Seeding after ultrasound-guided percutaneous biopsy of liver metastases in patients with colorectal or breast cancer

<p><i>Background</i>: Neoplasm seeding is a serious complication after liver metastases biopsy. Reported incidences vary between 10% and 19% for colorectal cancer (CRC) and are unknown for breast cancer (BC). The aim of this retrospective study was to determine the frequency of tumor seeding after ultrasound-guided percutaneous biopsy of CRC and BC liver metastases.</p> <p><i>Material and methods</i>: Unselected liver biopsies performed in the period of 2005–2012 at our institution were extracted from the National Pathology Registry. Medical records including imaging from patients with biopsy-verified BC and CRC liver metastases were retrospectively reviewed. The endpoint was the development of abdominal wall recurrence following liver biopsy.</p> <p><i>Results</i>: Of total 2981 biopsies we identified 278 patients with CRC and 155 patients with BC biopsy-verified liver metastases. During the median follow-up of 25 months after biopsy (range 3–253 months), no seeding was recorded in patients with BC. Within the median follow-up of 34 months (3–111 months), seeding was registered in 17/278 (6%) of patients with CRC; three patients of 278 (1%) had undoubtedly biopsy-related seeding, which became apparent six, nine, and 26 months after biopsy, respectively; and in nine patients (3%) seeding occurred due to either biopsy or other interventions; and five patients had seeding, which were assessed as a consequence of other invasive procedures than biopsies. The median overall survival of the 17 patients with seeding was 70 months compared to 39 months of patients without seeding.</p> <p><i>Conclusions</i>: The results showed no seeding in BC patients. Seeding rate after biopsy in CRC patients is not negligible, however, without affecting outcome.</p

A New Type of Methacrylate-Substituted Oxozirconium Clusters: [Zr3O(OR)5(OMc)5]2 and [Zr3O(OR)3(OMc)7]2

 The new clusters Zr6O2(OBu)10(OMc)10 and Zr6O2(OMe)4(OBu)2(OMc)14 were prepared from Zr(OBu)4 and methacrylic acid. For the preparation of Zr6O2(OMe)4(OBu)2(OMc)14, partial exchange of the butoxy groups is necessary. The clusters consist of two Zr3 subunits that dimerize via alkoxide bridges. The structures are of the same type, except that four terminal butoxy ligands in Zr6O2(OBu)10(OMc)10 are exchanged for chelating methacrylate ligands in Zr6O2(OMe)4(OBu)2(OMc)14

List of prognostic miRNAs for overall survival. Hazard ratios with confidence intervals, Wald <i>P</i>-values and Bonferroni adjusted <i>P</i>-values are given.

<p>List of prognostic miRNAs for overall survival. Hazard ratios with confidence intervals, Wald <i>P</i>-values and Bonferroni adjusted <i>P</i>-values are given.</p

Baseline characteristics of the patients.

<p>(N = 138).</p

Concordance, Univariable and Multivariable Cox analyses of overall survival and progression-free survival in 138 patients, with metastatic colorectal cancer treated with 3^rd line cetuximab and irinotecan according to a miRNAs, gender, age, performance status and <i>KRAS</i> and, <i>PI3KCA</i> mutation status. miRNAs are tested as continuous variables in interquartile ranges units.

<p>Concordance, Univariable and Multivariable Cox analyses of overall survival and progression-free survival in 138 patients, with metastatic colorectal cancer treated with 3^rd line cetuximab and irinotecan according to a miRNAs, gender, age, performance status and <i>KRAS</i> and, <i>PI3KCA</i> mutation status. miRNAs are tested as continuous variables in interquartile ranges units.</p

Box plot showing the association between miR-345 expression and response to treatment (partial response, stable disease and progression). Mann-Whitney test; <i>KRAS</i> wt patients (green dots), <i>KRAS</i> mutated patients (red dots).

<p>If we restrict our set of patients to those with partial response (n = 24) and progressive disease (n = 37), a significant relationship between miR-345 expression and response to therapy was obtained with an odds ratio of 5.37, (<i>P</i>-value = 0.004 and 95% CI: 1.56–20.94).</p

Overall survival according to quartiles of mir-664-3p expression.

<p>Kaplan-Meier plots are shown for patients treated with CAPEOXBEV using raw (A) or mean-normalized (B) expression and patients treated with CAPEOX alone using raw (C) and mean-normalized (D) expression. Hazard ratios (HR) are unadjusted and confidence intervals (CI) are calculated using bootstrapping. The expression intervals shown in the upper right-hand corner are 40-C_t, so higher values correspond to higher expression. Black line = lowest quartile; red line = second quartile; green line = third quartile; blue line = highest quartile.</p

Focused miRNA panel – miRNAs significantly associated with time to disease progression.

a<p> Interaction tests were performed for all patients and for patients with distal (sigmoid and rectum) and proximal (cecum to descending) primary tumor location, separately.</p>b<p> Hazard ratio is per inter-quartile range expression increase and is adjusted for age, sex, number of metastatic sites, prior adjuvant treatment and primary tumor location.</p>c<p> miRNA was missing in >10% of samples so interaction was not tested.</p><p>Abbreviations: HR, hazard ratio; CI, confidence interval.</p><p>Focused miRNA panel – miRNAs significantly associated with time to disease progression.</p

Focused miRNA panel – miRNAs significantly associated with overall survival.

a<p> Interaction was tested for all patients and for patients with distal (sigmoid to rectum) and proximal (cecum to descending colon) primary tumor location separately.</p>b<p> Hazard ratio is per inter-quartile range expression increase and is adjusted for age, sex, number of metastatic sites, prior adjuvant treatment and primary tumor location.</p><p>Abbreviations: HR, hazard ratio; CI, confidence interval.</p><p>Focused miRNA panel – miRNAs significantly associated with overall survival.</p

MiR-664-3p <i>in situ</i> hybridization (ISH).

<p>Panels A and B show examples of miR-664-3p ISH in infiltrating lymphocytes (A) and fibroblasts (B). Consecutive sections were stained with LNA probes against miR-664-3p, miR-126-3p and a scramble sequence. MiR-664-3p ISH signal is seen in infiltrating lymphocytes (A, arrows; B, red arrow) and in fibroblasts (B, black arrows), whereas no ISH signal is obtained with scramble probe. A strong ISH signal is seen in endothelial cells with the positive control probe miR-126-3p. The “A” in panel B indicates an artery.</p