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T cell receptor-engineered T cells (TCR-Ts) therapy is promising for cancer immunotherapy. Most studies have focused on identifying tumor-specific T cell receptors (TCRs) through predicted tumor neoantigens. However, current algorithms for predicting tumor neoantigens are unreliable and many neoantigens are derived from non-coding regions. Thus, the technological platform for identifying tumor-specific TCRs using natural antigens expressed on tumor cells is urgently needed. In this study, tumor organoids-enriched tumor infiltrating lymphocytes (oeT) were obtained by repeatedly stimulation of autologous patient-derived organoids (PDO) in vitro. The oeT cells specifically responded to autologous tumor PDO by detecting CD137 expression and the secretion of IFN-γ using enzyme-linked immunospot assay. The measurement of oeT cell-mediated killing of three-dimensional organoids was conducted using a caspase3/7 flow cytometry assay kit. Subsequently, tumor-specific T cells were isolated based on CD137 expression and their TCRs were identified through single-cell RT-PCR analysis. The specificity cytotoxicity of TCRs were confirmed by transferring to primary peripheral blood T cells. The co-culture system proved highly effective in generating CD8+ tumor-specific oeT cells. These oeT cells effectively induced IFN-γ secretion and exhibited specificity in killing autologous tumor organoids, while not eliciting a cytotoxic response against normal organoids. The analysis conducted by TCRs revealed a significant expansion of T cells within a specific subset of TCRs. Subsequently, the TCRs were cloned and transferred to peripheral blood T cells generation engineered TCR-Ts, which adequately recognized and killed tumor cell in a patient-specific manner. The co-culture system provided an approach to generate tumor-specific TCRs from tumor-infiltrating lymphocytes of patients with colorectal cancer, and tumor-specific TCRs can potentially be used for personalized TCR-T therapy.
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Técnicas de Cocultivo , Linfocitos Infiltrantes de Tumor , Organoides , Receptores de Antígenos de Linfocitos T , Humanos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/metabolismo , Organoides/inmunología , Antígenos de Neoplasias/inmunología , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/patologíaRESUMEN
BACKGROUND: Colorectal cancer (CRC) is a serious global health burden because of its high morbidity and mortality rates. Hypoxia and massive lactate production are hallmarks of the CRC microenvironment. However, the effects of hypoxia and lactate metabolism on CRC have not been fully elucidated. This study aimed to develop a novel molecular subtyping based on hypoxia-related genes (HRGs) and lactate metabolism-related genes (LMRGs) and construct a signature to predict the prognosis of patients with CRC and treatment efficacy. METHODS: Bulk and single-cell RNA-sequencing and clinical data of CRC were downloaded from the TCGA and GEO databases. HRGs and LMRGs were obtained from the Molecular Signatures Database. The R software package DESeq2 was used to perform differential expression analysis. Molecular subtyping was performed using unsupervised clustering. A predictive signature was developed using univariate Cox regression, random forest model, LASSO, and multivariate Cox regression analyses. Finally, the sensitivity of tumor cells to chemotherapeutic agents before and after hypoxia was verified using in vitro experiments. RESULTS: We classified 575 patients with CRC into three molecular subtypes and were able to distinguish their prognoses clearly. The C1 subtype, which exhibits high levels of hypoxia, has a low proportion of CD8 + T cells and a high proportion of macrophages. The expression of immune checkpoint genes is generally elevated in C1 patients with severe immune dysfunction. Subsequently, we constructed a predictive model, the HLM score, which effectively predicts the prognosis of patients with CRC and the efficacy of immunotherapy. The HLM score was validated in GSE39582, GSE106584, GSE17536, and IMvigor210 datasets. Patients with high HLM scores exhibit high infiltration of CD8 + exhausted T cells (Tex), especially terminal Tex, and oxidative phosphorylation (OXPHOS)-Tex in the immune microenvironment. Finally, in vitro experiments confirmed that CRC cell lines were less sensitive to 5-fluorouracil, oxaliplatin, and irinotecan under hypoxic conditions. CONCLUSION: We constructed novel hypoxia- and lactate metabolism-related molecular subtypes and revealed their immunological and genetic characteristics. We also developed an HLM scoring system that could be used to predict the prognosis and efficacy of immunotherapy in patients with CRC.
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Neoplasias Colorrectales , Ácido Láctico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Pronóstico , Ácido Láctico/metabolismo , Regulación Neoplásica de la Expresión Génica , Masculino , Hipoxia/genética , Hipoxia/metabolismo , Microambiente Tumoral/genética , Femenino , Línea Celular Tumoral , Persona de Mediana Edad , Hipoxia de la Célula/genética , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacologíaRESUMEN
Background: Mucinous adenocarcinoma (MAC) is a unique subtype of colorectal cancer and its prognostic value remains controversial. This study aimed to compare the clinicopathological characteristics and prognostic differences between patients with MAC and non-mucinous adenocarcinoma (NMAC). Methods: 674 patients with NMAC, 110 patients with adenocarcinoma with mucinous component (ACWM) and 77 patients with MAC between 2016-2019 were enrolled in the study. Univariate and multivariate Cox regression were performed to analyze the factors associated with prognosis. Predictive nomograms of overall survival (OS) and cancer-specific survival (CSS) for patients with colorectal adenocarcinoma were constructed. Confounding factors were eliminated by propensity score matching (PSM). Results: Compared with patients with NMAC, patients with MAC were more likely to have a tumor located at the proximal colon, present with a larger tumor diameter, more advanced T stage, higher frequency of metastasis, deficiency of mismatch repair, and elevated preoperative carcinoembryonic antigen. Patients with MAC were related to worse OS (HR=2.53, 95%CI 1.73-3.68, p<0.01) and CSS (HR=3.09, 95%CI 2.10-4.57, p<0.01), which persisted after PSM. Subgroup analysis demonstrated that patients with left-sided or stage III/IV MAC exhibited a comparatively worse OS and CSS than those with NMAC. Furthermore, in patients with stage II with a high-risk factor and stage III MAC, adjuvant chemotherapy was associated with an improved OS, CSS, and RFS. Conclusion: Compared with the NMAC phenotype, the MAC phenotype was an independent risk factor for poor prognosis in colorectal adenocarcinoma with worse OS and CSS, particularly patients with left-sided colorectal cancer and stage III/IV. However, patients with MAC can still benefit from adjuvant chemotherapy.
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OBJECTIVE: There is no scientific consensus about the treatment of perforated gastric cancer (PGC). Therefore, the aim of this study was to investigate which is the better treatment option for PGC between the single-stage and two-stage strategies. METHODS: All 81 PGC patients from 13 medical institutions were retrospectively enrolled in this study. The PGC patients who underwent R0 gastrectomy were divided into one-stage surgery and two-stage surgery groups. The clinicopathological characteristics of the two groups were compared, and 415 regular gastric cancer patients without perforation were randomly selected as a control. The propensity score matching (PSM) method was used to find matched regular GC patients with similar clinicopathological parameters. The OS (overall survival) and the number harvested lymph nodes from PGC patients and regular GC patients were compared. RESULTS: Compared with PGC patients who underwent one-stage surgery, those who underwent two-stage surgery harvested significantly more lymph nodes [31(27, 38) vs 17 (12, 24), P < 0.001], required less blood transfusion [0 (0, 100) vs 200 (0, 800), P = 0.034], had a shorter ICU stay [0 (0, 1.5) vs 3 (0, 3), P = 0.009], and had a significantly better OS (Median OS: 45 months vs 11 months, P = 0.007). Compared with propensity score-matched regular GC patients without perforation, PGC patients who underwent one-stage gastrectomy had a poorer quality of lymphadenectomy [17 (12, 24) vs 29 (21, 37), P < 0.001] and suffered a worse OS (Median OS: 18 months vs 30 months, P = 0.024). Conversely, two-stage gastrectomy can achieve a comparable quality of lymphadenectomy (P = 0.506) and a similar OS (P = 0.096) compared to propensity score-matched regular GC patients. CONCLUSIONS: For PGC patients in poor condition, two-stage treatment is a better option when D2 radical gastrectomy cannot be achieved in emergency surgery, based on our findings that two-stage gastrectomy could provide PGC patients with a better quality of lymphadenectomy and a better OS.
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Laparoscopía , Neoplasias Gástricas , Humanos , Estudios Retrospectivos , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/cirugía , Puntaje de Propensión , Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Gastrectomía/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Although adjuvant chemotherapy (ACT) is widely used to treat patients with Stage II/III colorectal cancer (CRC), administering ACT to specific patients remains a challenge. The decision to ACT requires an accurate assessment of recurrence risk and absolute treatment benefit. However, the traditional TNM staging system does not accurately assess a patient's individual risk of recurrence. METHODS: To identify recurrence risk-related genetic factors for Stage II/III CRC patients after radical surgery, we conducted an analysis of whole-exome sequencing of 47 patients with Stage II/III CRC who underwent radical surgery at five institutions. Patients were grouped into non-recurrence group (NR, n = 24, recurrence-free survival [RFS] > 5 years) and recurrence group (R, n = 23, RFS <2 years). The TCGA-COAD/READ cohort was employed as the validation dataset. RESULTS: A recurrence-predictive model (G8plus score) based on eight gene (CUL9, PCDHA12, HECTD3, DCX, SMARCA2, FAM193A, AATK, and SORCS2) mutations and tumor mutation burden/microsatellite instability (TMB/MSI) status was constructed, with 97.87% accuracy in our data and 100% negative predictive value in the TCGA-COAD/READ cohort. For the TCGA-COAD/READ cohort, the G8plus-high group had better RFS (HR = 0.22, p = 0.024); the G8plus-high tumors had significantly more infiltrated immune cell types, higher tertiary lymphoid structure signature scores, and higher immunological signature scores. The G8plus score was also a predict biomarker for immunotherapeutic in advanced CRC in the PUCH cohort. CONCLUSIONS: In conclusion, the G8plus score is a powerful biomarker for predicting the risk of recurrence in patients with stage II/III CRC. It can be used to stratify patients who benefit from ACT and immunotherapy.
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Neoplasias Colorrectales , Inestabilidad de Microsatélites , Humanos , Pronóstico , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/tratamiento farmacológico , Estadificación de Neoplasias , Biomarcadores de Tumor/genéticaRESUMEN
AIM: The aim of this study was to investigate the efficacy of multiple perineal perforator flaps in repairing deep perineal defects after pelvic exenteration for locally advanced or recurrent rectal cancer. METHOD: We investigated the outcomes of eight patients whose repairs involved a novel method of using an internal pudendal artery perforator (IPAP) flap combined with an inferior gluteal artery perforator (IGAP) flap. RESULTS: There were four male and four female patients with a mean age of 56 years (36-72 years). Bilateral IPAP flaps combined with bilateral IGAP flaps were used in five patients, unilateral IPAP flaps combined with bilateral IGAP flaps were used in two patients and bilateral IPAP flaps were used in one patient. There were no functional limitations in daily activities during the 6-month follow-up period. CONCLUSION: Our study showed that using multiple perineal perforator flaps combined with lining repair is feasible for repairing deep perineal defects in patients who have undergone rectal cancer surgery that includes pelvic exenteration.
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Exenteración Pélvica , Colgajo Perforante , Procedimientos de Cirugía Plástica , Neoplasias del Recto , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias del Recto/cirugía , Perineo/cirugía , Colgajo Perforante/cirugíaRESUMEN
Numerous studies have revealed the importance of tumor-derived exosomes in rectal cancer (RC). This study aims to explore the influence of tumor-derived exosomal integrin beta-1 (ITGB1) on lung fibroblasts in RC along with underlying mechanisms. Exosome morphology was observed using a transmission electron microscope. Protein levels of CD63, CD9, ITGB1, p-p65 and p65 were detected using Western blot. To determine ITGB1's mRNA expression, quantitative real-time polymerase chain reaction was used. Moreover, levels of interleukin (IL)-8, IL-1ß, and IL-6 in cell culture supernatant were measured via commercial ELISA kits. ITGB1 expression was increased in exosomes from RC cells. The ratio of p-p65/p65 as well as levels of interleukins in lung fibroblasts was raised by exosomes derived from RC cells, while was reduced after down-regulation of exosomal ITGB1. The increased ratio of p-p65/p65 as well as levels of pro-inflammatory cytokines caused by exosomes from RC cells was reversed by the addition of nuclear factor kappa B (NF-κB) inhibitor. We concluded that the knockdown of RC cells-derived exosomal ITGB1 repressed activation of lung fibroblasts and the NF-κB pathway in vitro.
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PURPOSE: Patients with ovarian metastasis of colorectal cancer (CROM) usually have poor prognosis. Metastasectomy is controversial in patients with CROM. This study aims to evaluate the prognostic value of ovarian metastasectomy and other factors in CROM patients. METHODS: We searched literature up to November 1, 2021 in MEDLINE (PubMed), Embase, Cochrane Library, and Clinicaltrials.gov. Retrospective studies were assessed if survival outcome of CROM patients was reported. Results were pooled in a random-effects model and reported as hazard ratios (HRs) with 95% confidence intervals (CI). Sensitivity was analyzed. RESULTS: Among 2497 studies screened, 15 studies with 997 patients, published between 2000 and 2021, were included. Longer overall survival (OS) was correlated with ovarian metastasectomy (pooled HR = 0.44, 95% CI: 0.34-0.58, P < 0.05) and R0 resection (pooled HR = 0.26, 95% CI: 0.16-0.41, P < 0.05). Longer disease-specific survival (DSS) was associated with systematic chemotherapy (pooled HR = 0.26, 95% CI: 0.15-0.45, P < 0.0001). Shorter OS was associated with extraovarian metastases (pooled HR = 3.00, 95% CI 1.68-5.36, P < 0.05) and bilateral OM (pooled HR = 1.66, 95% CI: 1.09-2.51, P < 0.05). No significant difference in OS was observed among patients with systematic chemotherapy (pooled HR = 0.68, 95% CI: 0.35-1.31, P > 0.05). CONCLUSION: Metastasectomy achieving R0 resection can significantly prolong OS and DSS of CROM patients as a reasonable treatment modality. Primary tumor resection and systematic chemotherapy can improve patients' outcomes. REGISTRATION NUMBER: CRD42022299185 (http://www.crd.york.ac.uk/PROSPERO).
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Neoplasias Colorrectales , Metastasectomía , Neoplasias Ováricas , Humanos , Femenino , Metastasectomía/métodos , Estudios Retrospectivos , Pronóstico , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/secundario , Neoplasias Colorrectales/patologíaRESUMEN
Colorectal cancer (CRC) is ranked as one of the most common malignancies with a high death rate. It has been discovered that breviscapine can alter the progression and development of various cancers. Nevertheless, the function and mechanisms of breviscapine in CRC progression have not yet been described. The cell proliferation capacity of HCT116 and SW480 cells was assessed using the CCK-8 and EdU assays. Cell apoptosis was tested through flow cytometry, and cell migration and invasion were examined using the transwell assay. Moreover, protein expression was examined through a western blot. Tumor weight and volume were assessed using the nude mice in vivo assay, and the Ki-67 protein expression was verified through the IHC assay. This study discovered that an increased dose of breviscapine (0, 12.5, 25, 50, 100, 200, and 400 µM) gradually reduced cell proliferation and increased apoptosis in CRC. Additionally, breviscapine restricted the migration and invasion CRC cells. Moreover, it was revealed that breviscapine inactivated the PI3K/AKT pathway and inhibited CRC progression. Finally, an in vivo assay demonstrated that breviscapine restrained tumor growth in vivo. It affected the CRC cells' proliferation, migration, invasion, and apoptosis through the PI3K/AKT pathway. This discovery may offer new insights into CRC treatment.
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Neoplasias Colorrectales , Fosfatidilinositol 3-Quinasas , Animales , Ratones , Proteínas Proto-Oncogénicas c-akt , Ratones Desnudos , Procesos Neoplásicos , Apoptosis , Proliferación CelularRESUMEN
Background: Mucinous adenocarcinoma (MAC) is a unique clinicopathological colorectal cancer (CRC) type that has been recognized as a separate entity from non-mucinous adenocarcinoma (NMAC), with distinct clinical, pathologic, and molecular characteristics. We aimed to construct prognostic signatures and identifying candidate biomarkers for patients with MAC. Methods: Differential expression analysis, weighted correlation network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO)-Cox regression model were used to identify hub genes and construct a prognostic signature based on RNA sequencing data from TCGA datasets. The Kaplan-Meier survival curve, gene set enrichment analysis (GSEA), cell stemness, and immune infiltration were analyzed. Biomarker expression in MAC and corresponding normal tissues from patients operated in 2020 was validated using immunohistochemistry. Results: We constructed a prognostic signature based on ten hub genes. Patients in the high-risk group had significantly worse overall survival (OS) than patients in the low-risk group (p < 0.0001). We also found that ENTR1 was closely associated with OS (p = 0.016). ENTR1 expression was significantly positively correlated with cell stemness of MAC (p < 0.0001) and CD8+ T cell infiltration (p = 0.01), whereas it was negatively associated with stromal scores (p = 0.03). Finally, the higher expression of ENTR1 in MAC tissues than in normal tissues was validated. Conclusion: We established the first MAC prognostic signature, and determined that ENTR1 could serve as a prognostic marker for MAC.
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Colorectal cancer (CRC) is a deadly form of cancer worldwide. Patients with locally advanced rectal cancer and metastatic CRC have a poor long-term prognosis, and rational and effective treatment remains a major challenge. Common treatments include multi-modal combinations of surgery, radiotherapy, and chemotherapy; however, recurrence and metastasis rates remain high. The combination of radiotherapy and immunotherapy (radioimmunotherapy [RIT]) may offer new solutions to this problem, but its prospects remain uncertain. This review aimed to summarize the current applications of radiotherapy and immunotherapy, elaborate on the underlying mechanisms, and systematically review the preliminary results of RIT-related clinical trials for CRC. Studies have identified several key predictors of RIT efficacy. Summarily, rational RIT regimens can improve the outcomes of some patients with CRC, but current study designs have limitations. Further studies on RIT should focus on including larger sample sizes and optimizing the combination therapy regimen based on underlying influencing factors.
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Neoplasias Colorrectales , Radioinmunoterapia , Humanos , Radioinmunoterapia/métodos , Terapia Combinada , Inmunoterapia , Resultado del Tratamiento , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/patologíaRESUMEN
BACKGROUND: Type 2 diabetes mellitus (T2DM) is an independent risk factor for colorectal cancer (CRC), and the patients with CRC and T2DM have worse survival. The human gut microbiota (GM) is linked to the development of CRC and T2DM, respectively. However, the GM characteristics in patients with CRC and T2DM remain unclear. METHODS: We performed fecal metagenomic and targeted metabolomics studies on 36 samples from CRC patients with T2DM (DCRC group, n = 12), CRC patients without diabetes (CRC group, n = 12), and healthy controls (Health group, n = 12). We analyzed the fecal microbiomes, characterized the composition and function based on the metagenomics of DCRC patients, and detected the short-chain fatty acids (SCFAs) and bile acids (BAs) levels in all fecal samples. Finally, we performed a correlation analysis of the differential bacteria and metabolites between different groups. RESULTS: Compared with the CRC group, LefSe analysis showed that there is a specific GM community in DCRC group, including an increased abundance of Eggerthella , Hungatella , Peptostreptococcus , and Parvimonas , and decreased Butyricicoccus , Lactobacillus , and Paraprevotella . The metabolomics analysis results revealed that the butyric acid level was lower but the deoxycholic acid and 12-keto-lithocholic acid levels were higher in the DCRC group than other groups ( P < 0.05). The correlation analysis showed that the dominant bacterial abundance in the DCRC group ( Parvimonas , Desulfurispora , Sebaldella , and Veillonellales , among others) was negatively correlated with butyric acid, hyodeoxycholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, chenodeoxycholic acid, cholic acid and glycocholate. However, the abundance of mostly inferior bacteria was positively correlated with these metabolic acid levels, including Faecalibacterium , Thermococci , and Cellulophaga . CONCLUSIONS: Unique fecal microbiome signatures exist in CRC patients with T2DM compared to those with non-diabetic CRC. Alterations in GM composition and SCFAs and secondary BAs levels may promote CRC development.
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Neoplasias Colorrectales , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Microbiota , Humanos , Microbioma Gastrointestinal/genética , Bacterias/genética , Ácidos Grasos Volátiles , Neoplasias Colorrectales/metabolismo , Butiratos , Heces/microbiologíaRESUMEN
BACKGROUND: Circulating tumor DNA (ctDNA) detection following curative-intent surgery could directly reflect the presence of minimal residual disease, the ultimate cause of clinical recurrence. However, ctDNA is not postoperatively detected in ≥ 50% of patients with stage I-III colorectal cancer (CRC) who ultimately recur. Herein we sought to improve recurrence risk prediction by combining ctDNA with clinicopathological risk factors in stage I-III CRC. METHODS: Two independent cohorts, both consisting of early-stage CRC patients who underwent curative surgery, were included: (i) the discovery cohort (N = 124) with tumor tissues and postoperative plasmas for ctDNA determination; and (ii) the external validation cohort (N = 125) with available ctDNA results. In the discovery cohort, somatic variations in tumor tissues and plasmas were determined via a 733-gene and 127-gene next-generation sequencing panel, respectively. RESULTS: In the discovery cohort, 17 of 108 (15.7%) patients had detectable ctDNA. ctDNA-positive patients had a significantly high recurrence rate (76.5% vs. 16.5%, P < 0.001) and short recurrence-free survival (RFS; P < 0.001) versus ctDNA-negative patients. In addition to ctDNA status, the univariate Cox model identified pathologic stage, lymphovascular invasion, nerve invasion, and preoperative carcinoembryonic antigen level associated with RFS. We combined the ctDNA and clinicopathological risk factors (CTCP) to construct a model for recurrence prediction. A significantly higher recurrence rate (64.7% vs. 8.1%, P < 0.001) and worse RFS (P < 0.001) were seen in the high-risk patients classified by the CTCP model versus those in the low-risk patients. Receiver operating characteristic analysis demonstrated that the CTCP model outperformed ctDNA alone at recurrence prediction, which increased the sensitivity of 2 year RFS from 49.6% by ctDNA alone to 87.5%. Harrell's concordance index, calibration curve, and decision curve analysis also suggested that the CTCP model had good discrimination, consistency, and clinical utility. These results were reproduced in the validation cohort. CONCLUSION: Combining postoperative ctDNA and clinical risk may better predict recurrence than ctDNA alone for developing a personalized postoperative management strategy for CRC.
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ADN Tumoral Circulante , Neoplasias Colorrectales , Humanos , ADN Tumoral Circulante/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Biomarcadores de Tumor/genética , Curva ROC , Factores de Riesgo , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patologíaRESUMEN
China ranks the first worldwide in the number of new colorectal cancer (CRC) cases and CRC-related deaths. The increasing incidence of early-onset CRC in recent years highlights the challenges related to CRC screening and prevention. High-quality colonoscopy is the universally used gold standard for CRC screening. Risk assessment combined with a two-step screening strategy based on colonoscopy and non-invasive examinations was proven to be highly effective. However, systematic use of well-established risk factors associated with CRC, beyond age, could better identify those who might harbor advanced colorectal neoplasia, improve the diagnostic yield of current screening modalities, and optimize the selection of individuals who might benefit most from preventive strategies. "Personalization" and "Standardization" are the future development directions of CRC screening, from the initiation of screening in those at high risk for CRC to follow-up after treatment, which are the key to ensure the screening efficiency.
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BACKGROUND: Due to the influence of traditional Chinese culture, many cholelithiasis patients refuse to undergo cholecystectomy. This has prompted surgeons to consider a new treatment option for gallstones, which preserves the gallbladder, termed as choledochoscopic gallbladder-preserving cholecystolithotomy. In this study, we reviewed the clinical outcomes of 23 years of single-center application of choledochoscopic gallbladder-preserving cholecystolithotomy. METHODS: A total of 5,451 patients with chronic cholelithiasis were selected from 1992 to 2011 as per the inclusion criteria for the choledochoscopic gallbladder-preserving cholecystolithotomy study, and clinicopathological and follow-up data were collected from 4,340 patients who underwent successful choledochoscopic gallbladder-preserving cholecystolithotomy. The endpoints of the follow-up were recurrence of stones, loss to follow-up, patient death, removal of the gallbladder for other reasons, or end of follow-up in December 2015. RESULTS: All 4,340 cases underwent choledochoscopic gallbladder-preserving cholecystolithotomy with a mean procedure time of 79.6 ± 35.4 minutes, among which 3,511 (80.9%) received at least 1 follow-up. The recurrence rate of gallstones gradually increased with increasing follow-up duration, with a recurrence rate of 0.83% within 1 year after surgery and a maximal cumulative recurrence rate of 7.94% at 23 years. The 5-year cumulative recurrence rate of gallstones in the age group ≤20 years was 16.80%, which was significantly higher than those of other age groups, and the 5-year recurrence rate in the single gallstone group was 2.87%, which was significantly lower than that in the multiple gallstone group. Age and number of gallstones were independent risk factors for gallstone recurrence after choledochoscopic gallbladder-preserving cholecystolithotomy. CONCLUSION: The recurrence rate of gallstones after choledochoscopic gallbladder-preserving cholecystolithotomy is low, and most patients with recurrence are asymptomatic or have only mild symptoms. Age and number of gallstones were independent risk factors. Choledochoscopic gallbladder-preserving cholecystolithotomy is a safe and effective surgical option for gallstone removal in patients who do not wish to undergo cholecystectomy.
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Cálculos Biliares , Adulto , Estudios de Seguimiento , Cálculos Biliares/diagnóstico , Cálculos Biliares/cirugía , Humanos , Recurrencia , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Preoperative neoadjuvant chemoradiation (nCRT) has been the standard treatment for locally advanced rectal cancer. Serum biomarkers to stratify patients with respect to prognosis and response to nCRT are needed due to the diverse response to the therapy. METHODS: Thirteen paired pre- and post-nCRT sera from rectal cancer patients were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ) method. Twenty-five proteins were selected for validation by parallel reaction monitoring (PRM) in ninety-one patients. RESULTS: Totally, 310 proteins were identified and quantified in sera samples. Reactome pathway analysis showed that the immune activation-related pathways were enriched in response to nCRT. Twenty-five proteins were selected for further validation. PRM result showed that the level of PZP was higher in pathological complete response (pCR) patients than non-pCR patients. The Random Forest algorithm identified a prediction model composed of 10 protein markers, which allowed discrimination between pCR patients and non-pCR patients (area under the curve (AUC) = 0.886 on testing set). Higher HEP2 and GELS or lower S10A8 in baseline sera were associated with better prognosis. Higher APOA1 in post nCRT sera was associated with better disease-free survival (DFS). CONCLUSIONS: We identified and confirmed a 10-protein panel for nCRT response prediction and four potential biomarkers HEP2, GELS, S10A8 and APOA1 for prognosis of rectal cancer based on iTRAQ-based comparative proteomics screening and PRM-based targeted proteomic validation.
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Terapia Neoadyuvante , Neoplasias del Recto , Biomarcadores , Quimioradioterapia , Geles , Humanos , Proteómica/métodos , Neoplasias del Recto/patología , Resultado del TratamientoRESUMEN
OBJECTIVE: To summarize the recent literature on surgical treatment of locally recurrent rectal cancer (LRRC). BACKGROUND: LRRC is a heterogeneous disease that requires a multidisciplinary treatment approach. The treatment and prognosis depend on the site and type of recurrence. Radical resection remains the primary method for achieving long-term survival and improving symptom control. Preoperative chemoradiotherapy can reduce tumor volume and improve the R0 resection rate. Surgeons must clearly understand pelvic anatomy, develop a detailed preoperative plan, adopt a multidisciplinary approach for the surgical resection of the tumor as well as any invaded soft tissues, vessels, and bones, and ensure proper reconstruction. However, extended radical surgery often leads to a higher risk of postoperative complications and a low quality of life. METHODS: We searched English-language articles with keywords "locally recurrent rectal cancer", "surgery" and "multidisciplinary team" in PubMed published between January 2000 to October 2020. CONCLUSIONS: LRRC is a complex problem. Long-term survival is not impossible following multidisciplinary treatment in appropriately selected LRRC patients. The management of LRRC relies on a specialist team that determines the biological behavior of the tumor and evaluates treatment options through multidisciplinary discussions, thereby balancing the surgical costs and benefits, alleviating postoperative complications, and improving patients' quality of life.