ABSTRACT

BACKGROUND: Despite high risk of venous thromboembolism (VTE) in patients with pancreatic cancer, there is little data on contact system activation in these patients.

OBJECTIVES: To quantify contact system and intrinsic pathway activation and subsequent VTE risk in patients with pancreatic cancer.

METHODS: Patients with advanced pancreatic cancer were compared to controls. Blood was drawn at baseline and patients were followed for six months. Complexes of proteases with their natural inhibitors, C1-esterase inhibitor (C1-INH), anti-thrombin (AT) or alpha-1 antitrypsin (α1at), were measured for complexes containing kallikrein (PKa:C1-INH), factor XIIa (FXIIa:C1-INH) and factor XIa (FXIa:C1-INH, FXIa:AT, FXIa:α1at). The association of cancer with complex levels was assessed in a linear regression model, adjusted for age, sex and body mass index. In a competing risk regression model we assessed associations between complex levels and VTE.

RESULTS: 109 patients with pancreatic cancer and 22 controls were included. The mean age was 66 years (SD 8.4) in the cancer cohort and 52 years (SD 10.1) in controls. In the cancer cohort, 18 (16.7%) patients developed VTE during follow-up. In the multivariable regression model, pancreatic cancer was associated with increased complexes of PKa:C1-INH (p<0.001),<0.001)<0.001).

CONCLUSION: Complexes of proteases with their natural inhibitors were elevated in patients with cancer. These data suggest that the contact system and intrinsic pathway activation are increased in patients with pancreatic cancer.

PMID:37331518 | DOI:10.1016/j.jtha.2023.06.009

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PubMed articles on: Cancer & VTE/PE

First-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomised, controlled, phase 3 study from the Dutch Colorectal Cancer Group

Lancet Oncol. 2023 Jun 14:S1470-2045(23)00219-X. doi: 10.1016/S1470-2045(23)00219-X. Online ahead of print. ABSTRACTBACKGROUND: Patients with initially unresectable colorectal cancer liver metastases might qualify for local treatment with curative intent after reducing the tumour size by induction systemic treatment. We aimed to compare the currently most active induction regimens.

METHODS: In this open-label, multicentre, randomised, phase 3 study (CAIRO5), patients aged 18 years or older with histologically confirmed colorectal cancer, known RAS/BRAFV600E mutation status, WHO performance status of 0-1, and initially unresectable colorectal cancer liver metastases were enrolled at 46 Dutch and one Belgian secondary and tertiary centres. Resectability or unresectability of colorectal cancer liver metastases was assessed centrally by an expert panel of liver surgeons and radiologists, at baseline and every 2 months thereafter by predefined criteria. Randomisation was done centrally with the minimisation technique via a masked web-based allocation procedure. Patients with right-sided primary tumour site or RAS or BRAFV600E mutated tumours were randomly assigned (1:1) to receive FOLFOX or FOLFIRI plus bevacizumab (group A) or FOLFOXIRI plus bevacizumab (group B). Patients with left-sided and RAS and BRAFV600E wild-type tumours were randomly assigned (1:1) to receive FOLFOX or FOLFIRI plus bevacizumab (group C) or FOLFOX or FOLFIRI plus panitumumab (group D), every 14 days for up to 12 cycles. Patients were stratified by resectability of colorectal cancer liver metastases, serum lactate dehydrogenase concentration, choice of irinotecan versus oxaliplatin, and BRAFV600E mutation status (for groups A and B). Bevacizumab was administered intravenously at 5 mg/kg. Panitumumab was administered intravenously at 6 mg/kg. FOLFIRI consisted of intravenous infusion of irinotecan at 180 mg/m2 with folinic acid at 400 mg/m2, followed by bolus fluorouracil at 400 mg/m2 intravenously, followed by continuous infusion of fluorouracil at 2400 mg/m2. FOLFOX consisted of oxaliplatin at 85 mg/m2 intravenously together with the same schedule of folinic acid and fluorouracil as in FOLFIRI. FOLFOXIRI consisted of irinotecan at 165 mg/m2 intravenously, followed by intravenous infusion of oxaliplatin at 85 mg/m2 with folinic acid at 400 mg/m2, followed by continuous infusion of fluorouracil at 3200 mg/m2. Patients and investigators were not masked to treatment allocation. The primary outcome was progression-free survival, analysed on a modified intention-to-treat basis, excluding patients who withdrew consent before starting study treatment or violated major entry criteria (no metastatic colorectal cancer, or previous liver surgery for colorectal cancer liver metastases). The study is registered with ClinicalTrials.gov, NCT02162563, and accrual is complete.

FINDINGS: Between Nov 13, 2014, and Jan 31, 2022, 530 patients (327 [62%] male and 203 [38%] female; median age 62 years [IQR 54-69]) were randomly assigned: 148 (28%) patients to group A, 146 (28%) patients to group B, 118 (22%) patients to group C, and 118 (22%) patients to group D. Groups C and D were prematurely closed for futility. 521 patients were included in the modified intention-to-treat population (147 in group A, 144 in group B, 114 in group C, and 116 in group D). The median follow-up at the time of this analysis was 51·1 months (95% CI 47·7-53·1) in groups A and B and 49·9 months (44·5-52·5) in in groups C and D. [...]

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PubMed articles on: Cancer & VTE/PE

Anticoagulant therapy in COVID-19: A narrative review

Clin Transl Sci. 2023 Jun 16. doi: 10.1111/cts.13569. Online ahead of print.

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest itself in several ways, including coagulopathy and thrombosis. These complications can be the first and sometimes only manifestations of SARS-CoV-2 infection and can occur early or late in the course of the disease. However, these symptoms are more prevalent in hospitalized venous thromboembolism (VTE) patients, particularly those admitted to intensive care units (ICUs). Moreover, various forms of arterial and venous thrombosis, or micro- or macro-vasculature embolisms, have been reported during the current pandemic. They have led to harmful consequences, such as neurological and cardiac events, nearly all resulting from the hypercoagulable state caused by this viral infection. The severe hypercoagulability observed in COVID-19 patients accounts for most cases of the disease that become critical. Therefore, anticoagulants seem to be one of the most vital therapeutics for treating this potentially life-threatening condition. In the current article, we present a thorough review of the pathophysiology of COVID-19-induced hypercoagulable state and the use of anticoagulants to treat SARS-CoV-2 infections in different patient groups, as well as their pros and cons.

PMID:37326220 | DOI:10.1111/cts.13569

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PubMed articles on: Cancer & VTE/PE

Interventional radiological therapies in colorectal hepatic metastases

Front Oncol. 2023 May 30;13:963966. doi: 10.3389/fonc.2023.963966. eCollection 2023.

ABSTRACT

Colorectal malignancy is the third most common cancer and one of the prevalent causes of death globally. Around 20-25% of patients present with metastases at the time of diagnosis, and 50-60% of patients develop metastases in due course of the disease. Liver, followed by lung and lymph nodes, are the most common sites of colorectal cancer metastases. In such patients, the 5-year survival rate is approximately 19.2%. Although surgical resection is the primary mode of managing colorectal cancer metastases, only 10-25% of patients are competent for curative therapy. Hepatic insufficiency may be the aftermath of extensive surgical hepatectomy. Hence formal assessment of future liver remnant volume (FLR) is imperative prior to surgery to prevent hepatic failure. The evolution of minimally invasive interventional radiological techniques has enhanced the treatment algorithm of patients with colorectal cancer metastases. Studies have demonstrated that these techniques may address the limitations of curative resection, such as insufficient FLR, bi-lobar disease, and patients at higher risk for surgery. This review focuses on curative and palliative role through procedures including portal vein embolization, radioembolization, and ablation. Alongside, we deliberate various studies on conventional chemoembolization and chemoembolization with irinotecan-loaded drug-eluting beads. The radioembolization with Yttrium-90 microspheres has evolved as salvage therapy in surgically unresectable and chemo-resistant metastases.

PMID:37324012 | PMC:PMC10266282 | DOI:10.3389/fonc.2023.963966

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PubMed articles on: Cancer & VTE/PE

Utility of the intraflap perfusion procedure for abdominal free flap in unilateral breast reconstruction

J Plast Reconstr Aesthet Surg. 2023 May 19;84:54-61. doi: 10.1016/j.bjps.2023.05.039. Online ahead of print.

ABSTRACT

BACKGROUND: Heparin prophylaxis for venous thromboembolism can be used in microsurgery. If vein anastomosis is performed before the artery, heparin irrigation into the artery can be performed locally without systematic effect. This study aimed to introduce this "intraflap perfusion procedure" in autologous breast reconstruction.

METHODS: Among the 220 patients with unilateral breast cancer who had received the free abdominal flap, we retrospectively compared those that had undergone the intraflap perfusion procedure (n = 108) and those who did not (n = 112). A 10 mL injection of heparinized physiological saline solution (100 units/mL) was administered into the deep inferior epigastric artery. Intraflap perfusion was performed before, during, and after vein anastomosis, without the vessel clip of the vein. Artery anastomosis was performed without the use of a vein clamp. Further, vein anastomosis was performed tightly to prevent leakage from the vein anastomosis site during artery anastomosis.

RESULTS: The rates of superficial inferior epigastric vein (SIEV) superdrainage (18.5% vs. 42.0%, P < 0.001), and intraoperative flap congestion (0.9% vs. 8.0%, P = 0.01) were significantly lower in patients undergoing this procedure. There were no significant differences regarding other factors (age, BMI, laterality, comorbidities, and other operative details).

CONCLUSIONS: Intraflap perfusion prevented long-term stasis at the venous anastomosis site and capillary level. It could reduce flap congestion. SIEV superdrainage was performed to manage flap congestion, particularly in patients who did not undergo this procedure. Consequently, it can be inferred that this procedure reduces the rate of superdrainage.

PMID:37320952 | DOI:10.1016/j.bjps.2023.05.039

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PubMed articles on: Cancer & VTE/PE

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Reduction of Venous Thromboembolic Disease in Colorectal Surgery

Dis Colon Rectum. 2023 Jun 12. doi: 10.1097/DCR.0000000000002975. Online ahead of print.

NO ABSTRACT

PMID:37318130 | DOI:10.1097/DCR.0000000000002975

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Median progression-free survival was 9·0 months (95% CI 7·7-10·5) in group A versus 10·6 months (9·9-12·1) in group B (stratified hazard ratio [HR] 0·76 [95% CI 0·60-0·98]; p=0·032), and 10·8 months (95% CI 9·9-12·6) in group C versus 10·4 months (9·8-13·0) in group D (stratified HR 1·11 [95% CI 0·84-1·48]; p=0·46). The most frequent grade 3-4 events in groups A and B were neutropenia (19 [13%] patients in group A vs 57 [40%] in group B; p<0·0001),<0·0001),<0·0001),

INTERPRETATION: In patients with initially unresectable colorectal cancer liver metastases, FOLFOXIRI-bevacizumab was the preferred treatment in patients with a right-sided or RAS or BRAFV600E mutated primary tumour. In patients with a left-sided and RAS and BRAFV600E wild-type tumour, the addition of panitumumab to FOLFOX or FOLFIRI showed no clinical benefit over bevacizumab, but was associated with more toxicity.

FUNDING: Roche and Amgen.

PMID:37329889 | DOI:10.1016/S1470-2045(23)00219-X

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PubMed articles on: Cancer & VTE/PE

Association of D-dimer Levels with Complications after Subcutaneous Implantable Central Venous Port Placement in Combination Chemotherapy with Bevacizumab for Colorectal Cancer

Gan To Kagaku Ryoho. 2023 Jun;50(6):713-717.