Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases

BACKGROUND Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality,with the liver being the primary organ of metastasis.Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases(CRLMs).Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy.However,the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy.Body mass index(BMI)is one of the factors affecting the tumori-genesis and progression of colorectal cancer as well as prognosis after various antitumour therapies.Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight,particularly when receiving first-line chemotherapy regimens in combination with bevacizumab.AIM To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs.METHODS A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023.Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response.The Kaplan-Meier method with log rank test was used to compare progression-free survival(PFS)between patients with high and low BMI.BMI<24.0 kg/m^(2) was defined as low BMI,and tumour regression grade 1-2 was defined as complete tumour response.RESULTS Low BMI was observed in 74(58.7%)patients and complete tumour response was found in 27(21.4%)patients.The rate of complete tumour response was significantly higher in patients with low BMI(29.7%vs 9.6%,P=0.007).Multivariate analysis revealed that low BMI[odds ratio(OR)=4.56,95%confidence interval(CI):1.42-14.63,P=0.011],targeted therapy with bevacizumab(OR=3.02,95%CI:1.10-8.33,P=0.033),preoperative carcinoembryonic antigen level<10 ng/mL(OR=3.84,95%CI:1.19-12.44,P=0.025)and severe sinusoidal dilatation(OR=0.17,95%CI:0.03-0.90,P=0.037)were independent predictive factors for complete tumour response.The low BMI group exhibited a significantly longer median PFS than the high BMI group(10.7 mo vs 4.7 mo,P=0.011).CONCLUSION In CRLM patients receiving preoperative chemotherapy,a low BMI may be associated with better tumour response and longer PFS.

Impact of homogeneous pathologic response to preoperative chemotherapy in patients with multiple colorectal liver metastases

AIM To analyze the homogeneity of pathologic response to preoperative chemotherapy(PRPC) after chemotherapy in patients with multiple liver metastases(LM).METHODS From September 2011 to August 2014,patients with at least two LM undergoing preoperative chemotherapy prior to resection were included in this retrospective,single-center study. The endpoints were PRPC homogeneity(according to both the Rubbia-Brandt and MD Anderson classifications),the impact of PRPC on the MDT decision,factors associated with homogeneous PRPC and overall survival of patients with vs. without homogeneous PRPC.RESULTS seventy-three patients with a total of 88 liver resections(including 15 two-stage procedures) were included in the study. The homogeneous PRPC rate was 55% according to the Rubbia-Brandt classification and 53% according to the MD Anderson classification. The MDT decision was modified by the PRPC in only 2.7% of patients(n = 2). CONCLUSION The PRPC was homogeneous in only one half of patients and had very little influence on the MDT decision.

EFFECT OF PREOPERATIVE CHEMOTHERAPY ON METASTASIZED LYMPH NODES IN PATIENTS WITH ADVANCED ESOPHAGEAL CARCINOMA

Objective To investigate the effect and clinical value of preoperative chemotherapy on the treatment of metastasized lymph nodes in patients with advanced esophageal carcinoma. Methods We studied the pathological results of primary lesions and lymph nodes of 97 patients with advanced esophageal cancer between 1996 and 1999,62 patients were treated by preoperative chemotherapy and 35 patients were treated by surgery only. Results The metas- tasized rate and degree of mediastinum in preoperative group were 16.1% and 4.7% ,whereas 65.7% and 34.2% in the surgery only group (P<0.05) ;That of abdomen in preoperative group were 25.8% and 6.6% ,whereas 48.6% and 12.0% in the surgery only group (P<0.05). Conclusion Preparative chemotherapy is effective not only against the primary lesions but also the metastasized lymph nodes. The lower complete response rate of the metastasized lymph may account for the unsatisfied long-term results. Whole resection of primary lesions and lymph nodes are still very important for a better prognosis even for patients who have a good response for the preoperative chemotherapy.

Comprehensive Analysis of Key mRNAs and lncRNAs in Osteosarcoma Response to Preoperative Chemotherapy with Prognostic Values

Objective:Osteosarcoma is one of the most common types of bone sarcoma with a poor prognosis.However,identifying the predictive factors that contribute to the response to neoadjuvant chemotherapy remains a significant challenge.Methods:A public data series(GSE87437)was downloaded to identify differentially expressed genes(DEGs)and differentially expressed lncRNAs(DElncRNAs)between osteosarcoma patients that do and do not respond to preoperative chemotherapy.Subsequently,functional analysis of the transcriptome expression profile,regulatory networks of DEGs and DElncRNAs,competing endogenous RNAs(ceRNA)and protein-protein interaction networks were performed.Furthermore,the function,pathway,and survival analysis of hub genes was performed and drug and disease relationship prediction of DElncRNA was carried out.Results:A total of 626 DEGs,26 DElncRNAs,and 18 hub genes were identified.However,only one gene and two lncRNAs were found to be suitable as candidate gene and lncRNAs respectively.Conclusion:The DEGs,hub genes,candidate gene,and candidate lncRNAs screened out in this context were considered as potential biomarkers for the response to neoadjuvant chemotherapy of osteosarcoma.

Predictive value of serum alpha-fetoprotein for tumor regression after preoperative chemotherapy for rectal cancer

BACKGROUND Preoperative therapy is widely used in locally advanced rectal cancer.It can improve local control of rectal cancer.However,there are few indicators that can predict the effect of preoperative chemotherapy accurately.AIM To investigate whether the increase in serumα-fetoprotein(AFP)can predict better efficacy of preoperative chemotherapy.METHODS This was a retrospective study.We analyzed 125 patients admitted between 2017 and 2019 with locally advanced rectal cancer.All patients received six cycles of preoperative chemotherapy(mFOLFOX6 every 2 wk).Serum AFP of 26 patients rose slightly after three or four cycles of chemotherapy,and fell to normal again within 2 mo.The other 99 patients had a normal level of serum AFP during chemotherapy.Patients were divided into two groups(AFP risen and AFP normal).According to postoperative pathology,we compared tumor regression and complete response rate between the two groups.The primary outcome measure was the tumor regression grade(TRG)after chemotherapy.The difference in pathological complete response between the two groups was also investigated.RESULTS There were no tumor progression and distant metastasis in both groups during preoperative chemotherapy.Patients in the AFP risen group achieved better TRG 0/1 than those in the AFP normal group(61.5%vs 39.4%).The increase in AFP was a significant predictor for better tumor regression[χ2=4.144,odds ratio(OR)=2.666,P=0.04].In the AFP risen group,the complete response rate was 30.8%,which was higher than in the AFP normal group(30.8%vs 12.1%,χ2=4.542,OR=3.251,P=0.03).CONCLUSION Patients with a slight increase in serum AFP can achieve better tumor regression during preoperative chemotherapy,and are more likely to achieve pathological complete response.

Impact of preoperative chemotherapy on surgical results in 139 patients with locally advanced pancreatic cancer

Background:The establishment of preoperative chemotherapy(PCT)with FOLFIRINOX and gemcitabine/nab-paclitaxel in recent years has enabled resectability in many patients with initially locally advanced pancreatic cancer(LAPC).Nevertheless,information about the impact of PCT on surgical results is scarce.Methods:All patients with initial LAPC who received surgery after chemotherapy at the high-volume centre for pancreatic surgery of St.Josef-Hospital Bochum between 2015 and 2022 were included in this retrospective cohort analysis.Results:A total of 139 patients underwent surgery after pre-treatment with FOLFIRINOX(76.3%),gemcitabine/nab-paclitaxel(11.5%),both(5.8%)and other regimens(6.5%).Eighty-five tumors(61.2%)were resectable after PCT.R0 resection was achieved in 92.9%,R1 in 7.1%and R2 in 0%of cases.Fifty-four tumors were still not resectable at the time of surgery.Surgical results of the patients did not show increased postoperative mortality and morbidity compared to the literature data.Postoperative 30-day mortality was 1.4%.Rates for pancreas-specific complications[postoperative pancreatic fistula(POPF),delayed gastric emptying(DGE),postpancreatectomy hemorrhage(PPH),and others]were not increased.POPF occurred in 10.5%and DGE in 26.3%after pancreaticoduodenectomy.After distal pancreatectomy,POPF was detected in 37.5%and DGE in 12.5%.Median postoperative survival(31 vs.13 months)and overall survival after initial diagnosis(40 vs.20 months)were significantly longer in resected patients(P<0.001).Postoperative recurrence-free survival in resected patients amounted to 12 months.Conclusions:This study underlines that PCT allows resectability of primarily unresectable patients with LAPC without increasing perioperative mortality and morbidity.It may lead to a significant prolongation of recurrence-free and overall survival in resected patients after PCT.

Apoptosis induced by preoperative oral 5′-DFUR administration in gastric adenocarcinoma and its mechanism of action

AIM： To study the apoptosis induced by preoperative oral 5＇-DFUR administration in gastric adenocarcinorna and its mechanism of action. METHODS： Sixty gastric cancer patients were divided randomly into three groups （20 each group） before operation： group one： 5＇-DFUR oral administration at the dose of 800-1200mg/d for 3 - 5 d, group two： 500mg 5-FU ± 200 mg/d CF by venous drip for 3 - 5 d, group three （control group）. One or two days after chemotherapy, the patients were operated. Fas/FasL, PD-ECGF and PCNA were examined by immunohistochemistry and apoptotic tumor cells were detected by in situ TUNEL method. Fifty-four patients received gastrectomy, including 12 palliative resections and 42 radical resections. Six patients were excluded. Finally 18 cases in 5＇-DFUR group, 16 cases in CF ± 5-FU group, and 20 cases in control group were analyzed. RESULTS： There was no significant difference in patient mean age, gender, white blood cell count, haernatoglobin （HB）, thromboplastin, perioperative complication incidence, radical or palliation resection, invasion depth （T）, Iymphonode involvement （N）, metastasis （M） and TNM staging among the three groups. However, the PCNA index （PI） in 5＇-DFUR group （40.51 ± 12.62） and 5-FU ±CF group （41.12± 15.26） was significantly lower than that in control group （58.33± 15.69） （F=9.083, P= 0.000）. The apoptotic index （AI） in 5＇-DFUR group （14.39 ±9.49） and 5-FU±CF group （14.11±9.68） was significantly higher than that in control group （6.88 ± 7.37） （F= 4.409, P= 0.017）. The expression rates of Fas and FasL in group one and group three were 66.7% （12/18） and 50% （9/18）, 43.8% （7/16） and 81.3% （13/16）, 45.0% （9/20） and 85% （17/20）, respectively. The expression rate of FasL in 5＇-DFUR group was significantly lower than that in the other two groups （X^2=6.708, P= 0.035）. Meanwhile, the expression rate of PD-ECGF was significantly lower in 5＇-DFUR group （4/18, 28.6%） than in CF±5-FU group （9/16, 56.3%） and control group （13/20, 65.0%） （7,2= 7.542, P= 0.023）. The frequency of Fas expression was significantly correlated with palliative or radical resection （X^2= 7.651, P= 0.006）, invasion depth （X^2= 8.927, P= 0.003）, lymphatic spread （7,2= 4.488, P=0.034） and UICC stages （X^2=8.063, P=0.045） respectively. By the end of March 2005, 45 patients were followed up. The 0.5-, 1-, 2-, 3-year survival rates were 96%, 73%, 60%, 48%, respectively, which were related with T, N, M and Fas expression, but not with PDECGF and FasL expression. CONCLUSION： Preoperative oral 5＇-DFUR administration may induce apoptosis of gastric carcinoma cells and decrease tumor cell proliferation index, but cannot improve the prognosis of patients with gastric cancer. Downregulation of FasL and PD-ECGF expression mediated by 5＇-DFUR may be one of its anti-cancer mechanisms. Fas expression correlates with the progression of gastric carcinoma and may be an effective prognostic factor.

Retrospective analysis of 56 patients with advanced gastric cancer treated with combination of intravenous and intra-arterial intensified neoadjuvant chemotherapy

Background Pre-operative chemotherapy has gained widespread interest while treating advanced gastric cancer in eastern countries. However, there is currently no established standard regimen for gastric cancer. The aim of this research was to explore the value of preoperative chemotherapy with a combination of intravenous and intra-arterial intensified chemotherapy in advanced .qastric cancer.

A contemporary evidence basis for neoadjuvant chemotherapy in upfront resectable pancreatic adenocarcinoma:a systematic review of the literature

Pancreatic ductal adenocarcinoma(PDAC)is an aggressive cancer with poor survival.Local control through surgical resection paired with radiotherapy and chemotherapy comprise the primary tenets of treatment.Debate exists regarding the timing of treatment and ordering of systemic therapy and resection in the management of early stage disease.The goal of this study was to review the literature and describe the contemporary evidence basis for the role of neoadjuvant therapy(NAT)in the setting of upfront resectable(UP-R)PDAC.Five databases were searched in parallel to identify relevant original articles investigating neoadjuvant therapy where at least 1 study arm contained UP-R PDAC;studies with only borderline resectable or locally advanced disease were excluded.Due to the diversity in NAT regimens and study design between trials,qualitative analyses were performed to investigate patient selection,impact on perioperative and survival outcomes,safety,and cost effectiveness.Thirty-five studies met inclusion criteria,of which 24 unique trials are discussed here in detail.These studies included those trials using single agents as well as more recent trials comparing modern multiagent therapies,and several large database analyses.Overall the data suggest that NAT is safe,may confer survival benefit for appropriately selected patients,is cost effective,and is an appropriate approach for UP-R PDAC.Nevertheless,the risk for disease progression during upfront medical therapy,requires appropriate patient identification and close monitoring,and emphasizes the need for further discovery of more effective chemotherapeutics,useful biomarkers or molecular profiles,and additional prospective comparative studies.

Correlation between dynamic contrast-enhanced MRI and histopathology in the measurement of tumor and breast volume and their ratio in breast cancer patients： a prospective study

Background Earlier studies have examined the association between the diameter of primary tumors measured by magnetic resonance imaging （MRI） and histopathology in breast cancer patients. However, the diameter does not completely describe the dimensions of the breast tumor or its volumetric proportion relative to the whole breast. The association between breast tumor volume/breast volume ratios measured by these two techniques has not been reported.