The Oxidative Drug Combination for Suppressing KRAS G12D Inducible Tumour Growth.

Background: Kirsten rat sarcoma (KRAS) protein is an essential contributor to the development of pancreatic ductal adenocarcinoma (PDAC). KRAS G12D and G12V mutant tumours are significant challenges in cancer therapy due to high resistance to the treatment. Objective: To determine how effective is the ATO/D-VC combination in suppression of PDAC the mouse transgenic model. This study investigated the antitumour effect of a novel combination of arsenic trioxide (ATO) and D-ascorbic acid isomer (D-VC). Such a combination can be used to treat KRAS mutant cancer by inducing catastrophic oxidative stress. Methods: In this study, we examined the effectiveness of ATO and D-VC on xenograft models-AK192 cells transplanted into mice. Previously, it has been shown that a high concentration of Vitamin C (VC) selectively can kill the cells expressing KRAS. Results: The results of this study demonstrated that the combination of VC with a low dose of the oxidizing drug ATO led to the enhancement of the therapeutic effect. These findings suggest that the combined treatment using ATO and D-VC is a promising approach to overcome the limitation of drug selectivity and efficacy.

Liver Peliosis: A Life-Threatening Condition With No Clear Indication for Liver Transplant.

We present a 21-year-old patient, remarkable for huge hepatomegaly with the liver, occupying almost the entire abdominal cavity, and mild portal hypertension due to splenic vein compression. After ultrasonography-guided liver biopsy, performed to establish the diagnosis, the patient had bleeding from the liver. Fortunately, emergency laparotomy was started immediately, and the patient was saved. Macroscopically, the liver appeared to be of purple-red color, flabby to the touch, and able to be easily wrinkled with fingers. When all available clinical data were considered, a diagnosis of liver peliosis was made. The patient was recommended close follow-up at the specialized liver surgery clinic with access to emergency surgical procedures, including liver transplant.

Prognosis of Patients Following Liver Transplant From Deceased and Living Donors.

OBJECTIVES: Liver transplant is the only treatment option for patients with end-stage liver disease. MATERIALS AND METHODS: Liver transplant procedures performed from June 2013 to March 2017 were evaluated. We evaluated the postoperative period in recipients of livers from deceased and living donors. RESULTS: Of 31 liver transplant procedures in 30 recipients, 12 were from deceased and 19 from living donors. The final analysis included 24 liver transplants (11 males, 13 females), with 10 from deceased and 14 from living donors. No deaths or life-threatening and debilitating complications were shown in liver donors. All living-donor liver transplants were performed utilizing the right lobe, the volume of which was calculated using contrast-enhanced computed tomography. Most living-donor liver recipients had viral hepatitis, whereas most deceased-donor liver recipients had autoimmune liver disease. Median age of recipients of deceased donations was 39.3 years (median admission duration of 28.1 days), and median age of recipients of donations from living donors was 45.4 years (median admission duration of 36.4 days). All patients were started on an immunosuppression protocol, which included basiliximab on days 0 and 4, tacrolimus, mycophenolate, and prednisolone. Of 24 recipients, 5 were taking prednisolone 10 mg/day or less at discharge. CONCLUSIONS: Most of our liver transplant procedures were living-donor liver transplants (61.3%). Most patients who received living donations had viral hepatitis, with all cases related to autoimmune liver disease receiving deceased donations. This may be related to the possibility of antiviral therapy controlling all stages of liver disease versus no chance of controlling autoimmune liver disease. Living-donor liver transplant recipients required more time to recover to reach initial liver volume; 20.8% of recipients were discharged with prednisolone of 10 mg/day or less. Our results suggest a need for further development of nonsteroidal immunosuppression strategies to minimize infections and steroid-related adverse effects.

Liver Transplant Outcomes in a Newly Started Program.

OBJECTIVES: Kazakhstan is experiencing a high demand for liver transplants. More than 1000 patients have end-stage liver disease in the country, and liver transplant is the only viable option for their treatment. MATERIALS AND METHODS: Liver transplant patients, treated from February 2013 to December 2014, were included in this retrospective analysis. RESULTS: From February 2013 to December 2014, seven patients received a liver transplant in our center (1 pediatric patient was excluded). Deceased liver recipients' (n = 3) median age was 52 years and median Model for End-Stage Liver Disease score 9. The indication for transplant was uncontrolled portal hypertension due to autoimmune liver disease. Cadaveric donors' median age was 45 years. Recipients' intensive care unit stay was > 5 days, time on inotropic support was > 3 days. Mean cold ischemic time was > 6 hours, and secondary ischemic time was 67 minutes. One patient in the deceased donor transplant group died during postoperative week 1 from hepatic artery thrombosis. Living donor liver recipients' (n = 3) median age was 47 years (43-48 y) and median Model for End-Stage Liver Disease score was 17 (range 14-20). Liver disease was hepatitis virus related (hepatitis C virus in 1 patient and hepatitis B and D virus in 2 patients). Mean cold ischemic time was 0.43 hours, and mean secondary ischemic time was 64 minutes. One recipient in the living donor liver group died early in the postoperative period from hemorrhage. CONCLUSIONS: Our experience was insufficient to adequately assess morbidity and survival rates in patients for whom the longest follow-up was 25 months. However, no episodes of rejection were observed. Survival rates between living and deceased donor recipients were equivalent, although cadaveric-donor liver conditions were imperfect. This analysis demonstrates the necessity for timely diagnosis of surgical complications, which accounted for all mortality incidence in our series.