Is Continuing Anticoagulation or Antiplatelet Therapy Safe Prior to Kidney Transplantation?

BACKGROUND Patients undergoing kidney transplantation are often placed on anticoagulation or antiplatelet therapy, and their perioperative management is often challenging. This study aimed to determine the safety of continuing anticoagulation or antiplatelet therapy prior to kidney transplantation. The primary outcome was bleeding after transplantation. MATERIAL AND METHODS Patients who underwent kidney transplantation between January 2017 and July 2019 were included and divided into 3 groups: pretransplant anticoagulation with warfarin (WARF; n=23); pretransplant antiplatelet therapy with clopidogrel/aspirin (ASA/CLOP; n=32); and control (CTL; n=197). Patients received kidneys from live or deceased donors. Preoperative INRs and platelet counts were compared to ensure therapeutic anticoagulation in the warfarin group and no significant platelet count variation among groups. The primary outcome was graft exploration for bleeding at 3 and 6 months after transplantation. Secondary outcomes included perioperative transfusion requirements, prolonged length of stay (>7 days), and outcomes at 3 and 6 months after transplantation, including hemodialysis and rejection rates and creatinine levels. RESULTS Pretransplant INR was significantly greater in the warfarin group (CTL 1.1, WARF 2.2, ASA/CLOP 1.2; P<0.01). There were no differences in pretransplant platelet count (CTL 202×10³, WARF 186×10³, ASA/CLOP 194×10³; P=0.31), graft exploration for bleeding at 3 (CTL 3%, WARF 0%, ASA/CLOP 3%; P=0.69) and 6 months after transplantation (CTL 1%, WARF 4%, ASA/CLOP 0%; P=0.12), or perioperative blood transfusion requirements (CTL 4%, WARF 4%, ASA/CLOP 14%; P=0.13). Prolonged length of stay was similar (CTL 24%, WARF 26%, ASA/CLOP 44%; P=0.08). There were no significant differences among groups at 3 months in dialysis (CTL 2%, WARF 0%, ASA/CLOP 0%; P=0.71), creatinine (CTL 1.5 mg/dL, WARF 1.7 mg/dL, ASA/CLOP 1.7; P=0.13), or rejection (CTL 6%, WARF 0%, ASA/CLOP 0%) or at 6 months in dialysis (CTL 3%, WARF 0%, ASA/CLOP 0%; P=0.49), creatinine (CTL 1.5 mg/dL, WARF 1.7 mg/dL, ASA/CLOP 1.5; P=0.49), or rejection (CTL 1%, WARF 0%, ASA/CLOP 3%). CONCLUSIONS Continuing anticoagulation or antiplatelet was safe in not increasing bleeding complications or perioperative transfusion requirements. Outcomes were similar at 3 and 6 months among groups. This strategy avoids exposing patients to risk of thrombosis if treatment is held and simplifies proceeding to transplantation.

Stereotactic Body Radiation Therapy: A New Strategy for Loco-Regional Treatment for Hepatocellular Carcinoma While Awaiting Liver Transplantation.

BACKGROUND: Trans-arterial chemoembolization and radiofrequency ablation are commonly used for control of hepatocellular carcinoma (HCC) on liver transplant (LTx) waiting list. Stereotactic body radiation therapy (SBRT) was introduced to our institution for HCC as a bridging or downsizing therapy to LTx. PATIENTS AND METHODS: Twenty-five HCC lesions in 22 patients were treated with SBRT while waiting for LTx from January 2010 to December 2015. Nineteen of these patients received deceased donor LTx. SBRT was defined as 40-50 Gy delivered in 4-6 fractions. Pre- and post-liver transplant outcome were analyzed in addition to the dropout rate and tumor response to SBRT. RESULTS: Median size of original tumors was 3.2 cm (2.0-8.9), and median size of tumor after SBRT was significantly smaller at 0.9 cm (0-3.2) in the explanted livers (p < 0.01). The dropout rate was 9%, and they were only downsized patients outside of Milan criteria. Liver disease did not progress between pre- and post-SBRT except one patient. Twenty-eight percent of treated HCCs showed complete pathologic response, and 22% had extensive partial response with some residual tumor. No HCC recurrence was experienced after LTx. CONCLUSION: SBRT is indicated to be safe, effective treatment for HCC on LTx waiting list, and it leads to satisfactory post-liver transplant outcomes.

Stereotactic body radiotherapy used as a bridge to liver transplant in patients with hepatocellular carcinoma and Child-Pugh score ≥8 cirrhosis.

INTRODUCTION: To report on SBRT as a bridge to OLT for patients with HCC and Child-Pugh ≥8 cirrhosis. METHODS: Retrospective review of 15 patients, treated from 2010-2017. Three patients excluded secondary to delisting from prohibitive substance. Twelve patients (17 lesions) included for final analysis. Hepatic SPECT functional treatment planning utilized. RESULTS: The median age of 60 years with a median CP 9 and MELD 14. The median SBRT dose was 40 Gy in 5 fractions, and median tumor size was 2.3cm (1.2-5.3cm). Median follow-up and survival was 40-months and 46-months, respectively. One patient succumbed to renal/hepatic failure before OLT. Radiographic response was 80%. pCR at explant was 46%. No grade ≥ 3 acute toxicities. Median time to progression of CP ≥ 2 was 9.7-months and MELD progression was not met before OLT. CONCLUSION: SBRT with functional treatment planning can be used safely as a bridge to OLT in select patients with CP ≥8 cirrhosis.

Intercostal and Glissonian Pedicle Approach in Laparoscopic Liver Resection for Bilobar Tumors.

BACKGROUND: Bilobar liver metastasis is challenging for laparoscopic liver resection. Especially, subphrenic liver tumors in S7 or S8 are technically difficult to be resected out because the space is limited and the angle of instruments to lesions cannot be perpendicular.1,2 Major liver lobectomy is also challenging for laparoscopic liver resection. Glissonian pedicle approach has benefit that any variation of vascular and bile duct elements does not need to be considered in the hepatoduodenal ligament under the hilar plate. Glissonian pedicle approach is simpler and faster than individual dissection of hepatoduodenal ligament. METHODS: This video illustrates a hand-assisted laparoscopic left lobectomy and partial liver resection of S8 in a 48-year-old male with metastatic colorectal carcinoma to the liver. He received 6 cycle of FOLFOX as neoadjuvant chemotherapy. The patient was positioned in semi left lateral decubitus so that a lesion in S8 was easily approached. A tumor in S8 was approached after right lobe mobilization. The liver resection was performed by a harmonic scalpel. A 5-mm balloon port was placed in 6th intercostal space to approach the lesion perpendicular. For left hepatectomy, glissonian pedicle approach was applied to control vascular inflow. Dissections was performed at bifurcation on the right glissonian and left glissonian pedicles. Dissection direction to the left side was above hepatogastric ligament. The tunnel was created including all left glissonian sheath, and a vessel loop was taped. An endovascular stapler was inserted and fired with dividing the left glissonian pedicle as en bloc. Hepatic parenchymal dissection was performed by the harmonic scalpel. Left hepatic vein was divided using an endoscopic vascular stapler. The specimens were removed from a hand-port. RESULTS: The operative time was 290 min. Blood loss was 250 ml, and no blood transfusion was required. He resumed a regular diet the next day and was discharged on postoperative day 4. CONCLUSIONS: Intercostal approach is useful for subphrenic liver tumors, and glissonian pedicle approach is also useful for major lobectomy for laparoscopic liver resection.

Health literacy assessment and patient satisfaction in surgical practice.

BACKGROUND: Individuals with limited health literacy have barriers to patient-physician communication. Problems in communication are known to contribute to malpractice litigation. Concern exists, however, about the feasibility and patient acceptance of a health literacy assessment. This study was performed to determine the feasibility of health literacy assessment in surgical practice and its effect on patient satisfaction. STUDY DESIGN: Every patient seen in a Breast Surgery Clinic during a 2-year period was asked to undergo a health literacy assessment with the Newest Vital Sign (NVS) as part of the routine history and physical examination. During the year before routine NVS assessments and during the 2-year study period, all patients were asked to rate their "overall satisfaction with clinic visit" on a 5-point scale. RESULTS: A total of 2,026 of 2,097 patients (96.6%) seen during the study were eligible for the health literacy assessment. Of those, no patients refused assessment, and only one patient was missed. Therefore, 2,025 of 2,026 eligible patients (99.9%) underwent the assessment. The average time for NVS assessment was 2:02 minutes. Only 19% of patients had adequate health literacy. Patient satisfaction ratings were slightly greater during the first year of the health literacy assessment (3.8 vs 3.7, P = .049) compared with the year prior to health literacy assessment and greater during the second year of health literacy assessment (4.1 vs 3.7, P < .0001). CONCLUSION: Routine health literacy assessment is feasible in surgical practice and results in no decrease in patient satisfaction. In fact, satisfaction was greater during the years when health literacy assessments were performed.

Decreased arginine bioavailability and increased serum arginase activity in asthma.

Recent studies suggest that a nitric oxide (NO) deficiency and elevated arginase activity may play a role in the pathogenesis of asthma. Although much attention has been directed toward measurements of exhaled NO in asthma, no studies to date have evaluated levels of plasma arginase or arginine, the substrate for NO production, in patients with asthma. This study, therefore, measured amino acid levels, arginase activity, and nitric oxide metabolites in the blood of patients with asthma, as well as NO in exhaled breath. Although levels of virtually all amino acids were reduced, patients with asthma exhibited a striking reduction in plasma arginine levels compared with normal control subjects without asthma (45 +/- 22 vs. 94 +/- 29 microM, p < 0.0001), and serum arginase activity was elevated (1.6 +/- 0.8 vs. 0.5 +/- 0.3 micromol/ml/hour, asthma vs. control, p < 0.0001). High arginase activity in patients with asthma may contribute to low circulating arginine levels, thereby limiting arginine bioavailability and creating a NO deficiency that induces hyperreactive airways. Addressing the alterations in arginine metabolism may result in new strategies for treatment of asthma.

Hydroxyurea and arginine therapy: impact on nitric oxide production in sickle cell disease.

PURPOSE: Recent data suggest that hydroxyurea (HU) increases the production of nitric oxide (NO), a potent vasodilator. NO is normally metabolized from l-Arginine (Arg). However, in vitro and animal experiments suggest that HU is the NO donor itself. In contrast, a recent study indicates that nitric oxide synthase (NOS) may play a role. Since adults with sickle cell disease (SCD) are Arg-deficient, Arg availability may limit the ability of HU to maximally impact NO production if an NOS mechanism is involved. The authors have previously shown that Arg supplementation alone induces a paradoxical decrease in NO metabolite (NO(x)) production. METHODS: The authors studied the effects of HU and Arg supplementation on NO(x) production. HU alone or HU + Arg was administered to patients with SCD at steady state, and sequential levels of Arg, serum NO(x) and exhaled NO were followed over 4 hours. RESULTS: After HU + Arg, all patients demonstrated a significant increase in serum NO(x) production within 2 hours. When the same patients were treated with HU alone (5.1 +/- 2 micromol/L), a mixed response occurred. NO(x) levels increased in four patients and decreased in one patient (-23.3 micromol/L). CONCLUSIONS: While Arg alone does not increase serum NO(x) production in SCD patients at steady state, it does when given together with HU. Hence, co-administration of Arg with HU may augment the NO(x) response in SCD and improve utilization of Arg in patients at steady state.

Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease?

Pulmonary hypertension is a life-threatening complication of sickle cell disease. L-Arginine is the nitrogen donor for synthesis of nitric oxide, a potent vasodilator that is deficient during times of sickle cell crisis. This deficiency may play a role in pulmonary hypertension. The enzyme arginase hydrolyzes arginine to ornithine and urea, and thus, it may compete with nitric oxide synthase, leading to decreased nitric oxide production. Nitric oxide therapy by inhalation has improved pulmonary hypertension associated with acute chest syndrome in sickle cell disease, and several studies demonstrate therapeutic benefits of arginine therapy for primary and secondary pulmonary hypertension. We sought to determine the effects of arginine therapy on pulmonary hypertension in patients with sickle cell disease. Arginase activity was also determined. Oral arginine produced a 15.2% mean reduction in estimated pulmonary artery systolic pressure (63.9 +/- 13 to 54.2 +/- 12 mm Hg, p = 0.002) after 5 days of therapy in 10 patients. Arginase activity was elevated almost twofold (p = 0.07) in patients with pulmonary hypertension and may limit arginine bioavailability. With limited treatment options and a high mortality rate for patients with sickle cell disease who develop pulmonary hypertension, arginine is a promising new therapy that warrants further investigation.