Improved recurrence-free survival in patients with HCC with post-transplant plasma exchange.

Total plasma exchange (TPE) can play a role in cancer treatment by eliminating immune checkpoint inhibitors. This study investigated whether TPE improved oncological outcomes in patients with HCC who underwent ABO-incompatible living donor liver transplantation (LT). The study included 152 patients who underwent ABO-incompatible living donor LT for HCC between 2010 and 2021 at Samsung Medical Center. Overall survival was analyzed using the Kaplan-Meier curve, whereas HCC-specific recurrence-free survival (RFS) was analyzed using the cumulative incidence curve after propensity score matching. Cox regression and competing risks subdistribution hazard models were used to identify the risk factors associated with overall survival and HCC-specific RFS, respectively. The propensity score matching resulted in 54 matched pairs, grouped according to whether they underwent postoperative TPE [post-transplant TPE(+)] or not [post-transplant TPE(-)]. The 5-year HCC-specific RFS cumulative incidence was superior in the post-transplant TPE (+) group [12.5% (95% CI: 3.1%-21.9%)] compared with the post-transplant TPE(-) group [38.1% (95% CI: 24.4%-51.8%), p = 0.005]. In subgroup analysis for patients with microvascular invasion and those beyond the Milan criteria, the post-transplant TPE(+) group showed significantly superior HCC-specific survival. The multivariable analysis also showed that postoperative TPE had a protective effect on HCC-specific RFS (HR = 0.26, 95% CI: 0.10-0.64, p = 0.004) and that the more post-transplant TPE was performed, the better RFS was observed (HR = 0.71, 95% CI: 0.55-0.93, p = 0.012). Post-transplant TPE was found to improve RFS after ABO-incompatible living donor LT for HCC, particularly in advanced cases with microvascular invasion and beyond Milan criteria. These findings suggest that TPE may have a potential role in improving oncological outcomes in patients with HCC undergoing LT.

Procarbazine and CCNU Chemotherapy for Recurrent Glioblastoma with MGMT Promoter Methylation.

BACKGROUND: While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation. METHODS: Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m2) on day 1 and procarbazine (60 mg/m2) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2-6). RESULTS: One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5-73), and the PFS rates were 25% and 12.5% at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95% confidence interval: 6.7-12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities. CONCLUSION: The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.

A comparative analysis of clinical outcomes between conversion to mTOR inhibitor and calcineurin inhibitor reduction in managing BK viremia among kidney transplant patients.

BK virus-associated nephropathy (BKVAN) exerts a substantial impact on allograft survival, however, the absence of robust clinical evidence regarding treatment protocols adds to the complexity of managing this condition. This study aimed to compare the two treatment approaches. The study population consisted of patients who underwent kidney transplantation between January 2016 and June 2020 at two tertiary hospitals in Korea. Patients diagnosed with BK viremia were evaluated based on their initial viral load and the treatment methods. The 'Reduction group' involved dose reduction of tacrolimus while the 'Conversion group' included tacrolimus discontinuation and conversion to sirolimus. A total of 175 patients with an initial viral load (iVL) ≥ 3 on the log10 scale were evaluated within two iVL intervals (3-4 and 4-5). In the iVL 4-5 interval, the Reduction group showed potential effectiveness in terms of viral clearance without statistically significant differences. However, within the iVL 3-4 interval, the Reduction group demonstrated superior viral clearance and a lower incidence of biopsy-proven acute rejection (BPAR) than the Conversion group. The renal function over 12 months after BKV diagnosis showed no statistically significant difference. Reducing tacrolimus compared to converting to mTORi would be a more appropriate treatment approach for BK viral clearance in kidney transplantation. Further research is warranted in a large cohort of patients.

Improved graft survival by using three-dimensional printing of intra-abdominal cavity to prevent large-for-size syndrome in liver transplantation.

Backgrounds/Aims: While large-for-size syndrome is uncommon in liver transplantation (LT), it can result in fatal outcome. To prevent such fatality, we manufactured 3D-printed intra-abdominal cavity replicas to provide intuitive understanding of the sizes of the graft and the patient's abdomen in patients with small body size between July 2020 and February 2022. Methods: Clinical outcomes were compared between patients using our 3D model during LT, and patients who underwent LT without 3D model by using 1 : 5 ratio propensity score-matched analysis. Results: After matching, a total of 20 patients using 3D-printed abdominal cavity model and 100 patients of the control group were included in this study. There were no significant differences in 30-day postoperative complication (50.0% vs. 64.0%, p = 0.356) and the incidence of large-for-size syndrome (0% vs. 7%, p = 0.599). Overall survival of the 3D-printed group was similar to that of the control group (p = 0.665), but graft survival was significantly superior in the 3D-printed group, compared to the control group (p = 0.034). Conclusions: Since it showed better graft survival, as well as low cost and short production time, our 3D-printing protocol can be a feasible option for patients with small abdominal cavity to prevent large-for-size syndrome after LT.

Left lobe living donor liver transplantation using the resection and partial liver segment 2-3 transplantation with delayed total hepatectomy (RAPID) procedure in cirrhotic patients: First case report in Korea.

In liver transplantation, the primary concern is to ensure an adequate future liver remnant (FLR) volume for the donor, while selecting a graft of sufficient size for the recipient. The living donor-resection and partial liver segment 2-3 transplantation with delayed total hepatectomy (LD-RAPID) procedure offers a potential solution to expand the donor pool for living donor liver transplantation (LDLT). We report the first case involving a cirrhotic patient with autoimmune hepatitis and hepatocellular carcinoma, who underwent left lobe LDLT using the LD-RAPID procedure. The living liver donor (LLD) underwent a laparoscopic left hepatectomy, including middle hepatic vein. The resection on the recipient side was an extended left hepatectomy, including the middle hepatic vein orifice and caudate lobe. At postoperative day 7, a computed tomography scan showed hypertrophy of the left graft from 320 g to 465 mL (i.e., a 45.3% increase in graft volume body weight ratio from 0.60% to 0.77%). After a 7-day interval, the diseased right lobe was removed in the second stage surgery. The LD-RAPID procedure using left lobe graft allows for the use of a small liver graft or small FLR volume in LLD in LDLT, which expands the donor pool to minimize the risk to LLD by enabling the donation of a smaller liver portion.

Factors associated with operational tolerance after liver transplantation: a single center retrospective study.

Background: Liver transplantation has adverse effects from life-long immunosuppression that limit the improvement of long-term outcomes. Achieving clinical operational tolerance is a major goal in organ transplantation. Methods: This study analyzed liver transplantation patients at a single institution from 1998 to 2020, excluding those who died within 1-year posttransplant. Operational tolerance was defined as normal liver function even after immunosuppressive drugs were discontinued. Propensity score matching was implemented at a 1:2 ratio for the tolerant group (TG) and the nontolerant group (NTG). Results: Out of 2,300 recipients, 99 achieved operational tolerance without rejection. No significant differences in sex or body mass index (BMI) were found between the TG and NTG. There was a significantly higher percentage of children in the TG (24.0%) than in the NTG (10.1%). The NTG had more living donor liver transplants. Among 2,054 adult recipients, no significant differences in age, sex, or BMI were found between the TG and the NTG. However, the rate of living donor liver transplantation was 40.3% (29/75) in the TG and 84.8% in the NTG (P<0.001). The propensity score-matched analysis showed higher chronic renal failure rates and a higher graft recipient weight ratio in the TG, along with shorter warm ischemic times during surgery. After immunosuppressant withdrawal, a significant increase in the ratio of CD4+CD25+ T cells to total CD4+ T cells was observed in the TG. Conclusions: These findings suggest that larger, healthier grafts are more conducive to inducing tolerance, and regulatory T cells are crucial in achieving tolerance.

The Oncologic Implications of Tumor Multiplicity in Intrahepatic Cholangiocarcinoma: Its Prognostic Value Might Be Underestimated.

PURPOSE: In the latest staging system of the American Joint Committee on Cancer for intrahepatic cholangiocarcinoma (IHCCC), solitary tumors with vascular invasion and multiple tumors are grouped together as T2. However, recent studies report that multifocal IHCCC has a worse prognosis than a single lesion. This study aimed to investigate the risk factors for IHCCC and explore the prognostic significance of multiplicity after surgical resection. Materials and Methods: A total of 257 patients underwent surgery for IHCCC from 2010 to 2019 and the clinicopathological data were retrospectively reviewed. Risk factor analysis was performed to identify variables associated with survival after resection. Survival outcomes were compared between patients with solitary and multiple tumors. RESULTS: In multivariable analysis, the presence of preoperative symptoms, tumor size, lymph node ratio, multiplicity, and tumor differentiation were identified as risk factors for survival. Among 82 patients with T2, overall survival was significantly longer in patients with solitary tumors (sT2) than in those with multiple tumors (mT2) (p=0.017). Survival was compared among patients with stage II-sT2, stage II-mT2, and stage III. The stage II-sT2 group showed prolonged survival when compared with stage II-mT2 or stage III. Survivals of stage II-mT2 and stage III patients were not statistically different. CONCLUSION: Tumor multiplicity was an independent risk factor for overall survival of IHCCC after surgical resection. Patients with multiple tumors showed poorer survival than patients with a single tumor. The oncologic significance of multiplicity in IHCCC should be reappraised and reflected in the next staging system update.

Graft-recipient-weight ratio and lowered immunosuppression is important for the success of adult liver retransplantation.

This study analyzed the risk of liver retransplantation and factors related to better outcome. Adult liver transplantations performed during 1996-2021 were included. Comparison between first transplantation and retransplantation were performed. Among retransplantation cases, comparison between whole liver and partial liver graft was performed. Multivariable Cox analyses for analyzing risk factors for primary graft and overall patient survival were performed for the entire cohort as well as the subgroup of patients with retransplantation. A total 2237 transplantations from 2135 adults were included and 103 cases were retransplantation. A total of 44 cases (42.7%) were related to acute graft dysfunction while 59 cases (57.3%) were related to subacute or chronic graft dysfunction. Retransplantation was related poor primary graft (HR 3.439, CI 2.230-5.304, P < 0.001) and overall patient survival. (HR 2.905, CI 2.089-4.040, P < 0.001) Among retransplantations, mean serum FK506 trough level ≥ 9 ng/mL was related to poor primary graft (HR 3.692, CI 1.288-10.587, P = 0.015) and overall patient survival. (HR 2.935, CI 1.195-7.211, P = 0.019) Graft-recipient-weight ratio under 1.0% was related to poor overall patient survival in retransplantations. (HR 3.668, CI 1.150-11.698, P = 0.028). Retransplantation can be complicated with poor graft and patient survival compared to first transplantation, especially when the graft size is relatively small. Lowering the FK506 trough level during the first month can be beneficial for outcome.

Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study).

PURPOSE: Glioblastoma (GBM) has a poor prognosis after standard treatment. Recently, metformin has been shown to have an antitumor effect on glioma cells. We performed the first randomized prospective phase II clinical trial to investigate the clinical efficacy and safety of metformin in patients with recurrent or refractory GBM treated with low-dose temozolomide. METHODS: Included patients were randomly assigned to a control group [placebo plus low-dose temozolomide (50 mg/m2, daily)] or an experimental group [metformin (1000 mg, 1500 mg, and 2000 mg per day during the 1st, 2nd, and 3rd week until disease progression, respectively) plus low-dose temozolomide]. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), disease control rate, overall response rate, health-related quality of life, and safety. RESULTS: Among the 92 patients screened, 81 were randomly assigned to the control group (43 patients) or the experimental group (38 patients). Although the control group showed a longer median PFS, the difference between the two groups was not statistically significant (2.66 versus 2.3 months, p = 0.679). The median OS was 17.22 months (95% CI 12.19-21.68 months) in the experimental group and 7.69 months (95% CI 5.16-22.67 months) in the control group, showing no significant difference by the log-rank test (HR: 0.78; 95% CI 0.39-1.58; p = 0.473). The overall response rate and disease control rate were 9.3% and 46.5% in the control group and 5.3% and 47.4% in the experimental group, respectively. CONCLUSIONS: Although the metformin plus temozolomide regimen was well tolerated, it did not confer a clinical benefit in patients with recurrent or refractory GBM. Trial registration NCT03243851, registered August 4, 2017.

The effect of donor against recipient one-way HLA mismatch on liver transplantation outcomes from a multicenter registry analysis.

Donor against recipient one-way Human leukocyte antigen (HLA) mismatch (D → R one-way HLA MM) seemed strongly associated with graft-versus-host disease (GVHD). The aim of this study is to investigate the relevance of D → R one-way HLA MM in outcome of liver transplantation (LT). We retrospectively analyzed 2670 patients in Korean Organ Transplantation Registry database between April 2014 and December 2020. The patients were categorized into two groups whether D → R one-way HLA MM or not and evaluated the outcomes of LT between the two groups. 18 patients were found to be D → R one-way HLA MM. The incidence of GVHD (0.3% vs. 22.2%, p < 0.001) and mortality rate (11.6% vs. 38.9%, p = 0.003) was much higher in D → R one-way HLA MM group. D → R one-way HLA MM at 3 loci was seemed to be strongly associated with the incidence of GVHD (OR 163.3, p < 0.001), and found to be the strongest risk factor for patient death (HR 12.75, p < 0.001). Patients with D → R one-way HLA MM at 3 loci showed significantly lower overall survival (p < 0.001) but there were no significant differences in rejection-free survival and death-censored graft survival. D → R one-way HLA MM at 3 loci not only affects the overall survival of LT patients but also the incidence of GVHD.

3D Printing Model of Abdominal Cavity of Liver Transplantation Recipient to Prevent Large-for-Size Syndrome.

The application of three-dimensional (3D) printing has been increasing and we invented cost-effective and time-saving 3D printed model of intra-abdominal cavity which was utilized in liver transplantation (LT) to prevent large-for-size syndrome. 3D printings were performed on potential adult recipients with small cavity and pediatric patients scheduled for transplantation during July 2020 - September 2021. Based on the computed tomography of the recipient, the inner surface of the abdominal cavity was outlined. The line was marked with a distance of 1 - 3 cm. Then, the outlined data were reconstructed as a 3D model and printed by a fused deposition modeling type 3D printer with a thickness of 2 mm. Pillars and footings for holding the lines were printed and assembled altogether. During deceased donor organ procurement, the size of the graft was compared to that of the printed model. For living donor LT, preoperatively planned liver graft was printed and was physically placed into the 3D printed abdominal cavity. All the 16 cases with 3D printed abdominal cavity showed appropriate fitting of the donor's liver graft to both the 3D printed model and actual recipient's abdominal cavity with no large-for-size syndrome after LT. Median time for manufacturing the model was 576 min (IQR 434 - 680) and estimated median cost for the filament was US$ 1.6 (IQR 1.2 - 1.7). The 3D printed abdominal cavity model can be manufactured in <10 h and was useful for preventing large-for-size syndrome in small-sized recipients.

The clinical impact of donor against recipient HLA one way mismatch on the occurrence of graft versus host disease in liver transplantation.

Graft versus host disease (GVHD) after liver transplantation (LT) is a rare, fatal disease. This study aimed to evaluate the risk factors of GVHD after LT including the human leukocyte antigen (HLA) donor-recipient relationship after LT. LT recipients, who underwent HLA typing together with donors, were included in the study. The donor against recipient (D → R) one-way mismatch of HLA loci was evaluated. HLA relationships, along with basic characteristics, were analyzed as variable factors of GVHD, graft survival, and patient survival. A total of 994 living donor LT (LDLT) and 393 deceased donor LT (DDLT) patients were included. Nine patients had suffered GVHD, four LDLT with D → R one-way at three loci, one LDLT without D → R one-way at three loci, and four DDLT without D → R one-way at three loci. Four (57.1%) of seven LDLT patients, with D → R one-way mismatch at three loci, developed GVHD. D → R one-way mismatch at three loci was related to high GVHD incidence (HR 787, p < 0.001, multivariate). D → R one-way mismatch at three loci was related to graft failure and patient death (HR 9.90, p = 0.020 and HR 12.8, p < 0.001, respectively, multivariate). Only one GVHD without D → R one-way mismatch at three loci, survived despite receiving multiple modalities including tumor necrosis factor-alpha inhibitors. D → R one-way mismatch at three loci was significantly related to GVHD incidence after LT.

Thermodynamic control over the competitive anchoring of N719 dye on nanocrystalline TiO2 for improving photoinduced electron generation.

TiO(2) electrodes, sensitized with the N719 dye at high immersion temperatures during the sensitization process, were found to have large fractions of weakly bound N719 on the electrode surface, which resulted in dye aggregation and decreased device longevity. These disadvantages were ameliorated using a low-temperature stearic acid (SA)-assisted anchoring method described here. The activation energy (ΔE(NS)(++)) and relative fraction of strongly bound N719 were twice as large as the respective values obtained without the use of SA. Slowing of adsorption, both by thermal means and through SA-mediated processes, effectively controlled the binding mode of N719 on the surface of TiO(2). The resulting sensitized electrodes displayed enhanced device longevity and improved generation of photoinduced electrons.

Dye-sensitized solar cells using polymer electrolytes based on poly(vinylidene fluoride-hexafluoro propylene) nanofibers by electrospinning method.

The dye-sensitized solar cell (DSSC) devices using polymer electrolytes based on electrospun poly(vinylidene fluoride-hexafluoro propylene) (PVDF-HFP) nanofibers were fabricated and investigated the photovoltaic performances. The electrospun PVDF-HFP nanofibers were prepared by various parameters such as; polymer concentrations, applied voltages, and tip to collector distances (TCD) by the electrospinning method. The open circuit voltage (V(OC)), short circuit current (J(SC)), fill factor (FF), and overall power conversion efficiency (eta) of DSSC devices using electro-spun PVDF-HFP nanofibers were 0.7180-0.7420 V, 9.7200-10.8837 mA/cm2, 0.5610-0.6250, and 4.1700-5.0186%, respectively. When 15 wt% of polymer concentration, 14 kV of applied voltage, and 14 cm of TCD is applied to fabricate the PVDF-HFP nanofiber, the electrospun PVDF-HFP nanofiber should be the regular diameter of a nanofiber, the power conversion efficiency of the DSSC device reached 5.0186% as the best result.

Acute simultaneous ruptures of the anterior cruciate ligament and patellar tendon.

Acute simultaneous rupture of the anterior cruciate ligament (ACL) and patellar tendon is a rare injury. We present a case report of a 32-year-old male patient with ruptured ACL and ipsilateral patellar tendon rupture sustained while playing baseball. Surgery was performed on the patellar tendon and the ACL simultaneously. The clinical and radiological outcomes of the treatment were successful. We present this case with a review of the literatures.

Popliteal artery pseudoaneurysm after anterior cruciate ligament re-revision using a rigidfix cross pin.

Popliteal artery injury is a very rare complication of anterior cruciate ligament (ACL) reconstruction. The authors experienced a case of popliteal arterial pseudoaneurysm after re-revision of ACL reconstruction using Rigidfix for femoral tunnel fixation. Pseudoaneurysm was detected in knee magnetic resonance imaging, which caused pain, limit of motion, common peroneal nerve palsy, leg swelling and symptoms similar to compartment syndrome. After excision and re-anastomosis of the popliteal artery using a greater saphenous vein graft, all symptoms were resolved within 3 months except for common peroneal nerve palsy. So we report on this case with a review of the literature.

Facile fabrication of aligned doubly open-ended TiO2 nanotubes, via a selective etching process, for use in front-illuminated dye sensitized solar cells.

A simple selective etching process easily removed a 2nd anodized TiO(2) nanotubes (TNTs) layer from a physically stable 1st anodized TNTs layer to produce noncurling, freestanding, large-area aligned doubly open-ended TNTs. These TNTs were easily transferred to a conducting glass for use in fabricating front-illuminated dye sensitized solar cells.