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Objective:To investigate the influence of different injection time of carbon nanoparticle tracer on the acquisition of lymph nodes in adenocarcinoma of esophagogastric junc-tion (AEG) treated by neoadjuvant chemoradiotherapy (nCRT) combined with surgical resection.Methods:The prospective randomized controlled study was conducted. The clinicopathological data of 120 AEG patients who were treated by nCRT combined with surgical resection in the Fourth Hospital of Hebei Medical University from March 2020 to March 2021 were selected. Based on random number table, patients were allocated into two groups. Patients undergoing endoscopic injection of carbon nanoparticle tracer 24 hours before nCRT were allocated into the experiment group, and patients undergoing endoscopic injection of carbon nanoparticle tracer 24 hours before surgical resection were allocated into the control group. All patients received the same plan of nCRT combined with D 2 radical gastrectomy. Observation indicators: (1) grouping situations of the enrolled patients; (2) surgical and postoperative pathological situations; (3) postoperative complications and treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement date with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the non-parameter rank sum test. Results:(1) Grouping situations of the enrolled patients. A total of 120 patients were selected for eligibility. There were 85 males and 35 females, aged (60±9)years. There were 60 patients in the experiment group and 60 patients in the control group, respectively. (2) Surgical and postoperative pathological situations. Patients in the two groups underwent D 2 radical gastrectomy successfully, with R 0 resection. The number of lymph nodes harvest, the number of lymph nodes stained, the number of metastatic lymph nodes stained, the number of micro lymph nodes, the number of inferior mediastinal lymph nodes, the number of inferior mediastinal lymph nodes stained, cases in postoperative pathological stage N0, stage N1, stage N2, stage N3a were 40.6±13.9,20.1±7.7, 1.0(0,3.0), 8.1±2.8, 3.7±1.3, 2.0(1.0,2.0), 18, 13, 23, 6 in patients of the experiment group, respectively. The above indicators were 30.4±8.3, 12.7±3.5, 0(0,1.0), 6.2±2.0, 2.4±1.2, 1.0(0,1.0), 23, 21, 15, 1 in patients of the control group, respectively. There were significant differences in the above indicators between the two groups ( t=-5.01, 6.85, Z=-3.78, t=-4.04, -5.57, Z=-5.48, -2.12, P<0.05). (3) Postoperative complications and treatment. There were 5 cases of the experiment group and 7 cases of the control group with postoperative complications, showing no significant difference between the two groups ( χ2=0.37, P>0.05). The patients with postoperative complications were improved after symptomatic treatment. Conclusion:Compared with injection of carbon nanoparticle tracer 24 hours before surgical resection, injection of carbon nanoparticle tracer 24 hours before nCRT can improve the acquisition of lymph nodes in AEG treated by nCRT combined with surgical resection.
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Objective: To systematically evaluate the efficacy and safety of total neoadjuvant therapy (TNT) in the comprehensive treatment of locally advanced rectal cancer. Methods: Literatures were screened from PubMed, Embase, Web of Science, Cochrane Library, CBM, Wanfang Data, VIP and CNKI from the inception date to May 2021 to collect the randomized controlled clinical trials (RCTs) of TNT followed by total mesorectal excision (TME) versus neoadjuvant chemotherapy (nCRT) followed by TME in the treatment of locally advanced rectal cancer. The data of overall survival, disease-free survival, R0 radical resection rate, pathological complete response (pCR) rate, T downstaging rate, the incidence of adverse events ≥ grade III, including neutropenia, nausea and vomiting, diarrhea, radiation dermatitis and nervous system toxicity, and the morbidity of complications within postoperative 30 days of the two groups were extracted from the included literatures. Review Manager 5.3 software was utilized for statistical meta-analysis. Results: Nine RCTs were finally enrolled including 2430 patients. Meta-analysis results showed that compared with nCRT group, patients in TNT group had longer overall survival (HR=0.80, 95%CI: 0.65-0.97, P=0.03) and higher pCR rate (RR=1.73, 95%CI: 1.44-2.08, P<0.01) with significant differences. Besides, there were no significant differences between two groups in disease-free survival (HR=0.86, 95%CI:0.71-1.05, P=0.14), R0 radical resection rate (RR=1.02, 95%CI: 0.99-1.06, P=0.17) and T downstaging rate (RR=1.04, 95%CI: 0.89-1.22, P=0.58) between two groups. In terms of treatment safety, the incidence of adverse events ≥ grade III (RR=1.09, 95%CI: 0.70-1.70, P=0.70) and morbidity of complications within postoperative 30 days (RR=1.07, 95%CI: 0.97-1.18, P=0.19) did not significantly differ between two groups. Conclusions: In the treatment of locally advanced rectal cancer, TNT may bring more survival benefits than nCRT and does not increase the incidence of adverse events and postoperative complications. Therefore, TNT could be used as a recommended treatment for patients with locally advanced rectal cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Chemoradiotherapy/methods , Disease-Free Survival , Humans , Neoadjuvant Therapy/methods , Neoplasm Staging , Neoplasms, Second Primary/pathology , Rectal Neoplasms/therapy , Rectum/pathology , Treatment OutcomeABSTRACT
Objective: To investigate quality of life (QoL) of patients with locally advanced rectal cancer (LARC) who underwent low anterior resection with protective stoma under neoadjuvant therapy mode, and to explore the changes of QoL of patients from before neoadjuvant therapy to 12 months after stoma reversal. Methods: A descriptive case series study was carried out. A retrospective study was performed on patients with mid and low LARC who received complete neoadjuvant long course radiotherapy and chemotherapy, followed by radical low anterior resection (LAR) combined with protective stoma at Peking Union Medical College Hospital from December 2017 to January 2020. Inclusion criteria: (1) patients with rectal MRI assessment of mT3-4b or mN1-2 without distant metastasis (M0) before neoadjuvant therapy; (2) distance from tumor lower margin to the anal verge <12 cm; (3) rectal adenocarcinoma confirmed by biopsy before neoadjuvant therapy; (4) complete cycle of neoadjuvant therapy; (5) patients undergoing radical LAR with sphincter preservation and protective ostomy; (6) patients receiving follow-up for more than 12 months after stoma reversal. Exclusion criteria: (1) patients as grade Ⅳ to Ⅴclassified by the American Society of Anesthesiologists (ASA); (2) patients with multiple primary colorectal cancer; (3) patients with history of other malignant tumors in the past 5 years; (4) patients of emergency surgery; (5) pregnant or lactating women; (6) patients with history of severe mental illness; (7) patients with contraindication of MRI, radiotherapy, chemotherapy, or surgical treatment. A total of 83 patients were enrolled, including 51 males and 28 females with median age of 59 years and mean BMI of (24.4±3.1) kg/m(2). EORTC QLQ-CR29, international erectile function index (IIEF), Wexner constipation score and low anterior resection syndrome (LARS) score were applied to investigate the QoL of the patients before neoadjuvant therapy, 3 and 12 months after ostomy reversal, including rectal anal function and sexual function. M (P25, P75) was used for the scores of the scale. Results: (1) EORTC QLQ-CR29 score showed that before neoadjuvant therapy, before surgery, 3 months and 12 months after ostomy reversal, anxiety [64.4 (52, 0, 82.5), 75.3 (66.0, 89.5), 82.6 (78.5, 90.0), 83.6 (78.0, 91.0)] and concern about body image [76.8 (66.0, 92.0), 81.1 (76.5, 91.5), 85.5 (82.5, 94.0), 86.1 (82.0, 92.0)] were improved (all P<0.01); pelvic pain [5.4 (2.0, 8.0), 5, 0 (2.0, 7.8), 3.9 (1.0, 5.0), 3.0 (1.0, 5.0)], urinary incontinence [15.7 (7.0, 22.0), 11.1 (0, 17.5), 10.0 (0, 17.0), 9.9 (0, 16.0)], impotence [14.3 (4.2, 19.0), 12.2 (0, 16.8), 5.6 (0, 10.0), 5.2 (0.2, 8.0)], urinate [26.4 (13.0, 38.5), 13.9 (0, 20.0), 13.4 (2.5, 21.5), 13.2 (2.0, 20.0)] and mucous bloody stool [4.7 (3.0, 6.0), 2.6 (0, 5.0), 2.2 (0, 5.0), 1.9 (0, 4.0)] were improved as well (all P<0.01). The scores fluctuated in the improvement of male sexual function, abdominal pain, dry mouth, worry about body mass change, skin pain and dyspareunia, but the symptoms were significantly improved after ostomy reversal compared with before neoadjuvant therapy (all P<0.05). There were no significant changes in female sexual function, dysuria, dysgeusia and fecal incontinence after ostomy reversal compared with before neoadjuvant therapy (all P>0.05). (2) IIEF scale showed that all scores were similar before and after neoadjuvant therapy (all P>0.05). (3) Rectal and anal function scale revealed that before neoadjuvant therapy, before operation, 3 months and 12 months after stoma reversal, gas incontinence [3.1 (0, 4.0), 2.3 (0, 4.0), 1.8 (0, 4.0), 1.2 (0, 3.0)] and urgent defecation [7.2 (0, 11.0), 5.2 (0, 11.0), 2.9 (0, 9.0), 1.7 (0, 0)] were improved (all P<0.001). In terms of improving incomplete emptying sensation, the symptoms fluctuated, but the symptoms improved significantly after ostomy reversal compared with before neoadjuvant therapy (all P<0.05). While the symptoms of assistance with defecation [0 (0, 0), 0.7 (0, 1.0), 0.6 (0, 1.0), 0.7 (0, 1.0)] and defecation failure [0.2 (0, 0), 1.0 (0, 2.0), 0.8 (0, 1.5), 0.8 (0, 1.0)] showed a worsening trend (all P<0.001). Stratified analysis was performed on patients with different efficacy of neoadjuvant therapy to compare the changes in QoL before and after neoadjuvant therapy. Patients with less sensitive and more sensitive neoadjuvant therapy showed similar changes in function and symptoms. Patients with less sensitive therapy showed significant improvement in dysuria, urinary incontinence, skin pain and dyspareunia (all P<0.05), and the symptom of defecation frequency in more sensitive patients was significantly improved (P<0.05). Conclusions: For patients with LARC, neoadjuvant radiochemotherapy combined with radical LAR and protective stoma can improve QoL in many aspects. It is noted that patients show a worsening trend in the need for assistance with defecation and in defecation failure.
Subject(s)
Dyspareunia , Dysuria , Female , Humans , Lactation , Male , Middle Aged , Neoadjuvant Therapy , Neoplasms, Second Primary , Pain , Postoperative Complications , Quality of Life , Rectal Neoplasms/surgery , Retrospective Studies , Syndrome , Treatment Outcome , Urinary IncontinenceABSTRACT
Objective: To construct a prediction model of pathologic complete response (pCR) in locally advanced rectal cancer patients who received programmed cell death protein-1 (PD-1) antibody and total neoadjuvant chemoradiotherapy by using radiomics based on MR imaging data and to investigate its predictive value. Methods: A clinical diagnostic test study was carried out. Clinicopathalogical and radiological data of 38 patients with middle-low rectal cancer who received PD-1 antibody combined with total neoadjuvant chemoradiotherapy and underwent TME surgery from January 2019 to September 2021 in our hospital were retrospectively collected. Among 38 patients, 23 were males and 15 were females with a median age of 68 (47-79) years and 13 (34.2%) a chieved pCR. These 38 patients were stratified and randomly divided into the training group (n=26) and test group (n=12) for modeling. All the patients underwent rectal MRI before treatment. The clinical, imaging and radiomics features of all the patients were collected, and the clinical feature model and radiomics model were constructed. The receiver operating characteristic (ROC) curves of each model were drawn, and the constructed model was evaluated through the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Results: There were no significant differences in age, gender, primary location of tumor and postoperative pathology between the two groups (all P>0.05). Forty-one features were extracted from region of interest in each modality, including 9 first-order features, 24 gray level co-occurrence matrix features and 8 shape features. From 38 patients, 41 features were extracted from each imaging modality of baseline and preoperative DWI and T2WI images, totally 164 features. Only 4 features were preserved after correlation analysis between each pair of features and t-test between pCR and non-pCR subjects. After LASSO cross validation, only the first-order skewness of the baseline DWI image before treatment and the volume in the baseline T2WI image before treatment were retained. The area under the curve, sensitivity, specificity, positive and negative predictive values of the prediction model established by applying these two features in the training group and the test group were 0.856 and 0.844, 77.8% and 100.0%, 88.2% and 75.0%, 77.8% and 66.7%, 88.2% and 100.0%, respectively. The decision curve analysis of the radiomics model showed that the strategy of this model in predicting pCR was better than that in treating all the patients as pCR and that in treating all the patients as non-pCR. Conclusion: The pCR prediction model for rectal cancer patients receiving PD-1 antibody combined with total neoadjuvant radiochemotherapy based on MRI radiomics has the potential to be used in clinical screening or rectal cancer patients who can be spared from radical surgery.
Subject(s)
Aged , Antibodies/therapeutic use , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neoadjuvant Therapy/methods , Programmed Cell Death 1 Receptor , Rectal Neoplasms/therapy , Retrospective StudiesABSTRACT
China is a country with high incidence of esophageal cancer. In recent years, with the deepening research, the value of neoadjuvant therapy in locally advanced resectable esophageal cancer has been widely approved by clinicians, compared with surgery alone or adjuvant therapy. However, the survival results of different neoadjuvant therapy options may be quite different, and many problems remain unresolved. In this article, a systemic literature review was carried out to summarize the radiotherapy target, radiotherapy dose, chemotherapy regimen of neoadjuvant chemoradiotherapy and time to surgery, as well as review the research status and progress on targeted therapy and immunotherapy as neoadjuvant therapy for esophageal cancer.
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Objective:To search for the key genes influencing the resistance of rectal cancer to chemoradiotherapy based on the weighted gene co-expression network analysis (WGCNA).Methods:The data were collected from gene expression omnibus. The whole genome expression data GSE119409 of patients receiving radiotherapy and chemotherapy were obtained by gene expression ominibus. The weighted gene co-expression networks of pathological complete response group and non-pathological complete response group were constructed respectively. NetRep conservative evaluation method was used to comprehensively analyze the three key network attributes of gene connectivity, gene significance and module membership of each node in the network module, and to determine the key genes closely related to the sensitivity of rectal cancer to radiotherapy and chemotherapy.Results:Network modules including black, blue, green, yellow and purple were obtained by WGCNA, and five key genes including SLC22A14, SIDT2, CABP4, EPHB6 and RAB11B were screened out.Conclusions:Five gene co-expression network modules and five key genes related to chemoradiotherapy resistance of rectal cancer were screened by weighted gene co-expression network analysis, which provided clues for finding molecular markers and potential therapeutic targets for neoadjuvant chemoradiotherapy resistance evaluation.
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Objective:To analyze the correlation between the Naples prognostic score (NPS) after preoperative neoadjuvant chemoradiotherapy in locally advanced rectal cancer (LARC) and evaluate the prognostic value of NPS in LARC.Methods:136 patients with LARC meeting the recruitment criteria from 2015 to 2020 were selected. Serum albumin, total cholesterol (TC) were collected and neutrophil-lymphocyte ratio and lymphocyte-monocyte ratio were calculated. All patients were scored and graded according to the NPS rule. The survival rate was calculated with Kaplan- Meier method. Multivariate prognostic analysis was performed by Cox models. Results:There was no significant correlation between NPS score and tumor regression or pathological complete response (pCR) of LARC patients after neoadjuvant therapy ( P=0.192, P=0.163). However, Cox multivariate analysis showed that NPS was an independent risk factor for overall survival (OS) and disease-free survival (DFS) of LARC ( P=0.009, P=0.003), and hierarchical analysis suggested that LARC patients with lower NPS score obtained better prognosis. Besides NPS, tumor size was also an independent risk factor for OS, and tumor size and N stage were the independent risk factors for DFS. Conclusion:NPS has no correlation with tumor regression or pCR for LARC after neoadjuvant chemoradiotherapy, whereas it could serve as an effective predictor for long-term prognosis of LARC.
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Objective:To establish a radiomics-based biomarker for predicting pathological response after preoperative neoadjuvant chemoradiotherapy (nCRT) in locally advanced esophageal cancer.Methods:From 2008 to 2018, 112 patients with locally advanced esophageal cancer who received nCRT were enrolled. All patients were treated with preoperative nCRT combined with surgery. Enhanced CT images and clinical information before nCRT were collected. A lesion volume of interest was manually delineated. In total, 670 radiomics features (including tumor intensity, shape and size, texture and wavelet characteristics) were extracted using the pyradiomics package in PYTHON. The stepwise regression combined with the best subset were employed to select the features, and finally the Logistic regression model was adopted to establish the prediction model. The performance of the classifier was evaluated by the area under the ROC curve (AUC). Results:The pathological complete remission (pCR) rate was 58.0%(65/112). 10 radiomics features were included in the final model, The most relevant radiomics feature was the gray feature (the texture information of the image), followed by the shape and voxel intensity-related features. In the training set, the AUC was 0.750 with a sensitivity of 0.711 and a specificity of 0.778, the corresponding values in the testing set were 0.870, 0.757 and 0.900, respectively.Conclusions:Models based on radiomics features from CT images can be utilized to predict the pathological response to nCRT in esophageal cancer. As it is efficient, non-invasive and economic model, it could serve as a promising tool for individualized treatment when validated by further prospective trials in the future.
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The incidence of esophageal cancer ranks third among all malignant tumors in China. Neoadjuvant chemoradiotherapy followed by radical surgery is the standard treatment for locally advanced esophageal cancer. Whether the tumor lesions can achieve complete pathological remission after neoadjuvant chemoradiotherapy provide profound guidance for subsequent treatment. In this article, research progresses on the application of pathological, radiological and biological approaches to evaluate and predict the tumor response to neoadjuvant chemoradiotherapy were reviewed.
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Objective:To systematically evaluate the efficacy and safety between neoadjuvant chemoradiotherapy followed by surgery and immediate surgery in the treatment of resectable and borderline resectable pancreatic cancer.Methods:Literature review was performed from PubMed, Embase, Cochrane Library, Web of Science, CBM, Wanfang, CNKI and VIP from the inception date to February, 2020 using the key words including "pancreatic neoplasm, pancreatic cancer, surgery, preoperative chemoradiotherapy, neoadjuvant chemoradiotherapy" in both English and Chinese. The randomized controlled clinical trials (RCTs) of neoadjuvant chemoradiotherapy followed by surgery versus immediate surgery in the treatment of resectable and borderline resectable pancreatic cancer were searches. Literature screening, data extraction and estimation of the risk of bias were independently conducted by two researchers. The HR and 95% CI were used for estimating the overall survival time. The R 0 resection rate, overall incidence of postoperative complications, and mortality rate throughout treatment were assessed by the RR and 95% CI. The heterogeneity of the studies was analyzed using the I2 test. Results:A total of 4 RCTs were included. Among 400 patients, 197 cases were assigned into the neoadjuvant chemoradiotherapy combined with surgery group and 203 in the immediate surgery group. The results of Meta-analysis showed that patients in the neoadjuvant chemoradiotherapy followed by surgery group obtained longer overall survival ( HR=0.76, 95% CI: 0.60-0.97, P=0.03) and higher R 0 resection rate ( RR=1.72, 95% CI: 1.40-2.13, P<0.01). Besides, the overall incidence of postoperative complications ( RR=1.02, 95% CI: 0.73-1.43, P=0.90) and mortality rate throughout treatment ( RR=1.19, 95% CI: 0.48-2.93, P=0.71) did not significantly differ between two groups. Conclusions:During the treatment of resectable or borderline resectable pancreatic cancer, neoadjuvant chemoradiotherapy followed by surgery may bring more survival benefits than immediate surgery and does not increase the incidence of postoperative complications and mortality rate throughout treatment. Therefore, neoadjuvant chemoradiotherapy followed by surgery can be used as a recommended treatment for patients with resectable or borderline resectable pancreatic cancer.
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Objective:To investigate the MRI differences between locally advanced rectal mucinous adenocarcinoma and non-mucinous adenocarcinoma before and after neoadjuvant chemoradiotherapy (NCR).Methods:A retrospective cohort study was conducted to collect the clinical and imaging data of 165 patients with locally advanced rectal adenocarcinoma treated by NCR combined with surgery from October 2016 to October 2019 in the Sixth Affiliated Hospital of Sun Yat-sen University, 36 cases were rectal mucinous adenocarcinoma and 129 cases were non-mucinous adenocarcinoma. The image features of the two groups before and after NCR were evaluated based on MRI, including the length and thickness of the tumor, the distance from the lower edge of the tumor to the anal edge, T stage, N stage, involvement of mesorectal fascia (MRF) and peritoneal reflux. The difference of NCR and the change of MRI characteristics after NCR were compared by independent sample t test, Mann-Whitney U test or χ 2 test. The accuracy of MRI re-staging after NCR was evaluated according by postoperative pathological staging results. Results:Before NCR, there was significant difference in length of tumor between mucinous adenocarcinoma and non-mucinous adenocarcinoma groups ( P=0.044), there was no significant difference in the distance from the lower edge of the tumor to the anal edge, thickness of the tumor, T stage, N stage, involvement of MRF and peritoneal reflux (all P>0.05). After NCR, in patients with non-mucinous adenocarcinoma, the distance reduction from the lower edge of the tumor to the anal edge, the length reduction of the tumor, the thickness reduction of the tumor, the T-stage decline rate were significantly higher than those in the mucinous adenocarcinoma group (all P<0.05). The N-stage decline rate of mucinous adenocarcinoma was higher than that in non-mucinous adenocarcinoma group ( P=0.008). After NCR, MRI overestimated T staging of patients with both mucinous adenocarcinoma and non-mucinous adenocarcinoma compared with pathological T-stage ( P<0.001). In patients with mucinous adenocarcinoma, MRI overstated the N-stage than pothology ( P=0.001). Conclusions:There is different sensitivity of mucinous adenocarcinoma and non-mucinous adenocarcinoma to NCR. Patients with non-mucinous adenocarcinoma benefit more from the efficacy of NCR. The accuracy of MRI in re-staging of rectal mucinous adenocarcinoma and non-mucinous adenocarcinoma after NCR needs to be improved.
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Objective:To investigate the clinical factors influencing the efficacy and prognosis of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC).Methods:The clinical data of 335 patients with LARC who underwent radical operation after nCRT in Liaoning Cancer Hospital were retrospectively analyzed.Through univariate and multivariate analysis, we found out the clinical factors that may affect the efficacy and prognosis of nCRT in patients with LARC.Results:Multivariate logistic regression analysis showed that the independent clinical factors influencing the curative effect of nCRT in LARC patients were tumor invasion circumference( OR=2.350, 95% CI: 1.438-3.842, P=0.01), cT stage( OR=2.101, 95% CI: 1.024-4.314, P=0.043) and cN stage( OR=5.836, 95% CI: 3.305-10.306, P<0.01). Competitive risk model analysis showed that the independent factors affecting the prognosis of LARC patients were tumor regression grading (TRG) ( HR=3.236, 95% CI: 1.714-6.110, P<0.01), cT stage ( HR=1.852, 95% CI: 1.061-3.230, P=0.030), cN stage ( HR=2.008, 95% CI: 1.083-0.372, P=0.027), and carcinoembryonic antigen (CEA) level before nCRT ( HR=7.038, P<0.01), 95% CI: 3.894-12.720, P<0.01) and serum carbohydrate antigen 199 (CA199) ( HR=3.849, 95% CI: 2.016-7.350, P<0.01). Conclusion:The larger the circumference of tumor invasion before nCRT, cT stage and the cN stage were independent clinical factors influencing the nCRT efficacy of LARC patients.The larger the degree of tumor invasion to the rectum, the higher cT stage and the higher the cN stage before nCRT, the worse the efficacy of nCRT in LARC patients may be. TRG grade, cT stage, cN stage, CEA and CA199 level before nCRT were independent factors affecting the prognosis of LARC patients who received nCRT. The higher the TRG grade, of LARC patients receiving nCRT, the higher cT and cN stage, and the higher the CEA and CA199 level before nCRT, the worse the prognosis of LARC patients may be.
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Lateral lymph node metastasis (LLNM) is one of the major causes for post-operative local recurrence of middle and low rectal cancer. At present, there are still controversies on the diagnosis and treatment of LLNM. The radiological assessment of LLNM generally relies on morphological criteria such as the size or shape of the node or the response to therapy, in which the diagnostic accuracy of MRI is superior to that of other imaging techniques. Neoadjuvant chemoradiotherapy could not achieve good local control for suspicious LLNM. Lateral lymph node dissection (LLND) can reduce tumor local recurrence significantly, but the clinical value of LLND in survival and quality of life of patients has been questioned. 4K laparoscope can decrease the incidence of perioperative complications and urinary and sexual dysfunction to a certain extent. Thus, selective LLND should be undertaken to patients with suspicious LLNM after neoadjuvant chemoradiotherapy, in order to reduce tumor local recurrence and improve the prognosis of patients. The authors elaborate on diagnosis and treatment including surgery or chemoradiotherapy of LLNM in 4K laparoscopic surgery for middle and low rectal cancer combined with their own experiences.
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Some patients with rectal cancer can achieve clinical complete response (cCR) after neoadjuvant chemoradiotherapy. The watch and wait strategy for cCR patients can achieve similar curative effects as radical surgery, avoid surgical complications, and significantly improve the quality of life of patients, which is attracting increasing attention. Although the existing research results support that the watch and wait strategy is safe and feasible, there is still a lack of high-level evidence-based medicine evidence. There are still many issues in the implementation of the watch and wait strategy that need to be further clarified, including long-term oncology efficacy, cCR diagnosis and evaluation criteria, appropriate patient selection, follow-up strategies during the observation period, and treatment methods for local tumor regeneration. This article will explain the above problems based on the results of the existing literature and the clinical experience of our center.
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Objective: Severe radiation-induced late rectal injury (sRLRI) directly affects the quality of life of patients with rectal cancer. Effective prediction of sRLRI before surgery may provide important information for the selection of surgical strategies and perioperative managements. The purpose of this study is to evaluate the feasibility of predicting sRLRI based on magnetic resonance imaging (MRI) features before and after radiotherapy for rectal cancer. Methods: This was a diagnostic study. Clinical and imaging data of 90 patients with rectal cancer receiving long-term radiotherapy from June 2013 to July 2018 in the Sixth Affiliated Hospital of Sun Yat-sen University were collected retrospectively. Case inclusion criteria: (1) rectal cancer was diagnosed by pathology and age of ≥ 18 years old; (2) patients received neoadjuvant chemoradiotherapy and anterior rectal resection; (3) follow up time ≥ 3 years; (4) patients had no history of other neoplasm. Exclusion criteria: (1) patients did not receive MRI examination in our hospital within 2 weeks before and/or 8 weeks after radiotherapy; (2) images were not good enough for evaluation; (3) medical records were incomplete; (4) patients had severe gastrointestinal diseases. According to the RTOG/EORTC classification criteria for radiation reactions, severe complications of grade 3-4 requiring surgical management were defined as sRLRI. T2WI and DWI images before and after radiotherapy were evaluated. The rectal wall thickness, bladder wall thickness, rectal sacral spacing and apparent diffusion coefficient (ADC) were measured. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the above indicators for sRLRI. Results: Among the 90 patients with rectal cancer, 34 (37.8%) developed sRLRI. Before radiotherapy, the median rectal wall thickness of sRLRI and non-sRLRI patients was 4.530 mm and 4.355 mm, respectively; the median bladder wall thickness was 3.962 mm and 3.868 mm, respectively; the median rectal sacral spacing was 15.557 mm and 12.433 mm, respectively; the median ADC value of rectal wall was 1.620 ×10(-3) mm(2)/s and 1.653 ×10(-3) mm(2)/s, respectively. There were no significant differences in above indicators between sRLRI and non-sRLRI patients (all P>0.05). After radiotherapy, compared with non-sRLRI patients, sRLRI patients had increased rectal wall thickness (median: 8.239 mm vs. 6.223 mm, Z=-3.512, P=0.001), rectal sacral spacing (median: 17.728 mm vs. 13.885 mm, Z=-2.247, P=0.025), and change of rectal wall thickness after radiotherapy (median: 98.106% vs. 49.584%, Z=-4.169, P<0.001). After radiotherapy, there were no significant differences in the bladder wall thickness and its change value, the ADC value of rectal wall and its change rate before and after radiotherapy between the two groups (all P>0.05). The area under the curve (AUC) of the change rates of rectal wall thickness after radiotherapy, rectal wall thickness and rectal sacral spacing after radiotherapy for predicting sRLRI was 0.763, 0.722 and 0.642, respectively, while the sensitivity was 85.3%, 70.6% and 76.5%, respectively, and the specificity was 64.3%, 71.4% and 57.1%, respectively. Conclusion: Based on MRI examinations, assessments of rectal wall thickness after radiotherapy, the change rate of rectal wall thickness after radiotherapy, and rectal sacral spacing after radiotherapy are helpful for evaluating the risk of sRLRI after radiotherapy for patients with rectal cancer.
Subject(s)
Adolescent , Chemoradiotherapy , Diffusion Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging , Neoadjuvant Therapy , Quality of Life , Rectal Neoplasms/radiotherapy , Retrospective Studies , Treatment OutcomeABSTRACT
Objective: To investigate whether protective colostomy and protective ileostomy have different impact on anastomotic leak for rectal cancer patients after neoadjuvant chemoradiotherapy (nCRT) and radical surgery. Methods: A retrospectively cohort study was conducted. Inclusion criteria: (1) Standard neoadjuvant therapy before operation; (2) Laparoscopic rectal cancer radical resection was performed; (3) During the operation, the protective enterostomy was performed including transverse colostomy and ileostomy; (4) The patients were followed up regularly; (5) Clinical data was complete. Exclusion criteria: (1) Colostomy and radical resection of rectal cancer were not performed at the same time; (2) Intestinal anastomosis is not included in the operation, such as abdominoperineal resection; (3) Rectal cancer had distant metastasis or multiple primary colorectal cancer. Finally 208 patients were included in this study. They suffered from rectal cancer and underwent protective stoma in radical surgery after nCRT at our hospital from January 2014 to December 2018. There were 148 males and 60 females with age of (60.5±11.1) years. They were divided into protective transverse colostomy group (n=148) and protective ileostomy group (n=60). The main follow up information included whether the patient has anastomotic leak and the type of leak according to ISREC Grading standard. Besides, stoma opening time, stoma flow, postoperative hospital stay, stoma related complications and postoperative intestinal flora were also collected. Results: A total of 28 cases(13.5%) suffered from anastomotic leak and 26 (92.9%) of them happened in the early stage after surgery (less than 30 days) . As for these early-stage leak, ISREC Grade A happened in 11 cases(42.3%), grade B in 15 cases(57.7%) and no grade C occurred. There was no significant difference in the incidence [12.8% (19/148) vs. 15.0% (9/60) , χ(2)=0.171, P=0.679] or type [Grade A: 5.4%(8/147) vs. 5.1%(3/59); Grade B: 6.8%(10/147) vs. 8.5%(5/59), Z=0.019, P=1.000] of anastomotic leak between the transverse colostomy group and ileostomy group (P>0.05), as well as operation time, postoperative hospital stay, drainage tube removal time or stoma reduction time (P>0.05). There were 10 cases (6.8%) and 24 cases (40.0%) suffering from intestinal flora imbalance in protective transverse colostomy and protective ileostomy group, respectively (χ(2)=34.503, P<0.001). Five cases (8.3%) suffered from renal function injury in the protective ileostomy group, while protective colostomy had no such concern (P=0.002). The incidence of peristomal dermatitis in the protective colostomy group was significantly lower than that in the protective ileostomy group [12.8% (9/148) vs. 33.3%(20/60), χ(2)=11.722, P=0.001]. Conclusions: It is equally feasible and effective for rectal cancer patients after nCRT to carry out protective transverse colostomy or ileostomy in radical surgery. However, we should pay more attention to protective ileostomy patients, as they are at high risk of intestinal flora imbalance, renal function injury and peristomal dermatitis.
Subject(s)
Aged , Anastomosis, Surgical , Anastomotic Leak/prevention & control , Cohort Studies , Colostomy , Female , Humans , Ileostomy , Male , Middle Aged , Neoadjuvant Therapy , Rectal Neoplasms/surgery , Retrospective StudiesABSTRACT
Objective: To explore clinical features and prognosis of anastomotic leak (AL) after anterior resection following neoadjuvant chemoradiotherapy for rectal cancer patients. Methods: A retrospective cohort study was performed. Data were retrieved from colorectal cancer database of the Sixth Affiliated Hospital, Sun Yat-sen University. The clinical data of 470 patients with rectal cancer who underwent anterior resection after neoadjuvant chemoradiotherapy at our department from September 2010 to December 2018 were enrolled. Clinical features and outcome of postoperative AL were analyzed. The primary outcomes were the short-term and long-term incidence and severity of AL (ISREC grading standard was adopted). The secondary outcomes were the prognostic indicators of AL, including the secondary chronic presacral sinus, anastomotic stenosis and persistent stoma. Patients received regular follow-up every 3-6 months after surgery, including physical examination, blood test, colonoscopy and image; those received follow-up once a year after postoperative 2-year; those who did not return to our hospital received telephone follow-up. Data of this study were retrieved up to January 2020. Univariate χ(2) test and multivariate logistic analysis were used to identify risk factors of AL and prognostic factors of persistent stoma. Results: There were 331 males (70.4%) with the average age of (53.5±11.6) years. Distance from tumor to anal verge ≤ 5 cm was found in 228 (48.5%) patients. The diverting stoma was performed in 440 (93.6%) patients. After a median follow-up of 28 months, AL was found in 129 (27.4%) patients, including 67 (14.3%) patients with clinical leak (ISREC grade B-C). The median time for diagnosis of AL was 70 days (2-515 days) after index surgery. Common symptoms included sacrococcygeal pain (27.9%, 36/129), purulent discharge through anus (25.6%, 33/129), and rectal irritation (17.8%, 23/129). Sixty five point one percent (84/129) of the defect site was at the posterior wall of the anastomosis. Transanal incision and drainage or lavage (27.9%, 36/129) and percutaneous drainage under ultrasound or CT (17.1%, 22/129) were the most common management. Chronic presacral sinus tract could not be evaluated in 12 patients because imaging was performed more than 1 year after the operation. Evaluation beyond 1 year showed that 73 of 458 eligible patients (15.9%) were found with chronic presacral sinus, accounting for 62.4% (73/117) of patients with AL; 69 of 454 (15.2%) were diagnosed with anastomotic stenosis, of whom 49 were secondary to AL; 59 of 470 (12.6%) had persistent stoma due to AL. Univariate analysis showed that male, operative duration > 180 minutes, intraoperative blood loss >150 ml, and pelvic radiation injury were associated with AL (all P<0.05). Multivariate analysis showed that male (OR=1.72, 95% CI: 1.04-2.86, P=0.036), intraoperative blood loss > 150 ml (OR=1.82, 95% CI: 1.11-2.97, P=0.017), and pelvic radiation injury (OR=4.90, 95% CI: 3.09-7.76, P<0.001) were independent risk factors of AL after anterior resection. For patients with AL, clinical leak (ISREC grade B-C) (OR=9.59, 95% CI: 3.73-24.69, P<0.001), age ≤55 years (OR=3.35, 95% CI: 1.35-8.30, P=0.009), distance from tumor to anal verge ≤ 5 cm (OR=3.33, 95% CI: 1.25-8.92, P=0.017), and pelvic radiation injury (OR=3.29, 95% CI: 1.33-8.14, P=0.010) were independent risk factors of persistent stoma. Conclusions: AL after anterior resection following neoadjuvant chemoradiotherapy for rectal cancer patients is common. Among patients with AL, the proportion of those needing persistent stoma is high. Pelvic radiation injury is significantly associated with occurrence of AL and subsequent persistent stoma. Sphincter-preserving surgery for rectal cancer should be selectively used based on the risk of pelvic radiation injury, which is beneficial to reduce the incidence of AL and improve the quality of life.
Subject(s)
Adult , Aged , Anastomosis, Surgical , Anastomotic Leak , Chemoradiotherapy , Humans , Male , Middle Aged , Neoadjuvant Therapy , Prognosis , Quality of Life , Rectal Neoplasms/surgery , Retrospective StudiesABSTRACT
Objective: Pelvic high-resolution magnetic resonance imaging (MRI) has now become a standard method for evaluating the efficacy of neoadjuvant treatment for locally advanced rectal cancer (LARC). However, this traditional morphological qualitative assessment method based on T2-weighted imaging (T2WI) is not effective in predicting pathological complete remission (pCR). The purpose of this study is to investigate whether combining the magnetic resonance tumor regression grade (mrTRG) with apparent diffusion coefficient (ADC) can improve diagnostic value for pCR after preoperative neoadjuvant chemoradiotherapy (nCRT) of LARC. Methods: This was a diagnostic study. Clinicopathological data of 134 LARC patients who received nCRT and radical surgery in the First Affiliated Hospital of Kunming Medical University from January 2017 to December 2019 were retrospectively analyzed. All the patients underwent MRI which included T2WI and DWI sequences before and 8 weeks after nCRT. Two radiologists independently drew ROIs on T2WI and DWI to estimate mrTRG stage and calculate the mean ADC value. Receiver operating characteristics (ROC) method was applied to evaluate the predict value of mrTRG combined with mean ADC value for pCR. Results: Of 134 LARC patients, 85 were male and 49 were female with median age of 58 (28-82) years. After nCRT, MRI suggested 21 patients (15.7%) had clinical complete remission (cCR), e.g. mrTRG stage 1-2. Postoperative pathology revealed 31 (23.1%) patients had pCR. The evaluations of mrTRG and ADC value by the two readers were highly consistent, and the intra-group correlation coefficients were 0.83 (95% CI: 0.703-0.881) and 0.96 (95% CI: 0.989-0.996), respectively. There was a negative correlation between mrTRG and pCR (r(s)=-0.505, P<0.01), and a positive correlation between mean ADC value and pCR (r(s)=0.693, P<0.01). The ROC curve showed that mrTRG alone had a medium predictive value for pCR, with an area under the curve (AUC) of 0.832 (95% CI: 0.743-0.921); the mean ADC value had a higher predictive value for pCR, with AUC of 0.906 (95% CI: 0.869-0.962). The predictive value of the combined model of mrTRG and ADC value for pCR was significantly better than that of mrTRG alone (P=0.015), and the AUC was 0.908 (95% CI: 0.849-0.968). Conclusion: Both mrTRG and mean ADC value can be non-invasive methods to predict the efficacy of nCRT for LARC. Combining the mean ADC value with mrTRG can result in better pCR prediction.
Subject(s)
Aged , Aged, 80 and over , Chemoradiotherapy , Diffusion Magnetic Resonance Imaging , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neoadjuvant Therapy , Rectal Neoplasms/therapy , Retrospective Studies , Treatment OutcomeABSTRACT
Objective: To investigate the prognosis and postoperative complications of local excision for rectal cancer after neoadjuvant chemoradiotherapy (nCRT). Methods: A descriptive case series study was carried out. Patient inclusion criteria: (1) patients who underwent local excision by transanal endoscopic microsurgery (TEM) after nCRT; (2) magnetic resonance evaluated tumor regression grade (mrTRG) as 1, 2 after nCRT;(3) American Society of Anesthesiologists class I to III. Patient exclusion criteria: (1) with multiple primary colorectal cancers; (2) with other malignant tumors within five years; (3) with emergency surgicery indications like digestive tract obstruction, perforation or bleeding. Clinicopathological and follow-up data of rectal cancer patients with obvious tumor regression after nCRT who underwent local excision in Peking Union Medical College Hospital from January 2010 to August 2019 were retrospectively collected. Outcome measures included disease-free survival (DFS), short-term postoperative complications, and at postoperative 1-year during follow up, gas continence, fecal continence, and quality of life (using the EORTC QLQ-CR29 scale, higher score indicated worse quality of life) at postoperative 1-year. Results: A total of 40 patients were included in this study. There were 27 males and 13 females with an average age of (66.7±12.3) years. Preoperative rectal ultrasound and other imaging examinations indicated that the tumor was located in the anterior wall in 16 cases, the lateral wall in 12 cases, and the posterior wall in 12 cases. The distance between the lower margin of the tumor and the anal verge was (4.3±1.2) cm before nCRT and (5.1±0.9) cm after nCRT. According to mrTRG, 31 cases were assessed as mrTRG 1 and 9 cases as mrTRG 2. All the patients received local extended excision of rectal cancer using TEM platform. A total of 19 cases(47.5%) suffered from complications within one month postoperatively. Clavien-Dindo grade I complications happened in 14 cases, grade II in 3 patients, and grade III in 2 cases, who all were healed by conservative treatment. Except that 2 patient presented severe low anterior resection syndrome (LARS) at 1 year postoperatively, no severe anal dysfunction was found in this cohort patients. EORTC QLQ CR29 scale results for quality of life showed that at 1 year after TEM excision, except taste (Z=-1.968, P=0.049), anxiety (Z=-3.624, P<0.001) and skin irritation (Z=-2.420, P=0.023) were worse than the situation before neoadjuvant therapy, there were no statistically significant differences in other assessment results between pre-operation and post-operation (all P>0.05). Postoperative pathological results indicated complete tumor regression (pTRG0) in 17 cases, moderate remission (pTRG1) in 13, and mild remission (pTRG2) in 10. During the follow-up of (49.1±29.6) months, 3 patients had local recurrence and 4 had distant metastasis (3 patients with liver metastasis and 1 patient with lung metastasis followed by liver metastasis). No death was found and the 5-year disease-free survival (DFS) was 84.3%. Conclusions: Local excision through TEM following nCRT not only can be adopted as an important means to accurately determine complete clinical remission (cCR), but also has high therapeutic value for rectal cancer patients presenting cCR or near cCR, with little impact on defecatory function and quality of life. However, the morbidity of complication of TEM excision after nCRT is relatively high and there is a risk of recurrence and metastasis. Therefore, it is still necessary to strictly select the indications of local excision.
Subject(s)
Aged , Chemoradiotherapy , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Recurrence, Local , Postoperative Complications , Prognosis , Quality of Life , Rectal Neoplasms/therapy , Retrospective Studies , Syndrome , Treatment OutcomeABSTRACT
Objective: To investigate the effectiveness, safety, and prognosis of neoadjuvant chemoradiotherapy (nCRT) for Siewert type II and III adenocarcinomas of the esophagogastric junction (AEG). Methods: This study is a prospective randomized controlled clinical study (NCT01962246). AEG patients who were treated at the Third Department of Surgery of the Fourth Hospital of Hebei Medical University from February 2012 to June 2016 were included. All of the enrolled patients were diagnosed with type II or III locally advanced AEG gastric cancer (T2-4N0-3M0 or T1N1-3M0) by gastroscopy and CT before operation; the longitudinal axis of the lesion was ≤ 8 cm; no anti-tumor treatment was previously given and no contraindications of chemotherapy and surgery were found. Case exclusion criteria: serious diseases accompanied by liver and kidney, cardiovascular system and other vital organs; allergy to capecitabine or oxaliplatin drugs or excipients; receiving any form of chemotherapy or other research drugs; pregnant or lactating women; patients with diseases resulting in difficulty to take capecitabine or with concurrent tumors. Based on sample size estimation, a total of 150 AEG patients were enrolled. Using the random number table method, the enrolled patients were divided into the nCRT group and the direct operation group with 75 cases in each group. The nCRT group received XELOX chemotherapy (capecitabine+ oxaliplatin) before surgery and concurrent radiotherapy (45 Gy, 25 times, 1.8 Gy/d, 5 times/week). Clinical efficacy of the nCRT group was evaluated by the solid tumor efficacy evaluation standard (RECIST1.1) and the tumor volume reduction rate was measured on CT. After completing the preoperative examination in the direct operation group, and 8-10 weeks after the end of nCRT in the nCRT group, surgery was performed. Laparoscopic exploration was initially performed. According to the Japanese "Regulations for the Treatment of Gastric Cancer", a transabdominal radical total gastrectomy combined with perigastric lymph node dissection was performed. The primary outcome was the 3-year overall survival (OS) and disease-free survival rate (DFS); the secondary outcomes were R0 resection rate, the toxicity of chemotherapy, and surgical complications. The follow-up ended on December 31, 2019. The postoperative recurrence, metastasis and survival time of the two groups were collected. Results: After excluding patients with incomplete clinical data, patients or family members requesting to withdraw informed consent, and those failing to follow the treatment plan, 63 cases in the nCRT group and 69 cases in the direct operation group were finally enrolled in the study. There were no statistically significant differences in baseline characteristics of the two groups (all P>0.05). Sixty-three patients in the nCRT group were evaluated by RECIST1.1 after treatment, the image based effective rate was 42.9% (27/63), and the stable disease rate was 98.4% (62/63); the tumor volume before and after nCRT measured on CT was (58.8±24.4) cm(3) and (46.6±25.7) cm(3), respectively, the effective rate of tumor volume reduction measured by CT was 47.6% (30/63). Incidences of neutrophilopenia [65.1% (41/63) vs. 40.6% (28/69), χ(2)=7.923, P=0.005], nausea [81.0% (51/63) vs. 56.5% (39/69), χ(2)=9.060, P=0.003] and fatigue [74.6% (47/63) vs. 42.0% (29/69), χ(2)=14.306, P=0.001] in the nCRT group were significantly higher than those in the direct surgery group. Radiation gastritis/esophagitis and radiation pneumonia were unique adverse reactions in the nCRT group, with incidences of 52.4% (33/63) and 15.9%(10/63), respectively. The classification of tumor regression of 63 patients in nCRT group presented as 11 cases of grade 0 (17.5%), 20 cases of grade 1 (31.7%), 28 cases of grade 2 (44.4%), and 5 cases of grade 3 (7.9%). Eleven (17.5%) patients achieved pathologic complete response. Sixty-one (96.8%) patients in the nCRT group underwent R0 resection, which was higher than 87.0% (60/69) in the direct surgery group (χ(2)=4.199, P=0.040). The mean number of harvested lymph nodes in the specimens in the nCRT group and the direct operation group was 27.6±12.4 and 26.8±14.6, respectively, and the difference was not statistically significant (t=-0.015, P=0.976). The pathological lymph node metastasis rate and lymph node ratio in the two groups were 44.4% (28/63) vs. 76.8% (53/69), and 4.0% (70/1 739) vs. 21.9% (404/1 847), respectively with statistically significant differences (χ(2)=14.552, P<0.001, and χ(2)=248.736, P<0.001, respectively). During a median follow-up of 52 (27-77) months, the 3-year DFS rate in the nCRT group and the direct surgery group was 52.4% and 39.1% (P=0.049), and the 3-year OS rate was 63.4% and 52.2% (P=0.019), respectively. According to whether the tumor volume reduction rate measured by CT was ≥ 12.5%, 63 patients in the nCRT group were divided into the effective group (n=30) and the ineffective group (n=33). The 3-year DFS rate of these two subgracps was 56.6% and 45.5%, respectively without significant difference (P=0.098). The 3-year OS rate was 73.3% and 51.5%,respectively with significant difference (P=0.038). The 3-year DFS rate of patients with the tumor regression grades 0, 1, 2 and 3 was 81.8%, 70.0%, 44.4%, and 20.0%, repectively (P=0.024); the 3-year OS rate was 81.8%, 75.0%, 48.1% and 40.0%, repectively (P=0.048). Conclusion: nCRT improves treatment efficacy of Siewert type II and III AEG patients, and the long-term prognosis is good.