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Background: Neoadjuvant chemotherapy (NACT) in carcinoma stomach was introduced in an effort to eliminate micro-metastasis and to improve resectablity before surgery which improves R0 resection rates. The aim of the current study was to evaluate the effect of neoadjuvant chemotherapy on downstaging and resectability rate in locally advanced gastric cancer. Material & Methods: This was a single-center quasi-experimental study conducted in the Department of Surgical Oncology in collaboration with the Departments of Medical Oncology, Radiation oncology, and Pathology at the National Institute of Cancer Research and hospital, Dhaka, which is a tertiary care cancer hospital in Bangladesh, between January 2021 and June 2022.Patients with locally advanced adenocarcinoma stomach staged by contrast-enhanced computed tomography (CECT) were randomly included in this study by purposive sampling. Patients in Group I underwent upfront surgery Patients in Group II were started on neoadjuvant chemotherapy, either XELOX or FLOT regimen. Surgery was done following the response assessment CECT. We assessed R0 resection rate, age, sex, comorbidities, tumour size, TNM stage and complications were compared between the two groups. Response to NACT was assessed in Group II. Results: The mean age of patients in groups 1 & 2 was 56 ± 11.06 and 55.70 ± 10.46 years of age respectively (p > 0.05). Majority of the respondents (55/74) were male and 19 patients (26%) were female. Male to female ratio was (24/37 &31/37) in group 1 and (31/37 & 6/37) groups respectively (p > 0.05). Out of 37 patients who received NACT, in 9 patients (24.32%) complete response was noted. Partial response was found in 20 cases (54.05%), p-value (<.0001) while a stable disease was reported in three (8.1%) cases. 5 patients (13.51%) had progressive disease. In the upfront surgery group, R0 resection was feasible in 16 (43.2%) cases, and in the NACT plus surgery group, R0 resection was done in 29 (78.4%) cases. In group 1, R1 resection was done in considerable numbers (19/37) compared to group 2 (5/37), P=0.001. Three patients (8.1%) in group 2 and one (2.7) in group 1 had irresectable lesions. Conclusion: In this study it can be concluded that neoadjuvant chemotherapy could downstage tumour and increase tumor resectability rate in patients with locally-advanced gastric adenocarcinoma. However, further studies are necessary to confirm the effect of this modality on patients’ overall survival. We await survival analysis to further validate the role of NACT.
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SUMMARY OBJECTIVE: Breast cancer is the most common malignancy in women. In the treatment of these patients, pathological complete response is defined as the absence of invasive cancer in breast or lymph node tissue after the completion of neoadjuvant chemotherapy. In this study, we aimed to investigate the relationship of enhancer of zeste homolog 2 and mucin 1 expressions with pathological complete response in patients with breast cancer receiving neoadjuvant chemotherapy. METHODS: A total of 151 patients were included in the study. Enhancer of zeste homolog 2 and mucin 1 expressions were evaluated in the biopsy materials pre-neoadjuvant chemotherapy and post-neoadjuvant chemotherapy surgical material, and their relationship with pathological complete response was investigated. RESULTS: The pathological complete response rates were significantly higher among the hormone receptor-negative patients, those with a high Ki-67 score, and patients with HER2-positive. Higher pathological complete response rates were obtained from patients with enhancer of zeste homolog 2 expression positivity pre-neoadjuvant chemotherapy. In addition, after neoadjuvant chemotherapy, enhancer of zeste homolog 2 expression was found to be completely negative in materials with pathological complete response; that is, in breast tissues considered to be tumor-free. While there was no significant relationship between mucin 1 expression and pathological complete response pre-neoadjuvant chemotherapy, mucin 1 expression was determined to significantly differ between the tissues with and without pathological complete response among the surgical materials examined. CONCLUSION: In our study investigating the relationship between enhancer of zeste homolog 2 and mucin 1 expression and pathological complete response in patients who received neoadjuvant chemotherapy, we found that enhancer of zeste homolog 2 expression could be used as a predictive marker for pathological complete response. However, mucin 1 expression was not associated with pathological complete response.
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Objective:To compare the effect of neoadjuvant chemotherapy vs. concurrent chemoradiotherapy on the target volume and organs at risk for locally advanced bulky (>4 cm) cervical cancer. Methods:From March 1, 2019 to June 30, 2021, 146 patients pathologically diagnosed with cervical cancer were selected and randomly divided into two groups using random number table method: the neoadjuvant chemotherapy (NACT) + concurrent chemoradiotherapy (CCRT) group ( n=73) and CCRT group ( n=73). Patients in the NACT+CCRT group received 2 cycles of paclitaxel combined with cisplatin NACT, followed by CCRT, the chemotherapy regimen was the same as NACT. In the CCRT group, CCRT was given. Statistical description of categorical data was expressed by rate. The measurement data between two groups were compared by Wilcoxon rank-sum test for comparison of two independent samples, and the rate or composition ratio of two groups was compared by χ2 test. Results:Before radiotherapy, GTV in the NACT+CCRT group was (31.95±25.96) cm 3, significantly lower than (71.54±33.59) cm 3 in the CCRT group ( P<0.01). Besides, CTV and PTV in the NACT+CCRT group were also significantly lower compared with those in the CCRT group (both P<0.05). In terms of target volume dosimetry, D 100GTV, D 95CTV, V 100GTV, V 100CTV and V 95PTV in the NACT+CCRT group were significantly higher than those in the CCRT group (all P<0.05). The complete remision (CR) rates in the NACT+CCRT and CCRT groups were 86.3% and 67.6%, with statistical significance between two groups ( P<0.01) . Regarding organs at risk, NACT+CCRT group significantly reduced the dose to the bladder, rectum, small intestine and urethra compared with CCRT group (all P<0.05). Conclusions:NACT can reduce the volume of tumors in patients with large cervical masses, increase the radiation dose to tumors, reduce the dose to organs at risk, and make the three-dimensional brachytherapy easier. Therefore, NACT combined with CCRT may be a new choice for patients with locally advanced cervical cancer with large masses.
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Objective:To investigate whether ultrasound features, mammographic features and immunohistochemical indicators show any association with rates of axillary pathologic complete response(pCR) in cN 1 breast cancer patients receiving neoadjuvant chemotherapy(NAC), and to construct prediction models of axillary pCR to predict axillary lymph nodes (ALN) status, so as to select suitable patients for less invasive axillary surgery after NAC. Methods:This retrospective study evaluated 134 consecutive cN 1 breast cancer patients with ALN metastasis who underwent NAC in the Second Affiliated Hospital and Tumor Hospital of Harbin Medical University from July 2020 to July 2022. According to the pathological results of ALN surgery after NAC, the cases were divided into pCR and non pathologic complete respose(npCR) groups. The ultrasound images, mammographic images and immunohistochemical indicators of the two groups were compared. In terms of logistic regression algorithm, the model A(the ultrasound model), the model B(the ultrasound combined with mammography model), the model C(the ultrasound combined with immunohistochemistry model) and the model D(the ultrasound combined with mammography and immunohistochemistry model) were respectively established for predicting the pathological state of axillary lymph nodes in breast cancer patients, ROC curves were plotted to evaluate the performance of the models, and the diagnostic efficiency of different models was compared by Delong′s test. The model with the best predictive performance was shown in a nomogram. Results:①The P values between two groups of the short diameter of ALN, the ratio of long/short diameter of ALN, fatty hilum and central hilar vascularity, mammographic spiculation, estrogen receptor(ER), progesterone receptor(PR), human epidermal growth factor receptor 2(HER2) were <0.05 by the t test and χ 2 test analysis. ②The ratio of long/short diameter and fatty hilum in the model A were independent factors for predicting the pathological status of ALN after NAC. The independent predictors of model B and Model C were respectively added with mammographic spiculation and immunohistochemical indicators (ER, PR) on the basis of model A. In the model D, the ratio of long/short diameter, short diameter, fatty hilum, mammographic spiculation, and immunohistochemical indicators (ER, PR) remained significant independent predictors associated with axillary pCR. ③The area under ROC curve (AUC) of the model A, B, C, D was 0.78, 0.84, 0.84 and 0.89, respectively. The sensitivity was 0.71, 0.80, 0.78 and 0.86, the specificity was 0.76, 0.74, 0.76 and 0.80, and the accuracy was 0.73, 0.76, 0.77 and 0.83, respectively. ④Delong′s test showed the model D had an improved AUC of 0.89(0.89 vs 0.78, 0.84, 0.84, all P<0.05). Conclusions:The prediction models combining bi-modal imaging and immunohistochemical indicators show good prediction ability and can provide reference for selecting suitable patients for less invasive axillary surgery after NAC.
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Objective:To investigate the feasibility of deep learning radiomics model in the prediction of neoadjuvant chemotherapy (NAC) response in breast cancer based on ultrasound images at an early stage.Methods:Between January 2018 and June 2021, 218 patients with breast cancer who underwent NAC were enrolled in the retrospective study. All patients received a full cycle of NAC before surgery and underwent standard ultrasound examination before NAC and after the second cycles of NAC. Of all the patients, 166 patients came from institution 1 (the First Affiliated Hospital of Nanjing Medical University) were allocated into a primary cohort.Based on the architecture of Resnet 50 convolutional neural, a deep learning prediction model was built.Further validation was performed in an external testing cohort ( n=52) from institution 2 (General Hospital of Eastern Theater Command, PLA). The clinical model was constructed using independent clinical variables. To evaluate the predictive performance, areas under the curve (AUCs) of these models and two radiologists were compared by using the DeLong method. Results:The Resnet 50 model predicted the response of NAC with accuracy. The deep learning model, achieving an AUC of 0.923 (95% CI=0.884-0.962) in the primary cohort and an AUC of 0.896 (95% CI=0.807-0.980) in the test cohort, outperformed the clinical model and also performed better than two radiologists′ prediction (all P<0.05). Furthermore, the two radiologists achieved a better predictive efficacy (AUC 0.832 and 0.808 for radiologists 1 and 2, respectively) when assisted by the DL model (all P<0.01). Conclusions:The deep learning radiomics model is able to predict therapy response in the early-stage of NAC for breast cancer patients, which could guide clinicians and provide benefit for timely treatment strategy adjustment.
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Objective:To investigate the effect of neoadjuvant chemotherapy on the safety of laparoscopic D 2 radical resection and prognosis of patients with locally advanced gastric cancer. Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 351 patients with locally advanced gastric cancer who underwent laparos-copic D 2 radical resection in the Second Affiliated Hospital of Air Force Medical University from December 2016 to December 2021 were collected. There were 256 males and 95 females, aged (58±9)years. Of the 351 patients, 124 cases undergoing neoadjuvant chemotherapy were divided into the neoadjuvant chemotherapy group, 227 patients undergoing postoperative adjuvant chemotherapy were divided into the adjuvant chemotherapy group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) effect evaluation of neoadjuvant chemotherapy; (3) intraoperative and postoperative situations; (4) postoperative histopathological examinations; (5) follow-up. Propensity score matching was done by the 1∶1 nearest neighbor matching method. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measure-ment data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curves, and the Log-Rank test was used for survival analysis. Results:(1) Propensity score matching conditions and comparison of general data of patients between the two groups of patients after matching. Of 351 patients, 154 cases were successfully matched, including 77 cases in the neoadjuvant chemotherapy group and 77 cases in the adjuvant chemotherapy group. The elimination of gender, age, preoperative body mass index, clinical T staging and clinical N staging confounding bias ensured comparability between the two groups after propensity score matching. (2) Effect evaluation of neoadjuvant chemotherapy. Of the 77 patients receiving neoadjuvant chemotherapy, none of patient achieved complete response, 26 patients achieved partial response, 46 patients showed stable disease, 5 patients had progression of disease, showing the objective response rate as 33.8%(26/77) and the disease control rate as 93.5%(72/77). There were 15 males and 11 females sensitive to neoadjuvant chemotherapy, while 46 males and 5 females not sensitive, showing a significant difference between them ( χ2=11.05, P<0.05). (3) Intra-operative and postoperative situations. The operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion, time to postoperative first flatus, time to postoperative first liquid food intake, duration of postoperative hospital stay, cases with postoperative immediate complications, cost of hospital stay were (308±71)minutes, 100(range, 20?600)mL, 5, 3.0(range, 2.0?10.0)days, 4.0(range, 2.0?12.0)days, 9.0(range, 4.0?31.0)days, 7, 7.96(7.37,8.58) ten thousand yuan in patients of the neoadjuvant chemotherapy group, versus (296±67)minutes, 100(range, 20?500)mL, 4, 3.5(range, 1.0?14.0)days, 4.0(range, 2.0?15.0)days, 8.0(range, 5.0?45.0)days, 11, 8.18(7.52,9.19) ten thousand yuan in patients of the adjuvant chemotherapy group, showing no signifi-cant difference in the above indicators between the two groups ( t=1.13, Z=?0.37, χ2=0.12, Z=?1.26, ?0.33, ?0.70, χ2=1.01, Z=?1.04, P>0.05). (4) Postoperative histopathological examinations. Results of postoperative histopatho-logical examinations showed that all 154 patients achieving R 0 resection. Cases with pathological T staging as stage T1, stage T2, stage T3, stage T4, cases with pathological N staging as stage N0, stage N1, stage N2, stage N3, number of positive lymph nodes, cases with human epidermal growth factor receptor 2 (negative, positive) were 3, 7, 5, 62, 27, 19, 19, 12, 1(range, 0?28), 59, 18 in patients of the neoadjuvant chemotherapy group, versus 0, 0, 2, 75, 17, 15, 21, 24, 3(range, 0?31), 44, 33 in patients of the adjuvant chemotherapy group, showing significant differences in the above indicators between the two groups ( Z=?3.39, ?2.55, ?3.12, χ2=6.60, P<0.05). (5) Follow-up. Of the 154 patients, 143 patients were followed up for 37(range, 5?69)months. The 3-year overall survival rate and 3-year disease-free survival rate was 72.1% and 70.0%, respectively, in patients of the neoadjuvant chemotherapy group, versus 74.8% and 76.6% in patients of the adjuvant chemo-therapy group, showing no significant difference in the above indicators between the two groups ( χ2=0.14, 0.60, P>0.05). Conclusions:Compared to postoperative adjuvant chemotherapy, neoadjuvant chemotherapy does not bring additional surgical risks, but can reduce the tumor stage of patients who underwent laparoscopic D 2 radical resection for locally advanced gastric cancer. However, it does not show any advantage in improving survival of patients.
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Objective:To explore the risk factors analysis and validation of anemia after triple-negative breast cancer (TNBC) and risk prediction model, to provide reference for reducing the incidence of anemia after TNBC-NAC.Methods:Retrospectively, 316 female TNBC-NAC patients in the breast department of our hospital from January 2016 to July 2021 were selected as the study subjects (modeling set), and the condition of anemia after the last chemotherapy was set as the observation group. In addition, 98 breast cancer patients in 2022 were selected for validation. Multivariate Logistic regression was used to analyze the effect of Fukangning capsule on TNBC-NAC anemia. We established the risk nomogram prediction model and calibration curve of anemia after chemotherapy by using R software and conducted internal and external verification. Hosmer-Lemeshow test was used to evaluate the prediction deviation between the risk prediction value of the nomogram model and the actual observed value, and the ROC curve was used to evaluate the prediction effect of the model.Results:A total of 75 (23.73%) among 316 patients developed anemia. The results of multivariate Logistic regression analysis showed that menopause [ OR (95% CI)=26.739 (5.063-141.227)], RBC [ OR (95% CI)=0.168 (0.098-0.286)], Hb level [ OR (95% CI)=0.952 (0.929-0.976)], and pathological stage Ⅲ[ OR (95% CI)=4.182 (1.759-9.946)] were independent risk factors for anemia after TNBC-NAC ( P<0.05). The nomogram prediction model established based on the above factors. Hosmer-Lemeshow test results showed that the difference between the risk prediction value and the actual observed value is ( χ2=3.68, P=0.885). The correction curve approaches to the ideal curve and the average absolute error was 0.012. The area under the ROC curve was 0.945, 95% CI was 0.918-0.972, sensitivity was 0.921 and specificity was 0.853, suggesting that the model has good differentiation and calibration degree. The external validation results showed that the nomogram predicted anemia with sensitivity of 88.7%, spectificity of 85.45% and accuracy of 86.73%. Conclusion:Menopausal status, RBC, Hb level before chemotherapy and pathological stage are independent risk factors for anemia after taking TNBC-NAC. The nomogram prediction model based on the above indicators had good discrimination and calibration, and accurately predicted the possibility of anemia after TNBC-NAC.
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The overall efficacy of neoadjuvant chemotherapy for locally advanced gastric cancer has been recognized. However, neoadjuvant chemotherapy is ineffective in a subset of patients due to tumor heterogeneity. The tumor regression grade (TRG) has unique advantages in assessing the efficacy of neoadjuvant chemotherapy for gastric cancer. Nonetheless, since TRG is dependent on postoperative pathology, it becomes a significant topic today to mine TRG predictors to more accurately select appropriate patients for neoadjuvant chemotherapy. Therefore, to understand the relevant research progress and current research challenges of TRG predictors after neoadjuvant chemotherapy for gastric cancer from the aspects of biomarkers, immunity, inflammatory indicators, body composition, imaging indicators, etc., is conducive to further clinical research and practice.
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Objective:To investigate the feasibility of sentinel lymph node biopsy in breast cancer patients with positive axillary lymph nodes turned to clinical negative after neoadjuvant chemotherapy.Methods:Full-text journal databases such as PubMed, Cochrane Library, Embase, Wanfang, VIP, and CNKI were searched to include research literature on sentinel lymph node biopsy in breast cancer patients who had axillary lymph nodes turned negative after neoadjuvant chemotherapy. The retrieval time was self-established to November 2020. Meta-analysis was performed on the literature that met the inclusion criteria. Heterogeneity among studies was analyzed by I2 test. If I2<30%, the heterogeneity among studies was considered to be small. If the value of I2 was between 30% and 70%, it was considered that there was a certain heterogeneity among the studies. If I2> 70%, it was considered that there was great heterogeneity among the studies. Small heterogeneity was analyzed by fixed effects model, otherwise, random effects model was used. Publication bias was evaluated by funnel plot and Egger′s test. Results:Finally, 14 literatures were included, including 4 Chinese literatures and 10 English literatures. The results of Meta-analysis showed that the sentinel lymph node detection rate was 90.7% and the false negative rate was 12.2%.Conclusions:In breast cancer patients with axillary lymph node turning negative, the detection rate of sentinel lymph node biopsy can meet the acceptable clinical standard for sentinel lymph node biopsy, but the false negative rate is still higher than the clinically acceptable standard. It is necessary to screen suitable patients and apply new techniques to reduce the false negative rate of sentinel lymph node biopsy.
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Bladder cancer is a common malignant tumor of the urinary system.The prognosis of patients with positive lymph nodes is worse than that of patients with negative lymph nodes.An accurate assessment of preoperative lymph node statushelps to make treatmentdecisions,such as the extent of pelvic lymphadenectomy and the use of neoadjuvant chemotherapy.Imaging examination and pathological examination are the primary methods used to assess the lymph node status of bladder cancer patients before surgery.However,these methods have low sensitivity and may lead to inaccuate staging of patients.We reviewed the research progress and made an outlook on the application of clinical diagnosis,imaging techniques,radiomics,and genomics in the preoperative evaluation of lymph node metastasis in bladder cancer patients at different stages.
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Humans , Lymphatic Metastasis , Neoplasm Staging , Cystectomy/methods , Urinary Bladder Neoplasms/pathology , Lymph Node Excision/methods , Lymph Nodes/pathologyABSTRACT
@#Objective To investigate the influencing factors for the clinical remission of advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemotherapy, establish an individualized nomogram model to predict the clinical remission of advanced ESCC with neoadjuvant chemotherapy and evaluate its efficacy, providing serve for the preoperative adjuvant treatment of ESCC. Methods The clinical data of patients with esophageal cancer who underwent neoadjuvant chemotherapy (nedaplatin 80 mg/m2, day 3+docetaxel 75 mg/m2, day 1, 2 cycles, 21 days per cycle interval) in the Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College from February 2016 to August 2020 were analyzed retrospectively. According to the WHO criteria for efficacy assessment of solid tumors, tumors were divided into complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD). CR and PR were defined as effective neoadjuvant chemotherapy, and SD and PD were defined as ineffective neoadjuvant chemotherapy. Univariate and multivariate analyses were used to analyze the influencing factors for the short-term efficacy of neoadjuvant chemotherapy. The R software was used to establish a nomogram model for predicting of the model. C-index, calibration curve and receiver operating characteristic (ROC) curve were used to evaluate the predictive performance of the nomogram. Results Finally 115 patients were enrolled, including 93 males and 22 females, aged 40-75 (64.0±8.0) years. After receiving docetaxel+nedaplatin neoadjuvant chemotherapy for 2 cycles, there were 9 patients with CR, 56 patients with PR, 43 patients with SD and 7 patients with PD. Among them, chemotherapy was effective (CR+PR) in 65 patients and ineffective (SD+PD) in 50 patients, with the clinical effective rate of about 56.5%(65/115). Univariate analysis showed that there were statistical differences in smoking history, alcoholism history, tumor location, tumor differentiation degree, and cN stage before chemotherapy between the effective neoadjuvant chemotherapy group and the ineffective neoadjuvant chemotherapy group (P<0.05). Logistic regression analysis showed that low-differentiation advanced ESCC had the worst clinical response to neoadjuvant chemotherapy, moderately-highly differentiated ESCC responded better (P<0.05). Stage cN0 advanced ESCC responded better to neoadjuvant chemotherapy than stage cN1 and cN2 (P<0.05). The C-index and the area under the ROC curve of the nomogram were both 0.763 (95%CI 0.676-0.850), the calibration curve fit well, the best critical value of the nomogram calculated by the Youden index was 70.04 points, and the sensitivity and specificity of the critical value were 80.0% and 58.0%, respectively. Conclusion The established clinical prediction model has good discrimination and accuracy, and can provide a reference for individualized analysis of the clinical remission of advanced ESCC with neoadjuvant chemotherapy and the screening of new adjuvant treatment subjects.
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Background: Pathological complete response (pCR) to Neo adjuvant chemotherapy (NACT) is a significant prognostic marker in breast cancer, so accurate diagnosis and grading of pathological chemo response of tumour is needed for an effective planning of treatment regimen. To study the various histopathological Aims: changes in Mastectomy specimens following NACT and to evaluate the pathological response of tumour to NACT, also to compare the expression of ER, PR, and HER2 in biopsies and post NACT mastectomy specimens by Immunohistochemistry (IHC). Methods And Materials: 50 breast carcinoma cases, who was diagnosed on trucut biopsies and treated with preoperative NACT followed by mastectomy was included. In post NACT mastectomy specimens, the chemoresponse was classified according to Union for International Cancer Control (UICC) guidelines. ER, PR, and HER2/ neu receptor expression was compared between trucut biopsy specimens (pre- NACT) and resection specimens (post- NACT). Results were analysed by Chi square test and McNemar chi square test. Among 50 cases, patients presented with lump, Results: involved more on the right and in upper outer quadrant. Most common stage at presentation is stage III A. Histologically all belong to IDCC -NST histological subtype. Significant reduction in mean tumour size by 52.7% after NACT was observed. pCR, pPR and pNR was observed in 20 %, 58 % and 22 %of the cases respectively. Most common histological change seen in post NACT is necrosis, desmoplasia, fibrosis, lymphocytic infiammatory response. Discordance in ER expression (17.5 %), PR expression (20%) and HER2 /neu (12.5 %) before and after NACT. But these were statistically insignificant. CONCLUSIONS: Pathological evaluation of chemo response of tumour is the gold standard. The discordance rate of ER, PR and HER-2/neu expression following NACT was statistically insignificant, larger studies needed to analyse their impact in patient management.
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Background: Neoadjuvant chemotherapy (NACT) is the standard of care for the treatment of locally advanced or non-metastatic breast cancer, which may increase the chances of breast conservative surgery (BCS) in place of radical mastectomy without compromising on the overall survival. The aim of this study was to evaluate the accuracy of mammography (MG), ultrasound (US), and magnetic resonance imaging (MRI) in predicting the complete response and to assess the extent of residual breast cancer in women treated with NACT. Materials and Methods: Fifty-six consecutive patients with stage II or III breast cancer, who underwent imaging evaluation of breast with digital mammogram, US, and MRI after NACT and before the breast surgery, were included in the study. For each patient, pathologic complete response (pCR) or residual tumor (non-pCR) was predicted and the maximum extent of the residual tumor was measured on each imaging modality. These measurements were subsequently compared with the final histopathology results. Results: Of 56 patients, 22 showed pCR with MRI having better accuracy for predicting complete response than the MG and US (area under the receiver operating characteristic curve: 0.86, 0.68, and 0.65, respectively; p = 0.0001 for MRI; p = 0.06 for MG, and p = 0.02 for US). The sensitivity of MRI for detecting pCR was 72.7%; specificity and positive predictive value were 100%. For pathological residual tumor, the size measured on MRI showed significantly higher correlation with the pathologic size (correlation coefficient, r = 0.786), than the MG (r = 0.293) and US (r = 0.508) with P < 0.05. Conclusions: Accuracy of MRI for predicting pathological complete response was significantly higher than the MG and US. Pathologic residual tumor size was also more precisely reflected by the longest tumor dimension on MRI with the strong positive correlation coefficient
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El adenocarcinoma pancreático ductal (APD) es la cuarta causa de muerte por cáncer y se proyecta que para el 2030 ocupe el segundo lugar. El pronóstico es sombrío, siendo la sobrevida menor a 9% en 5 años. Se consideró durante mucho tiempo a la resección quirúrgica como el único tratamiento curativo, sin embargo, sólo el 15 a 20% de los pacientes pueden ser beneficiados con la misma. La clasificación pre terapéutica más utilizada es la del National Comprehensive Cáncer Network (NCCN), basada en la relación del tumor con estructuras vasculares, clasificándolos en tumores "resecables", de resección límite "Borderlines" y "localmente avanzados". Se presenta el primer caso registrado en Paraguay de APD con infiltración de la Vena Mesentérica Superior (VMS) tratado con duodenopancreatectomía cefálica (DPC) asociada a resección vascular mayor.
Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer death and is projected to rank second by 2030. The prognosis is bleak, with survival being less than 9% in 5 years. For a long time, surgical resection was considered the only curative treatment, however, only 15 to 20% of patients can benefit from it. The most widely used pre-therapeutic classification is that of the National Comprehensive Cancer Network (NCCN), based on the relationship of the tumor with vascular structures, classifying them into "resectable", "borderline" and "locally advanced" tumors. We present the first registered case in Paraguay of PDA with infiltration of the Superior Mesenteric Vein (SMV) treated with cephalic duodenopancreatectomy (CPD) associated with major vascular resection.
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Adenocarcinoma , Pancreaticoduodenectomy , Proctectomy/methodsABSTRACT
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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Neoadjuvant chemotherapy followed by surgery (NCS) is a common therapy pattern of non-small cell lung cancer (NSCLC). However, patients treated with NCS still suffer from relatively high locoregional recurrence. Postoperative radiotherapy (PORT) plays an important role in improving locoregional control, whereas its effect on survival remains controversial. Some studies propose that PORT yields no survival benefits for stage Ⅱ-Ⅲ A(N 2) patients treated with NCS, whereas other researches indicate that PORT can bring survival benefits for high-risk patients. The indications of PORT include R 1/R 2 resection and ypN 2. PORT is recommended with three-dimensional conformal therapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) within the dose range of 50-54 Gy (R 0 resection). The target volume is inconclusive and the irradiation range of mediastinum involving with the metastatic lymph node regions is recommended in many studies. The adverse effects of PORT are acceptable in most studies.Nevertheless, the evidence level of relevant studies is relatively low. These results remain to be clarified by prospective randomized clinical trials.
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Objective:To observe the clinical effect on patients of invasive ductal carcinoma of the breast by neoadjuvant chemotherapy, and to analyze the changes of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) and Ki67 in neoplasm.Methods:A total of 83 patients which were treated by neoadjuvant chemotherapy in breast invasive ductal carcinoma diagnosed were selected in North China University of Science and Technology Affiliated Hopital from January 2014 to December 2020. There were 30 cases of Luminal type A, 31 cases of Luminal type B, 10 cases of HER-2 positive type and 12 cases of triple negative type. To observe the clinical effect of different molecular subtypes, detect the expression of Er, PR, HER-2 and Ki67 in pathological tissues before and after neoadjuvant chemotherapy, and conduct a retrospective case-control study. Comparison between the two groups use χ2 test, matched χ2 and accurate probability method. Results:Fifty-eight cases were clinically effective, the total effective rate was 69.8% (58/83), and 9 cases were pathological complete response (pCR), accounting for 10.8% (9/83). After neoadjuvant chemotherapy, the highest clinical efficacy was luminal type B in 26 cases, and the highest PCR was triple negative type in 3 cases. The pathological results showed that the expression of ER (6 cases of positive expression were increased, χ2=1.03, P=0.310), PR (8 cases of positive expression were increased, χ2=1.56, P=0.210) and HER-2 (2 cases of positive expression were decreased, χ2=0.10, P=0.748) was not different before and after neoadjuvant chemotherapy. The expression of Ki67 was decreased in 25 cases (30.1%) after chemotherapy compared with 59 cases (71.1%) before chemotherapy (34 cases of positive expression were decreased, χ2=27.85, P<0.001). Five cases were added among Luminal type A after chemotherapy, all of which were transformed from Luminal type B, but the kappa value was 0.919 (>0.75), the consistency rate was 91.9%. The consistency was idea before and after chemotherapy. Five cases were added after Luminal type A chemotherapy, all of which were transformed from Luminal type B, but the kappa value was 0.919 ( P>0.75), and the consistency rate was 91.9%,The consistency before and after chemotherapy was good. After chemotherapy, HER-2 expression remained unchanged in 59 cases (clinically effective in 48 cases), up-regulated in 9 cases (clinically effective in 4 cases) and down regulated in 15 cases (clinically effective in 6 cases)( χ2=12.82, P=0.002). Ki67 expression remained unchanged in 35 cases (20 cases were clinically effective), up-regulated in 7 cases (2 cases were clinically effective) and down regulated in 41 cases (36 cases were clinically effective)( χ2=14.63, P=0.001). Conclusion:The clinical effect of neoadjuvant chemotherapy in the treatment of breast invasive ductal carcinoma is ideal. The clinical effective rate of Luminal B type is the highest, and the pCR rate of triple negative type is the highest.And it can significantly reduce the expression of Ki67. The down-regulation of HER-2 and Ki67 is significant for clinical efficiency.
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Objective:To investigate the influence of perioperative probiotics supplement on short-term clinical outcomes in gastric cancer patients receiving neoadjuvant chemotherapy combined with radical gastrectomy.Methods:The prospective randomized controlled study was conducted. The clinicopathological data of 80 patients who underwent neoadjuvant chemotherapy combined with radical gastrectomy in the Affiliated Hospital of Qingdao University from July 2020 to September 2021 were selected. Based on random number table, patients were allocated into two groups. Patients undergoing perioperative probiotics supplement were allocated into the experiment group, and patients undergoing perioperative conventional treatment were allocated into the control group, respectively. Observation indicators: (1) grouping situations of the enrolled patients; (2) intraoperative situations; (3) follow-up and postoperative situations; (4) inflammation related hematological indexes. Follow-up was conducted using telephone interview and outpatient examina-tion to detect postoperative complications and startup of adjuvant chemotherapy up to October 31,2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was performed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the Mann-Whitney U test. Repeated measurement data were analyzed by the repeated ANOVA or generalized estimating equation. Results:(1) Grouping situations of the enrolled patients. A total of 80 patients were selected for eligibility. There were 51 males and 29 females, aged 64(42-80)years. Of the 80 patients, there were 40 patients in the experiment group and 40 patients in the control group, respectively. (2) Intraoperative situations. All patients in the experiment group and the control group underwent radical gastrectomy successfully. Cases with yield pathologic TNM (ypTNM) stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲ after neoadjuvant chemotherapy, cases undergoing laparoscopic radical gastrectomy or Da Vinci robotic radical gastrectomy, the operation time, the volume of intraoperative blood loss, cases undergoing digestive tract recons-truction as Billroth Ⅱ anastomosis or Roux-en-Y anastomosis were 2, 7, 15, 13, 19, 21,205(180-240)minutes, 50(30-60)mL, 6, 34 in the experiment group, versus 4, 6, 12, 16, 23, 17, 218(190-251)minutes, 50(43-60)mL, 11, 29 in the control group, showing no significant difference in the above indicators between the two groups ( U=683.00, χ2=0.80, U=668.00, 681.00, χ2=1.87, P>0.05). (3) Follow-up and postoperative situations. All the 80 patients were followed up for 1 month after surgery. Cases with postoperative infectious complications were 6 in the experiment group, versus 15 in the control group, showing a significant difference between the two groups ( χ2=5.23, P<0.05). The application of antimicrobial agent, time to postoperative first flatus, time to postoperative first defecation, time to tolerance of solid food, duration of postoperative hospital stay, time to postopera-tive startup of adjuvant chemotherapy were 3(3-6)doses, 53(49-66)hours, 72(62-82)hours, (72±18)hours, 6.0(5.5-7.0)days, 26.0(25.0-28.0)days in the experiment group, versus 6(3-10)doses, 66(60-88)hours, 94(82-112)hours, (107±23)hours, 7.0(6.4-8.3)days, 30.0(28.0-33.0)days in the control group, showing significant differences in the above indicators between the two groups ( U=471.50, 432.00, 343.50, t=-7.62, U=411.50, 319.50, P<0.05). (4) Inflam-mation related hematological indexes. ① The white blood cell counts before surgery and at postoperative day 1, 3, 5 were (5.6±1.4)×10 9/L, (9.9±3.2)×10 9/L, (7.7±2.6)×10 9/L, (6.8±1.8)×10 9/L in the experiment group, versus (6.1±1.9)×10 9/L, (12.3±2.9)×10 9/L, (9.7±3.6)×10 9/L, (7.8±2.7)×10 9/L in the control group, meeting the mauchly′s test of sphericity ( χ2=4.17, P>0.05). Results of intrasubject effect test showed that there were significant differences in the time effect, intervention effect and interaction effect of white blood cell counts between the two groups ( F=106.61, 10.45, 4.56, P<0.05). ② The neutrophilic granulocyte percentages before surgery and at postoperative day 1, 3, 5 were 55%±10%, 76%±11%, 73%±9%, 69%±9% in the experiment group, versus 56%±9%, 84%±5%, 79%±8%, 74%±9% in the control group, not meeting the mauchly′s test of sphericity ( χ2=16.63, P<0.05). Results of multi-variate test showed that there were significant differences in the time effect, intervention effect and interaction effect of neutrophilic granulocyte percentages between the two groups ( F=92.42, 11.46, 5.55, P<0.05). ③ The levels of C-reactive protein before surgery and at postoperative day 1, 3, 5 were 1.35(1.15-1.97)mg/L, 14.94(8.24-21.22)mg/L, 33.39(13.02-66.02)mg/L, 18.36(8.27-60.43)mg/L in the experiment group, versus 1.62(0.97-2.27)mg/L, 24.03(10.42-36.52)mg/L, 81.66(31.20-116.76)mg/L, 46.84(28.30-80.26)mg/L in the control group, not meeting the normal distribution. Results of generalized estimation equation test showed that there were significant differences in the time effect, intervention effect and interaction effect of levels of C-reactive protein between the two groups ( Waldχ2=145.74, 9.48, 9.90, P<0.05). ④ The levels of procalcitonin before surgery and at postoperative day 1, 3, 5 were 0.02(0.02-0.04)μg/L, 0.08(0.06-0.12)μg/L, 0.12(0.07-0.21)μg/L, 0.09(0.06-0.15)μg/L in the experiment group, versus 0.02(0.02-0.04)μg/L, 0.14(0.07-0.71)μg/L, 0.35(0.14-0.71)μg/L, 0.24(0.10-0.48)μg/L in the control group, not meeting the normal distribution. Results of generalized estimation equation test showed that there were signifi-cant differences in the time effect, intervention effect and interaction effect of levels of procalcitonin between the two groups ( Waldχ2=62.88, 14.71, 18.33, P<0.05). Conclusion:Perioperative supple-ment of probiotics can reduce the incidence of postoperative infectious com-plications and the application of antimicrobial agent, promote recovery of gastrointestinal function, reduce the level of inflammation related indexes, shorten the duration of postoperative hospital stay and the time to postoperative startup of chemotherapy in patients undergoing neoadjuvant chemotherapy combined with radical gastrectomy.
ABSTRACT
Objective:To investigate the role of Caspase-1/gasdermin D (GSDMD) -mediated cell pyroptosis in anti-tumor effect of cisplatin (DDP) in triple-negative breast cancer (TNBC) .Methods:HE staining and immunohistochemical staining were performed to detect the morphological changes and the expression of pyroptosis/apoptosis pathway related proteins in TNBC tissues before and after DDP-based neoadjuvant chemotherapy (NACT) . The TNBC cell line MDA-MB-231 was treated with DDP and the morphological changes were observed. The type of cell death induced by DDP was analyzed by Annexin V-FITC/PI double staining and flow cytometry. Lactate dehydrogenase (LDH) release assay and ELISA were performed to detect the release of LDH and inflammatory factors (IL-18 and IL-1β) in cell culture supernatant after DDP treatment. Western blot (WB) was performed to detect the expression of pyroptosis/apoptosis pathway related proteins in cells after DDP treatment. MDA-MB-231 cells treated with DDP were co-treated with caspase-1 specific inhibitor to inhibit pyroptois or co-treated with caspase-3 specific inhibitor to inhibit apoptosis. The effect of caspase-1 inhibitor or caspase-3 inhibitor on the anti-tumor effect of DDP was detected by MTT assay, clone formation assay, transwell assay and would healing test.Results:Reactive changes in the breast surgical specimen after DDP-based NACT included cell swelling and inflammatory cell aggregation around the tumor bed, which were more similar to pyroptosis. The up-regulation of key molecules of pyroptosis pathway post-NACT was significantly higher than that of key molecules of apoptosis pathway. Further experiments in vitro showed that DDP could induce MDA-MB-231 cells to show pyroptosis-like changes characterized by large bubbles blowing from the cellular membrane. Flow-cytometry analyses showed that the death type of MDA-MB-231 cells caused by DDP was mainly Annexin V +PI + cells (mainly lytic cells, such as pyroptosis) . Additionally, DDP treatment induced significant activation of caspase-1 and GSDMD, increased the release of LDH, IL-18 and IL-1β, however, the activation level of caspase-3, which dominates the apoptosis pathway, was significantly lower than that of caspase-1/GSDMD. Moreover, caspase-1 inhibitors (blocking the classical pyroptosis pathway) had a significantly greater inhibitory effect on the anti-tumor effect of DDP than caspase-3 inhibitors (blocking the apoptosis pathway) . Conclusion:Caspase-1/GSDMD mediated pyroptosis may play a leading role in the anti-tumor effect of DDP in triple-negative breast cancer.
ABSTRACT
Objective:To investigate the expression of miR-211-5p in peripheral blood of patients with myelosuppression after neoadjuvant chemotherapy for breast cancer and its effect on Notch signaling pathway by targeting cyclooxygenase 2 (COX2) gene Regulation mechanism.Methods:From Jan. 2018 to Jan. 2021, 185 breast cancer patients who received neoadjuvant chemotherapy in Linyi People’s Hospital for the first time were included as the research objects. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the mRNA expression levels of miR-211-5p, COX2 gene and Notch signaling pathway related genes (Notch1, Jagged1 and Hes1) . The miR-211-5p mimic, inhibitor, mimic NC, and inhibitor NC were transfected into SD rat bone marrow mesenchymal stem cells, and the mRNA expression of miR-10a-3p and COX2 genes was detected by qRT-PCR for 48 hours. Western blot method was used to detect the protein expression levels of Notch signaling pathway related genes.Results:The relative expression of miR-211-5p in patients with severe myelosuppression was 2.41±0.32, which was significantly higher than that in patients with mild myelosuppression (1.53±0.18) ( t=6.385, P<0.001) ; The relative expression of COX2 gene mRNA in patients with severe myelosuppression was 3.64±0.74, which was significantly lower than that in patients with mild myelosuppression (5.37±1.02) ( t=7.469, P<0.001) . In patients with severe myelosuppression, there was a significant negative correlation between miR-211-5p and COX2 gene mRNA levels ( r=-0.694, P=0.006) . The results of the dual luciferase report experiment confirmed that COX2 was the target gene of miR-211-5p. The relative expression of Notch1, Jagged1, and Hes1 mRNA in peripheral blood of patients with severe myelosuppression were 2.35±0.41, 2.76±0.46 and 3.04±0.52, respectively, which were significantly lower than those in patients with mild myelosuppression (4.12±0.63, 4.53±0.58 and 5.12±0.67) ( t=5.367, 6.114 and 6.135, respectively, P<0.001) . After transfecting SD rat bone marrow mesenchymal stem cells with miR-211-5p mimics and inhibitors, the relative expression of miR-211-5p in the mimic group was 3.46±0.49, significantly higher than that in the mimic NC group (2.24±0.32) The relative expression of miR-211-5p in the inhibitor group was (1.28±0.19) and (2.33±0.37) inhibitor NC group ( P<0.001) , while the relative expression of miR-211-5p in the inhibitor group was significantly lower than that in the other three groups ( P<0.001) . The mRNA expression of COX2 gene in mimic group was 2.73±0.36, which was significantly lower than that in mimic NC group (4.05±0.59) , inhibitor group (6.15±0.86) and inhibitor NC group (4.18±0.65) ( P<0.001) , while mRNA expression of COX2 gene in the inhibitor group was significantly higher than that in the other three groups ( P<0.001) . The expression of Notch1, Jagged1, and Hes1 in the inhibitor group was significantly increased, while the expression of Notch1, Jagged1, and Hes1 in the mimic group was significantly decreased. Conclusion:The expression level of miR-211-5p in peripheral blood of severe myelosuppressed patients with breast cancer after neoadjuvant chemotherapy is significantly increased, and the Notch signaling pathway can be inhibited by targeted down-regulation of COX2 gene expression.