ABSTRACT
Escherichia coli Nissle 1917 (EcN) is one of the most widely used probiotics to treat gastrointestinal diseases. Recently, many studies have engineered EcN to release therapeutic proteins to treat specific diseases. However, because EcN exhibits intestinal metabolic activities, it is difficult to predict outcomes after administration. In silico and fermentation profiles revealed mucin metabolism of EcN. Multiomics revealed that fucose metabolism contributes to the intestinal colonization of EcN by enhancing the synthesis of flagella and nutrient uptake. The multiomics results also revealed that excessive intracellular trehalose synthesis in EcN, which is responsible for galactose metabolism, acts as a metabolic bottleneck, adversely affecting growth. To improve the ability of EcN to metabolize galactose, otsAB genes for trehalose synthesis were deleted, resulting in the ΔotsAB strain; the ΔotsAB strain exhibited a 1.47-fold increase in the growth rate and a 1.37-fold increase in the substrate consumption rate relative to wild-type EcN.
Subject(s)
Escherichia coli , Intestines , Metabolic Engineering , Escherichia coli/genetics , Escherichia coli/metabolism , Intestines/microbiology , Escherichia coli Proteins/genetics , Escherichia coli Proteins/metabolism , Probiotics/metabolism , Galactose/metabolism , Fermentation , Trehalose/metabolism , Humans , Fucose/metabolismABSTRACT
PURPOSE: As introduced, multimodal pain management bundle for ileostomy reversal may be considered to reduce postoperative pain and hospital stay. The aim of this study was to evaluate clinical efficacy of perioperative multimodal pain bundle for ileostomy. METHODS: Medical records of patients who underwent ileostomy reversal after rectal cancer surgery from April 2017 to March 2020 were analyzed. Sixty-seven patients received multimodal pain bundle protocol with ileostomy reversal (group A) and 41 patients underwent closure of ileostomy with conventional pain management (group B). RESULTS: Baseline characteristics, including age, sex, body mass index, American Society of Anesthesiologists classification, diabetes mellitus, and smoking history, were not significantly different between the groups. The pain score on postoperative day 1 was significant lower in group A (visual analog scale, 2.6 ± 1.3 vs. 3.2 ± 1.2; P = 0.013). Overall consumption of opioid in group A was significant less than group B (9.7 ± 9.5 vs. 21.2 ± 8.8, P < 0.001). Hospital stay was significantly shorter in group A (2.3 ± 1.5 days vs. 4.1 ± 1.5 days, P < 0.001). There were no significant differences between the groups in postoperative complication rate. CONCLUSION: Multimodal pain protocol for ileostomy reversal could reduce postoperative pain, usage of opioid and hospital stay compared to conventional pain management.
ABSTRACT
Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.
ABSTRACT
BACKGROUND: High-risk stage III colon cancer has a considerably poorer prognosis than stage II and low-risk stage III colon cancers. Nevertheless, most guidelines recommend similar adjuvant treatment approaches for all these stages despite the dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis with intensive adjuvant treatment. Given the the proven efficacy of triplet chemotherapy in metastatic colorectal cancer treatment, the goal of this study is to evaluate the oncologic efficacy and safety of mFOLFIRINOX in comparison to those of the current standard of care, mFOLFOX 6, as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer after radical resection. METHODS: This multicenter, randomized (1:1), open-label, phase II trial will assess and compare the effectiveness and toxicity of mFOLFIRINOX and mFOLFOX 6 in patients with high-risk stage III colon cancer after radical resection. The goal of the trial is to enroll 312 eligible patients, from 11 institutes, aged between 20 and 70 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or between 70 and 75 with an ECOG performance status of 0. Patients will be randomized into two arms - Arm A, the experimental arm, and Arm B, the reference arm - and will receive 12 cycles of mFOLFIRINOX and mFOLFOX 6 every 2 weeks, respectively. The primary endpoint of this study is the 3-year disease-free survival, and secondary endpoints include the 3-year overall survival and treatment toxicity. DISCUSSION: The Frost trial would help determine the oncologic efficacy and safety of adjuvant triplet chemotherapy for high-risk stage III colon cancers and ultimately improve prognoses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05179889, registered on 17 December 2021.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Colonic Neoplasms , Adult , Aged , Humans , Middle Aged , Young Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemotherapy, Adjuvant , Clinical Trials, Phase II as Topic , Colonic Neoplasms/pathology , Disease-Free Survival , Multicenter Studies as Topic , Progression-Free Survival , Randomized Controlled Trials as Topic , Fluorouracil/therapeutic useABSTRACT
Mushroom laccases play a crucial role in lignin depolymerization, one of the most critical challenges in lignin utilization. Importantly, laccases can utilize a wide range of substrates, such as toxicants and antibiotics. This study isolated a novel laccase, named HeLac4c, from endophytic white-rot fungi Hericium erinaceus mushrooms. The cDNAs for this enzyme were 1569 bp in length and encoded a protein of 523 amino acids, including a 20 amino-acid signal peptide. Active extracellular production of glycosylated laccases from Saccharomyces cerevisiae was successfully achieved by selecting an optimal translational fusion partner. We observed that 5 and 10 mM Ca2+, Zn2+, and K+ increased laccase activity, whereas 5 mM Fe2+ and Al3+ inhibited laccase activity. The laccase activity was inhibited by the addition of low concentrations of sodium azide and L-cysteine. The optimal pH for the 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt was 4.4. Guaiacylglycerol-ß-guaiacyl ether, a lignin model compound, was polymerized by the HeLac4c enzyme. These results indicated that HeLac4c is a novel oxidase biocatalyst for the bioconversion of lignin into value-added products for environmental biotechnological applications.
Subject(s)
Hericium , Laccase , Lignin , Saccharomyces cerevisiae , Laccase/metabolism , Laccase/genetics , Laccase/chemistry , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/enzymology , Saccharomyces cerevisiae/metabolism , Hericium/metabolism , Hericium/genetics , Hericium/enzymology , Hydrogen-Ion Concentration , Lignin/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Fungal Proteins/chemistry , Amino Acid Sequence , Cloning, Molecular , Sodium Azide/pharmacology , Agaricales/enzymology , Agaricales/genetics , GlycosylationABSTRACT
Pseudomonas putida is a promising strain for lignin valorisation. However, there is a dearth of stable and efficient systems for secreting enzymes to enhance the process. Therefore, a novel secretion system for recombinant lignin-depolymerising peroxidase was developed. By adopting a flagellar type III secretion system, P. putida KT-M2, a secretory host strain, was constructed and an optimal secretion signal fusion partner was identified. Application of the dye-decolourising peroxidase of P. putida to this system resulted in efficient oxidation activity of the cell-free supernatant against various chemicals, including lignin model compounds. This peroxidase-secreting strain was examined to confirm its lignin utilisation capability, resulting in the efficient assimilation of various lignin substrates with 2.6-fold higher growth than that of the wild-type strain after 72 h of cultivation. Finally, this novel system will lead efficient bacterial lignin breakdown and utilization through enzyme secretion, paving the way for sustainable lignin-consolidated bioprocessing.
Subject(s)
Lignin , Pseudomonas putida , Lignin/chemistry , Pseudomonas putida/genetics , Peroxidase/metabolism , Peroxidases/genetics , Peroxidases/metabolism , Oxidoreductases/metabolism , Coloring Agents/metabolismABSTRACT
Kex2 protease (Kex2p) is a membrane-bound serine protease responsible for the proteolytic maturation of various secretory proteins by cleaving after dibasic residues in the late Golgi network. In this study, we present an application of Kex2p as an alternative endoprotease for the in vitro processing of recombinant fusion proteins produced by the yeast Saccharomyces cerevisiae. The proteins were expressed with a fusion partner connected by a Kex2p cleavage sequence for enhanced expression and easy purification. To avoid in vivo processing of fusion proteins by Kex2p during secretion and to guarantee efficient removal of the fusion partners by in vitro Kex2p processing, P1', P2', P4, and P3 sites of Kex2p cleavage sites were elaborately manipulated. The general use of Kex2p in recombinant protein production was confirmed using several recombinant proteins.
Subject(s)
Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae , Peptide Hydrolases/metabolism , Proprotein Convertases/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism , Serine Endopeptidases/metabolism , Subtilisins/chemistryABSTRACT
PURPOSE: The Da Vinci SP robot system was recently introduced, but its safety and feasibility for rectal cancer compared with the currently used robot system have not been reported. METHODS: This was a single-centre retrospective study. Data from patients who underwent abdominal total mesorectal excision (TME) from October 2015 to October 2022 were analysed. After propensity score matching, the short-term outcomes were compared. RESULTS: A total of 56 patient data were analysed. Intersphincteric resection was more common in the SP group (7 cases (25%) vs. 0 case (0%), p = 0.001). The operation time was significantly shorter in SP (184 vs. 227.5 min, p < 0.0001), but the docking time was similar. The postoperative complications were similar. There were no differences in the postoperative pain score and length of hospital stay. CONCLUSION: The SP robotic system for abdominal TME has acceptable short-term and is safe and technically feasible.
ABSTRACT
PURPOSE: The Enhanced Recovery After Surgery protocol for colorectal surgery recommends early urinary catheter (UC) removal after surgery. However, the optimal timing remains controversial. We aimed to evaluate the safety of immediate UC removal and risk factors of postoperative urinary retention (POUR) after colorectal cancer surgery. METHODS: From November 2019 and April 2022, patients who underwent elective colorectal cancer surgery at Seoul St. Mary's hospital were collected retrospectively. A UC was inserted in the operating room after general anesthesia and removed in the operating room immediately after surgery. The primary outcome was the occurrence of POUR following immediate UC removal after surgery, and the secondary outcomes were the identification of POUR-related risk factors and postoperative complications. RESULTS: Among 737 patients, 81 (10%) had POUR immediately after UC removal. No patient had urinary tract infection. The incidence of POUR was significantly higher in male and in those with a history of urinary disease. However, there were no significant differences in tumor location, surgical procedure, or approach. The mean operative time was significantly longer in the POUR group. Postoperative morbidity and mortality rates did not differ significantly between two groups. Multivariate analysis showed that risk factors for POUR were male, a history of urinary disease, and intrathecal morphine injection. CONCLUSIONS: Immediate removal of UC immediately after colorectal surgery is safe and feasible in the trend of ERAS. Male, a history of benign prostatic hyperplasia, and intrathecal morphine injection were risk factors for POUR.
Subject(s)
Colorectal Neoplasms , Colorectal Surgery , Enhanced Recovery After Surgery , Urinary Retention , Humans , Male , Female , Urinary Catheters/adverse effects , Retrospective Studies , Colorectal Surgery/adverse effects , Urinary Retention/etiology , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Colorectal Neoplasms/surgery , Colorectal Neoplasms/complications , Morphine Derivatives , Risk FactorsABSTRACT
Lateral pelvic lymph node dissection (LPND) is a technically demanding procedure. This study aimed to compare the short-term outcomes of laparoscopic and robotic LPNDs. This multi-institutional retrospective study included 108 consecutive patients who underwent laparoscopic or robotic total mesorectal excision with LPND for locally advanced rectal cancer. There were 74 patients in the laparoscopic and 34 in the robotic groups. The median operation time was longer in the robotic group than in the laparoscopic group (353 vs. 275 min, p < 0.001). No patients underwent conversion to open surgery in either group. Pathological LPN metastases were observed in 24 and 8 patients in the laparoscopic and robotic groups, respectively (p = 0.347). Although the number of harvested mesorectal lymph nodes was similar (15.5 vs. 15.0, p = 0.968), the number of harvested LPNs was higher in the robotic than in the laparoscopic group (7.0 vs. 5.0, p = 0.004). Postoperative complications and length of hospital stay were similar (robotic vs. laparoscopic, 35.3% and 7 days vs. 37.8% and 7 days, respectively). Both laparoscopic and robotic LPND are safe and feasible for locally advanced rectal cancers, but robotic LPND showed more harvested lateral lymph node than laparoscopic LPND.
ABSTRACT
BACKGROUND: Lateral pelvic lymph node dissection improves oncological outcomes in rectal cancer patients with suspected lateral pelvic lymph node metastasis. However, the indication for this procedure remains unclear. OBJECTIVE: This study aimed to identify the predictive factors for lateral lymph node metastasis and the indications for lateral pelvic lymph node dissection. DESIGN: A multi-institutional retrospective study. SETTINGS: This study was conducted at 3 university hospitals. PATIENTS: This study involved 105 patients with locally advanced mid/low rectal cancer and clinically suspected lateral pelvic lymph node metastasis who underwent total mesorectal excision with lateral pelvic lymph node dissection between 2015 and 2020. MAIN OUTCOME MEASURES: Indications were set using lateral pelvic lymph node metastasis-associated preoperative factors. RESULTS: Among 105 patients, 36 (34.3%) had pathologically confirmed lateral pelvic lymph node metastasis and 77 (73.3%) underwent preoperative chemoradiation. Tumors located within 5 cm distance from the anal verge ( p = 0.02) and initial node size ≥ 6 mm ( p = 0.001) were significant predictors of lateral pelvic lymph node metastasis. The sensitivity was 100% (36/36) with a cutoff of 6 mm for the initial node size and 94.4% (34/36) with a cutoff of 8 mm for the initial node size. When using initial node size cutoffs of 8 mm for anal verge-to-tumor distance of >5 cm and 6 mm for anal verge-to-tumor distance of ≤5 cm, the sensitivity of lateral pelvic lymph node metastasis was found to be 100%. LIMITATIONS: The retrospective design and small sample size were the limitations of this study. CONCLUSION: Initial node size and tumor height were significant predictors of lateral pelvic lymph node metastasis. This study proposed that an initial node size of ≥8 mm with an anal verge-to-tumor distance of >5 cm and ≥6 mm with an anal verge-to-tumor distance of ≤5 cm are optimal indications for lateral pelvic lymph node dissection in rectal cancer. See Video Abstract at http://links.lww.com/DCR/C101 . EL TAMAO DEL GANGLIO LINFTICO LATERAL Y LA DISTANCIA DEL TUMOR DESDE EL BORDE ANAL PREDICEN CON PRECISIN LOS GANGLIOS LINFTICOS PLVICOS LATERALES POSITIVOS EN EL CNCER DE RECTO UN ESTUDIO DE COHORTE RETROSPECTIVO MULTIINSTITUCIONAL: ANTECEDENTES:La disección de los ganglios linfáticos pélvicos laterales mejora los resultados oncológicos en pacientes con cáncer de recto con sospecha de metástasis en los ganglios linfáticos pélvicos laterales. Sin embargo, la indicación de este procedimiento sigue sin estar clara.OBJETIVO:Nuestro objetivo fue identificar los factores predictivos de la metástasis de los ganglios linfáticos laterales y las indicaciones para la disección de los ganglios linfáticos pélvicos laterales.DISEÑO:Estudio retrospectivo multiinstitucional.AJUSTES:Este estudio se realizó en tres hospitales universitarios.PACIENTES:Este estudio involucró a 105 pacientes con cáncer de recto medio/bajo localmente avanzado y sospecha clínica de metástasis en los ganglios linfáticos pélvicos laterales que se sometieron a una escisión mesorrectal total con disección de los ganglios linfáticos pélvicos laterales entre 2015 y 2020.PRINCIPALES MEDIDAS DE RESULTADO:Las indicaciones se establecieron utilizando los factores preoperatorios asociados con la metástasis de los ganglios linfáticos pélvicos laterales.RESULTADOS:Entre 105 pacientes, 36 (34,3%) tenían metástasis en los ganglios linfáticos pélvicos laterales confirmada patológicamente y 77 (73,3%) se sometieron a quimiorradiación preoperatoria. Los tumores ubicados dentro de los 5 cm desde el borde anal ( p = 0,02) y el tamaño inicial del ganglio ( p = 0,001) fueron predictores significativos de metástasis en los ganglios linfáticos pélvicos laterales. La sensibilidad fue del 100 % (36/36), con un punto de corte de 6 mm para el tamaño inicial del ganglio, seguido de 8 mm para el tamaño inicial del ganglio (94,4%, 34/36). Cuando se utilizó un tamaño de corte inicial del ganglio de 8 mm para una distancia entre el borde anal y el tumor >5 cm y 6 mm para una distancia entre el borde anal y el tumor ≤5 cm, la sensibilidad de la metástasis en los ganglios linfáticos pélvicos laterales fue del 100 %.LIMITACIONES:El diseño retrospectivo y el pequeño tamaño de la muestra.CONCLUSIONES:El tamaño inicial del ganglio y la altura del tumor fueron predictores significativos de metástasis en los ganglios linfáticos pélvicos laterales. Este estudio propuso que un tamaño de ganglio inicial de ≥8 mm con un tumor a >5 cm del margen anal y ≥6 mm con un tumor a ≤5 cm del margen anal son indicaciones óptimas para la disección de los ganglios linfáticos pélvicos laterales en el cáncer de recto. Consulte Video Resumen en http://links.lww.com/DCR/C101 . (Traducción-Dr. Yolanda Colorado ).
Subject(s)
Anus Neoplasms , Rectal Neoplasms , Humans , Retrospective Studies , Lymphatic Metastasis/pathology , Neoplasm Staging , Lymph Nodes/pathology , Rectal Neoplasms/surgery , Lymph Node Excision/methods , Anus Neoplasms/pathologyABSTRACT
Human epidermal growth factor (hEGF) has been a subject of extensive research as its wide range of physiological functions has many potential applications. However, due to the low stability of hEGF, its physiological effect is easily lost under conditions of use. To compensate for this, we developed a stable delivery system using levan-based nanoparticles. The entrapment yield of various tested proteins was significantly improved by employing carboxymethyl levan (CML) instead of levan; the entrapment yield of the CML-hEGF nanoparticles was 84.1 %. The size and zeta potential of the nanoparticles were identified as 199.9 ± 3.87 nm and -19.1 mV, respectively, using scanning electron microscopy (SEM) and particle size analysis. Dual biological functions of the nanoparticles (skin regeneration and moisturizing) were identified through collagen synthesis activity and aquaporin 3 expression level analysis. Stability of the prepared nanoparticles was also investigated via cell proliferation activity comparison under mimicked physiological conditions. The CML-hEGF nanoparticles maintained cell proliferation activity over 100 % for 6 weeks, while free hEGF was almost inactivated within 2 weeks. Taken together, our results indicate that the CML-based hEGF nanoparticles can be used in pharma- and cosmeceutical applications, guaranteeing a high entrapment capability, functionality, and stability.
Subject(s)
Cosmeceuticals , Humans , Cosmeceuticals/metabolism , Cell Proliferation , Epidermal Growth Factor/metabolism , Skin/metabolism , Fructans/metabolismABSTRACT
Fructan is a polysaccharide composed of fructose and can be classified into several types, such as inulin, levan, and fructo-oligosaccharides, based on their linkage patterns and degree of polymerization. Owing to its structural and functional diversity, fructan has been used in various fields including prebiotics, foods and beverages, cosmetics, and pharmaceutical applications. With increasing interest in fructans, efficient and straightforward production methods have been explored. Since the 1990s, yeast cells have been employed as producers of recombinant enzymes for enzymatic conversion of fructans including fructosyltransferases derived from various microbes and plants. More recently, yeast cell factories are highlighted as efficient workhorses for fructan production by direct fermentation. In this review, recent advances and strategies for fructan biosynthesis by yeast cell factories are discussed.
Subject(s)
Fructans , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Fructans/chemistry , Inulin/metabolism , Carbohydrate Metabolism , OligosaccharidesABSTRACT
Protein expression with a fusion partner followed by the removal of the fusion partner via in vitro processing with a specific endoprotease is a favored method for the efficient production of intact recombinant proteins. Due to the high cost of commercial endoproteases, this process is restricted to laboratories. Kex2p is a membrane-bound serine protease that cleaves after dibasic residues of substrates in the late Golgi network. Although Kex2p is a very efficient endoprotease with exceptional specificity, it has not yet been used for the in vitro processing of fusion proteins due to its autolysis and high production cost. In this study, we developed an alternative endoprotease, autolysis-proof Kex2p, via site-directed mutagenesis of truncated KEX2 from Candida albicans (CaKEX2). Secretory production of manipulated CaKex2p was improved by employing target protein-specific translational fusion partner in Saccharomyces cerevisiae. The mass production of autolysis-proof Kex2p could facilitate the use of Kex2p for the large-scale production of recombinant proteins. KEY POINTS: ⢠A soluble and active CaKex2p variant was produced by autocatalytic cleavage of the pro-peptide after truncation of C-terminus ⢠Autolysis-proof CaKex2p was developed by site-directed mutagenesis ⢠Secretion of autolysis-proof CaKex2p was improved by employing optimal translational fusion partner in Saccharomyces cerevisiae.
Subject(s)
Fungal Proteins , Proprotein Convertases , Saccharomyces cerevisiae , Candida albicans/enzymology , Candida albicans/genetics , Peptide Hydrolases/metabolism , Peptides/metabolism , Proprotein Convertases/metabolism , Recombinant Fusion Proteins/biosynthesis , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Serine Endopeptidases/metabolism , Subtilisins/metabolism , Fungal Proteins/biosynthesisABSTRACT
The gal80 mutant of yeast Saccharomyces cerevisiae is used for the constitutive expression under strong GAL promoters without galactose induction. To enhance productivity of gal80 mutant, an alternative strain, allgal, was developed by removing all galactose-utilizing genes that consume significant cellular resources in the gal80 strain when cultured in non-galactose conditions. The efficacy of the allgal mutant (gal80, gal1, gal2, gal7, and gal10) was verified by assessing the secretory expression of three recombinant proteins, Candida antarctica lipase B (CalB), human serum albumin (HSA), and human epidermal growth factor (hEGF), using the GAL10 promoter. The growth of the allgal mutant was enhanced by 15-38% compared to the gal80 mutant, and the secretion of recombinant proteins also increased by 16-22% in fed-batch fermentation. Thus, the expression of recombinant proteins using GAL10 promoter in the allgal mutant is suitable for the economical production of recombinant proteins in S. cerevisiae.
ABSTRACT
Purpose: Vascular invasion is a well-known independent prognostic factor in colon cancer and tumor sidedness is also being considered a prognostic factor. The aim of this study was to compare the oncological impact of vascular invasion depending on the tumor location in stages I to III colon cancer. Methods: A retrospective analysis was performed using data from patients who underwent curative resection between 2004 and 2015. Patients were divided into right-sided colon cancer (RCC) and left-sided colon cancer (LCC) groups according to the tumor location. Disease-free survival (DFS) and overall survival (OS) were compared between the RCC and LCC groups, depending on the presence of vascular invasion. Results: A total of 793 patients were included, of which 304 (38.3%) had RCC and 489 (61.7%) had LCC. DFS and OS did not differ significantly between the RCC and LCC groups. Vascular invasion was a poor prognostic factor for DFS in both RCC (hazard ratio [HR], 2.291; 95% confidence interval [CI], 1.186-4.425; p = 0.010) and LCC (HR, 1.848; 95% CI, 1.139-2.998; p = 0.011). Additionally, it was associated with significantly worse OS in the RCC (HR, 3.503; 95% CI, 1.681-7.300; p < 0.001), but not in the LCC group (HR, 1.676; 95% CI, 0.885-3.175; p = 0.109). Multivariate analysis revealed that vascular invasion was independently poor prognostic factor for OS in the RCC (HR, 3.186; 95% CI, 1.391-7.300; p = 0.006). Conclusion: This study demonstrated that RCC with vascular invasion had worse OS than LCC with vascular invasion.
ABSTRACT
The lipolytic yeast Candida aaseri SH14 contains three Acyl-CoA oxidases (ACOXs) which are encoded by the CaAOX2, CaAOX4, and CaAOX5 genes and catalyze the first reaction in the ß-oxidation of fatty acids. Here, the respective functions of the three CaAOX isozymes were studied by growth analysis of mutant strains constructed by a combination of three CaAOX mutations in minimal medium containing fatty acid as the sole carbon source. Substrate specificity of the CaAOX isozymes was analyzed using recombinant C. aaseri SH14 strains overexpressing the respective genes. CaAOX2 isozyme showed substrate specificity toward short- and medium-chain fatty acids (C6-C12), while CaAOX5 isozyme preferred long-chain fatty acid longer than C12. CaAOX4 isozyme revealed a preference for a broad substrate spectrum from C6-C16. Although the substrate specificity of CaAOX2 and CaAOX5 covers medium- and long-chain fatty acids, these two isozymes were insufficient for complete ß-oxidation of long-chain fatty acids, and therefore CaAOX4 was indispensable.
Subject(s)
Acyl-CoA Oxidase , Isoenzymes , Saccharomycetales , Acyl-CoA Oxidase/genetics , Fatty Acids , Fungal Proteins/genetics , Isoenzymes/genetics , Saccharomycetales/enzymology , Substrate SpecificityABSTRACT
Purpose: Enhanced Recovery After Surgery (ERAS) reduces postoperative complications and shortens hospital stays. We aimed to describe the implementation and improvement of ERAS protocols in our institution through a multidisciplinary team approach. Methods: A multidisciplinary team comprised of colorectal surgeons, anesthesiologists, nurses, pharmacists, nutritionists, and a performance improvement team was launched to develop the ERAS protocol. The ERAS protocol was followed in patients who underwent colonic and rectal surgery between January and November 2017. The ERAS protocol comprised 22 elements in the preoperative, intraoperative, and postoperative phases. After the initial application, ERAS compliance was monitored and audited every 4-6 months and improvements made as necessary. Results: The length of hospital stay significantly decreased after the application of the ERAS protocols for colon cancer in 2017 and 2018. And there was no significant difference in the duration of hospital stay after applying the rectal cancer ERAS protocol. Moreover, after starting the colon ERAS, there was a significant decrease in the complication rate. Since December 2017, there was a continuous increase in the colorectal ERAS clinical pathway application rate, which remained high (>90%). The patient compliance rate significantly increased between 2017 and 2018, but slightly decreased again in 2019. Conclusion: The application and continual improvement of an ERAS protocol are crucial. Improving compliance may result in better clinical outcomes. Additionally, the basic guidelines of ERAS must be applied and developed according to each hospital's situation based on the team approach.
ABSTRACT
Background: Laparoscopic complete mesocolic excision (CME) with D3 lymph node dissection for the right colon is becoming popular, but still technically challenging. Several articulating laparoscopic instruments had been introduced to reduce technical difficulties; however, those were not practical. This study aimed to report the first clinical experience of using ArtiSential®, a new laparoscopic articulating instrument in laparoscopic complete mesocolic with D3 lymph node dissection for right colon cancer. Patients and Methods: This was a retrospective, single-institution, consecutive case study. From October 2018 to March 2020, a total of 33 patients underwent laparoscopic right hemicolectomy using ArtiSential®, a new articulating instrument. We compared the short-term outcomes of patients who underwent surgery using ArtiSential® (AG) to the conventional instrument (CG). Results: In total, there were 33 cases in AG and 43 cases in CG. There were no significant differences in operation time (141.0 ± 22.5 vs. 156.0 ± 50.6 min, P = 0.09), mean estimated blood loss (46.8 ± 36.2 vs. 100.8 ± 300.6 ml, P = 0.31) and intra-operative and post-operative complications. However, the number of harvested lymph nodes was higher and the length of hospital stay was shorter in AG than in CG (32.6 ± 12.2 vs. 24.6 ± 7.4, P < 0.01 and 3.0 ± 1.2 vs. 4.1 ± 2.2 days, P = 0.01, respectively). Conclusions: Laparoscopic CME with D3 lymph node dissection for right colon cancer using ArtiSential®, the new articulating laparoscopic instrument is safe and technically feasible.
ABSTRACT
PURPOSE: To evaluate the postoperative outcomes of a multimodal perioperative pain management protocol with rectus sheath blocks (RSBs) or intrathecal morphine (ITM) injection for minimally invasive colorectal cancer surgery. METHODS: A total of 112 patients underwent minimally invasive colorectal surgery. Forty-one patients underwent RSB (group 1), whereas 71 patients underwent ITM (group 2) in addition to multimodal pain management using enhanced recovery after the surgery protocol. To adjust for the baseline differences and selection bias, baseline characteristics and postoperative outcomes were compared using propensity score matching. RESULTS: Forty patients were evaluated in each group. There was no significant difference in the length of hospital stay between the two groups. According to the Comprehensive Complication Index (CCI) score, the postoperative complication rate was significantly lower in the RSB group (3.0 ± 7.8) than in the ITM group (8.1 ± 10.9; p = 0.016). During the first 24 h after surgery, the median postoperative visual analog scale score was significantly higher in the RSB group than in the ITM group (2.0 ± 1.1 vs. 1.5 ± 1.2; p = 0.048). Postoperative morphine use was also significantly higher in the RSB group than in the ITM group in the first 24 h (23.7 ± 19.8 vs 11.6 ± 15.6%; p = 0.003) and 48 h (16.9 ± 24.8 vs. 7.5 ± 11.9; p = 0.036) after surgery. Significant urinary retention occurred after the in the RSB and ITM groups (5% vs. 45%; p < 0.001). CONCLUSION: Although the RSB group had higher morphine use during the first 48 h after surgery, the length of hospital stay remained the same and the complications were less in terms of the CCI score. Thus, transperitoneal RSB is a safe and feasible approach for postoperative pain management following minimally invasive procedures.