ABSTRACT

Upper gastrointestinal cancer is frequently complicated by venous thromboembolisms (VTE), especially pulmonary embolisms (PE) increase the mortality rate. Monocytes are a part of the innate immune system and up-regulation may indicate an ongoing inflammatory response or infectious disease and has lately been associated with a moderate risk of suffering from VTE. This prospectively study aims to compare the incidence of pulmonary embolism with markers of coagulation and compare it to the absolute monocyte count. A consecutive cohort of 250 patients with biopsy proven upper gastrointestinal cancer (i.e. pancreas, biliary tract, esophagus and gastric cancer) where included at the time of cancer diagnosis and before treatment. All patients underwent bilateral compression ultrasonography for detection of deep vein thrombosis (DVT). Of these 143 had an additionally pulmonary angiografi (CTPA) with the staging computer tomography. 13 of 250 patients (5.2%) had a DVT and 11 of 143 (7.7%) had CTPA proven PE. PE was significantly more common among patients with elevated D-dimer (OR 11.62, 95%CI: 1.13-119, P = 0.039) and elevated absolute monocyte count (OR 7.59, 95%CI: 1.37-41.98, P = 0.020). Only patients with pancreatic cancer had a significantly higher risk of DVT (OR 11.03, 95%CI: 1.25-97.43, P = 0.031). The sensitivity of absolute monocyte count was 63.6 (95%CI: 30.8-89.1) and specificity 80.3 (95%CI: 72.5-86.7), with a negative predictive value of 96.4 (95%CI: 91-99) in PE. An increased absolute monocyte count was detected in patients suffering from PE but not DVT, suggesting a possible interaction with the innate immune system.

PMID:37792208 | DOI:10.1007/s11239-023-02897-5

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PubMed articles on: Cancer & VTE/PE

Machine-Learning-Assisted Procoagulant Extracellular Vesicle Barcode Assay toward High-Performance Evaluation of Thrombosis-Induced Death Risk in Cancer Patients

ACS Nano. 2023 Oct 4. doi: 10.1021/acsnano.3c04615. Online ahead of print.

ABSTRACT

Venous thromboembolism (VTE) is the most fatal complication in cancer patients. Unfortunately, the frequent misdiagnosis of VTE owing to the lack of accurate and efficient evaluation approaches may cause belated medical intervention and even sudden death. Herein, we present a rapid, easily operable, highly specific, and highly sensitive procoagulant extracellular vesicle barcode (PEVB) assay composed of TiO2 nanoflower (TiNFs) for visually evaluating VTE risk in cancer patients. TiNFs demonstrate rapid label-free EV capture capability by the synergetic effect of TiO2-phospholipids molecular interactions and topological interactions between TiNFs and EVs. From ordinary plasma samples, the PEVB assay can evaluate potential VTE risk by integrating TiNFs-based EV capture and in situ EV procoagulant ability test with machine-learning-assisted clinical data analysis. We demonstrate the feasibility of this PEVB assay in VTE risk evaluation by screening 167 cancer patients, as well as the high specificity (97.1%) and high sensitivity (96.8%), fully exceeding the nonspecific and posterior traditional VTE test. Together, we proposed a TiNFs platform allowing for highly accurate and timely diagnosis of VTE in cancer patients.

PMID:37791763 | DOI:10.1021/acsnano.3c04615

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PubMed articles on: Cancer & VTE/PE

D-Dimers Variability in the Perioperative Period of Breast Cancer Surgery Helps to Predict Cancer Relapse: A Single-Centre Prospective Study

Cancer Control. 2023 Jan-Dec;30:10732748231204713. doi: 10.1177/10732748231204713.

ABSTRACT

BACKGROUND: The importance of D-dimers (DD) assessment in the diagnostic algorithm of venous thromboembolic (VTE) disease is well known. Increase of DD concentration may be also associated with neoplastic disease. Many studies documented that high concentration of DD before solid tumour surgery indicates more advanced disease and poor life expectancy. The prognostic value of the DD concentration variability in the perioperative period, in women undergoing breast cancer surgery, has not been analysed so far. Thus, the aim of the present prospective study was to assess whether the trend of DD concentration changes in the perioperative period may predict cancer recurrence in women undergoing breast cancer surgery.

MATERIALS AND METHODS: 189 consecutive women with histopathological diagnosis of breast cancer (BC) referred for surgical treatment were included. DD concentration was measured twice in each patient: at the time of admission to hospital and at the time of discharge home. Enoxaparin in standard dose of 40 mg daily s. c. was used as primary VTE prophylaxis in all of the patients.

RESULTS: The recurrence of BC, within 1 year observation time, occurred in 13 patients (6.8%), in 11 (5.8%) patients with DD increase after surgery and only in 2 (1.1%) without an increase in DD, P = .0179. Increase in DD concentration after BC surgery was an independent positive predictor of disease relapse (OR 8.600, LCI 1.451, UCI 96.80, P = .0371) together with the lack of postoperative radiotherapy (OR 6.009, LCI 1.305, UCI 31.95, P = .0245), whereas the lack of postoperative chemotherapy predicted no BC relapse (OR .07355, LCI .0056, UCI .58, P = .0245).

CONCLUSIONS: Increase of DD in the early postoperative period may be considered as additional independent predictor of recurrence of BC within 1 year.

PMID:37791647 | PMC:PMC10552458 | DOI:10.1177/10732748231204713

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PubMed articles on: Cancer & VTE/PE

Risk of venous thromboembolism in patients undergoing gastric cancer surgery: a systematic review and meta-analysis

BMC Cancer. 2023 Oct 3;23(1):933. doi: 10.1186/s12885-023-11424-x.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a common postoperative complication in patients undergoing surgery for gastric cancer (GC). Although VTE incidence may vary among cancers, guidelines rarely stratify preventive methods for postoperative VTE by cancer type. The risk of VTE in patients undergoing surgery for GC remains unclear.

METHODS: A systematic review and meta-analysis was undertaken to determine the risk of VTE after GC surgery and discuss the clinical value of pharmacological thromboprophylaxis in these cases. Medline, Embase, Web of Science, and Cochrane Library databases were searched for articles published from their inception to September 2022.

RESULTS: Overall, 13 studies (111,936 patients) were included. The overall 1-month incidence of VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE) after GC surgery was 1.8% (95% CI, 0.8-3.1%; I²=98.5%), 1.2% (95% CI, 0.5-2.1%; I²=96.1%), and 0.4% (95% CI, 0.1-1.1%; I²=96.3%), respectively. The prevalence of postoperative VTE was comparable between Asian and Western populations (1.8% vs. 1.8%; P > 0.05). Compared with mechanical prophylaxis alone, mechanical plus pharmacological prophylaxis was associated with a significantly lower 1-month rate of postoperative VTE and DVT (0.6% vs. 2.9% and 0.6% vs. 2.8%, respectively; all P < 0.05), but not PE (P > 0.05). The 1-month postoperative incidence of VTE was not significantly different between laparoscopic and open surgery (1.8% vs. 4.3%, P > 0.05).

CONCLUSION: Patients undergoing GC surgery do not have a high risk of VTE. The incidence of VTE after GC surgery is not significantly different between Eastern and Western patients. Mechanical plus pharmacological prophylaxis is more effective than mechanical prophylaxis alone in postoperative VTE prevention. The VTE risk is comparable between open and laparoscopic surgery for GC.

PMID:37789268 | PMC:PMC10546706 | DOI:10.1186/s12885-023-11424-x

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PubMed articles on: Cancer & VTE/PE

Extended Venous Thromboembolism Prophylaxis after Robotic Staging for Endometrial Cancer

South Med J. 2023 Oct;116(10):790-794. doi: 10.14423/SMJ.0000000000001611.

ABSTRACT

OBJECTIVES: Our objectives were to estimate the incidence of venous thromboembolism (VTE) after robotic staging for endometrial cancer and to compare the incidence of VTE in patients who received a single dose of preoperative prophylaxis of enoxaparin with those who received extended postoperative prophylaxis.

METHODS: This study is a retrospective chart review of patients who underwent robot-assisted surgical staging for endometrial cancer. Patients were categorized into two groups: preoperative prophylaxis (PP), patients who received a single dose of enoxaparin preoperatively, and extended prophylaxis (EP), patients who received 28 days of enoxaparin postoperatively.

RESULTS: In total, 148 patients were included, with 117 patients in the PP group and 31 patients in the EP group. The overall incidence of VTE within 30 days postoperatively was 0.67%. No significant difference was found between the PP and the EP groups (0.9% and 0%, respectively; P = 1.00). Most patients in the cohort had endometrioid adenocarcinoma (78%) with low-grade disease (70%), although there were a greater number of patients in the PP group with uterine serous carcinoma compared with the EP group (17% vs 10%; P = 0.034). The PP group had higher estimated blood loss (106 vs 81 mL; P = 0.009) and longer operative times (178 vs 151 min; P = 0.028) compared with the EP group. Significantly more patients in the PP group underwent lymph node dissection compared with the EP group (32% vs 7%; P = 0.008).

CONCLUSIONS: The incidence of VTE following robot-assisted surgical staging for endometrial cancer in this study was 0.67%. No significant difference was found in VTE incidence between the PP group compared with the EP group. Mechanical prophylaxis plus a single dose of preoperative pharmacologic prophylaxis may suffice for low-risk patients following robotic surgical staging for endometrial cancer.

PMID:37788812 | DOI:10.14423/SMJ.0000000000001611

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PubMed articles on: Cancer & VTE/PE

Major Intraoperative Complications During Minimally Invasive Esophagectomy

Ann Surg Oncol. 2023 Oct 2. doi: 10.1245/s10434-023-14340-3. Online ahead of print.

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

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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

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PubMed articles on: Cancer & VTE/PE

Obstructive Sleep Apnea and Venous Thromboembolism: Unraveling the Emerging Association

Cureus. 2023 Aug 30;15(8):e44367. doi: 10.7759/cureus.44367. eCollection 2023 Aug.