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BACKGROUND: The selection of hyperthermic intraperitoneal chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC) for peritoneal metastases from colorectal cancer or appendiceal neoplasms following cytoreductive surgery (CRS) depends on the surgeon's discretion. This study was designed to compare postoperative and oncologic outcomes of HIPEC and EPIC using inverse probability of treatment weighting (IPTW). METHODS: This study included 175 patients who received HIPEC or EPIC following CRS at a single tertiary university hospital between December 1999 and December 2020. Inverse probability of treatment weighting analysis was performed to control for pretreatment characteristics between the two groups. Multivariate analysis was performed to determine factors associated with postoperative and survival outcomes. RESULTS: After IPTW, no significant differences in baseline demographics and tumor characteristics were observed between the two groups. The HIPEC group had a significantly longer operation time than the EPIC group. The EPIC group showed a significantly higher postoperative mortality rate than the HIPEC group. Operation time (odds ratio [OR] 1.01; 95% confidence interval [CI] 1.01-1.02; p < 0.001), bowel anastomosis (OR 7.25; 95% CI 1.16-45.2; p = 0.034), neoadjuvant chemotherapy (OR 7.62; 95% CI 1.85-31.4; p = 0.005), and EPIC (OR 8.76; 95% CI 2.16-35.5; p = 0.002) were independent risk factors for major surgical complications. No association was observed between intraperitoneal chemotherapy type and major hematologic toxicity, overall survival, progression-free survival, or peritoneal progression-free survival. CONCLUSIONS: EPIC was a risk factor for major surgical complications. Survival outcomes were similar between the two types of intraperitoneal chemotherapy.
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Piper attenuatum Buch-Ham, a perennial woody vine belonging to the Piperaceae family, is traditionally used in Southeast Asia for treating various ailments such as malaria, headache, and hepatitis. This study described the isolation and identification of three new compounds, piperamides I-III (1-3), which belong to the maleimide-type alkaloid skeletons, along with fifteen known compounds (4-18) from the methanol extract of the aerial parts of P. attnuatum. Their chemical structures were elucidated using spectroscopic methods (UV, IR, ESI-Q-TOF-MS, and 1D/2D NMR). All the isolates were evaluated for their ability to inhibit IL-6 activity in the human embryonic kidney-Blue™ IL-6 cell line and their cytotoxic activity against ovarian cancer cell lines (SKOV3/SKOV3-TR) and chemotherapy-resistant variants (cisplatin-resistant A2780/paclitaxel-resistant SKOV3). The compounds 3, 4, 11, 12, 17, and 18 exhibited IL-6 inhibition comparable to that of the positive control bazedoxifene. Notably, compound 12 displayed the most potent anticancer effect against all the tested cancer cell lines. These findings highlight the importance of researching the diverse activities of both known and newly discovered natural products to fully unlock their potential therapeutic benefits.
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Antineoplásicos Fitogênicos , Interleucina-6 , Neoplasias Ovarianas , Piper , Componentes Aéreos da Planta , Extratos Vegetais , Humanos , Interleucina-6/metabolismo , Piper/química , Feminino , Linhagem Celular Tumoral , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Componentes Aéreos da Planta/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Estrutura Molecular , Proliferação de Células/efeitos dos fármacosRESUMO
Systemic inflammatory response (SIR) is a crucial determinant of disease progression and survival in patients with colorectal cancer. This study investigated the prognostic relevance of changes in the platelet count on survival and the predictive value of changes in the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) on the pathological tumor response to preoperative chemoradiotherapy (CRT) in patients with microsatellite instability-high (MSI-H) rectal cancer. From 2011 to 2022, data of 46 consecutive patients with MSI-H rectal cancer who were treated with preoperative CRT followed by curative surgery at Kyungpook National University Chilgok Hospital (Daegu, South Korea) were retrospectively analyzed. A 235 cut-off value was used to define whether PLR was high or low. Any change in the PLR or NLR was calculated on the basis of subtracting the pre-CRT PLR or NLR from the post-CRT values. Both pre-CRT and post-CRT values of the NLR and PLR were not significantly associated with clinical outcomes. Simple logistic regression analysis showed that a change in the PLR following CRT was not significantly associated with survival outcomes; however, patients who maintained a high change in the PLR following CRT showed significantly better pathologic T-stage. No statistically significant association was noted between changes in the platelet count and clinical outcomes of patients. The results suggested that changes in the PLR following CRT are associated with pathologic T-stage of the group. However, the SIR markers showed no prognostic values on the survival outcomes of the patients with MSI-H/mismatch repair-deficient (dMMR) locally advanced rectal cancer (LARC).
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Based on the fact that substances with a ß-phenyl-α,ß-unsaturated carbonyl (PUSC) motif confer strong tyrosinase inhibitory activity, benzylidene-3-methyl-2-thioxothiazolidin-4-one (BMTTZD) analogs 1-8 were prepared as potential tyrosinase inhibitors. Four analogs (1-3 and 5) inhibited mushroom tyrosinase strongly. Especially, analog 3 showed an inhibitory effect that was 220 and 22 times more powerful than kojic acid in the presence of l-tyrosine and l-dopa, respectively. A kinetic study utilizing mushroom tyrosinase showed that analogs 1 and 3 competitively inhibited tyrosinase, whereas analogs 2 and 5 inhibited tyrosinase in a mixed manner. A docking simulation study indicated that analogs 2 and 5 could bind to both the tyrosinase active and allosteric sites with high binding affinities. In cell-based experiments using B16F10 cells, analogs 1, 3, and 5 effectively inhibited melanin production; their anti-melanogenic effects were attributed to their ability to inhibit intracellular tyrosinase activity. Moreover, analogs 1, 3, and 5 inhibited in situ B16F10 cellular tyrosinase activity. In three antioxidant experiments, analogs 2 and 3 exhibited strong antioxidant efficacy, similar to that of the positive controls. These results suggest that the BMTTZD analogs are promising tyrosinase inhibitors for the treatment of hyperpigmentation-related disorders.
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Agaricales , Antioxidantes , Inibidores Enzimáticos , Melaninas , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Agaricales/enzimologia , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Camundongos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Melaninas/antagonistas & inibidores , Melaninas/biossíntese , Tiazolidinas/química , Tiazolidinas/farmacologia , Linhagem Celular Tumoral , Cinética , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Compostos de Benzilideno/farmacologia , Compostos de Benzilideno/química , PironasRESUMO
We propose a genetic algorithm for optimizing oil skimmer assignments, introducing a tailored repair operation for constrained assignments. Methods essentially involve simulation-based evaluation to ensure adherence to South Korea's regulations. Results show that the optimized assignments, compared to current ones, reduced work time on average and led to a significant reduction in total skimmer capacity. Additionally, we present a deep neural network-based surrogate model, greatly enhancing efficiency compared to simulation-based optimization. Addressing inefficiencies in mobilizing locations that store oil skimmers, further optimization aimed to minimize mobilized locations and was validated through scenario-based simulations resembling actual situations. Based on major oil spills in South Korea, this strategy significantly reduced work time and required locations. These findings demonstrate the effectiveness of the proposed genetic algorithm and mobilized location minimization strategy in enhancing oil spill response operations.
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Age-related macular degeneration (AMD) severely affects central vision due to progressive macular degeneration and its staggering prevalence is rising globally, especially in the elderly population above 55 years. Increased oxidative stress with aging is considered an important contributor to AMD pathogenesis despite multifaceted risk factors including genetic predisposition and environmental agents. Wet AMD can be managed with routine intra-vitreal injection of angiogenesis inhibitors, but no satisfactory medicine has been approved for the successful management of the dry form. The toxic carbonyls due to photo-oxidative degradation of accumulated bisretinoids within lysosomes initiate a series of events including protein adduct formation, impaired autophagy flux, complement activation, and chronic inflammation, which is implicated in dry AMD. Therapy based on antioxidants has been extensively studied for its promising effect in reducing the impact of oxidative stress. This paper reviews the dry AMD pathogenesis, delineates the effectiveness of dietary and nutrition supplements in clinical studies, and explores pre-clinical studies of antioxidant molecules, extracts, and formulations with their mechanistic insights.
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This study investigated the impact of activated carbon, palm activated carbon, and zeolite on horse oil (HO) extracted from horse neck fat using supercritical fluid extraction with deodorant-untreated HO (CON) as a comparison. The yield and lipid oxidation of deodorant untreated HO (CON) were not significantly affected by the three deodorants. However, deodorant-treated HOs exhibited significantly elevated levels of α-linolenic acid (C18:3n3) and eicosenoic acid (C20:1n9) compared to CON (p<0.05), while other fatty acids remained consistent. Zeolite-purified HO demonstrated significantly lower levels of volatile organic compounds (VOCs) than other treatments (p<0.05). Remarkably, zeolite decreased the concentration of pentane, 2,3-dimethyl (gasoline odor), by over 90%, from 177.17 A.U. ×106 in CON to 15.91 A.U. ×106. Zeolite also effectively eliminates sec-butylamine (ammonia and fishy odor) as compared to other deodorant-treated HOs (p<0.05). Additionally, zeolite reduced VOCs associated with the fruity citrus flavor, such as nonanal, octanal, and D-limonene in HO (p<0.05). This study suggests that integrating zeolite in supercritical fluid extraction enhances HO purification by effectively eliminating undesirable VOCs, presenting a valuable approach for producing high-quality HO production in the cosmetic and functional food industries.
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This study aimed to investigate the potential of beef peptides (BPs) in mitigating muscle atrophy induced by dexamethasone (DEX) with underlying three mechanisms in vitro (protein degradation, protein synthesis, and the oxidative stress pathway). Finally, the anti-atrophic effect of BPs was enhanced through purification and isolation. BPs were generated using beef loin hydrolyzed with alcalase/ProteAX/trypsin, each at a concentration of 0.67%, followed by ultrafiltration through a 3 kDa cut-off. BPs (10-100 µg mL-1) dose-dependently counteracted the DEX-induced reductions in myotube diameters, differentiation, fusion, and maturation indices (p < 0.05). Additionally, BPs significantly reduced FoxO1 protein dephosphorylation, thereby suppressing muscle-specific E3 ubiquitin ligases such as muscle RING-finger containing protein-1 and muscle atrophy F-box protein in C2C12 myotubes at concentrations exceeding 25 µg mL-1 (p < 0.05). BPs also enhanced the phosphorylation of protein synthesis markers, including mTOR, 4E-BP1, and p70S6K1, in a dose-dependent manner (p < 0.05) and increased the mRNA expression of antioxidant enzymes. Fractionated peptides derived from BPs, through size exclusion and polarity-based fractionation, also demonstrated enhanced anti-atrophic effects compared to BPs. These peptides downregulated the mRNA expression of primary muscle atrophy markers while upregulated that of antioxidant enzymes. Specifically, peptides GAGAAGAPAGGA (MW 924.5) and AFRSSTKK (MW 826.4) were identified from fractionated peptides of BPs. These findings suggest that BPs, specifically the peptide fractions GAGAAGAPAGGA and AFRSSTKK, could be a potential strategy to mitigate glucocorticoid-induced skeletal muscle atrophy by reducing the E3 ubiquitin ligase activity.
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Fibras Musculares Esqueléticas , Atrofia Muscular , Estresse Oxidativo , Peptídeos , Animais , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/farmacologia , Bovinos , Proteólise/efeitos dos fármacos , Linhagem Celular , Biossíntese de Proteínas/efeitos dos fármacos , Carne Vermelha , Proteínas Musculares/metabolismo , Dexametasona/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Fosforilação , Serina-Treonina Quinases TOR/metabolismoRESUMO
PURPOSE: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2021. MATERIALS AND METHODS: Incidence, survival, and prevalence rates of cancer were calculated using the Korea National Cancer Incidence Database, from 1999 to 2021, with survival follow-up until December 31, 2022. Deaths from cancer were assessed using causes-of-death data obtained from Statistics Korea. RESULTS: The number of new cancer diagnoses in 2021 increased by 27,002 cases (10.8%) compared to 2020. In 2021, newly diagnosed cancer cases and deaths from cancer were reported as 277,523 (age-standardized rate [ASR], 289.3 per 100,000) and 82,688 (ASR, 67.6 per 100,000), respectively. The overall cancer incidence rates increased by 3.3% annually from 1999 to 2012, and decreased by 5.3% from 2012 to 2015, thereafter, followed by non-significant changes. Cancer mortality rates have been decreasing since 2002, with more rapid decline in recent years (annual decrease of 2.8% from 2002 to 2013; 3.2% from 2013 to 2021). The 5-year relative survival between 2017 and 2021 was 72.1%, which contributed to prevalent cases reaching over 2.4 million in 2021. CONCLUSION: In 2021, the number of newly diagnosed cancer patients increased as healthcare utilization recovered from the coronavirus disease 2019-related declines of 2020. Revised cancer registration guidelines expanded the registration scope, particularly for stomach and colorectal cancer. Survival rates have improved over the years, leading to a growing population of cancer survivors, necessitating a comprehensive cancer control strategy. The long-term impact of the pandemic on cancer statistics requires future investigation.
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Neoplasias , Humanos , Incidência , Prevalência , Taxa de Sobrevida , República da Coreia/epidemiologiaRESUMO
PURPOSE: This study aimed to report the projected cancer incidence and mortality for the year 2024 to estimate Korea's current cancer burden. MATERIALS AND METHODS: Cancer incidence data from 1999 to 2021 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2022 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and multiplying the projected age-specific rates by the anticipated age-specific population for 2024. A joinpoint regression model was used to determine the year in which the linear trend changed significantly; we only used the data of the latest trend for prediction. RESULTS: In total, 292,221 new cancer cases and 83,770 cancer deaths are expected to occur in Korea in 2024. The most common cancer site is expected to be the thyroid, followed by the colon and rectum, lung, breast, and stomach. These five cancers are expected to represent 55.7% of the overall burden of cancer in Korea. The most common type of cancer leading to death is expected to be lung cancer, followed by liver, colorectal, pancreatic, and stomach cancers. CONCLUSION: The age-standardized incidence rates for female breast and prostate cancers are estimated to continue to increase. These up-to-date estimates of the cancer burden in Korea could be an important resource for planning and evaluating cancer-control programs.
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Neoplasias Pulmonares , Neoplasias , Neoplasias da Próstata , Masculino , Humanos , Incidência , Neoplasias/epidemiologia , Coreia (Geográfico)/epidemiologia , República da Coreia/epidemiologiaRESUMO
Liposomes are widely used as drug delivery nanoplatforms because of their versatility and biocompatibility; however, their ability to load certain drugs may be suboptimal. In this study, we generated liposomes using a combination of DSPE and DSPE-PEG-2 k lipids and loaded them with doxorubicin (DOX) and paclitaxel (PTX), to investigate the effects of light emitting diode (LED) irradiation on liposome structure and drug loading efficiency. Scanning and transmission electron microscopy revealed that the surface of liposomes irradiated with blue or near-infrared LEDs (LsLipo) was rougher and more irregular than that of non-LED-irradiated liposomes (NsLipo). Nuclear magnetic resonance analysis showed that the hydrogen peak originating from the lipid head groups was lower in LsLipo than in NsLipo preparations, indicating that LED irradiation changed the chemical and physical properties of the liposome. Structural changes, such as reduced rigidity, induced by LED irradiation, increased the loading efficiency of DOX and PTX. In vitro and in vivo experiments showed that LsLipo were more effective at inhibiting the growth of cancer cells than NsLipo. Our findings suggest that LED irradiation enhances the drug delivery efficacy of liposomes and offer new possibilities for improving drug delivery systems.
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Lipossomos , Neoplasias , Humanos , Lipossomos/química , Sistemas de Liberação de Medicamentos , Paclitaxel/química , Doxorrubicina/química , Neoplasias/tratamento farmacológico , Linhagem Celular TumoralRESUMO
Immunotherapy based on adoptive transfer of natural killer (NK) cells is a promising strategy for circumventing the limitations of cancer treatments. However, components of the immunosuppressive tumor microenvironment (TME), such as transforming growth factor-beta (TGF-ß), compromise the therapeutic efficacy of NK cells significantly. To address these limitations, we developed a novel method of engineering NK cells for adaptive transfer. The method is based on nanogels that serve two functions: (1) they overcome the TGF-ß-mediated stress environment of the TME, and (2) they enhance the direct anti-tumor activity of NK cells. Previously, we demonstrated that cationic compounds such as 25 K branched polyethylenimine (25 K bPEI) prime NK cells, putting them in a 'ready-to-fight' state. Based on these findings, we designed nanogels that have two primary characteristics: (1) they encapsulate galunisertib (Gal), which is used clinically to inhibit TGF-ß receptor activity, thereby blocking TGF-ß signaling; and (2) they provide cells with a surface coating of 25 K bPEI. When grown in culture medium containing TGF-ß, nanogel-treated NK cells demonstrated greater migration ability, degranulation activity, and cytotoxicity towards cancer cells than untreated NK cells. Additionally, the in vivo efficacy of nanogel-treated NK cells against PC-3 xenografts was significantly greater than that of Chem_NK cells primed by 25 K bPEI alone. These findings suggest that Gal-loaded 25 K bPEI-coated nanogels exert anti-tumor effects via chemical priming, as well suppressing the effects of TGF-ß on NK cells. We also expect 25 K bPEI-based nanogels to have great potential to overcome the suppressive effects of the TME through their NK cell-priming activity and delivery of the desired chemicals.
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Citotoxicidade Imunológica , Polietilenoglicóis , Polietilenoimina , Fator de Crescimento Transformador beta , Humanos , Nanogéis , Fator de Crescimento Transformador beta/farmacologia , Linhagem Celular Tumoral , Células Matadoras Naturais , Microambiente TumoralRESUMO
BACKGROUND: Patients with rectal cancer who underwent lateral pelvic node dissection might be at a higher risk of postoperative complications derived from technical complexity. However, little is known regarding the long-term complications after lateral pelvic node dissection. OBJECTIVES: The study aimed to investigate the long-term complications of preoperative chemoradiotherapy, followed by total mesorectal excision with lateral pelvic node dissection for locally advanced rectal cancers. DESIGN: A retrospective analysis of a prospectively collected database. SETTINGS: This study was conducted in a tertiary cancer center. PATIENTS: Patients with rectal cancer who underwent total mesorectal excision with lateral pelvic node dissection after preoperative chemoradiotherapy between 2011 and 2019 were analyzed. All operations were performed via a laparoscopic or robotic approach. MAIN OUTCOME MEASURES: Long-term complications were defined as adverse events that persisted or newly appeared ≥90 days after surgery and could be related to the surgery. RESULTS: A total of 164 patients underwent total mesorectal excision with lateral pelvic node dissection after preoperative chemoradiotherapy. Short-term and long-term complication rates were 36.0% and 36.6%, respectively. Lymphocele was the most common long-term complication (17.7% of patients), and 11.6% had anastomotic leakage with chronic sinus. Of the patients with long-term complications, 20.7% of patients needed readmission for treatment. Of the 29 patients with lymphocele, 13 (41.0%) experienced spontaneous absorption and 11 (37.9%) required surgical or percutaneous catheter drainage or antibiotics use. Multivariate analysis showed pathologic pelvic node metastases ( p = 0.008), and a higher number of unilateral harvested pelvic nodes ( p = 0.001) were significantly associated with long-term complications. At the last follow-up (median duration of 43 months), 15.9% of patients had unresolved complications. LIMITATIONS: The retrospective design. CONCLUSIONS: Patients undergoing lateral pelvic node dissection experienced a higher frequency of long-term complications, but half of them had asymptomatic lymphoceles, most of which resolved spontaneously. However, further efforts should be paid to reduce anticipated complications related to lateral pelvic node dissection. See Video Abstract . COMPLICACIONES A LARGO PLAZO DE LA DISECCIN DE LOS GANGLIOS LIFTICOS PLVICOS LATERALES LAPAROSCPICA O ROBTICA DESPUS DE LA QUIMIORRADIOTERAPIA PREOPERATORIA CONTRA EL CNCER DEL RECTO LOCALMENTE AVANZADO: ANTECEDENTES:Los pacientes con cáncer del recto sometidos a disección ganglionar linfática pélvica lateral podrían tener mayor riesgo de complicaciones postoperatorias derivadas de la complejidad técnica. Sin embargo, se sabe poco sobre las complicaciones a largo plazo después de la disección de los ganglios linfáticos pélvicos laterales.OBJETIVOS:Investigar las complicaciones a largo plazo de la quimiorradioterapia preoperatoria, seguida de escisión mesorrectal total con disección de los ganglios linfáticos pélvicos laterales contra el cáncer de recto localmente avanzado.DISEÑO:Un análisis retrospectivo de una base de datos recopilada prospectivamente.AJUSTES:Este estudio se llevó a cabo en un centro oncológico terciario.PACIENTES:Se analizaron pacientes con cáncer de recto que se sometieron a escisión mesorrectal total con disección de ganglios linfáticos pélvicos laterales después de quimiorradioterapia preoperatoria entre 2011 y 2019. Todas las operaciones se realizaron mediante abordaje laparoscópico o robótico.PRINCIPALES MEDIDAS DE RESULTADO:Las complicaciones a largo plazo se definieron como eventos adversos que persistieron o aparecieron recientemente ≥ 90 días después de la cirugía y podrían estar relacionados con la cirugía.RESULTADOS:Un total de 164 pacientes se sometieron a escisión mesorrectal total con disección de los ganglios linfáticos pélvicos laterales después de quimiorradioterapia preoperatoria. Las tasas de complicaciones a corto y largo plazo fueron del 36,0% y 36,6%, respectivamente. El linfocele fue la complicación a largo plazo más común (17,7% de los pacientes) y el 11,6% tuvo fuga anastomótica con seno crónico. De los pacientes con complicaciones a largo plazo, el 20,7% de los pacientes necesitaron reingreso para recibir tratamiento. De 29 pacientes con linfocele, 13 (41,0%) experimentaron absorción espontánea y 11 (37,9%) requirieron drenaje quirúrgico o percutáneo con catéter o uso de antibióticos. El análisis multivariado mostró metástasis patológicas en los ganglios linfáticos pélvicos ( p = 0,008) y un mayor número de ganglios pélvicos extraídos unilateralmente ( p = 0,001) se asociaron significativamente con complicaciones a largo plazo. En el último seguimiento (mediana de 43 meses), el 15,9% de los pacientes tuvieron complicaciones no resueltas.LIMITACIÓN:El diseño retrospectivo.CONCLUSIONES:Los pacientes sometidos a disección de ganglios pélvicos linfáticos laterales experimentaron una mayor frecuencia de complicaciones a largo plazo, pero la mitad de ellos tuvieron linfoceles asintomáticos, la mayoría de los cuales se resolvieron espontáneamente. Sin embargo, se deben realizar mayores esfuerzos para reducir las complicaciones previstas relacionadas con la disección de los ganglios linfáticos pélvicos laterales. (Traducción-Dr. Aurian Garcia Gonzalez ).
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Laparoscopia , Linfocele , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Excisão de Linfonodo , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Estudos Retrospectivos , Linfocele/patologia , Linfocele/cirurgia , Linfonodos/patologia , Laparoscopia/efeitos adversos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Quimiorradioterapia/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Whether lateral pelvic node metastasis should be considered as a regional or systemic disease is a long-standing debate. Although previous Japanese studies have considered it to be locoregional disease, Western countries consider it a systemic disease and do not perform lateral pelvic node dissection after preoperative chemoradiotherapy. OBJECTIVE: To evaluate whether lateral pelvic node metastasis is a systemic or regional disease that is amenable to curative resection. DESIGN: Retrospective analysis of a prospectively collected database. SETTING: This study was conducted at a tertiary cancer center. PATIENTS: There were 616 consecutive patients who underwent curative total mesorectal excision alone or with lateral pelvic node dissection after preoperative chemoradiotherapy for locally advanced rectal cancer between 2011 and 2019. MAIN OUTCOME MEASURES: Three-year disease-free and overall survival. RESULTS: A total of 360 patients underwent total mesorectal excision, and 160 patients underwent total mesorectal excision with lateral pelvic node dissection. There was no difference in the 3-year disease-free survival (DFS; p = 0.844) or overall survival rates ( p = 0.921) between the groups. Patients with lateral pelvic node metastasis showed DFS similar to those with perirectal lymph node metastasis in the total mesorectal excision group. In a subgroup analysis, patients with internal iliac pelvic node metastasis showed a disease-free survival comparable to those with perirectal node involvement, and patients with other lateral pelvic node metastasis showed a DFS similar to those with intermediate node involvement. In the lateral pelvic node dissection group, the lateral pelvic node metastatic rate was 32.5%. On multivariate analysis, fewer than 8 of the unilateral harvested lateral pelvic nodes and advanced ypT stage were significantly associated with poor disease-free survival. LIMITATION: The retrospective design. CONCLUSIONS: Lateral lymphatic metastasis showed oncologic outcomes similar to those of upward spread, especially perirectal lymph nodes metastasis. Large cohort studies with long-term follow-up are required to confirm these results. See Video Abstract . LAS METSTASIS LINFTICAS SECUENCIALES LATERALES MUESTRAN RESULTADOS ONCOLGICOS SIMILARES EN LA PROPAGACIN ASCENDENTE DEL CNCER RECTAL AVANZADO DESPUS DE LA RADIOQUIMIOTERAPIA PREOPERATORIA: ANTECEDENTES:Es un debate muy antiguo si las metástasis en los ganglios pélvicos laterales deben considerarse una enfermedad regional o sistémica. Si bien estudios japoneses anteriores las consideran como una enfermedad locorregional, en los países de occidente se las considera como una enfermedad sistémica por la cual no se realiza disección de ganglios pélvicos laterales después de una radioquimioterapia preoperatoria.OBJETIVOS:Evaluar si la metástasis en los ganglios pélvicos laterales se consideran como enfermedad sistémica o enfermedad regional susceptible de resección curativa.DISEÑO:Análisis retrospectivo de una base de datos recopilada prospectivamente.AJUSTE:Este estudio se realizó en un centro oncológico terciario.PACIENTES:616 pacientes consecutivos se sometieron a excisión total del mesorrecto curativa sola o con disección de los ganglios pélvicos laterales después de radioquimioterapia preoperatoria en casos de cáncer de recto localmente avanzado entre 2011 y 2019.PRINCIPALES MEDIDAS DE RESULTADO:Sobrevida global y libre de enfermedad a 3 años.RESULTADOS:Un total de 360 pacientes se sometieron a excisión total del mesorrecto y 160 pacientes se sometieron a excisión total del mesorrecto con disección de ganglios pélvicos laterales.No hubo diferencias en la sobrevida libre de enfermedad a 3 años (p = 0,844) ni en las tasas de sobrevida general (p = 0,921) entre los grupos. Los pacientes con metástasis en los ganglios pélvicos laterales mostraron una sobrevida libre de enfermedad similar a aquellos con metástasis en los ganglios linfáticos perirrectales que se encontraban en el grupo de excisión total del mesorrecto.En el análisis de subgrupos, los pacientes con metástasis en los ganglios pélvicos ilíacos internos mostraron una sobrevida libre de enfermedad comparable a aquellos con afección de los ganglios perirrectales y los pacientes con otras metástasis en los ganglios pélvicos laterales mostraron una sobrevida libre de enfermedad similar a aquellos con afección de los ganglios intermedios.En el grupo de disección de los ganglios pélvicos laterales, la tasa de metástasis en dichos ganglios fué del 32,5%. En el análisis multivariado, < de 8 ganglios pélvicos laterales resecados unilateralmente y el estadio ypT avanzado se asociaron significativamente con una menor sobrevida libre de enfermedad.LIMITACIÓN:El diseño retrospectivo del estudio.CONCLUSIONES:Las metástasis linfáticas laterales mostraron resultados oncológicos similares a la diseminación ascendente, especialmente las metástasis en los ganglios linfáticos perirrectales. Se requieren grandes estudios de cohortes con seguimiento a largo plazo para confirmar estos resultados. (Traducción-Dr. Xavier Delgadillo ).
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Neoplasias Retais , Humanos , Metástase Linfática , Estudos Retrospectivos , Neoplasias Retais/terapia , Oncologia , Quimiorradioterapia , Estadiamento de NeoplasiasRESUMO
BACKGROUND: It is unknown whether the da Vinci single-port system performs similarly to the previous multi-port system during complicated procedures, such as rectal cancer surgery. Therefore, we compared the short-term clinical outcomes of single-port and multi-port robotic total mesorectal excision for the treatment of rectal cancer. METHODS: This retrospective study reviewed 128 patients who underwent robotic total mesorectal excision between July 2020 and June 2022, of whom 84 (42 each: single-port versus multi-port) were included in the propensity score-matched cohort. Perioperative and pathologic outcomes were compared between groups. RESULTS: Median tumor height was similar between groups (single-port versus multi-port, 5.9 ± 2.1 vs 5.6 ± 1.8 cm, P = .719). Preoperative chemoradiotherapy was performed equally. The total operative time was less (160.0 ± 42.2 minutes vs 199.6 ± 78.6 minutes, P = .005), the total length of incision was shorter (4.0 ±0.3 vs 5.4 ± 0.7 cm, P = .003), postoperative hospital stay was shorter (6.2 ±1.7 vs 7.2 ±2.8 days, P = .050), and C-reactive protein levels on postoperative day 3 trended to be lower (7.3 ± 4.7 vs 8.9 ± 5.6 mg/L, P = .096) in the single-port group, compared with the multi-port group. Postoperative complications did not differ between groups (single-port versus multi-port, 11.9% vs 16.6%, P = .864). Anastomotic leakage occurred in 1 and 2 patients in the single-port and multi-port groups, respectively. The circumferential resection margins were positive in 1 patient in the multi-port group. CONCLUSION: The perioperative outcomes of single-port robotic total mesorectal excision were comparable to those of multi-port robotic TME. The single-port robot can be considered a surgical option for treating rectal cancer.
Assuntos
Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Pontuação de Propensão , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Mechanical power (MP), the rate of mechanical energy (ME) delivery, is a recently introduced unifying ventilator parameter consisting of tidal volume, airway pressures, and respiratory rates, which predicts pulmonary complications in several clinical contexts. However, ME has not been previously studied in the perioperative context, and neither parameter has been studied in the context of thoracic surgery utilizing one-lung ventilation. METHODS: The relationships between ME variables and postoperative pulmonary complications were evaluated in this post hoc analysis of data from a multicenter randomized clinical trial of lung resection surgery conducted between 2020 and 2021 (n = 1,170). Time-weighted average MP and ME (the area under the MP time curve) were obtained for individual patients. The primary analysis was the association of time-weighted average MP and ME with pulmonary complications within 7 postoperative days. Multivariable logistic regression was performed to examine the relationships between energy variables and the primary outcome. RESULTS: In 1,055 patients analyzed, pulmonary complications occurred in 41% (431 of 1,055). The median (interquartile ranges) ME and time-weighted average MP in patients who developed postoperative pulmonary complications versus those who did not were 1,146 (811 to 1,530) J versus 924 (730 to 1,240) J (P < 0.001), and 6.9 (5.5 to 8.7) J/min versus 6.7 (5.2 to 8.5) J/min (P = 0.091), respectively. ME was independently associated with postoperative pulmonary complications (ORadjusted, 1.44 [95% CI, 1.16 to 1.80]; P = 0.001). However, the association between time-weighted average MP and postoperative pulmonary complications was time-dependent, and time-weighted average MP was significantly associated with postoperative pulmonary complications in cases utilizing longer periods of mechanical ventilation (210 min or greater; ORadjusted, 1.46 [95% CI, 1.11 to 1.93]; P = 0.007). Normalization of ME and time-weighted average MP either to predicted body weight or to respiratory system compliance did not alter these associations. CONCLUSIONS: ME and, in cases requiring longer periods of mechanical ventilation, MP were independently associated with postoperative pulmonary complications in thoracic surgery.
Assuntos
Ventilação Monopulmonar , Respiração com Pressão Positiva , Humanos , Respiração com Pressão Positiva/efeitos adversos , Pulmão , Respiração Artificial/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Volume de Ventilação Pulmonar , Ventilação Monopulmonar/efeitos adversosRESUMO
The purpose of this study was to evaluate the physicochemical properties of whey protein hydrolysate and determine changes in absorption rate due to enzymatic hydrolysis. The molecular weight distribution analysis of whey protein concentrate (WPC) and low-molecule whey protein hydrolysate (LMWPH) using the Superdex G-75 column revealed that LMWPH is composed of peptides smaller than those in WPC. Fourier-transform infrared spectroscopy indicated differences in peak positions between WPC and LMWPH, suggesting hydrolysis-mediated changes in secondary structures. Moreover, LMWPH exhibited higher thermal stability and faster intestinal permeation than WPC. Additionally, oral LMWPH administration increased serum protein content at 20 min, whereas WPC gradually increased serum protein content after 40 min. Although the total amount of WPC and LMWPH absorption was similar, LMWPH absorption rate was higher. Collectively, LMWPH, a hydrolysate of WPC, has distinct physicochemical properties and enhanced absorptive characteristics. Taken together, LMWPH is composed of low-molecular-weight peptides with low antigenicity and has improved absorption compared to WPC. Therefore, LMWPH can be used as a protein source with high bioavailability in the development of functional materials.
Assuntos
Hidrolisados de Proteína , Subtilisinas , Hidrolisados de Proteína/química , Subtilisinas/metabolismo , Soro do Leite/metabolismo , Proteínas do Soro do Leite , Peptídeos/química , Proteínas SanguíneasRESUMO
BACKGROUND: Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). METHODS: A multicenter randomized phase II trial involving 364 patients with LARC (cT3-4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45-50.4 Gy in 25-28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2-5 weeks from the last cycle of chemotherapy in the experimental arm and 6-8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. DISCUSSION: This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. TRIAL REGISTRATION: This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.
Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Terapia Neoadjuvante/métodos , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fluoruracila/uso terapêutico , Neoplasias Retais/radioterapia , Neoplasias Retais/tratamento farmacológico , Quimiorradioterapia/métodos , Estadiamento de NeoplasiasRESUMO
Background: The increase in internal diameter (ID) and cross-sectional area (CSA) may facilitate better arterial catheterization. Since an increase in body temperature can cause peripheral vasodilation, we aimed to determine if local warming of the radial artery (RA) catheterization site could improve the success rate of catheterization. Methods: This randomized, controlled study enrolled 160 patients aged >18 years who were scheduled for heart surgery. They were randomized into non-warming palpation (NP), non-warming ultrasonography-guided (NU), warming palpation (WP), and warming ultrasonography-guided (WU) groups. After induction, the baseline RA ultrasonography images were collected. In the warming groups (WP, WU), local warming was applied on the catheterization site. Before catheterization, the RA ultrasonography images were collected. The primary outcome was the first-attempt success rate. The secondary outcomes included the ID and CSA of the RA and overall complications. Results: Totally 152 adults were included in the analysis. The first-attempt success rates in each of the four groups were not significantly different (P=0.985). The rates in the non-warming (NP + NU) and warming (WP + WU) groups were also not different (P=0.827). Unlike non-warming group, the warming group had increased ID (3.34±0.78 vs. 3.02±0.73 mm; P<0.001) and CSA (6.9±2.8 vs. 5.8±2.4 mm2; P<0.001) compared with baseline. Conclusions: Local warming for peripheral artery catheterization does not increase the first-attempt success rate in adults undergoing cardiac surgery; however, it can increase the ID and CSA of the RA and prevent vasospasm. Trial Registration: ClinicalTrials.gov NCT04969692.