR, 0.38; 95 % CI, 0.28-0.51) for PCS of 40 or higher. CONCLUSION: Based on retrospective data, thresholds higher than those promulgated would better improve the safety of high-risk DCS. New policies aiming to further centralize high-risk DCS should be considered, associated with a clear clinical pathway of care for patients to improve accessibility to complex health care in France.

Management of Pathogenic CDH1 Variant Carriers Within the FREGAT Network: A Multicentric Retrospective Study.

OBJECTIVE: To describe the management of pathogenic CDH1 variant carriers (pCDH1vc) within the FREGAT (FRench Eso-GAsTric tumor) network. Primary objective focused on clinical outcomes and pathological findings, Secondary objective was to identify risk factor predicting postoperative morbidity (POM). BACKGROUND: Prophylactic total gastrectomy (PTG) remains the recommended option for gastric cancer risk management in pCDH1vc with, however, endoscopic surveillance as an alternative. METHODS: A retrospective observational multicenter study was carried out between 2003 and 2021. Data were reported as median (interquartile range) or as counts (proportion). Usual tests were used for univariate analysis. Risk factors of overall and severe POM (ie, Clavien-Dindo grade 3 or more) were identified with a binary logistic regression. RESULTS: A total of 99 patients including 14 index cases were reported from 11 centers. Median survival among index cases was 12.0 (7.6-16.4) months with most of them having peritoneal carcinomatosis at diagnosis (71.4%). Among the remaining 85 patients, 77 underwent a PTG [median age=34.6 (23.7-46.2), American Society of Anesthesiologists score 1: 75%] mostly via a minimally invasive approach (51.9%). POM rate was 37.7% including 20.8% of severe POM, with age 40 years and above and low-volume centers as predictors ( P =0.030 and 0.038). After PTG, the cancer rate on specimen was 54.5% (n=42, all pT1a) of which 59.5% had no cancer detected on preoperative endoscopy (n=25). CONCLUSIONS: Among pCDH1vc, index cases carry a dismal prognosis. The risk of cancer among patients undergoing PTG remained high and unpredictable and has to be balanced with the morbidity and functional consequence of PTG.

To What Extent Does Posthospital Discharge Chemoprophylaxis Prevent Venous Thromboembolism After Bariatric Surgery?: Results From a Nationwide Cohort of More Than 110,000 Patients.

OBJECTIVE: The aim of the present study was to assess the incidence, risk factors, and the impact of posthospital discharge (PHD) chemoprophylaxis on venous thromboembolism (VTE) in patients undergoing bariatric surgery (BS). BACKGROUND: VTE is a major concern after BS, especially during the PHD period. No large-scale study has previously focused on the clinical value of PHD chemoprophylaxis. METHODS: In this nationwide observational population-based cohort study, all data from patients undergoing BS were extracted from the French National Health Insurance database (SNIIRAM) from 1st January 2012 to 31st September 2014. Logistic regression models were used to compute odds ratios for potential risk factors for VTE occurring within 90 postoperative days (PODs). The association between use of PHD chemoprophylaxis (heparin) and VTE was also assessed. RESULTS: The majority (56%) of the 110,824 patients had sleeve gastrectomy. VTE rates during the first 30 and 90 PODs were 0.34% and 0.51%, respectively. On multivariate analyses, the major risk factors for VTE during the first 90 PODs were history of VTE [odds ratio = 6.33 95% confidence interval (4.44-9.00)], postoperative complications [9.23 (7.30-11.70)], heart failure [2.45 (1.48-4.06)], and open surgery [2.38 (1.59-3.45)]. PHD chemoprophylaxis was delivered to 75% of patients. No use of PHD chemoprophylaxis [1.27 (1.01-1.61)] was an independent predictive factor of VTE during the first 90 PODs [in the gastric bypass group: 1.51 (1.01-2.29)). CONCLUSIONS: In the modern era of BS, this nationwide study shows a non-negligible rate of VTE especially after sleeve gastrectomy, depending on the individual risk level. Use of PHD chemoprophylaxis may decrease the risk of PHD VTE.

Salvage Surgery for Esophageal Cancer: How to Improve Outcomes?

BACKGROUND: Locoregional recurrence rates after definitive chemoradiotherapy (dCRT) for locally advanced esophageal cancer (EC) are high. Salvage surgery (SALV) is considered the best treatment option in case of persistent or recurrent disease for operable patients, but SALV has been associated with increased morbidity and mortality. The aim of this study is to identify factors linked to outcomes after SALV to better select candidates and to optimize perioperative care. STUDY DESIGN: We retrospectively analyzed data from 308 consecutive SALV patients from a large multicenter European cohort. Univariate and multivariate analyses were performed to identify factors associated with in-hospital postoperative morbidity, anastomotic leakage (AL), and overall survival (OS). RESULTS: The in-hospital postoperative mortality and morbidity rates were 8.4 and 34.7%, respectively. Squamous cell histology (p = 0.040) and radiation dose ≥ 55 Gy (p = 0.047) were independently associated with major morbidity. The AL rate was 12.7%, and cervical anastomosis was independently associated with AL (p = 0.002). OS at 5 years was 34.0%. Radiation dose ≥ 55 Gy (p = 0.003), occurrence of postoperative complications (p = 0.006), ypTNM stage 3 (p = 0.019), and positive surgical margins (p < 0.001) were linked to poor prognosis. CONCLUSIONS: SALV is a valuable option for patients with persistent or recurrent disease after dCRT and offers long-term survival. Factors such as radiation dose and anastomosis location identified here will help to optimize outcomes after SALV, which may be considered a standard treatment in the EC therapeutic armamentarium.

Survival Benefit of Neoadjuvant Treatment in Clinical T3N0M0 Esophageal Cancer: Results From a Retrospective Multicenter European Study.

BACKGROUND: Based on current guidelines, clinical T3N0M0 esophageal tumors may or may not receive neoadjuvant treatment, according to their perception as locally advanced (cT3) or early-stage tumors (stage II). The study aim was to assess the impact of neoadjuvant treatment upon survival for cT3N0M0 esophageal cancer patients, with subgroup analyses by histological type (squamous cell carcinoma vs adenocarcinoma) and type of neoadjuvant treatment (chemotherapy vs radiochemotherapy). METHODS: Data from patients operated on for esophageal cancer in 30 European centers were collected. Among the 382 of 2944 patients with clinical T3N0M0 stage at initial diagnosis (13.0%), we compared those treated with primary surgery (S, n = 193) versus with neoadjuvant treatment plus surgery (NS, n = 189). RESULTS: The S and NS groups were similar regarding their demographic and surgical characteristics. In-hospital postoperative morbidity and mortality rates were comparable between groups. Patients were found to be pN+ in 64.2% versus 42.9% in the S and NS groups respectively (P < 0.001), pN2/N3 in 35.2% versus 21.2% (P < 0.001), stage 0 in 0% versus 16.4% (P < 0.001), and R0 in 81.3% versus 89.4% of cases (P = 0.026). Median overall and disease-free survivals were significantly better in the NS group, 38.4 versus 27.9 months (P = 0.007) and 31.6 versus 27.5 months (P = 0.040), respectively, and this difference remained for both histological types. Radiotherapy did not offer a benefit compared with chemotherapy alone (P = 0.687). In multivariable analysis, neoadjuvant treatment was an independent favorable prognostic factor (HR 0.76, 95% CI 0.58-0.99, P = 0.044). CONCLUSION: Neoadjuvant treatment offers a significant survival benefit for clinical T3N0M0 esophageal cancer.

Discrepancy Between Clinical and Pathologic Nodal Status of Esophageal Cancer and Impact on Prognosis and Therapeutic Strategy.

BACKGROUND: The impact of discrepancies between clinical (c) and pathologic (p) stages of esophageal cancer remains a poorly understood issue. This study aimed to compare the prognosis of patient groups treated by primary surgery including clinical N0/pathologic N0 (cN0pN0), clinical N0/pathologic N+ (cN0pN+), clinical N+/pathologic N0 (cN+pN0), and clinical N+/pathologic N+ (cN+pN+). METHODS: Data were collected from 30 European centers during the years 2000 to 2010. Among 2944 recruited patients, 1554 patients receiving primary surgery met the inclusion criteria including 613 cN0pN0, 403 cN0pN+, 220 cN+pN0, and 318 cN+pN+ patients. Analyses with adjustment of the propensity score were used to compensate for differences in baseline characteristics. RESULTS: Clinical T stages 3 and 4 were increased in cN+pN+ (73.0%), cN0pN+ (49.6%), and cN+pN0 (51.8%) compared with cN0pN0 (32.8%). Compared with cN0pN0, cN+pN+ and cN0pN+ showed an increase in the proportion of adenocarcinoma histologic subtype, poor tumor differentiation, pathologic T3 and T4 stages, and R1/2 resection margin. Adjusted 5-year overall survival (hazard ratio [HR] 3.12; 95% confidence interval [CI] 2.57-3.78; P < 0.001) and event-free survival (HR 2.87; 95% CI 2.39-3.45; P < 0.001) were significantly reduced in cN0pN+ compared with cN0pN0. No significant differences in 5-year overall survival or event-free survival between cN0pN+ and cN+pN+ were observed. Regression analysis identified an association of distal tumor location, advanced clinical T stage, and poor tumor differentiation with pN+ disease. CONCLUSIONS: This large multicenter study showed that cN0pN+ has a prognosis similar to that of cN+pN+ and worse than that of cN0pN0. Patients with clinical N0 disease but risk factors for pathologic N+ disease may benefit from neoadjuvant therapy before surgery.

Upfront immunohistochemistry improves specificity of Helicobacter pylori diagnosis. A French pathology laboratory point of view.

BACKGROUND: There is no consensus about the histopathologic methods to detect Helicobacter pylori in gastric biopsies to date. We aimed to question about the value of upfront anti-H. pylori immunohistochemistry in this field. MATERIAL AND METHODS: We led a retrospective study about the rate of H. pylori-positive gastric biopsies before and after the implementation of upfront immunohistochemistry, the inter-rater and intermethods agreements in H. pylori identification about Hematoxylin-Eosin Saffron (HES), Giemsa, and immunohistochemistry stains and the histopathologic features associated with low amounts of H. pylori. RESULTS: First, the rate of H. pylori-positive gastric biopsies significantly diminished after the implementation of upfront immunohistochemistry (from 21.15% to 12.56%, P<.0001), suggesting potential overdiagnosis of H. pylori infection before the use of immunohistochemistry. Secondly, immunohistochemistry was the most reproducible and performing stain (kappa values >0.80), but HES and Giemsa stains also presented good-to-very good agreements. Finally, less than 1% of gastric biopsies with inconspicuous H. pylori infection showed no mucosal injury pointing out that any HES-detected mucosal injury could help to preselect the gastric biopsies requiring ancillary stains for the detection of H. pylori. CONCLUSIONS: Albeit being considered as a gold standard in the detection of H. pylori, the interest of using immunohistochemistry as an upfront stain on gastric biopsies is still debated. In our opinion, its use in second line in case of ambiguous HE/HES-Giemsa result is more appropriate. Further effort is needed to optimize the inexpensive but feasible HE/HES-based detection of H. pylori.

Significance of Microscopically Incomplete Resection Margin After Esophagectomy for Esophageal Cancer.

OBJECTIVE: The objectives of this study were to establish if R1 resection margin after esophagectomy was (i) a poor prognostic factor independent of patient and tumor characteristics, (ii) a marker of tumor aggressiveness and (iii) to look at the impact of adjuvant treatment in this subpopulation. METHODS: Data were collected from 30 European centers from 2000 to 2010. Patients with an R1 resection margin (n = 242) were compared with those with an R0 margin (n = 2573) in terms of short- and long-term outcomes. Propensity score matching and multivariable analyses were used to compensate for differences in baseline characteristics. RESULTS: Independent factors significantly associated with an R1 resection margin included an upper third esophageal tumor location, preoperative malnutrition, and pathological stage III. There were significant differences between the groups in postoperative histology, with an increase in pathological stage III and TRG 4-5 in the R1 group. Total average lymph node harvests were similar between the groups; however, there was an increase in the number of positive lymph nodes seen in the R1 group. Propensity matched analysis confirmed that R1 resection margin was significantly associated with reduced overall survival and increased overall, locoregional, and mixed tumor recurrence. Similar observations were seen in the subgroup that received neoadjuvant chemoradiation. In R1 patients adjuvant therapy improved survival and reduced distant recurrence however failed to affect locoregional recurrence. CONCLUSIONS: This large multicenter European study provides evidence to support the notion that R1 resection margin is a prognostic indication of aggressive tumor biology with a poor long-term prognosis.

Impact of Adjuvant Chemotherapy on Patients with Lymph Node-Positive Esophageal Cancer who are primarily Treated with Surgery.

BACKGROUND: Whereas the optimal therapeutic strategy in node positive esophageal cancer primarily treated by surgery remains unknown, the study was designed to evaluate the impact of adjuvant chemotherapy on survival in such population. METHODS: Among 2944 consecutive patients operated on for esophageal cancer between 2000 and 2010 in 30 European centers, patients with lymph node metastasis treated by adjuvant treatment (n = 178) were compared to patients who did not received adjuvant treatment (n = 378). Multivariable analyses and propensity score matching were used to compensate for differences in baseline characteristics. RESULTS: After matching, patients were comparable between the two groups. When comparing adjuvant treatment and nonadjuvant treatment groups, there was no significant differences in 3-year overall (40.9 vs. 35.8 %, P = 0.560) and disease-free (33.9 vs. 28.5 %, P = 0.190) survivals. Locoregional recurrence was lower in the adjuvant treatment group (14.4 vs. 30.9 %, P = 0.012). In the adjuvant treatment group, 94 patients received chemotherapy and 84 chemoradiotherapy, without significant survival benefit over chemoradiotherapy compared with chemotherapy alone (P = 0.280). Predictive factors of overall survival were age ≥60 years, ASA III-IV score, and pN+ classification. No survival benefit was observed according to histological subtype or occurrence of postoperative complications. CONCLUSIONS: Adjuvant chemo(radio)therapy did not offer survival benefit in lymph node-positive esophageal cancer patients primarily treated with surgery.

Is laparoscopy a safe approach for diffuse appendicular peritonitis? Feasibility and determination of risk factors for post-operative intra-abdominal abscess.

BACKGROUND: Several studies have assessed feasibility and early outcomes of the laparoscopic approach for complicated appendicitis (CA). However, these studies suffer from limitations due to the heterogeneous definitions used for CA. No studies have assessed feasibility and early post-operative outcomes of the laparoscopic approach in the specific management of diffuse appendicular peritonitis (DAP). Consequently, outcomes of the laparoscopic approach for the management of DAP are poorly documented. METHODS: The laparoscopic approach is the first-line standardised procedure used by our team for the management of DAP. All patients (aged >16 years) who underwent laparoscopy for DAP (CA with the presence of purulent fluid with or without fibrin membranes in at least a hemi abdomen) between 2004 and 2012 were prospectively included. Post-operative outcomes were analysed according to the Clavien-Dindo classification. RESULTS: Laparoscopy for DAP was performed for 141 patients. Mean age was 39.6 ± 20 (16-92) years. A total of 45 patients (31.9%) had pre-operative contracture. The mean pre-operative leukocyte count was 14,900 ± 4,380 mm(-3). The mean pre-operative C-reactive protein (CRP) serum concentration was 135 ± 112 (2-418) mg/dl. The conversion rate was 3.5%. The mean operative time was 80 ± 27 (20-180) min. There were no deaths. The rate of grade III morbidity was 6.5%. Ten patients (7.1%) experienced intra-abdominal abscess (IAA); seven of these cases were treated conservatively. The mean length of hospital stay was 6.9 ± 5 (2-36) days. A pre-operative leukocyte count >17,000 mm(-3), and CRP serum concentration >200 mg/dl were significant predictive factors for IAA in multivariate analyses [odds ratio (OR) 25.0, 95% confidence interval (CI) 2.4-250, p = 0.007 and OR 16.4, 95% CI 1.6-166, p = 0.02, respectively]. CONCLUSION: The laparoscopic approach for DAP is a safe and feasible procedure with a low conversion rate and an acceptable rate of IAA in view of the severity of the disease. Pre-operative leukocyte counts >17,000 mm(-3) and pre-operative CRP serum concentrations >200 mg/dl indicate a high risk of IAA.

From early risk to 1-year mortality: a comprehensive assessment of postoperative venous thromboembolism in upper gastrointestinal cancer patients - a nationwide cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a well-recognized complication following gastrointestinal cancer surgery, particularly early postoperatively. The incidence and risk factors of VTE within 1-year after esophageal (including esophago-gastric junction) (ECS) and gastric (GCS) cancer surgeries, and especially its impact on 1-year global mortality, are yet under-explored. METHODS: This nationwide observational population-based cohort study used data extracted from all patients undergoing ECS and GCS in France between 1 January 2015 and 31 December 2017. Multivariate logistic regression was used to identify risk factors for 90 postoperative days (POD) VTE (OR 95% CI). Cox proportional hazards models investigated the impact of 1-year postoperative VTE on 1-year global mortality [HR (95% CI)]. RESULTS: During the study period, 8005 patients underwent ECS ( N =3429) or GCS ( N =4576) (31.8% female; 66.7±12.1 years old). Majority ( N =4951) of patients had preoperative treatment (chemotherapy or radiochemotherapy). Ninety POD incidence of VTE were 4.7% (ECS=6.2%) (GCS=3.6%) (44.7% during first hospitalization, 19.0% needing readmission, and 36.3% ambulatory management). Main risk factors were three and two field esophagectomy [3.6 (2.20-5.83) and 2.2 (1.68-3.0)], obesity [1.9 (1.40-2.58)] and history of VTE [5.1 (2.72-9.45)]. Late-onset VTE rates (occurring between the 6th and 12th month) represented 1.80 and 1.46% of the overall ECS and GCS groups. Patients with VTE within 1-year had higher risks of 1-year global mortality: (2.04 1.52; 2.73) and 2.71 (2.09; 3.51), respectively. CONCLUSION: Our extensive analysis of a nationwide database highlights the significant risk of postoperative VTE after ECS and GCS, persisting within 90 POD and up to 1-year. Crucially, a higher risk of global mortality within 1-year for patients experiencing early or late VTE was found. These findings could advocate for further research into extended prophylactic regimens, particularly for those most at risk.

Cost-Effectiveness of Sleeve Gastrectomy and Gastric Bypass as Revisional Surgery on Antidiabetic Reimbursement: A Nationwide Cohort Study.

Objective: This study compared the effectiveness of 4 main revisional bariatric surgery (RBS) sequences after sleeve gastrectomy (SG) and adjustable gastric banding (AGB), on the reimbursement of antidiabetic treatments in France. Background: Few large-scale prospective cohort studies have assessed the changes in antidiabetic treatments after RBS. Method: This nationwide observational population-based cohort study analyzed data from the French National Health Insurance Database. All patients who underwent primary SG and AGB in France between January 2012 and December 2014 were included and followed up until December 31, 2020. The changes in categories and costs of reimbursed antidiabetic treatments across different RBS sequences were assessed (presented as follows: bariatric surgery (BS)-RBS). Results: Among the 107,088 patients who underwent BS, 6396 underwent RBS, 2400 SG-GBP (SG converted to gastric bypass [GBP] during follow-up), 2277 AGB-SG, 1173 AGB-GBP, and 546 SG-SG. Pre-RBS insulin was used in 10 (2.9%), 4 (0.9%), 8 (2.4%), and 10 (2.6%) patients, respectively. Two years after RBS, the treatment discontinuation or decrease (the change of treatment to a lighter one category rates [eg, insulin to bi/tritherapy]) was 47%, 47%, 49%, and 34%, respectively. Four years after RBS, the median annual cost per patient compared with baseline was lower (P < 0.01) for all sequences, except SG-SG (P = 0.24). The most notable effect concerned AGB-GBP (median of more than 220 euros to 0). Conclusions: This study demonstrated the positive impact of RBS over a 4-year follow-up period on antidiabetic treatments reimbursement, through the reduction or discontinuation of treatments and a significant decrease in costs per patient.

Survival of patients managed in France for duodenal neuroendocrine tumors (D-NET): a 20-year multicenter cohort study from the GTE group: a cohort study.

INTRODUCTION: Duodenal neuroendocrine tumours (D-NETs) have a low incidence; however, their diagnosis has been increasing. Features such as tumour location, size, type, histological grade, and stage were used to adapt the treatment to either endoscopic (ER) or surgical (SR) resections. There is no consensus regarding the definitive treatment. The authors' study aimed to describe the management of non-metastatic, well-differentiated D-NETs in France and its impact on patient survival. METHODS: A registry-based multicenter study using prospectively collected data between 2000 and 2019, including all patients managed for non-metastatic G1 and G2 D-NETs, was conducted in the GTE group. RESULTS: A total of 153 patients were included. Fifty-eight benefited from an ER, and 95 had an SR. No difference in recurrence-free survival (RFS) was observed regardless of treatment type. There was no significant difference between the two groups (ER vs. SR) in terms of location, size, grade, or lymphadenopathy, regardless of the type of incomplete resection performed or regarding the pre-therapeutic assessment of lymph node invasion in imaging. The surgery allowed for significantly more complete resection (patients with R1 resection in the SR group: 9 vs. 14 in the ER group, P<0.001). Among the 51 patients with positive lymph node dissection after SR, tumour size was less than or equal to 1 cm in 25 cases. Surgical complications were more numerous (P=0.001). In the sub-group analysis of G1-G2 D-NETs between 11 and 19 mm, there was no significant difference in grade (P=0.977) and location (P=0.617) between the two groups (ER vs. SR). No significant difference was found in both morphological and functional imaging, focusing on the pre-therapeutic assessment of lymph node invasion (P=0.387). CONCLUSION: Regardless of the resection type (ER or SR) of G1-G2 non-metastatic D-NETs, as well as the type of management of incomplete resection, which was greater in the ER group, long-term survival results were similar between ER and SR. Organ preservation seems to be the best choice owing to the slow evolution of these tumours.

Prognostic impact of positive microscopic margins (R1 resection) in patients with GIST (gastrointestinal stromal tumours): Results of a multicenter European study.

BACKGROUND: Although several prognostic factors in GIST have been well studied such as tumour size, mitotic rate, or localization, the influence of microscopic margins or R1 resection remains controversial. The aim of this study was to evaluate the influence of R1 resection on the prognosis of GIST in a large multicentre retrospective series of patients. METHODS: From 2001 to 2013, 1413 patients who underwent surgery for any site of GIST were identified from 61 European centers. 1098 patients were included, excluding synchronous metastases, concurrent malignancies, R2 resection or GIST recurrence. Tumour rupture (TR) was reclassified according to the Oslo sarcoma classification. Cox proportional hazards ratio and Kaplan-Meier survival estimates were used to analyse 5-year recurrence-free survival (RFS). RESULTS: Of 1098 patients, 38 (3%) underwent R1 resection with a risk of TR of 11%. The 5-year RFS was 89.6% with a median follow-up of 81 months [range: 31.2-152 months]. On univariate analysis, lower RFS was significantly associated with R1 resection [HR = 2.13; p = 0.04], high risk score according to the modified NIH classification, administration of adjuvant therapy [HR = 2.24; p < 0.001] and intraoperative complications [HR = 2.82; p < 0.001]. Only intraoperative complications [HR = 1.79; p = 0.02] and high risk according to the modified NIH classification including the updated definition of TR [HR = 3.43; p = 0.04] remained significant on multivariate analysis. CONCLUSION: This study shows that positive microscopic margins are not an independent predictive factor for RFS in GIST when taking into account the up-dated classification of TR. R1 resection may be considered a reasonable alternative to avoid major functional sequelae and should not lead to reoperation.

Transferability of Published Population Pharmacokinetic Models for Apixaban and Rivaroxaban to Subjects with Obesity Treated for Venous Thromboembolism: A Systematic Review and External Evaluations.

Apixaban and rivaroxaban have first-line use for many patients needing anticoagulation for venous thromboembolism (VTE). The pharmacokinetics of these drugs in non-obese subjects have been extensively studied, and, while changes in pharmacokinetics have been documented in obese patients, data remain scarce for these anticoagulants. The aim of this study was to perform an external validation of published population pharmacokinetic (PPK) models of apixaban and rivaroxaban in a cohort of obese patients with VTE. A literature search was conducted in the PubMed/MEDLINE, Scopus, and Embase databases following the PRISMA statement. External validation was performed using MonolixSuite software, using prediction-based and simulation-based diagnostics. An external validation dataset from the university hospitals of Brest and Rennes, France, included 116 apixaban pharmacokinetic samples from 69 patients and 121 rivaroxaban samples from 81 patients. Five PPK models of apixaban and 16 models of rivaroxaban were included, according to the inclusion criteria of the study. Two of the apixaban PPK models presented acceptable performances, whereas no rivaroxaban PPK model did. This study identified two published models of apixaban applicable to apixaban in obese patients with VTE. However, none of the rivaroxaban models evaluated were applicable. Dedicated studies appear necessary to elucidate rivaroxaban pharmacokinetics in this population.

Sleep Apnea and Incident Unprovoked Venous Thromboembolism: Data from the Pays de la Loire Sleep Cohort.

BACKGROUND: Previous studies have reported inconsistent findings regarding the association between obstructive sleep apnea (OSA) and incident venous thromboembolism (VTE). More specifically, the association between OSA and unprovoked VTE was barely evaluated. We aimed to evaluate whether apnea hypopnea index (AHI) and nocturnal hypoxemia markers were associated with unprovoked VTE incidence in patients investigated for OSA. MATERIAL AND METHODS: Data from the Pays de la Loire Sleep Cohort were linked to the French health administrative data to identify incident unprovoked VTE in patients suspected for OSA and no previous VTE disease. Cox proportional hazards models were used to evaluate the association of unprovoked VTE incidence with AHI and nocturnal hypoxemia markers including the time spent under 90% of saturation (T90), oxygen desaturation index, and hypoxic burden (HB), a more specific marker of respiratory events related to hypoxia. The impact of continuous positive airway pressure (CPAP) was evaluated in the subgroup of patients who were proposed the treatment. RESULTS: After a median [interquartile range] follow-up of 6.3 [4.3-9.0] years, 104 of 7,355 patients developed unprovoked VTE, for an incidence rate of 10.8 per 1,000 patient-years. In a univariate analysis, T90 and HB predicted incident VTE. In the fully adjusted model, T90 was the only independent predictor (hazard ratio: 1.06; 95% confidence interval: [1.01-1.02]; p = 0.02). The CPAP treatment has no significant impact on VTE incidence. CONCLUSION: Patients with more severe nocturnal hypoxia are more likely to have incident unprovoked VTE.

[Venous thromboembolic risk after bariatric surgery]. / Risque thromboembolique veineux après une chirurgie bariatrique.

VENOUS THROMBOEMBOLIC RISK AFTER BARIATRIC surgeryvenous thromboembolism is widely considered as the first medical postoperative complication after bariatric surgery with a rate around 0.5% during the first 90 postoperative days. Pulmonary embolism is often associated With septic complication, increasing the risk of postoperative death. Chemoprophylaxis with a minimum lenght of 10 days remains the corner stone of preventive treatment.

Risque thromboembolique veineux après une chirurgie bariatrique La maladie thromboembolique veineuse est la première complication médicale postopératoire de la chirurgie bariatrique, dont la mortalité est dominée par le risque d'embolie pulmonaire, souvent associé à une complica¬tion chirurgicale septique. Avec une incidence de 0,5 % dans les 90 jours, elle reste tout de même une compli¬cation rare mais qui peut se déclarer après la sortie du patient. Sa prévention repose toujours sur une mobili¬sation précoce et une thromboprophylaxie d'au moins 10 jours.

Seventy years of bariatric surgery: A systematic mapping review of randomized controlled trials.

While research publications on bariatric surgery (BS) have grown significantly over the past decade, there is no mapping of the existing body of evidence on this field of research. We performed a systematic review followed by a mapping of randomized controlled trials (RCTs) in BS for people with obesity. From January 2020 to December 2020, we performed a systematic review of RCTs evaluating BS, versus another surgical procedure, or versus a medical control group, through a search of Embase and PubMed. There was no restriction on outcomes for study selection. A total of 114 RCTs were included, most (73.7%) of which were based on a comparison with Roux-en-Y gastric bypass (RYGB) and conducted between 2010 and 2020. Only 15% of the trials were multicenter and few (3.5%) were international. The median number of patients enrolled was 61 (interquartile range [IQR]: 47.3-100). Follow-up time was 1 to 2 years in 36% and 22.8% of the trials, respectively. Weight loss was the most studied criterion (87% of RCTs), followed by obesity-related diseases, and medical and surgical complications (73%, 54%, and 47% of RCTs, respectively). Nutritional deficiency frequency, body composition, and mental health were little studied (20%, 18% and 5% of RCTs, respectively). Our literature review revealed that much research in BS is wasted because of replication of RCTs on subjects for which there is already body of evidence, with small populations and follow-up times mostly below 2 years. Yet several research questions remain unaddressed, and there are few long-term trials. Future studies should take into account the experience of the past 70 years of research in this field.

Impact of bariatric surgery on oral anticoagulants pharmacology, and consequences for clinical practice: a narrative review.

The prevalence of obesity has been steadily increasing in recent years worldwide. At the same time bariatric surgery, the best therapeutic strategy to date in terms of sustainable weight loss and improvement of associated comorbidities has been also increasing. However, these surgeries, whether primarily restrictive or malabsorptive, raise questions about the pharmacology of oral drugs. Among widely used drugs, anticoagulants are the referent therapy to treat some cardiovascular diseases such as atrial fibrillation and venous thromboembolism. How bariatric surgery may impact pharmacological properties of oral anticoagulants, and more specifically, direct oral anticoagulants (DOACs) are difficult to anticipate. In this review, we describe available data concerning the potential impact of bariatric surgery on the pharmacology of oral anticoagulants. The vitamin K antagonists (VKAs) requirements for the same international normalized ratio target are reduced after bariatric surgery. Limited data available for dabigatran 150 mg twice daily indicate a risk of insufficient efficacy in atrial fibrillation after gastric bypass due to probable impaired absorption. Data for rivaroxaban at the prophylactic dose of 10 mg per day suggest no impact of bariatric surgery from 3 days to 8 months post-surgery. However, no conclusive data are available for other anticoagulants or the use of DOACs at therapeutic doses. To date, DOACs are not recommended in patients who have undergone bariatric surgery, because of limited available data. Pending new studies to confirm the predictable pharmacokinetics and safety of DOACs in this population, especially at therapeutic doses, VKAs remain the first option for chronic anticoagulation.