The effect of pasireotide on intestinal anastomotic healing with and without whole-body irradiation in a rat model.

OBJECTIVE: To examine pasireotide's effect on intestinal anastomotic healing under physiological conditions and following preoperative whole-body irradiation. MATERIAL AND METHODS: Forty-five male Wistar rats received an ileoileal end-to-end anastomosis. Group 1 (Co, n = 9) served as control. Group 2 (SOM, n = 10) received pasireotide (60 mg/kg) 6 days preoperatively. Group 3 (R-Co, n = 13) was subjected to 8 Gy whole-body irradiation 4 days preoperatively. Finally, group 4 (R-SOM, n = 13) received pasireotide 6 days preoperatively and whole-body irradiation 4 days preoperatively. On postoperative day 4, anastomotic bursting pressure, histology, IGF-1 staining, and collagen density were examined. RESULTS: Mortality was higher in irradiated animals (30.8% vs. 5.3%, p = 0.021), and anastomotic bursting pressure was significantly lower (median, R-Co = 83 mmHg; R-SOM = 101 mmHg; Co = 149.5 mmHg; SOM = 169 mmHg). Inflammation measured by leukocyte infiltration following irradiation was reduced (p = 0.023), and less collagen was observed, though this was not statistically significant. Bursting pressure did not significantly differ between Co and SOM and between R-Co and R-SOM animals respectively. Semi-quantitative scoring of IGF-1, fibroblast bridging, or collagen density did not reveal significant differences among the groups. CONCLUSION: Whole-body irradiation decreases the quality of intestinal anastomotic wound healing and increases mortality. Pasireotide does not significantly lessen this detrimental effect.

Searching for the molecular benchmark of physiological intestinal anastomotic healing in rats: an experimental study.

PURPOSE: This investigation focuses on the physiological characteristics of gene transcription of intestinal tissue following anastomosis formation. METHODS: In eight rats, end-to-end ileo-ileal anastomoses were performed (n = 2/group). The healthy intestinal tissue resected for this operation was used as a control. On days 0, 2, 4 and 8, 10-mm perianastomotic segments were resected. Control and perianastomotic segments were examined with an Affymetrix microarray chip to assess changes in gene regulation. Microarray findings were validated using real-time PCR for selected genes. In addition to screening global gene expression, we identified genes intensely regulated during healing and also subjected our data sets to an overrepresentation analysis using the Gene Ontology (GO) and Kyoto Encyclopedia for Genes and Genomes (KEGG). RESULTS: Compared to the control group, we observed that the number of differentially regulated genes peaked on day 2 with a total of 2,238 genes, decreasing by day 4 to 1,687 genes and to 1,407 genes by day 8. PCR validation for matrix metalloproteinases-3 and -13 showed not only identical transcription patterns but also analogous regulation intensity. When setting the cutoff of upregulation at 10-fold to identify genes likely to be relevant, the total gene count was significantly lower with 55, 45 and 37 genes on days 2, 4 and 8, respectively. A total of 947 GO subcategories were significantly overrepresented during anastomotic healing. Furthermore, 23 overrepresented KEGG pathways were identified. CONCLUSION: This study is the first of its kind that focuses explicitly on gene transcription during intestinal anastomotic healing under standardized conditions. Our work sets a foundation for further studies toward a more profound understanding of the physiology of anastomotic healing.

Percutaneous transcatheter aspiration of pulmonary embolism leading to diagnosis of hepatocellular carcinoma tumor embolus and change in systemic chemotherapy.

The management of metastatic hepatocellular carcinoma (HCC) is complex, particularly when complicated by pulmonary embolism. In these cases, atezolizumab-bevacizumab therapy is contraindicated due to an elevated risk of thromboembolic events. Differentiating pulmonary tumor embolism from thromboembolic disease is diagnostically challenging. This report outlines the benefit of transcatheter aspiration to obtain pathological evidence of pulmonary artery tumor embolus in an HCC patient. The intervention enabled a significant shift in the management strategy, leading to an escalation of systemic HCC therapy. This case underscores the importance of precise diagnostic techniques such as transcatheter aspiration in guiding treatment decisions, particularly in cases where pulmonary embolism may signify an underlying malignancy-driven process.

Single-cell deconvolution reveals high lineage- and location-dependent heterogeneity in mesenchymal multivisceral stage 4 colorectal cancer.

Metastasized colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Besides hepatic metastasis, peritoneal carcinomatosis is the major cause of death in Union for International Cancer Control (UICC) stage IV CRC patients. Insights into differential site-specific reconstitution of tumor cells and the corresponding tumor microenvironment are still missing. Here, we analyzed the transcriptome of single cells derived from murine multivisceral CRC and delineated the intermetastatic cellular heterogeneity regarding tumor epithelium, stroma, and immune cells. Interestingly, we found an intercellular site-specific network of cancer-associated fibroblasts and tumor epithelium during peritoneal metastasis as well as an autologous feed-forward loop in cancer stem cells. We furthermore deciphered a metastatic dysfunctional adaptive immunity by a loss of B cell-dependent antigen presentation and consecutive effector T cell exhaustion. Furthermore, we demonstrated major similarities of this murine metastatic CRC model with human disease and - based on the results of our analysis - provided an auspicious site-specific immunomodulatory treatment approach for stage IV CRC by intraperitoneal checkpoint inhibition.

Does the site of primary colorectal cancer influence the outcome after resection of isolated liver metastases?

INTRODUCTION: In unresectable patients with metastatic colorectal cancer (CRC), the site of the primary is a strong prognostic factor warranting major adjustments in palliative medical treatment. Initial results suggested that the site of CRC influences prognosis after curative resection of colorectal liver metastases (CLM). In this study, we evaluated outcome after resection of isolated CLM with regard to the location of the primary. METHODS: 221 patients with macroscopically complete resection of CLM and no known extrahepatic disease were identified. 63 patients had right-sided and 158 had left-sided CRC. Tumors of the transverse colon and rectum were excluded. Survival was evaluated using the Kaplan-Meier method. RESULTS: Characteristics of CLM, primary tumor stage and chemotherapeutic regimens were not significantly different between the two groups. Kaplan-Meier five-year survival was comparable (41%) in patients with right- or left-sided CRC (p = 0.64). Microscopic resection margin, number of liver metastases, age and nodal status but not the site of the primary tumor significantly influenced survival. CONCLUSION: The site of the colorectal primary in this well-defined group of patients after resection of isolated CLM did not prove to be of significant prognostic value. Whether the primary tumor in CLM is located on the left side or the right should not preclude patients from surgery.

Intraoperative crystalloid overload leads to substantial inflammatory infiltration of intestinal anastomoses-a histomorphological analysis.

BACKGROUND: It has been shown that crystalloid fluid-overload promotes anastomotic instability. As physiologic anastomotic healing requires the sequential infiltration of different cells, we hypothesized this to be altered by liberal fluid regimes and performed a histomorphological analysis. METHODS: 36 Wistar rats were randomized into 4 groups (n=8-10 rats/group) and treated with either liberal (+) or restrictive (-) perioperative crystalline (Jonosteril = Cry) or colloidal fluid (Voluven = Col). Anastomotic samples were obtained on postoperative day 4, routinely stained and histophathologically reviewed. Anastomotic healing was assessed using a semiquantitative score, assessing inflammatory cells, anastomotic repair and collagenase activity. RESULTS: Overall, the crystalloid overload group (Cry (+)) showed the worst healing score (P < 0.01). A substantial increase of lymphocytes and macrophages was found in this group compared to the other three (P < 0.01). Both groups that received colloidal fluid (Col (+) and Col (-)) as well as the group that received restricted crystalloid fluid resuscitation (Cry (-)) had better intestinal healing. Collagenase activity was significantly higher in the Cry (+) group. CONCLUSION: Intraoperative infusion of high-volume crystalloid fluid leads to a pathological anastomotic inflammatory response with a marked infiltration of leukocytes and macrophages resulting in accelerated collagenolysis.