Clinical Significance of De Novo Malignancy After Liver Transplant: A Single-Center Study

BackgroundSeveral studies have reported that solid organ transplant recipients have a high risk for malignant tumors because the suppressed immune system fails in preventing malignant transformations. De novo malignancy after transplantation is the most common cause of death in the late period after liver transplant (LT). This study investigated the clinical significance of de novo malignancy after LT, and it is the largest study based in Korea to report long-term follow-up results associated with de novo malignancy after LT.MethodsData of 1793 adults who underwent LT in Seoul National University Hospital were retrospectively collected, and medical charts and data from the Ministry of Public Administration and Security were reviewed to examine the causes of death and de novo malignancy status. The Fisher exact test and Kaplan-Meier survival analysis were used to analyze the data.ResultsOf the 1793 recipients, 27 died of de novo malignancies. Of 875 hepatocellular carcinoma (HCC) patients, 12 died, and of 918 non-HCC patients, 15 died. De novo malignancy was the main cause of death at 5 years after LT but was not in the initial 5 years. In Korea the most common cancers that developed after LT were gastric cancer (21.4%) and lymphoma (14.3%). De novo HCC in non-HCC cases was found in 2 patients.ConclusionDe novo malignancy is a key factor affecting long-term survival after LT. Therefore, regular screening and education are important for improving long-term survival and quality of life in these patients after LT.     

ASO Visual Abstract: Association of Obesity with Worse Operative and Oncologic Outcomes Among Patients Undergoing Gastric Cancer Resection

Annals of Surgical Oncology -     

Culture-Expanded Autologous Adipose-Derived Mesenchymal Stem Cell Treatment for Osteonecrosis of the Femoral Head

BackgroudOutcomes of traditional treatment for osteonecrosis of the femoral head (ONFH) are not always satisfactory. Hence, cell-supplementation therapy has been attempted to facilitate necrotic-tissue regeneration. Adipose-derived mesenchymal stem cell (ADMSC) transplantation is potentially advantageous over bone marrow-derived MSC implantation, but its outcomes for ONFH remain unclear. The aim of this study was to determine 2-year radiological and clinical outcomes of culture-expanded autologous ADMSC implantation for ONFH.MethodsEighteen hips with necrotic lesions involving ≥ 30% of the femoral head were included. ADMSCs were harvested by liposuction and culture expanded for 3 passages over 3 weeks. With a 6-mm single drilling, ADMSCs were implanted into the necrotic zone. All patients underwent magnetic resonance imaging (MRI), single-photon emission computed tomography/computed tomography (SPECT/CT) at screening and 6 months, 12 months, and 24 months postoperatively. The primary outcome was the change in the size of necrotic area on MRI. Secondary outcomes were changes in clinical scores and radioisotope uptake on SPECT/CT. Conversion total hip arthroplasty (THA) was defined as the endpoint.ResultsPreoperatively, the necrotic lesion extent was 63.0% (38.4%–96.7%) of the femoral head. The mean Harris hip score was 89.2, the University of California at Los Angeles (UCLA) score was 5.6, and Western Ontario and McMaster Universities Arthritis index (WOMAC) was 79.4. Three patients underwent THA and 1 patient died in an accident. Finally, 11 patients (14 hips) were available for ≥ 2-year follow-up. At the last follow-up, no surgery-related complications occurred, and 14 of 17 hips (82%) were able to perform daily activities without THA requirement. There was no significant decrease in lesion size between any 2 intervals on MRI. However, widening of high signal intensity bands on T2-weighted images inside the necrotic lesion was observed in 9 of 14 hips (64%); 11 of 14 hips (79%) showed increased vascularity on SPECT/CT at 2 years postoperatively. No significant differences were observed between preoperative and 24-month mean Harris hip score (89.2 vs. 88.6), WOMAC (79.4 vs. 75.7), and UCLA score (5.6 vs. 6.2).ConclusionsOur outcomes suggest that culture-expanded ADMSC implantation is a viable option for ONFH treatment without adverse events.     

The beneficial impacts of splanchnic vasoactive agents on hepatic functional recovery in massive hepatectomy porcine model

BackgroundExcessive portal pressure after massive hepatectomy can cause hepatic sinusoidal injury and have deleterious impacts on hepatic functional recovery, contributing to developing post-hepatectomy liver failure. This study aimed to assess the effects of splanchnic vasoactive agents on hepatic functional recovery and regeneration while clarifying the underlying mechanism, using a 70% hepatectomy porcine model.MethodsEighteen pigs undergoing 70% hepatectomy were involved in this study and divided into three groups: control (n=6), terlipressin (n=6), and octreotide (n=6). Terlipressin (0.5 mg) and octreotide (0.2 mg) were administered 3 times a day for each group with the first dose starting just before surgery until the 7th postoperative day, at which time the surviving pigs were sacrificed. During the period, portal pressure, liver weight, biochemical analysis, histological injury score, and molecular markers were evaluated and compared between groups.ResultsThe 7-day survival rates in the octreotide, terlipressin, and control groups were 100%, 83.3%, and 66.7%, respectively. The portal pressures decreased in both terlipressin and octreotide groups than the control group at 30 minutes, 1 hour and 6 hours after hepatectomy. The amount of regeneration measured by liver weight to body weight ratio at the time of sacrifice in the terlipressin group was smaller than that in the control group (117% vs. 129%, P=0.03). Serum aspartate aminotransferase (AST) and total bilirubin levels at 1 and 6 hours after hepatectomy and prothrombin time/international normalized ratio (PT/INR) at 6 hours after hepatectomy were significantly improved in the terlipressin and octreotide groups compared to the control group. Serum endothelin-1 (ET-1) was significantly lower in the terlipressin group than that in the control group 6 hours after hepatectomy (P<0.01). The histological injury score in the control group was significantly higher than that in the terlipressin group on the 7th postoperative day (P<0.01).ConclusionsSplanchnic vasoactive agents, such as terlipressin and octreotide, could effectively decrease portal pressure and attenuate liver injury after massive hepatectomy.     

A case of leukemia-associated arthritis--identification of leukemic cells in synovial fluid by light microscopy

One case of arthritis complicating leukemia is described in which leukemic cells were identified in synovial fluid by light microscopy. Although arthritis is a well-known manifestation of leukemia with an incidence of 13.5%, the pathogenesis often is unclear, and the direct demonstration of leukemic cells in synovial fluid has been very uncommon. A 16 year-old male patient was admitted due to left elbow joint pain and swelling. Synovial fluid examination revealed blast cells and this finding has directed to a final diagnosis of acute lymphoblastic leukemia.     

Effect of protease inhibitors on degradation of recombinant human epidermal growth factor in skin tissue

Recombinant human epidermal growth factor (rhEGF), a polypeptide of 53 amino acid residues, is subject to degradation by numerous enzymes, especially proteases, when it is applied on the skin for the treatment of open wound. Amastatin, aprotinin, bestatin, EDTA, EGTA, gabexate, gentamicin, leupeptin, and TPCK were investigated for the possible protease inhibitors, which may use to protect rhEGF from degradation by the enzymes in the skin. Skin homogenates containing protease inhibitors and rhEGF were incubated at 37°C for 30 minutes. After the reaction was stopped with trifluoroacetic acid, the amount of rhEGF remaining in the sample was determined with an HPLC method. The percentages of rhEGF degraded, at the skin/PBS ratio of 0.25, in the mouse, rat, and human skin homogenate were 85%, 70%, and 46%, respectively. The degree of degradation of rhEGF in the cytosolic fraction was higher than that in the membrane fraction and these enzyme reactions were completed in 30 minutes. Bestatin, EGTA, and TPCK showed significant inhibitory effects on the degradation of rhEGF in the two fractions (p<0.05), while the other protease inhibitors had no significant inhibitory effects or, even resulted in deleterious effects. Therefore, the formulation containing one or several inhibitors among these effective inhibitors would be a promising topical preparation of rhEGF for the treatment of open wound.