Tumor immune microenvironment of primary colorectal adenocarcinomas metastasizing to the liver or lungs.

BACKGROUND: Because of the heterogeneity of metastatic colorectal cancer (mCRC), a genome-wide analysis was performed to characterize the tumor immune microenvironment (TIME). METHODS: RNA-seq analysis of 62 primary CRCs without and 63 with systemic metastasis (SM- and SM+ groups) was conducted, and the data were used in a training set after adjustment by propensity score matching. Samples were further subdivided into those with hepatic metastasis (CHM subgroup), pulmonary metastasis (CPM subgroup), or concurrent CHM and CPM (concurrent group). Validation was done by quantitative reverse-transcription polymerase chain reaction using another 40 primary CRC samples. RESULTS: Compared with the CHM or CPM subgroups, the concurrent group showed upregulated in inflammatory or immune processes, cytokine secretion, and myeloid leukocyte migration. Nine candidate genes were selected: SM-specific IDO1, JAM3, and PDE2A; CHM- or CPM-specific BIRC7; CPM-specific HISI1H2BK, and both SM-specific and CHM- or CPM-specific EPHB6, LPL, THBD, and PPBP. In a validation set of primary CRCs, JAM3 and IDO1 (p = 0.044 and p = 0.036, respectively) were confirmed to show significant upregulation and downregulation, respectively, in the SM+ group, whereas HIST1H2BK (p = 0.017) was significantly upregulated in the CPM subgroup. CONCLUSIONS: Our findings indicate that a host-suppressive TIME is established in the primary tumor of mCRC and identify immune-related site-specific markers of mCRC.

Central Sensitization Is a Risk Factor for Persistent Postoperative Pain and Dissatisfaction in Patients Undergoing Revision Total Knee Arthroplasty.

BACKGROUND: The objective of this study is to investigate whether central sensitization (CS) was associated with patient dissatisfaction after revision total knee arthroplasty (TKA). METHODS: Between 2012 and 2016, 68 cases (68 patients) of revision TKA performed by a single surgeon were included in this study with a minimum follow-up of 2 years. Patients were categorized into 2 groups by 40-point preoperative Central Sensitization Inventory (CSI) scores. The control group consisted of 48 patients (48 knees) with CSI scores of less than 40 points, while the CS group consisted of 20 patients (20 knees) with CSI scores of 40 points or more. Clinical outcomes were evaluated using an 11-point visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index scores. Patient satisfaction was evaluated using the satisfaction items of the new Knee Society Scores, where scores ≥20 indicated satisfaction. RESULTS: Higher preoperative pain VAS scores in the CS group were maintained 3, 6, 12, and 24 months postoperatively (all P < .05). The CS group showed significantly worse pain, function subscores, and total scores of the Western Ontario and McMaster Universities Osteoarthritis Index preoperatively and at 2 years postoperatively. Forty-four (91.7%) patients in the control group and 3 (15.0%) patients in the CS group were satisfied with their revision TKAs (P < .001). Multivariate logistic regression analysis demonstrated that the odds of dissatisfaction after revision TKAs were increased 39.081 times (95% confidence interval 6.926-220.504, P < .001) in patients with CSI scores ≥40. Higher VAS intensity 2 years postoperatively also predicted dissatisfaction following revision TKA (odds ratio 1.864, 95% confidence interval 1.086-3.199, P = .024). CONCLUSION: CS is a risk factor for persistent postoperative pain and dissatisfaction in patients undergoing revision TKAs. LEVEL OF EVIDENCE: III.

Comparison of Anterior-Stabilized and Posterior-Stabilized Total Knee Arthroplasty in the Same Patients: A Prospective Randomized Study.

BACKGROUND: A highly conforming, anterior-stabilized (AS) insert is designed to provide anteroposterior (AP) stability of the posterior-stabilized (PS) insert without a post. The purpose of this study was to compare the static and dynamic stability and function of AS and PS total knee arthroplasty (TKA) in the same patients. METHODS: A prospective, randomized controlled trial was performed in 45 patients scheduled to undergo same-day bilateral TKA. One knee was randomly assigned to receive an AS TKA, and the other knee was scheduled for a PS TKA from the same knee system. At 2 years postoperatively, the static AP stability was compared using anterior and posterior drawer stress radiographs at 90° knee flexion. Dynamic AP stability was evaluated using one-leg standing lateral fluoroscopic images throughout the range of motion. Knee function was compared using the Knee Society Score and Western Ontario and McMaster Universities Osteoarthritis Index score. RESULTS: At 2 years postoperatively, there was a significant difference in knee AP laxity at 90° of flexion between the two groups (7.6 ± 3.9 mm in the AS group vs 2.2 ± 2.3 in the PS group, P < .001). However, there were no differences in dynamic AP stability under one-leg standing fluoroscopic lateral images at 30°, 60°, and 90° knee flexion (P = .732, P = .764, and P = .679, respectively). The Knee Society Score and Western Ontario and McMaster Universities Osteoarthritis Index scores were not significantly different between the two groups (P = .641 and P = .582, respectively). CONCLUSION: Despite the fact that the AS TKA group showed significantly more static posterior displacement than the PS TKA group at 90° of knee flexion, both the AS and PS TKA groups showed similar dynamic stability under weight-bearing conditions and knee function at 2 years postoperatively.

Systems Metabolic Engineering Strategies for Non-Natural Microbial Polyester Production.

Plastics, used everyday, are mostly synthetic polymers derived from fossil resources, and their accumulation is becoming a serious concern worldwide. Polyhydroxyalkanoates (PHAs) are naturally produced polyesters synthesized and intracellularly accumulated by many different microorganisms. PHAs are good alternatives to petroleum-based plastics because they possess a wide range of material properties depending on monomer types and molecular weights. In addition, PHAs are biodegradable and can be produced from renewable biomass. Thus, producing PHAs through the development of high-performance engineered microorganisms and efficient bioprocesses gained much interest. In addition, non-natural polyesters comprising 2-hydroxycarboxylic acids as monomers have been produced by fermentation of metabolically engineered bacteria. For example, poly(lactic acid) and poly(lactic acid-co-glycolic acid), which have been chemically synthesized using the corresponding monomers either fermentatively or chemically produced, can be produced by metabolically engineered bacteria by one-step fermentation. Recently, PHAs containing aromatic monomers could be produced by fermentation of metabolically engineered bacteria. Here, metabolic engineering strategies applied in developing microbial strains capable of producing non-natural polyesters in a stepwise manner are reviewed. It is hoped that the detailed strategies described will be helpful for designing metabolic engineering strategies for developing diverse microbial strains capable of producing various polymers that can replace petroleum-derived polymers.

Overexpression of Rosea1 From Snapdragon Enhances Anthocyanin Accumulation and Abiotic Stress Tolerance in Transgenic Tobacco.

The co-expression of Rosea1 (Ros1) and Delila (Del) regulates anthocyanin levels in snapdragon flowers, as well as in tomato, petunia, and tobacco. However, there is little information on how Ros1 expression alone controls anthocyanin regulation and whether it is involved in the mechanism that leads to abiotic stress tolerance. In the present study, tobacco (Nicotiana tabacum 'Xanthi') transgenic plants overexpressing Ros1 (T2-Ros1-1, T2-Ros1-2, T2-Ros1-3, and T2-Ros1-4) promoted accumulation of anthocyanin in leaves and flowers by elevating the transcription of all key genes involved in the biosynthesis of this pigment. This promotion largely occurred through the upregulation of dihydroflavonol 4-reductase (DFR), and anthocyanidin synthase genes in leaves and upregulation of DFR in flowers. Under normal conditions, the transgenic lines and wild type (WT) plants showed well-developed broad leaves and regular roots, whereas a reduction in plant growth was observed under cold and drought stresses. However, the transgenic T2-Ros1 lines were able to tolerate the stresses better than the WT line by inducing reactive oxygen species scavenging activities, and the expression of antioxidant-related and stress-responsive genes. In addition, phylogenetic analysis clustered Ros1 with many transcription factors (TFs) that confer tolerance to different abiotic stresses. Overall, the results obtained here suggest that Ros1 overexpression upregulates anthocyanin biosynthetic, antioxidant-related, and stress-responsive genes thereby enhancing anthocyanin accumulation and abiotic stress tolerance.

The Leukocyte Esterase Strip Test has Practical Value for Diagnosing Periprosthetic Joint Infection After Total Knee Arthroplasty: A Multicenter Study.

BACKGROUND: Leukocyte esterase (LE) was recently reported to be an accurate marker for diagnosing periprosthetic joint infection (PJI) as defined by the Musculoskeletal Infection Society (MSIS) criteria. However, the diagnostic value of the LE test for PJI after total knee arthroplasty (TKA), the reliability of the subjective visual interpretation of the LE test, and the correlation between the LE test results and the current MSIS criteria remain unclear. METHODS: This study prospectively enrolled 60 patients undergoing revision TKA for either PJI or aseptic failure. Serological marker, synovial fluid, and histological analyses were performed in all cases. The PJI group comprised 38 cases that met the MSIS criteria and the other 22 cases formed the aseptic group. All the LE tests were interpreted using both visual judgment and automated colorimetric reader. RESULTS: When "++" results were considered to indicate a positive PJI, the sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy were 84, 100, 100, 79, and 90%, respectively. The visual interpretation agreed with the automated colorimetric reader in 90% of cases (Cronbach α = 0.894). The grade of the LE test was strongly correlated with the synovial white blood cell count (ρ = 0.695) and polymorphonuclear leukocyte percentage (ρ = 0.638) and moderately correlated with the serum C-reactive protein and erythrocyte sedimentation rate. CONCLUSION: The LE test has high diagnostic value for diagnosing PJI after TKA. Subjective visual interpretation of the LE test was reliable and valid for the current battery of PJI diagnostic tests according to the MSIS criteria.

Comparison of Flow-cytometric Antibody Secreting Cell Assay and Mabtech Immunoglobulin ELISpot Assay.

BACKGROUND: The increase of donor-specific antibodies (DSA) after transplantation could be a more important marker than the level of DSA in pre-transplantation sera. The assessment of sensitized cells that can secrete DSA is needed. We developed an assay for antibody-secreting cells (ASCs) measured with the use of flow cytometry and compared it with the Mabtech immunoglobulin (IgG) ELISpot assay. METHODS: Thirteen patients who were awaiting or received organ transplantation and 15 healthy control subjects were included. All subjects were positive for anti-cytomegalovirus (CMV) IgG. Peripheral blood mononuclear cells (PBMCs) were seeded with CpG 2006 (5'-TCGTCGTTTTGTCGTTTTGTCGTT-3'), 500 ng/mL human CD40 ligand, and 50 ng/mL interleukin-21 in complete RPMI media. Eight micrograms of CMV pp28 antigen were added to test wells and compared with nonstimulated PBMCs. After 72 hours, analysis with the use of the human IgG ELISpot kit (Mabtech) and flow cytometry with anti-CD19-PE, CD27-PE-Cy7, CD38-APC, IgG-FITC antibodies was performed. RESULTS: The flow-cytometric ASC assay was moderately correlated with Mabtech IgG ELISpot assay (r = 0.554; P < .001). The ASCs measured by means of flow cytometry were significantly higher in healthy control subjects compared with patients (P < .001). ASCs measured by means of flow cytometry in CMV antigen-stimulated PBMCs were significantly higher compared with nonstimulated PBMCs (P < .001). The IgG-secreting cells measured by means of Mabtech ELISpot assay was not different between healthy control subjects and patients nor between CMV antigen-stimulated and nonstimulated PBMCs. CONCLUSIONS: Flow-cytometric ASC assay can differentiate ASCs for CMV antigen better than Mabtech IgG ELISpot assay. Flow-cytometric ASC assay might be useful for assessing sensitization status in patients awaiting organ transplantation.

Does Patient Perception Differ Following Adductor Canal Block and Femoral Nerve Block in Total Knee Arthroplasty? A Simultaneous Bilateral Randomized Study.

BACKGROUND: Femoral nerve block (FNB) has been used as part of the multimodal analgesia after total knee arthroplasty (TKA), but leads to weakness in the quadriceps muscles. Recently, adductor canal block (ACB) was reported to provide effective pain relief while sparing the strength of the quadriceps. This simultaneous bilateral randomized study investigated whether patients perceived differences between ACB and the FNB after same-day bilateral TKA. METHODS: We performed a prospective simultaneous bilateral randomized study in 50 patients scheduled to undergo same-day bilateral TKA. One knee was randomly assigned to ACB and the other knee was assigned to FNB. All ACB and FNB were performed using ultrasound-guided single-shot procedures. These 2 groups were compared for pain visual analogue scale, straight leg raising ability and knee extension while sitting, and motor grade. At postoperative week 1, the peak torque for the quadriceps muscle was measured in both knees with an isokinetic dynamometer. RESULTS: There were no differences in pain levels between ACB and FNB during the entire study period. During the first 48 h after TKA, more of the knees that received ACB could perform straight leg raising and knee extension with greater quadriceps strength compared with FNB. However, no group differences in quadriceps functional recovery were found after postoperative 48 h and isometric quadriceps strength at postoperative 1 week. CONCLUSION: This simultaneous bilateral randomized study demonstrates that patients did not perceive differences in pain level, but experienced substantial differences in quadriceps strength recovery between knees during the first 48 h (Identifier: NCT02513082).

Resection after preoperative chemotherapy versus synchronous liver resection of colorectal cancer liver metastases: A propensity score matching analysis.

This study aimed to determine the prognostic effects of preoperative chemotherapy for colorectal cancer liver metastasis (CLM).We retrospectively evaluated 2 groups of patients between January 2006 and August 2012. A total of 53 patients who had ≥3 hepatic metastases underwent resection after preoperative chemotherapy (preoperative chemotherapy group), whereas 96 patients who had ≥3 hepatic metastases underwent resection with a curative intent before chemotherapy for CLM (primary resection group). A propensity score (PS) model was used to compare the both groups.The 3-year disease-free survival (DFS) rates were 31.7% and 20.4% in the preoperative chemotherapy and primary resection groups, respectively (log-rank = 0.015). Analyzing 32 PS matched pairs, we found that the DFS rate was significantly higher in the preoperative chemotherapy group than in the primary resection group (3-year DFS rates were 34.2% and 16.8%, respectively [log-rank = 0.019]). Preoperative chemotherapy group patients had better DFSs than primary resection group patients in various multivariate analyses, including crude, multivariable, average treatment effect with inverse probability of treatment weighting model and PS matching.Responses to chemotherapy are as important as achieving complete resection in cases of multiple hepatic metastases. Preoperative chemotherapy may therefore be preferentially considered for patients who experience difficulty undergoing complete resection for multiple hepatic metastases.

Oncologic and Functional Hazards of Obesity Among Patients With Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiation Therapy.

OBJECTIVE: Obesity is a major health concern and risk factor for colorectal cancer that may also impact cancer treatment and outcomes. Rectal cancer response to chemoradiotherapy (CXRT) is associated with long-term survival and sphincter preservation. The purpose of this study was to evaluate the impact of obesity on treatment outcomes after neoadjuvant CXRT for rectal cancer. METHODS: A retrospective cohort study of patients diagnosed (1993 to 2010) with cT3-4 or cN+ (by endorectal ultrasound, computed tomography, or magnetic resonance imaging) rectal carcinoma and treated with CXRT and total mesorectal excision was performed. Patients were classified as obese (body mass index ≥30 kg/m) or nonobese (body mass index <30 kg/m), and by response to CXRT: complete (pCR) or incomplete (pIR). Associations between obesity, tumor response, and sphincter preservation were evaluated using multivariate logistic regression analysis and survival outcomes by Cox regression. RESULTS: A total of 753 patients met criteria and 28.7% (n=216) patients were obese. Obese and nonobese groups did not differ in age, sex, tumor location, grade, or number of examined lymph nodes. However, obesity was associated with a lower rate of pCR (ORmulti=0.60; 95% confidence interval, 0.38-0.94; P=0.04) and among mid to low rectal cancer patients, a lower rate of sphincter preservation (ORmulti=0.67; 95% confidence interval, 0.45-0.99). Among both obese and nonobese patients, CR was associated with more favorable recurrence-free survival than pIR. CONCLUSIONS: Considering the increasing obesity prevalence and its association with CXRT response, oncologic outcomes, and sphincter preservation, further study is needed regarding the impact of obesity on neoadjuvant treatment response. Moreover, obesity should be targeted as a modifiable risk factor for adverse outcomes following multimodality treatment for rectal cancer.

Differences in Patient-Reported Outcomes Between Unicompartmental and Total Knee Arthroplasties: A Propensity Score-Matched Analysis.

BACKGROUND: The purpose of this study was to compare the patient-reported outcomes regarding joint awareness, function, and satisfaction after unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA). METHODS: We identified all patients who underwent a UKA or TKA at our institution between September 2011 and March 2014, with a minimum follow-up of 2 years. Propensity score matching was performed for age, gender, body mass index, operation side, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. One hundred UKAs to 100 TKAs were matched. Each knee was evaluated according to the WOMAC score, Forgotten Joint Score (FJS), High Flexion Knee Score (HFKS) and patient's satisfaction at postoperative 2 years. RESULTS: There was no significant difference in WOMAC score at postoperative 2 years between UKA and TKA groups. However, the FJS of the UKA group was significantly higher than that of the TKA group (67.3 ± 19.8 and 60.6 ± 16.6, respectively; P = .011). The HFKS was also significantly higher in the UKA group compared with the TKA group (34.4 ± 6.4 and 31.3 ± 5.2, respectively; P < .001). Eighty-six percent of all patients who underwent UKA were satisfied compared with 71% of those who underwent TKA (P = .027). CONCLUSION: Patients who underwent UKA had higher FJS, HFKS, and satisfaction rate when compared with patients who underwent TKA, indicating that UKA facilitated less knee awareness and better function and satisfaction than TKA.

Correcting Severe Varus Deformity Using Trial Components During Total Knee Arthroplasty.

BACKGROUND: Extensive medial soft tissue release may be necessary to correct severe varus deformity during total knee arthroplasty (TKA). However, this procedure may result in instability. Here, we describe a novel soft tissue balancing technique, which can minimize medial release in severe varus deformity during TKA. METHODS: Fifty knees (40 patients) with hip-knee-ankle angle of more than 20° of varus were corrected using this technique (group 1). After achieving flexion gap balancing by needle puncturing and spreading of the superficial medial collateral ligament, extension gap balancing was obtained by gradual extension with the trial components in place. After group 1 was set, a one-to-one patient-matched control group who had mild varus deformity was selected by propensity score matching (50 knees, 48 patients, group 2). At postoperative 1 year, mediolateral laxity was compared between the 2 groups using the stress radiographs. Clinical outcomes were also compared using the Knee Society Score and Western Ontario and McMaster Universities Osteoarthritis Index score. RESULTS: There were no differences in mean medial and lateral laxities between groups 1 and 2 at 1 year after the operation (medial laxity: 2.3° ± 1.4° and 2.7° ± 1.3°, respectively, P = .310) (lateral laxity: 3.6° ± 1.7° and 3.2° ± 2.0°, respectively, P = .459). There were no significant differences in postoperative clinical scores and knee alignment. CONCLUSION: Our technique of obtaining extension gap balancing using trial components led to safe and effective balancing by avoiding unnecessary extensive release in severe varus deformity during TKA.

Are Midterm Patient-Reported Outcome Measures Between Rotating-Platform Mobile-Bearing Prosthesis and Medial-Pivot Prosthesis Different? A Minimum of 5-Year Follow-Up Study.

BACKGROUND: Both rotating-platform (RP) mobile-bearing and medial-pivot (MP) fixed-bearing prostheses allow axial femorotibial rotation using a highly conforming polyethylene insert. However, limited comparative data are available between the 2 designs. This study was performed to compare the midterm clinical outcomes and patient-reported outcome measures (PROMs) of RP and MP prostheses. METHODS: We retrospectively reviewed the records of 52 total knee arthroplasties using RP mobile-bearing prosthesis and 49 total knee arthroplasties using MP fixed prosthesis with a minimum follow-up period of 5 years. Clinical and radiological outcomes, failure rates, and PROMs, including the Western Ontario and McMaster Universities Osteoarthritis Index score and satisfaction, were compared. RESULTS: There was no difference in clinical or radiographic outcomes (P > .1 for all comparisons), with the exception of the larger flexion contracture (FC) in the MP group (0.3° in RP vs 2.3° in MP, P < .01). No failure in either group was recorded during the study period. PROMs were comparable (P > .1 in all comparisons), with the exception of higher satisfactions in the RP group while performing light household duties (P < .01) and leisure or recreational activities (P = .014) in patients without FC. CONCLUSION: The midterm clinical results with both the RP mobile-bearing and MP fixed-bearing prostheses were satisfactory. Although both prostheses provided comparable PROMs, patients with an RP prosthesis were more satisfied than those with an MP prosthesis for highly demanding activities that are strongly associated with the presence of postoperative FC.

The Thiol Reductase Activity of YUCCA6 Mediates Delayed Leaf Senescence by Regulating Genes Involved in Auxin Redistribution.

Auxin, a phytohormone that affects almost every aspect of plant growth and development, is biosynthesized from tryptophan via the tryptamine, indole-3-acetamide, indole-3-pyruvic acid, and indole-3-acetaldoxime pathways. YUCCAs (YUCs), flavin monooxygenase enzymes, catalyze the conversion of indole-3-pyruvic acid (IPA) to the auxin (indole acetic acid). Arabidopsis thaliana YUC6 also exhibits thiol-reductase and chaperone activity in vitro; these activities require the highly conserved Cys-85 and are essential for scavenging of toxic reactive oxygen species (ROS) in the drought tolerance response. Here, we examined whether the YUC6 thiol reductase activity also participates in the delay in senescence observed in YUC6-overexpressing (YUC6-OX) plants. YUC6 overexpression delays leaf senescence in natural and dark-induced senescence conditions by reducing the expression of SENESCENCE-ASSOCIATED GENE 12 (SAG12). ROS accumulation normally occurs during senescence, but was not observed in the leaves of YUC6-OX plants; however, ROS accumulation was observed in YUC6-OX(C85S) plants, which overexpress a mutant YUC6 that lacks thiol reductase activity. We also found that YUC6-OX plants, but not YUC6-OX(C85S) plants, show upregulation of three genes encoding NADPH-dependent thioredoxin reductases (NTRA, NTRB, and NTRC), and GAMMA-GLUTAMYLCYSTEINE SYNTHETASE 1 (GSH1), encoding an enzyme involved in redox signaling. We further determined that excess ROS accumulation caused by methyl viologen treatment or decreased glutathione levels caused by buthionine sulfoximine treatment can decrease the levels of auxin efflux proteins such as PIN2-4. The expression of PINs is also reduced in YUC6-OX plants. These findings suggest that the thiol reductase activity of YUC6 may play an essential role in delaying senescence via the activation of genes involved in redox signaling and auxin availability.

Fly DPP10 acts as a channel ancillary subunit and possesses peptidase activity.

Mammalian DPP6 (DPPX) and DPP10 (DPPY) belong to a family of dipeptidyl peptidases, but lack enzyme activity. Instead, these proteins form complexes with voltage-gated K(+) channels in Kv4 family to control their gating and other properties. Here, we find that the fly DPP10 ortholog acts as an ancillary subunit of Kv4 channels and digests peptides. Similarly to mammalian DPP10, the fly ortholog tightly binds to rat Kv4.3 protein. The association causes negative shifts in voltage dependence of channel activation and steady state inactivation. It also results in faster inactivation and recovery from inactivation. In addition to its channel regulatory role, fly DPP10 exhibits significant dipeptidyl peptidase activity with Gly-Pro-MCA (glycyl-L-proline 4-methylcoumaryl-7-amide) as a substrate. Heterologously expressed Flag-tagged fly DPP10 and human DPP4 show similar Km values towards this substrate. However, fly DPP10 exhibits approximately a 6-times-lower relative kcat value normalized with anti-Flag immunoreactivity than human DPP4. These results demonstrate that fly DPP10 is a dual functional protein, controlling Kv4 channel gating and removing bioactive peptides.

Evaluation of Changes in New Calculated Panel Reactive Antibody Adopting HLA-Cw, DR51/52/53, and DQ Antigens in Koreans.

BACKGROUND: Calculated panel reactive antibody (cPRA) (%) is percentage of donors that would be incompatible with the candidate, based on the candidate's unacceptable HLA antigens. cPRA based on antigen frequencies of HLA-A, B, and DR has been used in Korea. We developed new cPRA including HLA-Cw, DR51/52/53, and DQ. Changes in new-cPRA were evaluated. METHODS: We analyzed the differences between cPRA based on HLA-A, -B, and -DR antigens (old-cPRA) from cPRA based on HLA-A, -B, -Cw, -DR, -DR51/52/53, and -DQ antigens (new-cPRA) on 125 waitlisted candidates for renal transplantation in Seoul National University Hospital. cPRA for unacceptable antigens was calculated according to 3 different cut-off values (MFI <1000, 3000, and 10000 for cPRAw, cPRAm, and cPRAs, respectively). RESULTS: For HLA class I, cPRAw and cPRAm were significantly increased in new-cPRA compared to old-cPRA (median 78.3% vs 71.7%, P < .001; 34.0% vs 23.5%, P = .029, respectively). For HLA class II, cPRAw, cPRAm, and cPRAs were significantly increased in new-cPRA compared to old-cPRA (median 86.8% vs 42.6%; 58.0% vs 0.0%; 0.0% vs 0.0%, P < .001 for all). CONCLUSIONS: cPRA (%) including HLA-Cw, -DR51/52/53, and -DQ showed remarkable increase, especially in HLA class II antigens. The meaning of this should be carefully interpreted through further studies considering clinical outcomes.

Outcomes of ultra-low anterior resection combined with or without intersphincteric resection in lower rectal cancer patients.

PURPOSE: We evaluated the current practice of ultra-low anterior resection (uLAR) in patients with lower rectal cancer and compared uLARs using mostly transabdominal approach with or without intersphincteric resection (ISR). METHODS: A total of 624 consecutive lower rectal cancer patients undergoing curative uLAR were prospectively enrolled as ISR+ vs. ISR- groups (329 vs. 295 patients) between 2005 and 2012. The ISR+ group additionally received levator-sphincter reinforcement after distal resection. RESULTS: The circumferential resection margin (CRM) + rate (≤1 mm) was 2.1 % in the two groups. Postoperative ileus occurred more in the ISR- group than in the ISR+ group (p = 0.02). Substantial erectile dysfunction occurred 1.8 times more frequently in the ISR- group than in the ISR+ group (32 vs. 18.1 %; p = 0.01) among male patients at 2 years postoperatively. The urge to defecate volume and maximal tolerance volume, closely correlated with maximal squeezing pressure and/or mean resting pressure, did not differ between patients with and without chemoradiotherapy until 24 months postoperatively. Nevertheless, the urge to defecate volume was lesser in the ISR- group than in the ISR+ group at 24 months postoperatively (p = 0.022). For 301 patients in which >5 years had elapsed postoperatively, the mean 5-year local recurrence rate was 4.3 %, and the 5-year disease-free and overall survival rates were 78.9 and 92 %, respectively, without differences between the two groups. CONCLUSIONS: Compared with uLAR without ISR, the transabdominal ISR with levator-sphincter reinforcement provides a safe resection plane with competent CRM, concurrently reduces substantial complications, and marginally promotes recovery of neorectal function.

Anti-angiotensin type 1 receptor antibodies associated with antibody-mediated rejection in patients without preformed HLA-donor-specific antibody.

INTRODUCTION: Angiotensin II is a peptide hormone involved in the renin-angiotensin system (RAS). Anti-angiotensin receptor 1 (AT1R) antibodies are implicated in stimulating RAS and are suspected to have some adverse impacts on renal transplantation outcome. METHODS: From November 2009 to February 2012, 37 remaining sera from renal transplantation recipients with biopsy-proven antibody-mediated rejection (AMR) (n = 6), acute cellular rejection (ACR) (n = 23), and AMR + ACR (n = 8) without preformed human leukocyte antigeon (HLA) antibodies were tested with anti-AT1R antibody assay. Forty-two control patients without rejection also were analyzed. RESULTS: The frequency of elevated anti-AT1R antibodies was higher in patients with AMR (n = 14) compared to controls (28.6% vs 4.9%, P = .03, OR = 8.0). It was also higher in patients with AMR + ACR (n=8) (37.5% vs 4.9%, P = .03, OR = 12.0). There was no difference in frequencies of elevated anti-AT1R antibody in patients with ACR. CONCLUSION: Anti-AT1R antibodies were suspected to be associated with occurrence of AMR without preformed HLA antibodies in renal transplantation. Further studies in a larger number of patients are needed.

A comparison of the technical and oncologic validity between robot-assisted and conventional open abdominoperineal resection.

PURPOSE: This study was to ascertain whether a robot-assisted (RA) approach to APR might facilitate a cylindrical APR by enabling a deeper pelvic dissection during an abdominal approach, concurrently comparing the feasibility and short-term oncologic outcomes. METHODS: Forty-eight consecutive patients with lower rectal cancer who had undergone curative APR (21 RA vs. 27 open) were prospectively enrolled. The short-term operative outcomes and oncologic feasibility were evaluated and compared. A levator muscle excision was performed concomitantly with the abdominal procedure in the RA group and with the perineal procedure in the open group. RESULTS: No patients in the RA group experienced intraoperative perforation or required conversion to open APR. Overall, a cylindrical APR was performed in 72 % of patients, and subtotal excision of the levator muscle, i.e., either one or both sides of the puborectalis and pubococcygeus muscles, was more likely in the RA group (P = 0.019). A positive CRM was exclusively identified in four open APR patients. The mean number of retrieved lymph nodes was greater in the RA group (20 vs. 16, P = 0.035). There was no difference in perineal morbidity between the two groups (P = 0.445). CONCLUSIONS: The RA approach facilitates an efficient excision in the pelvic region than open APR during the abdominal procedure. The RA approach also demonstrated a trend toward improved oncologic outcomes with equivalent postoperative morbidities than with the open approach.

Completely abdominal intersphincteric resection for lower rectal cancer: feasibility and comparison of robot-assisted and open surgery.

BACKGROUND: Most previous studies of intersphincteric resection (ISR) adopted a two-stage procedure involving abdominal and transanal approaches. We performed completely abdominal ISR via open and a robot-assisted (RA) approaches as treatments for lower rectal cancer (LRC). The RA approach might enable deep dissection and facilitate ISR in patients with restrictive pelvic anatomy. METHODS: A consecutive cohort of 222 LRC patients who underwent completely abdominal ISR (RA ISR, n = 108; open ISR, n = 114) was enrolled prospectively, and their short-term outcomes were evaluated. RESULTS: In a multivariate analysis, ISR was performed more frequently in the RA than in the open group (82.6 vs. 67.9 %, p = 0.008). The number of harvested lymph nodes was >12 in both groups. A positive distal resection margin was not observed in either group, and a positive circumferential resection margin was found in one patient in the RA group. Overall morbidity did not differ between the groups. Moderate to severe sexual dysfunction occurred 2.7-fold more frequently in the open group (p = 0.023) among male patients ≤65 years. Mean Wexner's fecal incontinence scores at postoperative months 6 and 12 were greater in the open group than in the RA group (p < 0.05). CONCLUSIONS: Completely abdominal ISR may be feasible in the treatment of LRC, based on a short-term study. Furthermore, RA ISR had equivalent oncological outcomes and slightly improved functional recovery relative to open ISR.