Long-term Changes in Low Anterior Resection Syndrome in Survivors of Rectal Cancer: Longitudinal Follow-up of a Randomized Controlled Trial.

BACKGROUND: Postoperative bowel dysfunction, also known as low anterior resection syndrome, is common in rectal cancer survivors and significantly impacts quality of life. Although long-term longitudinal follow-up is lacking, improvement of the syndrome is commonly believed to happen only within the first 2 years. OBJECTIVE: This study aimed to depict the longitudinal evolvement of low anterior resection syndrome beyond 3 years and explore factors associated with changes. DESIGN: Longitudinal long-term follow-ups were performed for the single center with the largest cohort within the multicenter FOWARC randomized controlled trial. SETTING: A quaternary referral center. PATIENTS: Individuals diagnosed with rectal cancer who received long-course neoadjuvant chemotherapy or chemoradiotherapy, followed by sphincter-preserving radical proctectomy. MAIN OUTCOME MEASUREMENTS: Change of low anterior resection syndrome score and stoma status. RESULTS: Of the 220 patients responding to the first follow-up at a median of 39 months, 178 (80.9%) responded to the second follow-up after a median of 83 months. During this interval, the mean low anterior resection syndrome score improved from 29.5 (95% CI, 28.3-30.7) to 18.6 (95% CI, 16.6-20.6). Fifty-six (31.5%) patients reported improvement from major to no/minor severity, and 6 (3.4%) patients had new stomas because of severe bowel dysfunction. Neoadjuvant radiotherapy ( p = 0.016) was independently and negatively associated with improvement of the score. LIMITATIONS: Loss of follow-up during the long-term follow-ups. CONCLUSIONS: Most rectal cancer survivors with low anterior resection syndrome continued to improve beyond 3 years after proctectomy. Neoadjuvant radiotherapy was negatively associated with long-term improvement of low anterior resection syndrome. See Video Abstract . CAMBIO A LARGO PLAZO DEL SNDROME DE RESECCIN ANTERIOR BAJA EN SUPERVIVIENTES DE CNCER DE RECTO SEGUIMIENTO LONGITUDINAL DE UN ENSAYO CONTROLADO ALEATORIO: ANTECEDENTES:La disfunción intestinal posoperatoria, también conocida como síndrome de resección anterior baja, es común en los sobrevivientes de cáncer de recto y afecta significativamente la calidad de vida. Aunque falta un seguimiento longitudinal a largo plazo, comúnmente se cree que la mejoría del síndrome ocurre sólo dentro de los primeros dos años.OBJETIVO:Este estudio tiene como objetivo representar la evolución longitudinal del síndrome de resección anterior baja más allá de los 3 años y explora los factores asociados con el cambio.DISEÑO:Se realizaron seguimientos longitudinales a largo plazo para el único centro con la cohorte más grande dentro del ensayo controlado aleatorio multicéntrico FOWARC.AJUSTE:Un centro de referencia cuaternario.PACIENTES:Individuos diagnosticados con cáncer de recto que recibieron quimioterapia neoadyuvante de larga duración o quimiorradioterapia, seguida de proctectomía radical con preservación del esfínter.PRINCIPALES MEDICIONES DE RESULTADO:Cambio en la puntuación del síndrome de resección anterior baja y el estado del estoma.RESULTADOS:De los 220 pacientes que respondieron al primer seguimiento con una mediana de 39 meses, 178 (80,9%) respondieron al segundo seguimiento después de una mediana de 83 meses. Durante el intervalo, la puntuación media del síndrome de resección anterior baja mejoró de 29,5 (intervalo de confianza [IC] del 95%: 28,3-30,7) a 18,6 (IC del 95%: 16,6-20,6). 56 (31,5%) pacientes informaron una mejoría de mayor a ninguna gravedad, y 6 (3,4%) pacientes tuvieron un nuevo estoma debido a una disfunción intestinal grave. La radiación neoadyuvante (p = 0,016) se asoció de forma independiente y negativa con la mejora de la puntuación.LIMITACIONES:Pérdida de seguimiento durante los seguimientos a largo plazo.CONCLUSIÓN:La mayoría de los sobrevivientes de cáncer de recto con síndrome de resección anterior baja continuaron mejorando más allá de los 3 años después de la proctectomía. La radiación neoadyuvante se asoció negativamente con la mejora a largo plazo del síndrome de resección anterior baja. (Traducción-Dr Yolanda Colorado ).

Targeting succinylation-mediated metabolic reprogramming as a potential approach for cancer therapy.

Metabolic reprogramming is a common hallmark of cancers and involves alterations in many metabolic pathways during tumor initiation and progression. However, the cancer-specific modulation of metabolic reprogramming requires further elucidation. Succinylation, a newly identified protein posttranslational modification (PTM), participates in many cellular processes by transferring a succinyl group to a residue of the target protein, which is related to various pathological disorders including cancers. In recent years, there has been a gradual increase in the number of studies on the regulation of tumors by protein succinylation. Notably, accumulating evidence suggests that succinylation can mediate cancer cell metabolism by altering the structure or activity of metabolism-related proteins and plays vital roles in metabolic reprogramming. Furthermore, some antitumor drugs have been linked to succinylation-mediated tumor-associated metabolism. To better elucidate lysine succinylation mediated tumor metabolic reprogramming, this review mainly summarizes recent studies on the regulation and effects of protein succinylation in tumors, focusing on the metabolic regulation of tumorigenesis and development, which will provide new directions for cancer diagnosis as well as possible therapeutic targets.

Lipid metabolism reprogramming of CD8+ T cell and therapeutic implications in cancer.

Effector, memory and exhaustion are three phenotypes of CD8+ T cell. In tumor microenvironment (TME), metabolism dysfunction of the three should take the blame for immune escape. Against background of CD8+ T cell in normal development, multiple determinants in TME, including nutrition competition, PD-1 signals and other cancer - CD8+ T cell interactions, cause metabolism reprograming, including failure in energy metabolism and other abnormal lipid metabolism. Further, incompatibility among metabolism patterns of three phenotypes results in unresponsiveness of immune checkpoint blockade (ICB). Therefore, combination of ICB and drugs aiming at abnormal lipid metabolism provides promising direction to improve cancer therapy. This review focuses on lipid metabolism of CD8+ T cell and aims to provide innovative therapy strategy to cure cancer.

Impact of long-course neoadjuvant radiation on postoperative low anterior resection syndrome and stoma status in rectal cancer: long-term functional follow-up of a randomized clinical trial.

BACKGROUND: Neoadjuvant radiation has been increasingly associated with postoperative bowel dysfunction, including low anterior resection syndrome (LARS). Although permanent stoma often results from severe bowel dysfunction and significantly impacts quality of life, the presence of stoma paradoxically excludes patients from functional follow-up. Hence, stoma status is rarely reported along with LARS, while assessment of both is essential for the comprehensive evaluation of bowel dysfunction in long-term survivors of rectal cancer. METHOD: Patients enrolled into the Neoadjuvant FOLFOX6 Chemotherapy with or without Radiation in Rectal Cancer (FOWARC) multicentre randomized clinical trial were randomized to receive long-course neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT) followed by sphincter-saving proctectomy and longitudinal follow-up. The primary outcome of the trial was disease-free survival. LARS score and stoma status were assessed secondarily for postoperative bowel function in the largest single-centre cohort of the trial. RESULTS: Overall, 327 patients with locally advanced rectal cancer were enrolled in the original trial and 203 responded after a median follow-up of 83.4 months, of whom 24 (11.8 per cent) had persistent stoma, and 48 patients (23.6 per cent) reported major LARS. Compared with the nCT group, the nCRT group reported more persistent stomas (16.5 per cent versus 4.9 per cent, P = 0.014), and more major LARS in patients without persistent stoma (34.7 per cent versus 16.7 per cent, P = 0.003). The combined prevalence of persistent stoma and major LARS was significantly higher in the nCRT group (45.5 per cent versus 20.7 per cent, P < 0.001). Long-course neoadjuvant radiation (OR 2.20, 95 per cent c.i. 1.10 to 4.40, P = 0.027), height of anastomosis (OR 0.74, 95 per cent c.i. 0.61 to 0.91, P = 0.004), and anastomotic leak (OR 4.97, 95 per cent c.i. 2.24 to 11.05, P < 0.001) were associated with persistent stoma and major LARS in multivariate analysis. CONCLUSION: More than one-third of patients receiving sphincter-saving proctectomy reported major LARS or persistent stoma at long-term follow-up. Long-course neoadjuvant radiation, low anastomosis, and postoperative leak are independent risk factors for persistent stoma and major LARS.

Erratum: Relationship between gene expression and the accumulation of catechin during spring and autumn in tea plants (Camellia sinensis L.).

[This corrects the article DOI: 10.1038/hortres.2015.11.][This corrects the article DOI: 10.1038/hortres.2015.11.].

Relationship between gene expression and the accumulation of catechin during spring and autumn in tea plants (Camellia sinensis L.).

The tea plant (Camellia sinensis L.) is an important commercial crop with remarkably high catechin concentrations. Tea is popular worldwide given the plant's health benefits. Catechins are the main astringent substance in tea and are synthesized mainly via the phenylpropanoid pathway. In this study, eight cultivars of tea plants harvested both in spring and autumn were used to investigate differences in catechin concentrations by using high-performance liquid chromatography. The expression levels of genes associated with catechin biosynthesis were investigated using reverse transcription-quantitative polymerase chain reaction. The results indicated that the total catechin (TC) concentrations were significantly higher in tea plants harvested in autumn than in those harvested in spring, based on higher concentrations of epigallocatechin (EGC) in autumn tea (P<0.01). The expression of the genes phenylalanine ammonia-lyase (PAL), flavanone 3-hydroxylase (F3H), flavonoid 3',5'-hydroxylase (F3'5'H), dihydroflavonol 4-reductase (DFR), and anthocyanidin synthase (ANS) is closely related to the TC content of tea plants in both spring and autumn. Positive correlations between PAL, cinnamate 4-hydroxylase (C4H), F3H, and DFR expression and EGC accumulation in autumn tea were identified, with correlation coefficients of 0.710, 0.763, 0.884, and 0.707, respectively. A negative correlation between ANS expression level and EGC concentrations in tea plants harvested in spring was noted (r=-0.732). Additionally, negative correlations between F3H and ANS expression levels and the catechin content were identified in spring tea, whereas the correlations were positive in autumn tea. Significant differences in the F3H and ANS expression levels between spring and autumn tea indicate that F3H and ANS are potentially key genes affecting catechin accumulation in tea plants.