Microbubble contrast-enhanced ultrasound in the vascular evaluation after pancreas transplantation: a single-center experience

Background: Arterial and venous thrombosis are feared complications of pancreas transplantation (PTx). Microbubble contrast-enhanced ultrasound (CEUS) is a non-invasive imaging technique that can augment diagnostic capabilities of transplant organ perfusion. Purpose: To document the state to which CEUS can improve the vascular evaluation of PTx compared to conventional Doppler ultrasound (US) directly after surgery. Material and Methods: A total of 129 consecutive PTx in 128 adult patients were eligible for inclusion. The duodenal segment of the graft was anastomosed to the native duodenum. Within 12 h postoperatively, graft- circulation was monitored by Doppler US in 116 PTx performed in 116 patients (69 men, 47 women; mean age 41 years). CEUS was performed with a sulfur hexafluoride-containing contrast agent (SonoVue) intravenously if the examiner was not able to confirm normal graft circulation. Image quality was documented by two independent observers on a 4-point scale: 1 excellent; 2 minor diagnostic limitations; 3 major diagnostic limitations; and 4 non-diagnostic. Results: In the early postoperative phase, 79 (68%) of 116 PTx were examined with Doppler US only. Of these, 52 were of excellent quality (grade 1), 22 of good quality (grade 2), and five were of grade 3 or 4 quality. Thirty-seven (32%) examinations were supplemented by CEUS. CEUS significantly improved examination quality compared to Doppler US alone (median visualization score 1.5 vs. 2.5, respectively; P < 0.0001). Conclusion: CEUS can significantly improve vascular evaluation of PTx compared to Doppler US alone in the early postoperative phase

Long-Term Efficacy of Ethanol Ablation as Treatment of Metastatic Lymph Nodes From Papillary Thyroid Carcinoma

Abstract Context Ethanol ablation (EA) is considered an alternative to surgery for metastatic lymph nodes from papillary thyroid carcinoma (PTC) in selected patients. Objective The aim of this study was to evaluate the long-term efficacy and safety of this treatment. Design and Setting Adult patients with PTC who had received EA in lymph node metastasis at a tertiary referral center, and were included in a published study from 2011, were invited to participate in this follow-up study. Methods Radiologic and medical history were reviewed. Ultrasound examination of the neck was performed by radiologists, and clinical examination was performed by an endocrine surgeon. Response was reported according to predefined criteria for satisfactory EA treatment. Adverse events associated with EA were evaluated. Cause of death was reported for deceased patients. Results From the 2011 study, 51 of 63 patients were included. Forty-four patients were reexamined (67/109 lesions) and 7 patients were deceased. Median follow-up time from primary surgery was 14.5 years. Median follow-up from the latest performed EA in the 2011 study was 11.3 years. Local control was permanently achieved in most patients (80%). Recurrence within an ablated node was registered in 13 metastases in 10 patients. Seven of these patients also had recurrent disease elsewhere in the neck. No major side effects were reported. Conclusion EA is a minimally invasive procedure with a low risk of complications. Our data suggest that EA is a safe and efficient treatment, providing excellent results for a large group of patients in the long term

Neoadjuvant chemotherapy is associated with a transient increase of intratumoral T-cell density in microsatellite stable colorectal liver metastases

Patients with colorectal liver metastases (CLM) commonly receive neoadjuvant chemotherapy (NACT) prior to surgical resection. NACT may induce immunogenic cell death with subsequent recruitment of T-cells to the tumor microenvironment, which could be exploited by immune checkpoint inhibition (ICI). In theory, this could expand the use of ICI to obtain responses also in microsatellite stable colorectal cancer, but evidence to suggest optimal treatment schedules are lacking. In this study, densities of total-, cytotoxic-, helper- and regulatory T-cells were quantified by immunohistochemistry in resected CLM from 92 patients included in the OSLO-COMET trial (NCT01516710). All but one patient had microsatellite stable tumors (91/92). Associations between T-cell densities and clinicopathological parameters were analyzed. Fluoropyrimidine-based NACT (in most cases with addition of oxaliplatin or irinotecan) was administered to 45 patients completed median 8 weeks prior to surgical resection. No overall association was found between NACT administration and intratumoral T-cell densities. However, within the NACT group, a short time interval (<9.5 weeks) between NACT completion and CLM resection was strongly associated with high intratumoral T-cell densities compared to the long-interval and no NACT groups (medians 491, 236, and 292 cells/mm2, respectively; P < .0001). The results from this study suggest that the observed increase in intratumoral T-cells after NACT administration may be transient. The significance of this finding should be further explored to ensure that optimal treatment schedules are chosen for studies combining cytotoxic chemotherapy and ICI

Early detection of complications in pancreas transplants by microdialysis catheters, an observational feasibility study

Background Despite advances in immunosuppression and surgical technique, pancreas transplantation is encumbered with a high rate of complication and graft losses. Particularly, venous graft thrombi occur relatively frequently and are rarely detected before the transplant is irreversibly damaged. Methods To detect complications early, when the grafts are potentially salvageable, we placed microdialysis catheters anteriorly and posteriorly to the graft in a cohort of 34 consecutive patients. Glucose, lactate, pyruvate, and glycerol were measured at the bedside every 1–2 hours. Results Nine patients with graft venous thrombosis had significant lactate and lactate–to-pyruvate-ratio increases without concomitant rise in blood glucose or clinical symptoms. The median lactate in these patients was significantly higher in both catheters compared to non-events (n = 15). Out of the nine thrombi, four grafts underwent successful angiographic extraction, one did not require intervention and four grafts were irreversibly damaged and explanted. Four patients with enteric anastomosis leakages had significantly higher glycerol measurements compared to non-events. As with the venous thrombi, lactate and lactate-to-pyruvate ratio were also increased in six patients with graft surrounding hematomas. Conclusions Bedside monitoring with microdialysis catheters is a promising surveillance modality of pancreatic grafts, but differentiating between the various pathologies proves challenging

Molecular signatures reflecting microenvironmental metabolism and chemotherapy-induced immunogenic cell death in colorectal liver metastases

Background: Metastatic colorectal cancer (CRC) is associated with highly variable clinical outcome and response to therapy. The recently identified consensus molecular subtypes (CMS1-4) have prognostic and therapeutic implications in primary CRC, but whether these subtypes are valid for metastatic disease is unclear. We performed multi-level analyses of resectable CRC liver metastases (CLM) to identify molecular characteristics of metastatic disease and evaluate the clinical relevance. Methods: In this ancillary study to the Oslo-CoMet trial, CLM and tumor-adjacent liver tissue from 46 patients were analyzed by profiling mutations (targeted sequencing), genome-wide copy number alteration (CNAs), and gene expression. Results: Somatic mutations and CNAs detected in CLM were similar to reported primary CRC profiles, while CNA profiles of eight metastatic pairs suggested intra-patient divergence. A CMS classifier tool applied to gene expression data, revealed the cohort to be highly enriched for CMS2. Hierarchical clustering of genes with highly variable expression identified two subgroups separated by high or low expression of 55 genes with immune-related and metabolic functions. Importantly, induction of genes and pathways associated with immunogenic cell death (ICD) was identified in metastases exposed to neoadjuvant chemotherapy (NACT). Conclusions: The uniform classification of CLM by CMS subtyping may indicate that novel class discovery approaches need to be explored to uncover clinically useful stratification of CLM. Detected gene expression signatures support the role of metabolism and chemotherapy in shaping the immune microenvironment of CLM. Furthermore, the results point to rational exploration of immune modulating strategies in CLM, particularly by exploiting NACT-induced ICD