Outcomes and Cost Comparison of 3 Different Laparoscopic Approach for Living Donor Nephrectomy: A Retrospective, Single-Center, Inverse Probability of Treatment Weighting Analysis of 551 Cases.

BACKGROUND: At our institution, we switched from hand-assisted retroperitoneal laparoscopic donor nephrectomy (HRN) to hand-assisted transperitoneal laparoscopic donor nephrectomy (HTN); we later switched to standard retroperitoneal laparoscopic donor nephrectomy (SRN). This study was performed to evaluate outcomes and hospital costs among the 3 techniques. METHODS: This retrospective, observational, single-center, inverse probability of treatment weighting analysis study compared the outcomes among 551 cases of living donor kidney transplantation between 2014 and 2022. RESULTS: After the inverse probability of treatment weighting analysis, there were 114 cases in the HRN group, 204 cases in the HTN group, and 213 cases in the SRN group. Donor complication rates were lowest in the SRN group but did not differ between the HRN and HTN groups (1.1 vs 4.4 and 5.9%, P = .021). Donors in the SRN group had the lowest serum C-reactive protein concentrations on postoperative day 1 (4.3 vs 10.5 and 7.8 mg/dL, P < .001) and the shortest postoperative stay (4.3 vs 7.4 and 8.4 days, P < .001). Donors in the SRN group had the lowest total cost among the 3 groups (8868 vs 9709 and 10,592 USD, P < .0001). Donors in the SRN group also had the lowest costs in terms of "basic medical fees," "medication and injection fees," "Intraoperative drug and material costs," and "testing fees." Furthermore, the presence of complications was significantly correlated with higher total hospital costs (P < .001). CONCLUSION: SRN appeared to have the least invasive and complication, and a potential cost savings compared with the HRN and HTN.

Functional Characterization of 29 Cytochrome P450 4F2 Variants Identified in a Population of 8380 Japanese Subjects and Assessment of Arachidonic Acid ω-Hydroxylation.

Cytochrome P450 4F2 (CYP4F2) is an enzyme that is involved in the metabolism of arachidonic acid (AA), vitamin E and K, and xenobiotics including drugs. CYP4F2*3 polymorphism (rs2108622; c.1297G>A; p.Val433Met) has been associated with hypertension, ischemic stroke, and variation in the effectiveness of the anticoagulant drug warfarin. In this study, we characterized wild-type CYP4F2 and 28 CYP4F2 variants, including a Val433Met substitution, detected in 8380 Japanese subjects. The CYP4F2 variants were heterologously expressed in 293FT cells to measure the concentrations of CYP4F2 variant holoenzymes using carbon monoxide-reduced difference spectroscopy, where the wild type and 18 holoenzyme variants showed a peak at 450 nm. Kinetic parameters [Vmax , substrate concentration producing half of Vmax (S50 ), and intrinsic clearance (CL int ) as Vmax /S50 ] of AA ω-hydroxylation were determined for the wild type and 21 variants with enzyme activity. Compared with the wild type, two variants showed significantly decreased CL int values for AA ω-hydroxylation. The values for seven variants could not be determined because no enzymatic activity was detected at the highest substrate concentration used. Three-dimensional structural modeling was performed to determine the reason for reduced enzymatic activity of the CYP4F2 variants. Our findings contribute to a better understanding of CYP4F2 variant-associated diseases and possible future therapeutic strategies. SIGNIFICANCE STATEMENT: CYP4F2 is involved in the metabolism of arachidonic acid and vitamin K, and CYP4F2*3 polymorphisms have been associated with hypertension and variation in the effectiveness of the anticoagulant drug warfarin. This study presents a functional analysis of 28 CYP4F2 variants identified in Japanese subjects, demonstrating that seven gene polymorphisms cause loss of CYP4F2 function, and proposes structural changes that lead to altered function.

Comprehensive Assessment of Human Accessory Renal Artery Periarterial Renal Sympathetic Nerve Distribution.

OBJECTIVES: The aim of this study was to understand the anatomy of periarterial nerve distribution in human accessory renal arteries (ARAs). BACKGROUND: Renal denervation is a promising technique for blood pressure control. Despite the high prevalence of ARAs, the anatomic distribution of periarterial nerves around ARAs remains unknown. METHODS: Kidneys with surrounding tissues were collected from human autopsy subjects, and histological evaluation was performed using morphometric software. An ARA was defined as an artery arising from the aorta above or below the dominant renal artery (DRA) or an artery that bifurcated within 20 mm of the takeoff of the DRA from the aorta. The DRA was defined as an artery that perfused >50% of the kidney. RESULTS: A total of 7,287 nerves from 14 ARAs and 9 DRAs were evaluated. The number of nerves was smaller in the ARA than DRA (median: 30 [interquartile range: 17.5 to 48.5] vs. 49 [interquartile range: 36 to 76]; p < 0.0001). In both ARAs and DRAs, the distance from the arterial lumen to nerve was shortest in the distal, followed by the middle and proximal segments. On the basis of the post-mortem angiography, ARAs were divided into large (≥3 mm diameter) and small (<3 mm) groups. The number of nerves was greatest in the DRA, followed by the large and small ARA groups (53 [41 to 97], 38 [25 to 53], and 24.5 [10.5 to 36.3], respectively; p = 0.001). CONCLUSIONS: ARAs showed a smaller number of nerves than DRAs, but these results were dependent on the size of the ARA. Ablation, especially in large ARAs, may allow more complete denervation with the potential to further reduce blood pressure.

The updated five-year overall survival and long-term oxaliplatin-related neurotoxicity assessment of the FACOS study.

PURPOSE: We previously reported the first evidence of oncological benefits from a Japanese phase II trial of oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (the FACOS study). We herein report the long-term survival and persistent oxaliplatin-related peripheral sensory neuropathy (PSN) for patients enrolled in this trial. METHODS: Patients were scheduled to receive the mFOLFOX6 or CAPOX regimen in the adjuvant setting. The five-year overall survival (OS) rate and persistent PSN were evaluated. RESULTS: A total of 130 patients (mFOLFOX6, n = 73; CAPOX, n = 57) were eligible. The 5-year OS rate was 91.4%. No significant difference in the OS rate was observed between regimens (mFOLFOX6, 94.4%; CAPOX, 87.4%; P = 0.25). The incidence of PSN during adjuvant treatment was 55.4% in grade 1 (G1), 30.0% in G2, and 4.6% in G3. No patients showed G3 PSN at 12 months, but G1 or G2 residual PSN after 5 years was observed in 21.8% (G1, 20%; G2, 1.8%). CONCLUSIONS: Updated results from the FACOS study support the benefits of oxaliplatin-based adjuvant chemotherapy in terms of the long-term survival among Japanese patients with stage III colon cancer. However, long-term persistent PSN occurs in about 20% of survivors, counterbalancing the favorable OS.