ObjectiveTo evaluate the effect of neoadjuvant chemotherapy and find the mechanism of multidrug resistance. MethodsTwenty patients with gastric cancer and 31 patients with colorectal cancer underwent neoadjuvant chemotherapy and then operations. The preoperative specimens were stained by immunohistochemical techniques for testing p53,multidrug resistanceassociated protein (MRP), glutathione S transferase（GST）, telomerase. Resection specimens were evaluated for chemotherapy effect by routine histology; at the same time, the postoperative morbidity and mortality were observed. ResultsIn 51 patients, the response rate of neoadjuvant chemotherapy was 27.45%(14/51),so multidrug resistance was a kind of common phenomena in gastrointestinal carcinomas. The postoperative morbidity was 15.69%(8/15), the main operation complication was infection,the mortality was 1.96%(1/51),only one person died from severe infection.The expression rate of p53, MRP, GST, telomerase was 58.0%,51.0%,66.7%,74.0%respectively, the location of p53 was at cell nucleus,location of MRP,GST was at cell memberane and cytoplasm,location of telomerase was at cytoplasm.The response rate had nothing to do with age, sex and metastasis. But it was related with p53 and telomerase expression. ConclusionNeoadjuvant chemotherapy is an effective, safe therapy. But the rate of drug resistance is high in gastrointestinal carcinomas, and the response rate is related to p53, telomerase expression.
Objective To study the long-term effect of neoadjuvant chemotherapy on advanced breast cancer. Methods The CAF neoadjuvant chemotherapy 〔CTX 500 mg/m2（1st day, 8th day), 5-FU 500 mg/m2（1st day, 8th day), and ADM 30 mg/m2 (1st day) every 3 weeks〕 was carried out in 31 breast cancer patients (stageⅢ,Ⅳ) for 2 cycles before operation, compared with 30 patients (stage Ⅲa) whose therapies were never done and operations could be feasible. Results The overall response rate was 87.1%(27/31). The stages of 19 patients among 31 (61.3%) declined (6 patients to stage Ⅲa, 8 to stageⅡb, 4 to stageⅡa, 1 to stage 0, 1 to complete response and none to pathological complete response). The diseasefree survival time of the patients was 56.3 months which was obviously longer than that of the patients without neoadjuvant chemotherapy (43.5 months, P＜0.05). The 5-year diseasefree survival rate of the patients with neoadjuvant chemotherapy was 38.7% which was a little higher than that (33.3%) of the patients without the chemotherapy, and the two groups had no significant difference. Conclusion The neoadjuvant chemotherapy can reduce the stages of patients with advanced breast cancer, obviously prolong the diseasefree survival time of patients, and reduce or delay recurrence or metastasis.
【 Abstract 】 Objective To discuss incidence of the complications in the rectal cancer patients ’ early postoperative being treated with neoadjuvant chemotherapy combined with surgical intervention. Methods The rectal cancer patients under surgical therapy being diagnosed definitely, with neoadjuvant chemotherapy under multi-disciplinary team (MDT) or without and firstly being discovered from April to October of 2007 were studied. The complication conditions of these patients 1 month after operation were studied and observed, and the differences between MDT group and non-MDT group were compared. Results According to the condition, 189 rectal cancer patients were internalized. Among all the patients, the distance of tumor to the dentate line were lt;3 cm 38 cases, 3 ～ 7 cm 86 cases, ≥ 7 cm 65 cases; pathological stage were Ⅰ stage 5 cases ， Ⅱstage 122 cases， Ⅲstage 50 cases， Ⅳstage 12 cases. There were 181 cases laparotomy, 8 cases laparoscopic operation; 33 cases stoma operation, 156 cases non-stoma operation. The total incidence of postoperative complication was 27.0% （51/189）. Of all, incision bleeding was 1 case, abdominal (deep) bleeding were 4 cases, anastomosis bleeding were 5 cases, pulmonary infection was 1 case, wound infection were 7 cases, urinary tract infection were 3 cases, abdominal (deep) infection was 1 case, unknown fever were 19 cases, superficial layer wound dehiscence was 1 case, wound co-liquation were 15 cases, anastomosis leakage were 3 cases, rectovaginal fistula were 2 cases; intestinal obstruction were 7 cases, urinary retention were 7 cases, stress ulcer were 2 cases. Follow-up in 2-10 months after operation, there was no death case. The baseline between MDT group and non-MDT group was equal. The ratio of postoperative blood transfusion of MDT group was obviously less than that of non-MDT group （P＜0.05）. Moreover, the operation time of MDT group was obviously shorter than that of non-MDT group, and the difference was statistically significant （P＜0.05）. But the ratio of laparotomy and laparoscopic operation, of stoma operation and non-stoma operation, as well as the types of radical excision operation of rectal cancer didn’t show any statistical difference between two groups (Pgt;0.05). The postoperative venting time, defecation time, intake time didn’t show any statistical difference between two groups too. But the postoperative out-of-bed activity time and the postoperative in-hospital days of MDT group was obviously shorter than that of non-MDT group, and the difference was statistically significant （P＜0.05）. In MDT group the postoperative total complication rate was less than non-MDT group, and the difference was statistically significant （P＜0.05）. Among all the complications, the MDT group had a lower rate of wound infection, wound co-liquation and urinary retention （P＜0.05）. Using multifactorial logistic regression analysis, the risk factor which influenced the postoperative complication rate in MDT group were: postoperative intake time and postoperative hospitalization time. But the risk factor in non-MDT group was only according to postoperative hospitalization time. Conclusion The patients who were treated by MDT, definite operative method combining neoadjuvant chemotherapy or not didn’t increase the postoperative complication rate and risk. So it could be believed that such a composite treatment was feasible and safe in early postoperative stage. But it needs further studies to evaluate the medium- and long-term clinical effect.
Objective To investigate the effect of radiotherapy after neoadjuvant chemotherapy and modified radical surgery on breast cancer specific survival (BCSS) of patients with stage cT1–2N1M0 breast cancer. Methods A total of 917 cT1–2N1M0 stage breast cancer patients treated with neoadjuvant chemotherapy and modified radical surgery from 2010 to 2017 were extracted from the The Surveillance, Epidemiology, and End Results (SEER) database. Of them 720 matched patients were divided into radiotherapy group (n=360) and non-radiotherapy group (n=360) by using propensity score matching (PSM). Cox proportional hazard regression model was used to explore the factors affecting BCSS. Results Patients were all interviewed for a median follow-up of 65 months, and the 5-year BCSS was 91.9% in the radiotherapy group and 93.2% in the non-radiotherapy group, there was no significant difference between the 2 groups (χ2=0.292, P=0.589). The results were the same in patients with no axillary lymph node metastasis, one axillary lymphnode metastasis, two axillary lymph node metastasis and 3 axillary lymph node metastasis group (χ2=0.139, P=0.709; χ2=0.578, P=0.447; χ2=2.617, P=0.106; χ2=0.062, P=0.803). The result of Cox proportional hazard regression analysis showed that, after controlling for Grade grade, time from diagnosis to treatment, efficacy of neoadjuvant chemotherapy, number of positive axillary lymph nodes, molecular typing, and tumor diameter at first diagnosis, radiotherapy had no statistically significant effect on BCSS [HR=1.048, 95%CI (0.704, 1.561), P=0.817]. Conclusions The effect of radiotherapy on the BCSS of patients with stage cT1–2N1M0 breast cancer who have received neoadjuvant chemotherapy and modified radical surgery with 0 to 3 axillary lymph nodes metastases is limited, but whether to undergo radiotherapy should still be determined according to the comprehensive risk of individual tumor patients.
Objective To investigate the impacts of neoadjuvant chemotherapy on the expression of insulin-like growth factor-1 receptor (IGF-1R) and on operation procedure and the significance of prognosis. Methods The expression of IGF-1R in 40 patients with breast cancer before and after neoadjuvant chemotherapy was measured by immunohistochemistry. The diagnosis was proved by core biopsy. All the patients took the TAC chemotherapy regimen. Modified radical operation was performed after two chemotherapy cycles and the IGF-1R expression was measured again. The clinical effect of neoadjuvant chemotherapy was assessed according to WHO criterion by measuring the size of tumor by physical examination and B type ultrasound. Results After neoadjuvant chemotherapy the tumor size shrank in 29 patients, there was no CR (complete response) or PD (progressed disease) to be documented. IGF-1R expression could be downregulated in 25 patients. Conclusion Neoadjuvant chemotherapy can inhibit the tumor growth by downregulation of the expression of IGF-1R.
Objective To explore the clinical effect of neo-adjuvant/adjuvant chemotherapy combined with operation on colorectal cancer patients in the multi-disciplinary team (MDT). Methods The data were collected retrospectively from January to December in 2007. The patients were classified as non-adjuvant chemotherapy group and adjuvant chemotherapy group according to the treatment strategy. Non-adjuvant chemotherapy group had accepted only surgery followed by preoperative neo-adjuvant chemotherapy, and adjuvant chemotherapy group had taken postoperative adjuvant chemotherapy after preoperative neo-adjuvant chemotherapy and operation. The clinical effect of two groups were compared. Results Totally 789 patients were treated among 2007, and 195 patients who were firstly diagnosed as colorectal cancer were included, and there were 109 males and 86 females, 59 colonic cancers and 136 rectal cancers. Average age was 59.98 years old. All of the included patients were followed up for 5-17 months. Three cases missed, no recurrence and no death happened. The baseline between non-adjuvant chemotherapy and adjuvant chemotherapy group was nearly same. There were no differences between two groups about the internal medicine complications, the cancer related obstruction, preoperative transfusion or not (P＞0.05). Whether the patients were transfused or not during the procedure and Dukes stage were significantly different between two groups(P＜0.05), while the other surgical and pathological index didnt show any statistical significance (P＞0.05). After operation, more patients in non-adjuvant chemotherapy group had accepted transfusion (P＜0.05). However, the postoperative rehabilitative indexes during hospitalization were not different between two groups. And the differences about the postoperative complications and defecation were not significant (P＞0.05). The values of CEA and CA19-9 were greatly different between two groups in the 1st and 3rd month follow-up. Conclusion The strategy of neo-adjuvant chemotherapy/operation/adjuvant chemotherapy didnt affect the rehabilitation and increase the risk of complications, however, more researches were necessary to prove whether the clinical effect were improved or not.
ObjectiveTo study value of long noncoding RNA H19 and HOTTIP in plasma in predicting efficacy of neoadjuvant chemotherapy (NAC) for resectable locally advanced gastric cancer. MethodsForty patients with T3–4aN+M0 gastric cancer and 40 patients with benign gastric diseases treated in the Yantai Yuhuangding Hospital Affiliated to Qingdao University from August 2020 to May 2021 were prospectively included. The expressions of H19 and HOTTIP in the plasma of gastric cancer and benign gastric diseases patients without any treatment after admission were detected before treatment (CAPEOX regimen was used in the patients with gastric cancer), then which were detected after 2 NAC courses for patients with gastric cancer. Meanwhile, some clinical items were detected and the efficacy of NAC was evaluated. The complete remission (CR) and partial remission (PR) were classified as objective remission, CR, PR, and disease stability were classified as disease control. The expressions of H19 and HOTTIP between the different patients were compared and the receiver operating characteristic (ROC) curve was used to evaluate their values in the diagnosis of resectable locally advanced gastric cancer. ResultsThere were 13 cases of T downstaging and 27 cases of T non-downstaging and 25 cases of objective remission and 35 disease control after NAC. The median relative expression levels of H19 and HOTTIP before NAC in the patients with gastric cancer were higher than those in the patients with benign gastric diseases (H19: 1.42 versus 0.98, Z=–3.835, P<0.001; HOTTIP: 2.15 versus 1.04, Z=–5.062, P<0.001), and which were in the patients with T downstaging and disease control were lower than those in the patients with T non-downstaging and 5 cases of disease progression (For T staging, H19: 1.12 versus 1.54, Z=–2.960, P=0.002; HOTTIP: 1.49 versus 2.30, Z=–2.310, P=0.019. For efficacy of NAC, H19: 1.39 versus 2.48, Z=–3.211, P<0.001; HOTTIP: 1.96 versus 3.25, Z=–2.393, P=0.014). The median relative expressions of H19 and HOTTIP after NAC were lower than those before NAC in the patients with gastric cancer (H19: 1.12 versus 1.42, Z=–3.965, P<0.001; HOTTIP: 1.30 versus 2.15, Z=–4.839, P<0.001). There were no significant differences in the changes of H19 and HOTTIP before and after NAC between the patients with T downstaging and T non-downstaging, and between disease control and disease progression (P>0.05). The areas of ROC curve of H19, HOTTIP, and combination of H19 and HOTTIP in diagnosis of resectable locally advanced gastric cancer were higher than 0.7. ConclusionsLncRNA H19 and HOTTIP might be potential tumor markers in gastric cancer, and their diagnostic values for resectable locally advanced gastric cancer are higher. Gastric cancer patients with low expressions of H19 and HOTTIP in plasma might be more sensitive to NAC.
Objective To investigate the clinicopathological characteristics of HER2 protein expression in different degrees in human epidermal growth factor receptor 2 (HER2) negative breast cancer and the factors related to the efficacy of neoadjuvant chemotherapy in breast cancer with low HER2 expression. Methods The clinicopathological data of 161 patients with HER2-negative breast cancer who received neoadjuvant chemotherapy in the Department of Breast Surgery, Affiliated Hospital of Southwest Medical University from March 2019 to March 2022 were retrospectively collected. The difference of clinical and pathological characteristics of patients with different levels of HER2 protein expression were analyzed, and the factors influencing the pathological complete remission (pCR) rate of breast cancer patients with low HER2 expression after neoadjuvant chemotherapy with unconditional logistic regression model were analyzed. Results Among 161 HER2 negative breast cancer patients, 108 cases were low HER2 expression, accounting for 67.1%. Compared with those with zero expression of HER2 [immunohistochemistry (IHC) 0], the patients with low HER2 expression had higher axillary lymph node metastasis rate (P=0.048), lower histological grade (P=0.006), and higher proportion of positive hormone receptor expression (P<0.001). There was no significant difference in pCR rate among the HER2 IHC 0, IHC 1+ and IHC 2+ / in situ hybridization (ISH)– (P=0.099) , and the pCR rate of low expression of HER2 was lower than that of zero expression of HER2 in the general population and Luminal subgroup, and the difference was statistically significant (P<0.05). There was no significant difference in triple negative breast cancer subgroup (P=0.814). The logistic regression analysis showed that age, histological grade and estrogen receptor expression status were independent influencing factors for pCR rate after neoadjuvant chemotherapy with low HER2 expression (P<0.05). Conclusions Different degrees of HER2 protein expressions in patients with HER2-negative breast cancer have unique clinicopathological characteristics. The pCR rate of neoadjuvant chemotherapy in patients with low HER2-expression breast cancer is lower than that in patients with zero HER2-expression breast cancer. Age, histological grade and estrogen receptor expression status are independent factors influencing the pCR rate of neoadjuvant chemotherapy in patients with low HER2-expression breast cancer.
Objective To evaluate the effect of neoadjuvant chemotherapy (NAC) on breast conserving surgery and the outcomes of treatment for women with operable breast cancer. Methods We searched The Cochrane Library (Issue 1, 2007), CENTRAL (1970 to 2007), PUBMED (1978 to March 2007), CBM (1978 to 2006), CNKI (1994 to 2007), CMCC (1994 to May 2007) and other relevant databases and journals. We identified randomized controlled trials (RCTs) comparing NAC plus breast conserving therapy (BCT) or mastectomy versus BCT or mastectomy plus postoperative chemotherapy in women with operable breast cancer. Two reviewers independently assessed trial quality and extracted data. Meta-analyses were performed for homogenous studies by using The Cochrane Collaboration’s RevMan 4.2.10. Results Three eligible studies involving 2 391 women were included. The median follow-up in the studies ranged from 17 to 137 months. The methodological quality of the three RCTs was high. Meta-analyses showed that NAC had no significant effect on overall survival (OS) (RR 0.99, 95%CI 0.92 to 1.07), disease-free survival (RR 1.04, 95%CI 0.94 to 1.15) and ipsilateral breast cancer recurrence (RR 1.34, 95%CI 0.84 to 2.13). Two RCTs revealed that NAC significantly increased the rate of BCT in operable breast cancer patients, but the other RCT reported similar rates of BCT in both groups. One RCT indicated that NAC did not increase the incidence of surgery-related local complications. Conclusions NAC is safe for the treatment of women with operable breast cancer, which may increase the rate of BCT and help to evaluate chemosensitivity. There is insufficient evidence to assess the effect of NAC on conserving surgery procedure and survival rate in operable BCT patients. More large-scale RCTs are needed to define further the role of NAC in the treatment of operable breast cancer patients.