ABSTRACT

BACKGROUND: Studies have shown minimally invasive esophagectomy (MIE) to be a feasible surgical technique in treating esophageal carcinoma. Postoperative complications have been extensively reviewed, but literature focusing on intraoperative complications is limited. The main objective of this study was to report major intraoperative complications and 90-day mortality during MIE for cancer.

METHODS: Data were collected retrospectively from 10 European esophageal surgery centers. All intention-to-treat, minimally invasive laparoscopic/thoracoscopic esophagectomies with gastric conduit reconstruction for esophageal and GE junction cancers operated on between 2003 and 2019 were reviewed. Major intraoperative complications were defined as loss of conduit, erroneous transection of vascular structures, significant injury to other organs including bowel, heart, liver or lung, splenectomy, or other major complications including intubation injuries, arrhythmia, pulmonary embolism, and myocardial infarction.

RESULTS: Amongst 2862 MIE cases we identified 98 patients with 101 intraoperative complications. Vascular injuries were the most prevalent, 41 during laparoscopy and 19 during thoracoscopy, with injuries to 18 different vessels. There were 24 splenic vascular or capsular injuries, 11 requiring splenectomies. Four losses of conduit due to gastroepiploic artery injury and six bowel injuries were reported. Eight tracheobronchial lesions needed repair, and 11 patients had significant lung parenchyma injuries. There were 2 on-table deaths. Ninety-day mortality was 9.2%.

CONCLUSIONS: This study offers an overview of the range of different intraoperative complications during minimally invasive esophagectomy. Mortality, especially from intrathoracic vascular injuries, appears significant.

PMID:37782412 | DOI:10.1245/s10434-023-14340-3

02:08

PubMed articles on: Cancer & VTE/PE

Hypoxia-induced exosomes facilitate lung pre-metastatic niche formation in hepatocellular carcinoma through the miR-4508-RFX1-IL17A-p38 MAPK-NF-κB pathway

Int J Biol Sci. 2023 Sep 4;19(15):4744-4762. doi: 10.7150/ijbs.86767. eCollection 2023.

ABSTRACT

Background: Hypoxia plays an important role in the lung metastasis of hepatocellular carcinoma (HCC). However, the process by which hypoxia promotes the formation of a pre-metastatic niche (PMN) and its underlying mechanism remain unclear. Methods: Exosomes derived from normoxic and hypoxic HCC cells were collected to induce fibroblast activation in vitro and PMN formation in vivo. The micro RNA (miR) profiles of the exosomes were sequenced to identify differentially expressed miRNAs. Gain- and loss-of-function analyses were performed to investigate miR-4508 function. Dual-luciferase, western blotting, and real-time reverse transcription-PCR analyses were used to identify the direct targets of miR-4508 and its downstream signaling pathways. To demonstrate the roles of hypoxic tumor-derived exosomes (H-TDEs) and miR-4508 in the lung metastasis of liver cancer, H22 tumor cells were injected through the tail vein of mice. Blood plasma-derived exosomes from patients with HCC who underwent transarterial chemoembolization (TACE) were applied to determine clinical correlations. Results: We demonstrated that H-TDEs activated lung fibroblasts and facilitated PMN formation, thereby promoting lung metastasis in mice. Screening for upregulated exosomal miRNAs revealed that miR-4508 and its target, regulatory factor X1 (RFX1), were involved in H-TDE-induced lung PMN formation. Moreover, miR-4508 was significantly upregulated in plasma exosomes derived from patients with HCC after TACE. We confirmed that the p38 MAPK-NF-κB signaling pathway is involved in RFX1 knockdown-induced fibroblast activation and PMN formation. In addition, IL17A, a downstream target of RFX1, was identified as a link between RFX1 knockdown and p38 MAPK activation in fibroblasts. Conclusion: Hypoxia enhances the release of TDEs enriched with miR-4508, thereby promoting lung PMN formation by targeting the RFX1-IL17A-p38 MAPK-NF-κB pathway. These findings highlight a novel mechanism underlying hypoxia-induced pulmonary metastasis of HCC.

PMID:37781522 | PMC:PMC10539707 | DOI:10.7150/ijbs.86767

02:09

PubMed articles on: Cancer & VTE/PE

A New Risk Prediction Model for Venous Thromboembolism and Death in Ambulatory Lung Cancer Patients

Cancers (Basel). 2023 Sep 15;15(18):4588. doi: 10.3390/cancers15184588.

ABSTRACT

(1) Background: Venous thromboembolism (VTE) is a frequent complication in ambulatory lung cancer patients during chemotherapy and is associated with increased mortality. (2) Methods: We analyzed 568 newly diagnosed metastatic lung cancer patients prospectively enrolled in the HYPERCAN study. Blood samples collected before chemotherapy were tested for thrombin generation (TG) and a panel of hemostatic biomarkers. The Khorana risk score (KRS), new-Vienna CATS, PROTECHT, and CONKO risk assessment models (RAMs) were applied. (3) Results: Within 6 months, the cumulative incidences of VTE and mortality were 12% and 29%, respectively. Patients with VTE showed significantly increased levels of D-dimer, FVIII, prothrombin fragment 1 + 2, and TG. D-dimer and ECOG performance status were identified as independent risk factors for VTE and mortality by multivariable analysis and utilized to generate a risk score that provided a cumulative incidence of VTE of 6% vs. 25%, death of 19% vs. 55%, and in the low- vs. high-risk group, respectively (p < 0.001). While all published RAMs significantly stratified patients for risk of death, only the CATS and CONKO were able to stratify patients for VTE. (4) Conclusions: A new prediction model was generated to stratify lung cancer patients for VTE and mortality risk, where other published RAMs failed.

PMID:37760562 | PMC:PMC10527104 | DOI:10.3390/cancers15184588

02:09

PubMed articles on: Cancer & VTE/PE

Safety and efficacy of oral anticoagulants in extreme weights

Thromb Res. 2023 Sep 12;231:1-6. doi: 10.1016/j.thromres.2023.09.001. Online ahead of print.

ABSTRACT

BACKGROUND: The 2021 International Society on Thrombosis and Haemostasis' (ISTH) recommends standard doses of apixaban and rivaroxaban regardless of high body mass index (BMI) and weight, but had not compare DOACs head-to-head in obesity or address underweight patients.

METHODS: Our aim is to evaluate the safety and efficacy of DOACs in underweight and obese patients compared to warfarin. The primary endpoints include incidence of thromboembolic and bleeding events. Descriptive statistics was used for continuous variables. The Kruskal-Wallis test was used to compare the four-groups for continuous measures and the chi-square test or Fisher's exact test was used to analyze categorical data. The chi-square test or Fisher's exact test, was used for categorical variables, and the Mann-Whitney test (the non-parametric counterpart to the two-sample t-test) for continuous data.

RESULTS: Of 2940 patients receiving anticoagulation for venous thromboembolism (VTE) treatment or atrial fibrillation (AF), 492 met eligibility criteria. Within each group, 248 patients received warfarin, 101 received apixaban, 100 received rivaroxaban and 43 received dabigatran. Patients were characterized in 4 body mass index (BMI) categories, in which 80 were underweight and 412 were obese.

CONCLUSIONS: When each DOAC was compared to warfarin in rates of VTE, apixaban showed statistically significant lower rate of VTE (p = 0.0149). However, no statistical significance was identified in the rate of VTE between DOACs combined vs. warfarin (p = 0.1529). When each DOAC was compared to warfarin, apixaban showed the lowest rate of overall bleeding (p = 0.0194). However, no statistical difference in the rate of bleeding was observed between DOACs combined vs. warfarin (p = 0.3284). Patients with extreme body weights requiring anticoagulation for VTE and AF may safety benefit from DOAC therapy. This evaluation showed apixaban with the lowest rate of VTE and bleeding compared to warfarin, rivaroxaban, and dabigatran. These results provide experience for the clinician to use DOACs, particularly apixaban, in underweight and obese populations.

PMID:37738772 | DOI:10.1016/j.thromres.2023.09.001

02:09

PubMed articles on: Cancer & VTE/PE

ReLiFiRa (Real Life Filgotinib in Rheumatoid Arthritis): Retrospective Study of Efficacy and Safety in Common Clinical Practice

J Pers Med. 2023 Aug 25;13(9):1303. doi: 10.3390/jpm13091303.

ABSTRACT

BACKGROUND: Filgotinib (FIL) is a selective JAK1 inhibitor with an affinity 30-fold higher than JAK2, approved to treat moderate to severe active rheumatoid arthritis (RA), in adults with inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).

METHODS: We conducted a retrospective, multicentric study in order to evaluate efficacy and safety of FIL 200 mg daily therapy, after 3 and 6 months, in 120 patients affected by RA, managed in Tuscany and Umbria rheumatological centers. The following clinical records were analyzed: demographical data, smoking status, previous presence of comorbidities (Herpes zoster -HZ- infection, venous thromboembolism -VTE-, major adverse cardiovascular events -MACE-, cancer, diabetes, and hypertension), disease duration, presence of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), number of biological failures, and prior csDMARDs utilized. At baseline, and after 3 (T3) and 6 (T6) months of FIL therapy, we evaluated mean steroid dosage, csDMARDs intake, clinimetric indexes (DAS28, CDAI, HAQ, patient and doctor PGA, VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and body mass index (BMI).

RESULTS: At baseline, the mean disease duration was 9.4 ± 7.5 years; the prevalence of previous HZ infection, VTE, MACE, and cancer was respectively 4.12%, 0%, 7.21%, and 0.83%, respectively. In total, 76.3% of patients failed one or more biologics (one biological failure, 20.6%; two biological failures, 27.8%; three biological failures, 16.5%; four biological failures, 10.3%; five biological failures, 1.1%). After 3 months of FIL therapy, all clinimetric index results significantly improved from baseline, as well as after 6 months. Also, ESR and CRP significatively decreased at T3 and T6. Two cases of HZ were recorded, while no new MACE, VTE, or cancer were recorded during the observation time.

CONCLUSION: Despite the limitations of the retrospective study and of the observational period of only 6 months, real-life data on the treatment of RA patients with FIL demonstrate that this Jak inhibitor therapy is safe in terms of CV, VTE events, and occurrence of cancer, and is also effective in a population identified as "difficult to treat" due to failure of previous b-DMARD therapy.

PMID:37763071 | PMC:PMC10532886 | DOI:10.3390/jpm13091303

02:09

PubMed articles on: Cancer & VTE/PE

Anti-Inflammatory and Anticancer Effects of Anticoagulant Therapy in Patients with Malignancy

Life (Basel). 2023 Sep 10;13(9):1888. doi: 10.3390/life13091888.