Outcomes of patients with borderline resectable and resectable pancreatic adenocarcinoma treated with neoadjuvant three-week course chemoradiotherapy using capecitabine-based versus gemcitabine-based concurrent chemotherapy

BackgroundNeoadjuvant chemoradiotherapy can provide downstaging and improve margin negativity for borderline resectable and resectable pancreatic adenocarcinoma [(B)RPC]. Little is known about the relative efficacy of capecitabine (CAPE)-based vs. gemcitabine (GEM)-based 3-week chemoradiation (3WCRT) with 36 Gy in 15 fractions. This study aimed to compare the odds of achieving surgical resection, time to progression (TTP), and overall survival (OS) of patients treated with 3WCRT with concurrent CAPE versus GEM.MethodsA retrospective cohort study was conducted, examining medical records from a single center for patients with (B)RPC treated with 3WCRT between 1/2009–12/2020. Odd ratios (OR) of achieving surgical resection were estimated using logistic regression for univariable and multivariable analyses. Median TTP (mTTP) and median OS (mOS) were estimated using the Kaplan-Meier method. Cox proportional hazards analysis was conducted to estimate hazard ratios (HR) of progression and survival in univariable and multivariable analyses.ResultsThirty-one patients were included in the analysis. Twenty-two (71%) patients were treated with CAPE, while 9 (29%) were treated with GEM. All patients in the GEM group were borderline resectable, vs. 18 (82%) patients in the CAPE group, P=0.30. Nineteen (86%) patients in the CAPE group were treated with neoadjuvant FOLFIRINOX, vs. 4 (44%) patients in the GEM group, P=0.03. The CAPE group had higher odds of achieving surgical resection [OR =9.33; 95% confidence interval (CI): 1.50–58.20]. Adjusting for covariates, the odds of achieving surgical resection were still statistically higher in the CAPE group vs. the GEM group (OR =25.34; 95% CI: 1.14–563.72). The CAPE group had superior mTTP compared to the GEM group (15.4 months, 95% CI: 4.9–71.1 vs. 4.0 months, 95% CI: 0.4–14.5; P=0.01), corresponding to a hazard ratio of 0.33 (95% CI: 0.14–0.81). Adjusting for covariates this effect persisted; the adjusted hazard ratio (AHR) for progression was 0.24 (95% CI: 0.08–0.77). Cox proportional hazards analysis also demonstrated that the CAPE group had superior OS compared to the GEM group in unadjusted (HR =0.13; 95% CI: 0.04–0.40) and adjusted models (HR =0.13, 95% CI: 0.03–0.52).ConclusionsFor neoadjuvant 3WCRT, this hypothesis-generating study suggests concurrent CAPE may be a more effective radiosensitizer than GEM for patients with (B)RPC.     

Improved sensitivity and positive predictive value of contrast-enhanced intraoperative ultrasound in colorectal cancer liver metastasis: a systematic review and meta-analysis

BackgroundSurgery is an effective treatment for improving the survival rate of patients with colorectal cancer liver metastases (CRLM). However, accurately determining the resection margin of liver lesions during surgery remains challenging. Therefore, this study aimed to evaluate the sensitivity and predictive value of intraoperative contrast-enhanced ultrasound (CE-IOUS) in CRLM patients undergoing surgery.MethodsWe performed a literature search of the PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu databases using the following search terms: metastatic liver cancer, colorectal cancer, sensitivity, contrast-enhanced intraoperative ultrasound, CE-IOUS, colorectal liver metastases, and CRLM. The search period was set from the date of establishment of the database to September 2021. Quality assessment of diagnostic accuracy studies 2 (QUADAS-2) recommended by the Cochrane Collaboration was used to assess the methodological quality of the included studies, and network meta-analysis was performed using Stata 15.0 software.ResultsA total of 10 articles met the inclusion criteria. The meta-analysis results showed that the overall sensitivity and specificity of CE-IOUS were 0.96 [95% confidence interval (CI), 0.95–0.97] and 0.75 (95% CI, 0.70–0.80), respectively. The overall sensitivity and specificity of IOUS were 0.84 (95% CI, 0.82–0.86) and 0.82 (95% CI, 0.77–0.87), respectively. The area under the summary receiving operating characteristic (SROC) curves (AUCs) of CE-IOUS and IOUS were 0.9753 and 0.8590, respectively. The odds ratio (OR) and 95% CI of CE-IOUS changed the surgical margin were 0.205 and 0.071–0.465, P=0.000, the difference was statistically significant.DiscussionBased on the results of this meta-analysis, CE-IOUS improved the sensitivity and predictive value of CRLM detection compared with IOUS, and is more suitable for intraoperative planning of surgical margins. At present, it is the most sensitive imaging method available, and is recommended for use during liver resection to provide doctors with more reliable information during surgery.     

Chemoradiotherapy for patients with locally advanced or unresectable extra-hepatic biliary cancer

BackgroundAlthough surgical resection is the preferred curative-intent treatment option for patients with non-metastatic, extra-hepatic biliary cancer (EBC), radiotherapy (RT) or chemoradiotherapy (CRT) may be utilized in select cases when surgical resection is not feasible. The purpose of this study is to report the efficacy and adverse events (AEs) associated with CRT for patients with locally advanced and unresectable EBC.MethodsThis was a retrospective cohort study of patients with EBC, including extra-hepatic cholangiocarcinoma or gallbladder cancer, deemed inoperable who received RT between 1998 and 2018. The median RT dose was 50.4 Gy in 28 fractions and 94% received concurrent 5-fluorouracil. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS) from the start of RT. The cumulative incidence of local progression (LP), locoregional progression (LRP), and distant metastasis (DM) were reported with death as a competing risk. Cox proportional hazards regression models were used to assess for correlation between patient and treatment characteristics and outcomes.ResultsForty-eight patients were included for analysis. The median OS was 12.0 months [95% confidence interval (CI): 2.3–73.2 months]. The 2-, 3-, and 5-year OS were 33% (95% CI: 22–50%), 20% (95% CI: 11–36%), and 7% (95% CI: 2–20%), respectively. The 2-year PFS, LP, LRP, and DM were 21% (95% CI: 12–36%), 27% (95% CI: 17–44%), 31% (95% CI: 20–48%), and 33% (95% CI: 22–50%), respectively. On univariate analysis, biologically effective dose (BED) >59.5 Gy₁₀ was associated with improved OS [hazard ratio (HR): 0.40, 95% CI: 0.18–0.92, P=0.03] and PFS (HR: 0.37, 95% CI: 0.16–0.84, P=0.02) and primary tumor size (per 1 cm increase) was associated with worsened PFS (HR: 1.29, 95% CI: 1.02–1.63, P=0.04). BED >59.5 Gy₁₀ remained associated with PFS on multivariate analysis (HR: 0.34, 95% CI: 0.15–0.78, P=0.01). Treatment-related grade 3+ acute and late gastrointestinal AEs occurred in 13% and 17% of patients, respectively.ConclusionsRT is associated with 3- and 5-year survival in a subset of patients with unresectable EBC. Further exploration of the role of RT as part of a multi-modality curative treatment strategy is warranted.     

Stereotactic body radiation therapy versus radiofrequency ablation for single small hepatocellular carcinoma: a propensity-score matching analysis of their impact on liver function and clinical outcomes

BackgroundStereotactic body radiation therapy (SBRT) has high efficacy for early-stage hepatocellular carcinoma (HCC) and is an accepted alternative to radiofrequency ablation (RFA). However, SBRT for HCC may cause subacute liver injury leading to negative clinical outcomes. In this study, we compared changes of liver function and prognosis after SBRT or RFA in patients with single, small HCC by using a propensity-score matching analysis.MethodsWe reviewed medical records of 140 patients with single ≤3 cm HCC treated with SBRT or RFA at Kurashiki Central Hospital between January 2014 and February 2019. Changes of albumin-bilirubin (ALBI) score, local recurrence, and overall survival were compared between the propensity-score matched groups (31 patients treated with SBRT and 62 treated with RFA).ResultsThe ALBI score increased modestly but significantly after SBRT, while it was unchanged in the RFA group; the intergroup difference was statistically significant (P=0.004). No local recurrence was identified in the SBRT group, whereas the cumulative recurrence incidence was 9.7% in the RFA group (P=0.023). Overall survival was not significantly different between the two groups (hazard ratio: 1.32, 95% confidence interval: 0.60–2.89, P=0.401).ConclusionsSBRT had modestly negative impact on liver function but with appraisable local control of HCC. Our findings should contribute to the selection of this modality for treatment of single, small HCC.     

Comparison of the safety and prognosis of sequential regorafenib after sorafenib and lenvatinib treatment failure in patients with unresectable hepatocellular carcinoma: a retrospective cohort study

BackgroundThere is lack of studies on sequential regorafenib after sorafenib and lenvatinib treatment failure in patients with unresectable hepatocellular carcinoma (HCC). This study was to explore the safety and prognosis of sequential regorafenib after sorafenib and lenvatinib failure in HCC patients.MethodsThis study was a retrospective, real-world study that included 50 HCC patients who received sequential regrafinib after sorafenib and lenvatinib failure. The safety and prognosis of two groups were compared.ResultsThe incidence of all grade and III/IV adverse events were 68% and 24%. According to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 and modified (m) RECIST standards, the objective response rates (ORRs) after receiving regorafenib were 14.0% and 22.0%, respectively. The disease control rates (DCRs) were 62.0% and 60.0%, respectively. Based on different first-line targeted drugs, 50 patients were divided into sorafenib (n=22) and lenvatinib group (n=28). There was no differences between two groups except age and bilirubin. And there was no differences in other treatments before or after regorafenib. The baseline between two groups was basically same and had good comparability. There was no difference in incidence of all grade and III/IV adverse events, ORR and DCR between two groups (P>0.05). On long-term prognosis, total overall survival (TOS) in sorafenib and lenvatinib group were 23.0 (95% CI: 15.1–30.9) vs. 29.7 (95% CI: 21.4–38.1) months. The difference was statistically significant (P=0.041). Besides, regorafenib overall survival (ROS) in sorafenib and lenvatinib group were 11.7 (95% CI: 7.1–16.3) vs. 15.9 (95% CI: 8.3–23.5) months. The difference was statistically significant ( P=0.045). The regorafenib progression-free survival (RPFS) was 5.6 (95% CI: 1.9–9.2) vs. 8.0 (95% CI: 5.1–10.9) months in sorafenib and lenvatinib group, respectively, and difference was not statistically significant (P=0.380).ConclusionsRegorafenib is an effective drug for second-line treatment of HCC, with fewer severe adverse events, ORR and DCR was 14–22% and 62–60%, respectively. Both TOS and ROS in lenvatinib group were better than those in sorafenib group. For HCC patients whose first-line targeted drug is lenvatinib, it is safe and effective to accept regorafenib after disease progresses.     

Clinical and pathologic features correlated with rare favorable survival in patients with BRAFV600E mutated colorectal cancer

BackgroundBRAF^V600E mutations occur in fewer than 10% of all patients with metastatic colorectal cancer (CRC) and arise from sessile serrated adenomas. Despite efficacy with targeted therapies against MAPK signaling and with immunotherapies in this population, survival outcomes for patients with BRAF^V600E mutated metastatic CRC in general are poor. Characteristics distinguishing patients with BRAF^V600E mutated metastatic CRC with favorable versus unfavorable outcomes have not been well annotated.MethodsRecords of 187 patients with BRAF^V600E mutated metastatic CRC evaluated at MD Anderson Cancer Center between 2005–2020 were reviewed. Patients with the shortest and longest metastatic survival (N=25 for each group) were compared. Associations between prognostic group and clinical/pathologic features were measured by odds ratio and for median survival by log-rank testing.ResultsMedian metastatic survival differed between the 2 BRAF^V600E mutated metastatic CRC populations (8.6 vs. 83.9 months, hazard ratio 32; P<0.0001). Patients with poor survival more commonly had hepatic involvement [75% vs. 28%, odds ratio (OR) 8.1, 95% confidence interval (CI): 2.3–29; P=0.001]. Patients with favorable survival were more likely to develop metachronous metastases (52% vs. 16%, OR 5.7, 95% CI: 1.5–21; P=0.01) and undergo definitive locoregional therapy to metastatic disease (40% vs. 0%, OR 34.5, 95% CI: 1.9–630; P=0.01). Microsatellite instability (36% vs. 4%, OR 19.8, 95% CI: 2.2–180; P=0.008) and prior tobacco exposure (44% vs. 16%, OR 4.1, 95% CI: 1.1–15.6, P=0.04) were associated with a favorable prognosis. Durable responses to MAPK-targeted therapies and immunotherapy were noted in the favorable group.ConclusionsA small fraction of patients with BRAF^V600E mutated metastatic CRC can achieve excellent long-term survival which belies conventional context and is driven by either surgical metastectomy or by systemic treatment options. While poor overall prognosis remains the recognized outcome for most patients with BRAF^V600E mutated metastatic CRC, it is possible that few may achieve exceptionally favorable survival.     

Clinical outcomes for hilar and extrahepatic cholangiocarcinoma with adjuvant,definitive, or liver transplant-based neoadjuvant chemoradiotherapy strategies: a single-center experience

BackgroundWe report our experience with 3 strategies for treating hilar and extrahepatic cholangiocarcinoma (CCA) including chemoradiotherapy: neoadjuvant chemoradiotherapy (nCRT) and orthotopic liver transplant, surgical resection and adjuvant chemoradiotherapy (aCRT), and definitive chemoradiotherapy (dCRT).MethodsWe included patients treated from 1998 through 2019. Kaplan-Meier estimates, log-rank testing, and univariate/multivariate Cox models were used to assess outcomes (local progression-free survival, disease-free survival, and overall survival).ResultsSixty-five patients (nCRT, n=20; aCRT, n=16; dCRT, n=29) met inclusion criteria [median (range) age 65 years (27–84 years)]. Median posttreatment follow-up was 19.1 months (0.8–164.8 months) for all patients and 38.6, 24.3, and 9.0 months for the nCRT, aCRT, and dCRT groups, respectively. At 3 and 5 years, overall survival was 78% and 59% for the nCRT group; 47% and 35%, aCRT group; and 11% and 0%, dCRT group. Compared with the dCRT group, the nCRT group (hazard ratio =0.13, 95% CI: 0.05–0.33) and the aCRT group (hazard ratio =0.29, 95% CI: 0.14–0.64) had significantly improved overall survival (P<0.001). The 5-year local progression-free survival (50% nCRT vs. 30% aCRT vs. 0% dCRT, P<0.001) and 5-year disease-free survival (61% nCRT vs. 30% aCRT vs. 0% dCRT, P=0.01) were significantly better for strategies combined with surgery.ConclusionsOutcomes for patients with extrahepatic CCA were superior for those who underwent nCRT/orthotopic liver transplant or postsurgical aCRT than for patients treated with dCRT. The excellent outcomes after nCRT/orthotopic liver transplant provide additional independent data supporting the validity of this strategy. The poor survival of patients treated with dCRT highlights a need for better therapies when surgery is not possible.     

Prediction of early recurrence of hepatocellular carcinoma after resection based on Gd-EOB-DTPA enhanced magnetic resonance imaging: a preliminary study

BackgroundEarly recurrence (ER) after radical resection of hepatocellular carcinoma (HCC) affects the prognosis of patients. Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) can improve the detection rate of small HCC. This study innovatively introduces a new quantitative index combined with qualitative index to compare the differences in clinical and imaging characteristics between ER and non-ER groups and evaluate the feasibility of Gd-EOB-DTPA-enhanced MRI in predicting ER.MethodsA total of 68 patients with HCC confirmed by operation and pathology in the Shandong Cancer Hospital and Institute were included retrospectively. All participants were examined by Gd-EOB-DTPA-enhanced MRI within 3 weeks before surgery. Regular follow-up was performed every 2 months within 1 year after operation. Among them, 18 cases with new lesions were in ER group, and 50 cases without new lesions were in non-ER group. The clinical and imaging data of the 2 groups were collected, and the differences of clinical data and preoperative MRI signs between the ER group and non-ER group were compared. The predictive factors of ER after HCC were analyzed by multivariate logistic regression.ResultsThe quantitative parameter lesion-to-liver contrast enhancement ratio (LLCER) can predict the pathological grade of HCC (P=0.023). The results of univariate analysis between the ER group and non-ER group showed that there were significant differences in pathological grade (P=0.008), lesion morphology (P=0.011), peritumoral low signal intensity in hepatobiliary phase (HBP) (P<0.001), satellite nodules (P<0.001), and LLCER (P<0.001) between the 2 groups. Multivariate logistic regression analysis showed that HBP peritumoral low signal intensity [odds ratio (OR) =7.214, 95% confidence interval (CI): 1.230–42.312, P=0.029], satellite nodules (OR =9.198, 95% CI: 1.402–60.339, P=0.021), and parameter LLCER value (OR =0.906, 95% CI: 0.826–0.995, P=0.039) were independent predictors of ER of HCC after resection.ConclusionsPreoperative Gd-EOB-DTPA enhanced MRI has important predictive value for early recurrence after radical resection of hepatocellular carcinoma.     

Imatinib-associated skin rash is related to treatment outcome in patients with unresectable and/or metastatic gastrointestinal stromal tumor

BackgroundImatinib-associated skin rash in gastrointestinal stromal tumor (GIST) patients is one of the most troublesome adverse effects, and can reduce imatinib adherence and persistence. However, the relationship between skin rash and adherence is unknown, and there are few published studies on the clinical outcomes of patients with severe skin rash.MethodsAdult patients (≥18 years) who were treated with 400 mg/day imatinib for unresectable or metastatic GIST were enrolled in this retrospective study. The skin rash was graded by physicians according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Progression-free survival (PFS) was compared using the Kaplan-Meier method between groups with and without skin rash. The risk factors for GIST progression were investigated by Cox regression analysis.ResultsA total of 125 GIST patients were finally included. Among them, 43 (34.4%) patients developed skin rash during imatinib treatment. Serial blood eosinophil levels were associated with skin rash and severity (P<0.001). Patients with skin rash tended to have poorer PFS than patients with no rash (P=0.035). Moreover, patients with rash had a significantly higher prevalence of non-adherence compared with patients without rash [odds ratio (OR): 3.42, 95% confidence interval (CI): 1.36–8.61, P=0.009 for grades 1–2; OR: 6.07, 95% CI: 1.42–26.11, P=0.015 for grades 3–4). Cox regression analysis indicated that the independent risk factors for GIST progression were non-adherence (OR: 4.20, 95% CI: 1.57–11.25, P=0.004) and medium- and high-risk GIST (OR: 5.38, 95% CI: 1.15–25.09, P=0.032).ConclusionsNon-adherence and medium- and high-risk GIST are independent risk factors for GIST progression. Skin rash can be associated with treatment adherence, which can in turn be associated with poor outcomes of GIST treatment. Measuring the blood eosinophil levels could be helpful in predicting risk of skin rash during imatinib treatment.     

Prediction of late recurrence after radiofrequency ablation of HBV-related hepatocellular carcinoma with the age-male-albumin-bilirubin-platelets (aMAP) risk score: a multicenter study

BackgroundLong-term survivals of patients with HBV-related hepatocellular carcinoma are limited by the high incidence of tumor recurrence after radiofrequency ablation (RFA), identification of the risk factors and understanding the patterns of recurrence can help to improve the comprehensive management of patients after RFA. Therefore, the purpose of the study is to explore the prognostic value of the age-male-albumin-bilirubin-platelets (aMAP) score in patients with early-stage HBV-related hepatocellular carcinoma (HCC) receiving RFA; investigate the risk factors and patterns of late recurrence (LR); and develop a nomogram to predict recurrence-free survival (RFS).MethodsA retrospective review of HBV-related HCC patients who underwent primary RFA from March 2012 to December 2020 was conducted. The prognostic value of the aMAP score was evaluated in a primary cohort (n=302) and then further validated in an independent validation cohort (n=143). The optimal threshold of aMAP scores was calculated by X-tile 3.6.1 software. A prognostic nomogram was constructed from multivariate analysis and validated in an external validation cohort.ResultsPatients with aMAP scores ≤63.8, 63.8–67.8, and >67.8 were classified into low-, medium-, and high-recurrence risk groups, respectively. The C-index to predict LR was 0.76 (95% CI: 0.700–0.810). The high-risk group was associated with the worst RFS (HR: 5.298; 95% CI, 2.697–10.408; P<0.001) and overall survival (OS) (HR: 2.639; 95% CI, 1.097–6.344; P=0.03) compared with medium- and low-risk groups. The aMAP score, multiple tumors and preoperative HBV DNA level were independent risk factors for LR. The proposed nomogram had excellent performance in predicting LR of HBV-related HCC [C-index: 0.82 (95% CI: 0.772–0.870)].ConclusionsThis study demonstrated that the aMAP score can serve as an objective predictor of LR for HBV-related HCC patients after RFA. The nomogram based on preoperative HBV DNA level, aMAP score, and number of tumors can reliably help clinicians to stratify the recurrence risk of HCC patients after RFA.     

Impact of postoperative lymph node status on the prognosis of esophageal squamous cell carcinoma after esophagectomy following neoadjuvant chemoradiotherapy: a retrospective study

BackgroundNeoadjuvant chemoradiotherapy (nCRT) and surgery are widely used treatments for locally advanced esophageal squamous cell carcinoma (ESCC). Thus, it is critically important to investigate risk factors that affect patient prognosis after preoperative chemoradiotherapy and surgery.MethodsWe conducted a retrospective analysis of 77 patients with ESCC who received nCRT and underwent surgery at our center from January 2015 to December 2019. We analyzed the primary clinical data, postoperative pathological results, recurrence, and death results.ResultsAmong the 77 ESCC patients who received nCRT and surgery, 19 achieved a postoperative pathologic complete response (pCR), and the overall pCR rate was 24.68%. The univariate analysis indicated that postoperative post-neoadjuvant treatment N stage (ypN) metastasis [hazards ratio (HR): 2.908; 95% confidence interval (CI): 0.874–9.676; P=0.082], a high lymph-node ratio [(LNR) >0.1] (HR: 7.149, 95% CI: 1.740–29.369; P=0.006), post-neoadjuvant treatment T3-4 (ypT3–4) (HR: 3.626, 95% CI: 0.824–15.956; P=0.088) affected disease-specific survival (DSS). The multivariate analysis indicated that a high LNR (>0.1) (HR: 6.170; 95% CI: 1.472–25.856; P=0.013) was a significant independent predictor of DSS. The univariate analysis indicated that postoperative ypN metastasis (HR: 2.283; 95% CI: 1.047–4.979; P=0.038) and a high LNR (>0.1) (HR: 4.210; 95% CI: 1.547–11.458; P=0.005) were associated with recurrence-free survival (RFS). The multivariate survival analysis showed that a high LNR (>0.1) (HR: 4.289; 95% CI: 1.538–11.965; P=0.005) was also a significant independent predictor of RFS. In this study, 57 positive lymph nodes were found in 30 of the 77 patients, including 16 left gastric lymph nodes, 9 pericardial lymph nodes, and 7 left supraclavicular lymph nodes.ConclusionsA high LNR (>0.1) in ESCC patients after nCRT is a risk factor of DSS and RFS. ypN metastasis is also an independent predictor of RFS. Left gastric-arterial lymph nodes, para-cardiac lymph nodes, and left supraclavicular lymph nodes are the most common sites of metastasis in ESCC after nCRT.     

Comparison of prognostic factors of esophageal cancer between a Chinese cohort and the Surveillance,Epidemiology, and End Results (SEER) database: a retrospective cohort study

BackgroundEsophageal cancer is a highly aggressive, early metastasis gastrointestinal malignancy, with geographic differences in prognosis. It is unknown whether there are differences in the survival in different regions among esophageal cancer patients who underwent the treatments. This study was to explore the influencing factors of esophageal cancer survival in patients from China and the Surveillance, Epidemiology, and End Results (SEER) database.MethodsThe retrospective cohort study were conducted with 605 Chinese esophageal cancer patients in the Wuxi People’s Hospital and 2,351 patients from the SEER database. The demographic and clinical data were collected from the two cohort, respectively. The outcome was the death during the follow-up. The follow-up ended on November 30, 2021. The Cox proportional hazards model was used in the univariate and multivariate survival analyses, with hazard ratio (HR) and 95% confidence interval (CI).ResultsIn group one, the following were identified as the prognostic factors: female gender (HR =0.568; 95% CI: 0.398–0.811), T3 and T4 stages (HR =3.312; 95% CI: 2.493–4.401), N2 and N3 stages (HR =3.562; 95% CI: 2.631–4.824), and other subtypes of cancer (HR =0.393; 95% CI: 0.223–0.693). The following prognostic were factors identified in group two: age ≥65 years (HR =1.16; 95% CI: 1.058–1.276), female gender (HR =0.843; 95% CI: 0.752–0.945), T3 and T4 stages (HR =1.523; 95% CI: 1.373–1.690), M1 stage (HR =2.554; 95% CI: 2.303–2.832), treatment with surgery and chemotherapy (HR =0.507; 95% CI: 0.457–0.562), and other subtypes of cancer (HR =1.432; 95% CI: 1.298–1.581).ConclusionsThere may be some differences in prognostic factors between Chinese and American patients with esophageal cancer. It is indicated that different management strategies of esophageal cancer should be considered in different populations to improve the prognosis of patients.     

Clinicopathological and prognostic significance of programmed death ligant-1 expression in gastric cancer: a meta-analysis

BackgroundGastric cancer (GC) is a common malignant tumor with a high incidence in China. The use of immune checkpoint inhibitors has become the focus of tumor immunotherapy in recent years. This study was to investigate the clinicopathological and prognostic significance of programmed death ligant-1 (PD-L1) expression in GC.MethodsWe searched the PubMed, ScienceNet, EMbase, CNKI, and Wanfang databases for retrospective cohort studies on the clinicopathology and prognosis of PD-L1 expression in GC published between January 2010 and April 2020. The literature was first selected to extract data according to the inclusion and exclusion criteria, then a meta-analysis performed using Stata15.0 software. Publication bias and sensitivity analysis were carried out for the included studies.ResultsA total of 3,218 patients in 15 studies were included in the meta-analysis. The positive expression of PD-L1 was related to a decrease in the 3-year survival rate (HR =1.32, 95% CI: 1.02–1.49, P=0.028) and 5-year survival rate (HR =1.39, 95% CI: 1.14–1.69, P=0.001). The difference in PD-L1 expression was related to lymph node metastasis (OR =1.73, 95% CI: 1.18–2.54, P<0.001), but not to tumor stage (OR =1.28, 95% CI: 0.81–2.02, P=0.292).ConclusionsThe results show that PD-L1 is related to the prognosis of GC. Its high expression decreases the 3- and 5-year survival rates and promotes lymph node metastasis, but does not reflect tumor stage. The results may provide a theoretical basis for the choice of clinical immunotherapy in GC patients.     

A systematic review and meta-analysis on the efficacy of Compound Kushen Injection in 3 kinds of digestive tract tumor

BackgroundChemotherapy has become the main means to prolong the life of patients with advanced digestive tract cancer; however, it is associated with serious toxicity and side effects. Compound Kushen Injection (CKI) is a pure Chinese herbal preparation, which can assist chemotherapy, inhibit tumor cell proliferation, and reduce adverse reactions of chemotherapy. In this study, we systematically evaluated reports of CKI as an adjuvant to chemotherapeutic treatment of digestive tract cancer in recent years and provided evidence for clinical diagnosis and treatment.MethodsThe databases of PubMed, Chinese Biomedical Literature (CBM), China National Knowledge Infrastructure (CNKI) and Web Of Science were searched for clinical randomized controlled trials (RCTs) related to adjuvant chemotherapy with CKI in the treatment of advanced gastrointestinal tumors published from January 2000 to September 2021. After screening the qualified literatures, RevMan 5.4 software was used to evaluate the bias of the included literatures and perform meta-analysis.ResultsA total of 12 articles were included in the selection, incorporating 1080 study participants in all; meta-analysis results showed that application of the CKI in the process of chemotherapy for digestive tract tumors could improve the efficacy [odds ratio (OR) =3.11; 95% confidence interval (CI): 2.26 to 4.47, Z=7.00, P<0.00001], increase the patients’ median survival time (months) (OR =3.00; 95% CI: 1.47 to 4.52, Z=3.84, P=0.0001), increase the level of CD3⁺ [mean difference (MD) =4.11; 95% CI: 3.24 to 4.98], CD4⁺ level (MD =8.24; 95% CI: 3.72 to 12.76), reduce the CD8⁺ level (MD =−5.42; 95% CI: −8.09 to −2.76), reduce the tumor markers carcinoembryonic antigen (CEA; MD =−14.26; 95% CI: −14.81 to −13.71), CA199 (MD =−138.87; 95% CI: −143.21 to −132.52), and reduce the adverse reactions of chemotherapy: leukopenia (OR =0.28; 95% CI: 0.19 to 0.43), thrombocytopenia (OR =0.38; 95% CI: 0.24 to 061), decreased hemoglobin (OR =0.55; 95% CI: 0.31 to 0.98), and nausea and vomiting symptoms (OR =0.35; 95% CI: 0.24 to 0.53).DiscussionAdjuvant chemotherapy with CKI in the treatment of digestive tract tumors can effectively improve the symptoms of patients, improve immunity, reduce the level of serum tumor markers, improve efficacy, and reduce toxic and side effects.     

Efficacy and safety of low-dose apatinib plus S-1 versus regorafenib and fruquintinib for refractory metastatic colorectal cancer: a retrospective cohort study

BackgroundAt present, regorafenib and fruquintinib are the standard regimens for refractory metastatic colorectal cancer patients in China, but both options have limited efficacy. The aim of this study was to investigate the efficacy and safety of low-dose apatinib plus S-1 compared with regorafenib and fruquintinib in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies.MethodsThe records of 114 patients with refractory mCRC in our center from April 2016 to September 2020 were retrospectively reviewed. Among these patients, 43 received apatinib 250 mg/day combined with S-1, 36 received regorafenib starting at 80 mg/day with weekly escalation, and 35 received fruquintinib 5 mg/day orally. Patients received radiographic examination every 1.5–2 months during the treatment period, progression-free survival time and overall survival time were analyzed and recorded.ResultsThe baseline clinical characteristics of the patients were broadly similar among the three groups. The median progression-free survival (mPFS) was 3.9 months [95% confidence interval (CI): 2.5–5.3] in the apatinib plus S-1 group, 3.1 months (95% CI: 1.9–4.2) in the fruquintinib group, and 2.4 months (95% CI: 2.1–2.7) in the regorafenib group, the mPFS of apatinib plus S-1 was significantly longer than that of regorafenib (HR =0.49, P=0.003) and fruquintinib (HR =0.60, P=0.048). The median overall survival (OS) was 8.2 months (95% CI: 5.4–11.0) in the apatinib plus S-1 group, 7.8 months (95% CI: 5.3–10.3) in the fruquintinib group, and 7.5 months (95% CI: 4.2–10.7) in the regorafenib group, which was comparable among the 3 groups. There was no statistical difference in disease control rate (DCR) among the three groups. Patients in the apatinib plus S-1 group had a higher incidence of hematological toxicity including anemia (62.8%), neutropenia (30.2%), and thrombocytopenia (39.5%), and the hand-foot skin reaction (58.3%) was more prevalent in the regorafenib group, while the adverse reaction of hypertension (45.7%) in the fruquintinib group was very significant.ConclusionsLow-dose apatinib plus S-1 prolonged PFS compared with regorafenib and fruquintinib, and is a potential alternative regimen for the treatment of refractory mCRC with tolerable and controlled toxicity.     

A retrospective study of clinicopathological characteristics and prognostic factors of Krukenberg tumor with gastric origin

BackgroundKrukenberg tumor (KT) of gastric origin has a poor prognosis. The present study of KTs are mainly case reports and clinical analysis with few samples. Therefore, it is urgent to explore the clinicopathologic characteristics of KTs through large sample studies. To improve the understanding of the clinical diagnosis and treatment of KT, this paper retrospectively analyzed 10 years of gastric cancer (GC) database data, including clinicopathological and prognostic features, aiming to provide a clinical reference for the diagnosis and treatment of the tumor.MethodsThe clinicopathological characteristics, treatments, and survival data were collected and analyzed from 130 patients with KTs of GC. Clinicopathological data included clinical manifestations, laboratory findings, imaging reports, pathology and immunohistochemistry (IHC) reports. We collected treatment regimens information on whether they had undergone surgery and chemotherapy and performed survival follow-up. Univariate and multivariate analysis were used to investigate the risk factors of KTs with gastric origin.ResultsThe median age of the patients was 41 years. A total of 63.1% of patients had synchronous ovarian metastasis, 70.8% had bilateral ovarian metastasis, 68.5% had peritoneum metastasis, and 98.5% had pathologically poorly differentiated adenocarcinoma. The positive rate of human epidermal growth factor receptor 2 (HER-2) was 1.8%. The follow-up rate was 90.8%, and the median overall survival (mOS) of ovarian metastasis was 13.0 months. Univariate analysis showed statistically significant prognostic factors including menstrual status, size of the gastric lesions and ovarian metastases, number of lymph node metastasis, interval to ovarian metastasis, resection of gastric lesions, peritoneal metastasis, oophorectomy, chemotherapy after ovarian metastases, two-drug regimen chemotherapy, albumin, serum cancer antigen 125 (CA-125) levels, platelet count, D-dimer, fibrinogen, and high pretreatment platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII). Fibrinogen [hazard ration (HR) =0.483; 95% confidence interval (CI): 0.300–0.777; P=0.003], size of ovarian metastasis (HR =1.808; 95% CI: 1.178–2.776; P=0.007), chemotherapy after ovarian metastasis (HR =0.195; 95% CI: 0.101–0.379; P=0.000), peritoneal metastasis (HR =2.742; 95% CI: 1.606–4.682; P=0.000) and oophorectomy (HR =1.720; 95% CI: 1.066–2.778; P=0.026) were independent prognostic factors.ConclusionsGC patients with KTs have some unique clinical features. Hypercoagulable states, peritoneal metastasis, and untimely chemotherapy and oophorectomy might be a worse predictor for KTs derived from gastric origin.     

Diabetes mellitus and postoperative blood glucose value help predict posthepatectomy liver failure in patients with hepatocellular carcinoma

BackgroundMany complications after hepatectomy can lead to perioperative death, among which posthepatectomy liver failure (PHLF) is the leading one. Existing studies suggest that one of the most important risk factors for PHLF is cirrhosis. Hepatitis B virus (HBV) infection is an important factor in the occurrence of cirrhosis, and the exact relationship between HBV infection and PHLF is not obvious. Diabetes mellitus and postoperative blood glucose are closely associated with liver regeneration, but its exact relationship with PHLF remains unclear.MethodsWe collected clinical indicators from 920 adult patients treated at the Liver Surgery and Transplantation Center of West China Hospital of Sichuan University from April 2009 and April 2019. We conducted a univariate analysis find out the risk factors of PHLF, follow by a multivariate analysis to ascertain the independent risk factors. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive efficiency of each risk factor.ResultsFollowing hepatectomy, 205 (22.2%) of patients were diagnosed with PHLF. Several variables were confirmed to related with PHLF significantly: diabetes [P<0.01, odds ratio (OR) =10.845, 95% confidence interval (CI): 5.450–21.579], HBV (P<0.01, OR =0.345, 95% CI: 0.187–0.635), blood glucose on the first postoperative day (post-BG1) (P=0.027, OR =1.059, 95% CI: 1.006–1.115), blood glucose on the third postoperative day (post-BG3) (P=0.021, OR =1.085, 95% CI: 1.012–1.162), blood glucose on the fifth postoperative day (post-BG5) (P=0.014, OR =1.119, 95% CI: 1.023–1.225), postoperative total bilirubin (post-TB) (P<0.01, OR =1.160, 95% CI: 1.133–1.187), and liver cirrhosis (P<0.01, OR =0.982, 95% CI: 0.561–1.717) identified to be independent risk factors of PHLF.ConclusionsDiabetes, HBV, post-BG1, post-BG3, and post-BG5 are related to the development of PHLF, and diabetes and post-BG can be used as predictors of the development of PHLF in patients with hepatocellular carcinoma (HCC).     

Comparison of neoadjuvant regimens for resectable gastroesophageal junction cancer: a systematic review of randomized clinical trials across three decades

BackgroundThe optimal perioperative treatment for adenocarcinoma of gastroesophageal junction (GEJ) tumor remains uncertain. The systematic review aims to assess the best neoadjuvant modality, namely chemotherapy (CT) versus chemoradiotherapy (CRT) based on randomized controlled trials (RCTs) for resectable gastric, esophageal and GEJ tumors.MethodsWe performed a comprehensive PubMed database and Cochrane Library search to identify relevant RCTs related to neoadjuvant treatment for resectable GEJ adenocarcinoma. We included all published RCTs (phase 2 or 3) that tested specific neoadjuvant therapies (CT or CRT) if the patient population included GEJ tumors. We applied the Version 2 Cochrane risk-of-bias tool (RoB 2) to all the eligible studies. Outcomes examined included R0 resection and pathological response based on intention-to-treat (ITT) analysis, surgical outcomes, notable adverse events, and overall survival (OS). Each randomized group of every study was noted to be neoadjuvant CRT, CT, or surgery alone in order to compare the outcomes among these treatment approaches.ResultsWe identified 25 RCTs with 7,855 patients published from 1996 to 2019. Seven studies tested preoperative CT versus surgery alone, 7 tested preoperative radiotherapy (RT) or CRT versus surgery alone, 4 tested preoperative RT or CRT versus preoperative CT, and 7 tested other combinations. The R0 resection ranged 47–100% and the 3-year OS ranged 6–66.1% in all the study arms. In an exploratory analysis, CRT strategies showed a superior R0 resection rate [80.2%; 95% confidence interval (CI): 79.8–80.6%] to surgery alone (60.9%; 95% CI: 60.4–61.3%; P<0.01) and to preoperative CT (63.9%; 95% CI: 63.6–64.2%; P<0.01). When comparing 3- and 5-year OS, improvement was noted when comparing CRT to surgery alone (P<0.01), and perioperative CT to surgery alone (P<0.01), but no definite difference was noted between CRT versus CT.DiscussionPreoperative CRT showed improvement in R0 resection rate to surgery alone and preoperative CT. However, there is no significant difference in OS between CRT and CT. Both neoadjuvant strategies remain clinically meaningful options for patients with resectable GEJ tumors. Lack of patient-level data and inconsistent reporting of key outcomes across studies were the main limitations of our study.     

Serum calcium improved systemic inflammation marker for predicting survival outcome in rectal cancer

BackgroundSystemic inflammation markers have shown prognostic values with variability in rectal cancer. Considering the association of serum calcium with inflammation, we aimed to examine whether it could improve systemic inflammation markers for survival prediction.MethodsWe enrolled 508 patients with stage I to III rectal cancer who underwent curative resection. The cohort was grouped by corrected serum calcium (cCa), platelet-to-lymphocyte ratio (PLR), and CaPLR (a score model combining cCa with PLR) for survival analysis. The LR (likelihood ratio) test and AIC (Akaike information criterion) were applied to compare models in survival prediction. The primary endpoint was disease-free survival (DFS).ResultsA total of 26.7% (136/508) patients reached recurrence after curative surgery. Both high cCa (HR 1.486; 95% CI, 1.018–2.171; P=0.040) and high PLR (HR 1.452; 95% CI, 1.059–1.991; P=0.021) were significantly associated with worse DFS. In model comparison, the AIC and LR were improved after cCa was added to PLR model in DFS prediction (AIC: 1,704.83 vs. 1,707.14 vs. 1,707.15; LR: 8.68 vs. 4.37 vs. 4.36; P=0.037). The CaPLR was developed for DFS prediction with adjusted HRs of 2.216 (95% CI, 1.256–3.909; P=0.006) and 1.679 (95% CI, 1.004–2.836; P=0.047) for high and intermediate score group respectively compared to low score group. A nomogram for predicting DFS was generated by using CaPLR and other clinical predictors, with a concordance index of 0.705 (95% CI, 0.620–0.789; P<0.001).ConclusionsSerum calcium could improve systemic inflammation markers in survival prediction for patients with rectal cancer.     

Efficacy and safety of sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a two-center study in China

BackgroundRegorafenib is a standard 2nd-line treatment for patients with advanced hepatocellular carcinoma (HCC), but the efficacy and safety of sequential therapy with sorafenib and regorafenib among advanced HCC patients in China is not clear.MethodsThis was a retrospective, two-center, cohort study of advanced HCC patients who received sequential therapy of sorafenib and regorafenib from October 2018 to April 2020 at 2 Chinese institutions. The patients were converted directly to regorafenib after failing to respond to sorafenib monotherapy. The patients underwent evaluations every 4–6 weeks to determine the efficacy and safety of the treatment according to physiological, laboratory, and radiological results. A radiological evaluation using computed tomography or magnetic resonance imaging scans was conducted. The outcomes included overall survival (OS) and progression-free survival (PFS).ResultsA total of 43 patients received regorafenib as a 2nd-line treatment after sorafenib progression. Of these patients, 26 (60.5%) and 17 (39.5%) were diagnosed with Barcelona Clinic Liver Cancer (BCLC) stages B and C, respectively. The median PFS was 11.0 [95% confidence interval (CI): 5.8–16.2] months, and the median OS was 17.0 (95% CI: 12.8–21.2) months. Conversely, the most common toxicities were hand-foot skin reaction (48.8%), diarrhea (32.6%), and hypertension (14%). The most common grade 3–4 toxicities were hypoalbuminemia (4.7%), anemia (4.7%), and thrombocytopenia (4.7%). Alpha-fetoprotein (AFP) ≥400, alanine transaminase (ALT) ≥60 IU/L, and aspartate aminotransferase (AST) ≥60 IU/L before 2nd-line treatment were associated with PFS in the univariable analyses. The Cox proportional-hazards regression analysis showed that AFP [hazard ratio (HR) =0.225; 95% CI: 0.073–0.688; P=0.009], ALT (HR =0.195; 95% CI: 0.051–0.741; P=0.016), AST (HR =0.209; 95% CI: 0.063–0.697; P=0.011), and presence of extrahepatic metastasis (HR =0.074; 95% CI: 0.009–0.608; P=0.015) before 2nd-line treatment were independently associated with PFS.ConclusionsThe sequential therapy of sorafenib and regorafenib is well-tolerated and effective in advanced HCC patients after sorafenib progression based on our two-center real-world data. Patients with good liver function reserve and a high level of AFP before 2nd-line treatment may benefit from sequential treatment. These results still need further validation.