First Resection of a Cavoatrial Renal Tumor Thrombus in a Pediatric Patient in Central America Based on a Multistage Surgical Safety Strategy Combining Liver Transplant Techniques and Cardiac Surgery.

We herein report the challenging evaluation and planning process involved in performing the first successful surgical resection of a renal tumor with extensive inferior vena cava tumor thrombosis reaching the right atrium in a pediatric patient within the Central American region. In November 2018, the Oncology Department of the National Children's Hospital in Costa Rica consulted our Center for Liver Transplantation and Hepatobiliary Surgery for the evaluation of a clinical case involving a 6-year-old female patient with progressive Budd-Chiari syndrome caused by a Wilms' tumor of the right kidney with tumor thrombosis of the inferior vena cava reaching the right atrium. A multistage surgical safety strategy combining liver transplant techniques and cardiac surgery was thereafter designed and implemented, achieving complete excision of the tumor thrombus from the inferior vena cava with right nephrectomy. Postoperatively, the patient exhibited complete clinical resolution of Budd-Chiari syndrome and has remained tumor free with excellent quality of life while pursuing her second grade of primary school education 22 months after the successful implementation of this multistage surgical safety strategy. The combination of liver transplantation techniques and cardiac surgery based on a multistage surgical safety strategy minimized the occurrence of unexpected intraoperative events and allowed for complete renal tumor resection and level IV thrombectomy for the first time in a pediatric patient of a public health system in a developing country within the Central American region.

Repeat Hepatectomy for Breast Cancer Liver Metastases.

BACKGROUND: Resection of breast cancer liver metastases (BCLM) combined with systemic treatment is increasingly accepted as a therapeutic option; however, the potential benefit of repeat hepatectomy for recurrent BCLM is unknown. METHODS: All consecutive female patients who underwent liver resection for BCLM at our center between January 1985 and December 2012 were included. Patients who had a single hepatectomy (N = 120) were compared with those who also underwent repeat hepatectomy (N = 19). Patients were selected for repeat hepatectomy based on operability and disease control. Prognostic factors of survival after repeat hepatectomy were determined. RESULTS: Median overall survival since first hepatectomy was 35 months, with a 3- and 5-year survival rate of 50 and 38 %, respectively. Overall survival following repeat hepatectomy was 64 and 46 % at 3 and 5 years, respectively. From the time of first hepatectomy, patients who underwent repeat hepatectomy had a better survival than those who had only one hepatectomy (95 and 84 vs. 50 and 38 % at 3 and 5 years, respectively) (p = 0.002). Median survival was 35 and 100 months, respectively, and median survival since the diagnosis of BCLM was 51 and 112 months in the single and repeat hepatectomy groups, respectively. Since the time of diagnosis, overall 3-, 5-, and 7-year survival rates were 75, 57, and 44 %, respectively, for all 139 patients. Improved overall survival after repeat hepatectomy was related to a time interval between breast cancer diagnosis and first hepatectomy of >2 years, a limited hepatectomy, solitary liver metastasis, positive progesterone receptor status, and chemotherapy following repeat hepatectomy. Patients with single BCLM at first hepatectomy had a 3- and 5-year overall survival rate of 76 and 76 % compared with 51 and 17 % in patients with multiple metastases (p = 0.023). CONCLUSION: In selected patients with BCLM, repeat hepatectomy for liver recurrence combined with systemic treatment provided survival rates comparable to those after first hepatectomy.

Neutrophil and platelet-to-lymphocyte ratio as new predictors of dropout and recurrence after liver transplantation for hepatocellular cancer.

There is increasing evidence that systemic inflammation markers like neutrophil (NLR) and platelet-to-lymphocyte ratios (PLR) may play a role in the outcome of hepatocellular cancer (HCC). Between January 1994 and March 2012, 181 patients with HCC were registered on the transplant waiting list: 35 (19.3%) patients dropped out during the waiting period and 146 (80.7%) patients underwent liver transplantation (LT). The median follow-up of this patient cohort was 4.2 years (IQR: 1.8-8.3). On c-statistics, the last NLR (AUROC = 67.4; P = 0.05) was the best predictor of dropout. The last PLR had an intermediate statistical ability (AUROC = 66.1; P = 0.07) to predict post-LT tumor recurrence. Patients with a NLR value >5.4 had poor 5-year intention-to-treat (ITT) survival rates (48.2 vs. 64.5%; P = 0.02). Conversely, PLR better stratified patients in relation to tumor-free survival (TFS) (80.7 vs. 91.6%; P = 0.02). NLR is a good predictor for the risk of dropout, while PLR is a good predictor for the risk of post-LT recurrence. Use of these markers, which are all available before LT, may represent an additional tool to refine the selection criteria of HCC liver recipients.

The role of ß2-integrins and CD44 in intrahepatic leukocyte sequestration.

BACKGROUND: Intrahepatic leukocyte sequestration is a component of the systemic inflammatory response, and can be triggered by systemic immune dysfunction during sepsis. METHODS: To examine leukocyte sequestration over time during endotoxemia, its influence on liver function, and the role of specific cell adhesion molecules, endotoxemia was induced in mice by intraperitoneal application of lipopolysaccharides. Leukocyte sequestration was measured at different times after induction using fluorescence microscopy. Liver injury was evaluated by measuring liver enzymes and tissue histology. RESULTS: Endotoxin induces a strong leukocyte sequestration in the liver microvasculature. This was associated with an induction of liver injury, as reflected by an increase in enzyme levels and histomorphologic changes. Intrahepatic leukocyte sequestration was reduced in CD44(-/-), but not in intercellular adhesion molecule-1 (ICAM-1)(-/-), lymphocyte function-associated antigen-1(-/-), and macrophage-1(-/-) antigen mice. Leukocyte sequestration dropped in ICAM-1(-/-), lymphocyte function-associated antigen-1(-/-), and macrophage-1(-/-) mice in later stages, but remained stable in wild-type and CD44(-/-) animals. Reduced leukocyte sequestration in CD44(-/-) mice was accompanied by a significant decrease in transferase levels. CONCLUSIONS: Endotoxemia induces stable intra-sinusoidal leukocyte sequestration, which contributes to liver injury. At the initial stage of the endotoxemia, leukocyte sequestration depends on CD44 but is independent of ICAM-1 and ß2-integrins. Intercellular adhesion molecule-1 and ß2-integrins, but not CD44, stabilize leukocyte sequestration during the later stage of endotoxemia. The molecular modulation of intrahepatic leukocyte sequestration may have important therapeutic implications in sepsis, reducing liver injury, and improving immune defense capabilities.

αL ß2 integrin is indispensable for CD8+ T-cell recruitment in experimental pancreatic and hepatocellular cancer.

Recruitment of activated leukocytes from peripheral blood into the tumor tissue is a crucial step of the immune response, which is controlled by the interaction between specific adhesion molecules such as endothelial ICAM-1 and leukocyte ß(2) -integrins. Although attenuated expression of adhesion molecules on tumor endothelium has been proposed to represent a mechanism, which suppresses the intratumoral leukocyte infiltration, the relevance of adhesion molecules for leukocyte recruitment in tumor tissue is poorly understood. The present study is the first investigation of the role of ICAM-1 and ß(2) -integrins in leukocyte recruitment in pancreatic and hepatocellular cancer in vivo, which was studied using knockout mice, intravital time-lapse microscopy and immunohistochemistry. We found that tumor tissue of both pancreatic and hepatocellular cancer was infiltrated with numerous active lymphoid and myeloid leukocytes, although the leukocyte extravasation rate in tumor blood vessels was very low. The knockout of LFA-1 (also known as α(L) ß(2) integrin) strongly suppressed recruitment of CD8(+) T cells whereas no significant differences of leukocyte adhesion and infiltration were found in ICAM-1(-/-) and Mac-1(-/-) mice. Analysis of the interstitial leukocyte migration demonstrated that intratumoral leukocytes used haptokinetic type of migration, however, no significant differences of leukocyte migration between any knockout strains were found. We concluded that leukocyte recruitment in pancreatic and hepatocellular cancer is a slow-going process whose dynamics clearly contrasts to a high-speed leukocyte recruitment during acute inflammation. In contrast to acute inflammatory reaction, only LFA-1 controls recruitment of CD8(+) T-cells in both pancreatic and hepatocellular cancer, whereas ICAM-1 and Mac-1 are dispensable.