Neutrophil-to-lymphocyte ratio and carbohydrate antigen 19-9 as prognostic markers for advanced pancreatic cancer patients receiving first-line chemotherapy

BACKGROUNDA decline in serum carbohydrate antigen 19-9 (CA19-9) levels during systemic chemotherapy is considered as a prognostic marker for patients with advanced pancreatic cancer. Neutrophil-to-lymphocyte ratio (NLR) has been extensively studied as a simple and useful indicator of prognosis in various cancers including pancreatic cancer.AIMTo assess the prognostic significance of NLR and CA19-9 in patients with advanced pancreatic adenocarcinoma received first-line chemotherapy according to CA19-9 positivity.METHODSWe retrospectively analyzed patients diagnosed with advanced pancreatic cancer who received first-line chemotherapy between January 2010 and July 2017 at the Catholic University of Seoul St. Mary’s Hospital. Patients were divided according to CA19-9 positivity (CA19-9-positive vs -negative groups) and pre-and post-treatment NLR levels. To determine cut-off value of NLR and CA19-9 reduction, time-dependent receiver operating characteristic curve was applied. We evaluated overall survival (OS) and progression-free survival (PFS) for each group using Kaplan-Meier method, and we performed multivariate analyses on the entire cohort.RESULTSWe included 271 patients in this study. Cut-off value of NLR and CA19-9 reduction was determined as 2.62 and 18%. Multivariate analysis showed that post-treatment NLR < 2.62 and reduction of ≥ 18% of baseline CA19-9 were significantly associated with OS and PFS. Post-treatment NLR ≥ 2.62 showed hazard ratio (HR) of 2.47 [95% confidence interval (CI): 1.84-3.32, P < 0.001] and CA19-9 decline (≥ 18%) showed HR of 0.51 (95%CI: 0.39-0.67, P < 0.001) for OS. When CA19-9-positive patients were divided into groups according to CA19-9 response (responder vs non-responder) and post-treatment NLR (< 2.62 vs ≥ 2.62), CA19-9 responder and post-treatment NLR < 2.62 group showed better survival than CA19-9 non-responder and post-treatment NLR ≥ 2.62 group (OS 11.0 mo vs 3.9 mo, P < 0.001; PFS 6.3 mo vs 2.0 mo, P < 0.001). The combination of CA19-9 decline and post-treatment NLR showed a significant correlation with clinical response in CA 19-9 positive group. Within the CA19-9-negative group, the post-treatment NLR < 2.62 group showed better survival than the post-treatment NLR ≥ 2.62 group (OS 12.7 mo vs 7.7 mo, P < 0.001; PFS 6.7 mo vs 2.1 mo, P < 0.001), and post-treatment NLR showed correlation with clinical response.CONCLUSIONIn advanced pancreatic cancer patients positive for CA19-9 and treated with systemic chemotherapy, the combination of post-treatment NLR < 2.62 and 18% decline of CA19-9 at the first response evaluation is a good prognostic marker. Post-treatment NLR < 2.62 alone could be used as a prognostic marker and an adjunctive tool for response evaluation in CA19-9-negative patients.     

Does chronic kidney disease affect the complications and prognosis of patients after primary colorectal cancer surgery?

BACKGROUNDThe effect of chronic kidney disease (CKD) on the outcomes of colorectal cancer (CRC) patients after primary CRC surgery is controversial.AIMTo analyze whether CKD had specific effect on the outcomes after CRC surgery.METHODSWe searched the PubMed, Embase, Cochrane Library databases and CNKI, from inception to March 14, 2022. Newcastle-Ottawa Scale was used for the quality assessment in this meta-analysis, and we used RevMan 5.3 was used for data analysis.RESULTSA total of nine studies including 47771 patients were eligible for this meta-analysis. No significant difference was found in terms of overall postoperative complications [odds ratio (OR) = 1.78, 95%CI: 0.64-4.94, P = 0.27]. We analyzed the specific complications and found that the CKD group had higher rates of pulmonary infection (OR = 2.70, 95%CI: 1.82-4.00, P < 0.01), cardiovascular complications (OR = 3.39, 95%CI: 2.34-4.91, P < 0.01) and short-term death (OR = 3.01, 95%CI: 2.20-4.11, P < 0.01). After pooling the hazard ratio (HR), the CKD group had worse overall survival (OS) (HR = 1.51, 95%CI: 1.04-2.20, P = 0.03). We performed subgroup analyses of the dialysis and non-dialysis groups, and no significant difference was found in the non-dialysis group (HR = 1.20, 95%CI: 0.98-1.47, P = 0.08). The dialysis group had worse OS (HR = 3.36, 95%CI: 1.92-5.50, P < 0.01) than the non-dialysis group. The CKD group had worse disease-free survival (DFS) (HR = 1.41, 95%CI: 1.12-1.78, P < 0.01), and in the subgroup analysis of the dialysis and non-dialysis groups, no significant difference was found in the non-dialysis group (HR = 1.27, 95%CI: 0.97-1.66, P = 0.08). The dialysis group had worse OS (HR = 1.95, 95%CI: 1.23-3.10, P < 0.01) than the non-dialysis group.CONCLUSIONPreexisting CKD was associated with higher rates of pulmonary infection, higher rates of short-term death, and worse OS and poorer DFS following CRC surgery.     

A signature of Prevotella copri and Faecalibacterium prausnitzii depletion,and a link with bacterial glutamate degradation in the Kenyan colorectal cancer patients

BackgroundColorectal cancer (CRC) is the fifth most diagnosed cancer in Sub-Saharan Africa. In Kenya, CRC incidence rates tripled from 1997 to 2017. In the Moi Teaching and Referral Hospital, Moi University, there has been an increase in CRC cases, notably for younger patients. A suggested pathobiology for this increase is gut microbiome dysbiosis. Since, for the Kenyan CRC patient population, microbiome studies are rare, there is a need for a better understanding of how microbiome dysbiosis influences CRC epidemiology in Kenya. In this single-center study, the focus was on profiling the gut microbiome of Kenyan CRC patients and healthy volunteers and evaluating associations between microbiome profiles and the age of CRC patients.MethodsThe gut mucosa-associated microbiome of 18 CRC patients and 18 healthy controls were determined by 16S rRNA sequencing and analyzed for alpha and beta diversity, differential abundance, and microbial metabolic profiling.ResultsAlpha diversity metrics showed no significant differences, but beta diversity metrics showed dissimilarities in the microbial communities between CRC patients and healthy controls. The most underrepresented species in the CRC group were Prevotella copri (P. copri) and Faecalibacterium prausnitzii (F. prausnitzii), although Bacteroides fragilis (B. fragilis) and Prevotella nigrescens were overrepresented (linear discriminant analysis, LDA score >2, P<0.05). Also, for CRC patients, significant metagenomic functional alterations were evident in microbial glutamate metabolic pathways (L-glutamate degradation VIII was enriched, and L-glutamate and L-glutamine biosynthesis were diminished) (P<0.05, log2 Fold Change >1). Moreover, the microbiome composition was different for patients under 40 years of age compared to older patients (LDA score >2, P<0.05).ConclusionsMicrobiome and microbial metabolic profiles of CRC patients are different from those of healthy individuals. CRC microbiome dysbiosis, particularly P. copri and F. prausnitzii depletion and glutamate metabolic alterations, are evident in Kenyan CRC patients.     

Positron emission tomography complete metabolic response as a favorable prognostic predictor in esophageal cancer following neoadjuvant chemotherapy with docetaxel/cisplatin/5-fluorouracil

BACKGROUND ¹⁸F-fluorodeoxyglucose-positron emission tomography (PET)/computed tomography is useful in diagnosing lymph node and distant metastases of esophageal cancer. However, its value for predicting survival is controversial.AIMTo evaluate the value of PET complete metabolic response (CMR) as a prognostic predictor for esophageal cancer.METHODSBetween June 2013 and December 2017, 58 patients with squamous cell esophageal cancer who underwent neoadjuvant chemotherapy (NAC) in Oita University were enrolled in this retrospective cohort study. Tumors were clinically staged using fluorodeoxyglucose-PET/computed tomography before and after NAC. After NAC, maximal standardized uptake value ≤ 2.5 was defined as PET-CMR, and maximal standardized uptake value > 2.5 was defined as non-PET-CMR. We compared short-term outcomes between the PET-CMR group and non-PET-CMR group and evaluated prognostic factors by univariate and multivariate analyses.RESULTSThe PET-CMR group included 22 patients, and the non-PET-CMR group included 36 patients. There were no significant differences in intraoperative and postoperative complications between the two groups. Five-year relapse-free survival and overall survival in the PET-CMR group were significantly more favorable than those in the non-PET-CMR group (38.6 mo vs 20.8 mo, P = 0.021; 42.8 mo vs 25.1 mo, P = 0.011, respectively). PET-CMR was a significant prognostic factor in terms of relapse-free survival by univariate analysis (hazard ratio: 2.523; 95% confidence interval: 1.034–7.063; P < 0.041). Particularly, PET-computed tomography negative N was an independent prognostic factor of relapse-free survival and overall survival by multivariate analysis.CONCLUSIONPET-CMR after NAC is considered a favorable prognostic factor for esophageal cancer. Evaluation by PET-computed tomography could be useful in clinical decision making for esophageal cancer.     

Phytochemically rich dietary components and the risk of colorectal cancer: A systematic review and meta-analysis of observational studies

BACKGROUNDPersonalized nutrition and protective diets and lifestyles represent a key cancer research priority. The association between consumption of specific dietary components and colorectal cancer (CRC) incidence has been evaluated by a number of population-based studies, which have identified certain food items as having protective potential, though the findings have been inconsistent. Herein we present a systematic review and meta-analysis on the potential protective role of five common phytochemically rich dietary components (nuts, cruciferous vegetables, citrus fruits, garlic and tomatoes) in reducing CRC risk.AIMTo investigate the independent impact of increased intake of specific dietary constituents on CRC risk in the general population.METHODSMedline and Embase were systematically searched, from time of database inception to January 31, 2020, for observational studies reporting CRC incidence relative to intake of one or more of nuts, cruciferous vegetables, citrus fruits, garlic and/or tomatoes in the general population. Data were extracted by two independent reviewers and analyzed in accordance with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) reporting guidelines and according to predefined inclusion/exclusion criteria. Effect sizes of studies were pooled using a random-effects model.RESULTSForty-six studies were identified. CRC risk was significantly reduced in patients with higher vs lower consumption of cruciferous vegetables [odds ratio (OR) = 0.90; 95% confidence interval (CI): 0.85-0.95; P < 0.005], citrus fruits (OR = 0.90; 95%CI: 0.84-0.96; P < 0.005), garlic (OR = 0.83; 95%CI: 0.76-0.91; P < 0.005) and tomatoes (OR = 0.89; 95%CI: 0.84-0.95; P < 0.005). Subgroup analysis showed that this association sustained when looking at case-control studies alone, for all of these four food items, but no significant difference was found in analysis of cohort studies alone. Nut consumption exhibited a similar trend, but overall results were not significant (OR = 0.72; 95%CI: 0.50-1.03; P < 0.07; I² = 90.70%). Putative anticarcinogenic mechanisms are proposed using gene-set enrichment analysis of gene/protein perturbations caused by active compounds within each food item.CONCLUSIONIncreased cruciferous vegetable, garlic, citrus fruit and tomato consumption are all inversely associated with CRC risk. These findings highlight the potential for developing precision nutrition strategies for CRC prevention.     

Comparison of survival between adolescent and young adult vs older patients with hepatocellular carcinoma

BACKGROUNDDue to the special clinical features and biologic characteristics of adolescent and young adult (AYA) cancers, AYA cancers are different from cancers in children and elderly individuals. However, there are few reports on AYA hepatocellular carcinoma (HCC).AIMTo investigate the overall survival (OS) of AYA (15-39 years) and elderly (40-74 years) patients with HCC.METHODSThe data of all the HCC cases were extracted from the Surveillance, Epidemiology, and End Results database from 2004 to 2015 and were then divided into two groups based on age: AYA group (15-39 years) and older group (40-74 years). Kaplan-Meier curves and log-rank tests were used to compare the OS of the two groups. Propensity score matching (PSM) was employed to analyze the OS difference between the two groups. The Cox proportional hazards regression model was used to perform multivariate analysis to explore the risk factors for OS of HCC patients.RESULTSCompared to elderly cancer patients, AYA patients with HCC had a worse Surveillance, Epidemiology, and End Results stage, including the distant stage (22.1% vs 15.4%, P < 0.001), and a more advanced American Joint Committee on Cancer (AJCC) stage, including AJCC III and IV (49.2% vs 38.3%, P < 0.001), and were more likely to receive surgery (64.5% vs 47.5%, P < 0.001). Before PSM, the AYA group had a longer survival in months (median: 20.00, interquartile range [IQR]: 5.00-62.50) than the older group (median: 15.00, IQR: 4.00-40.00) (P < 0.001). After PSM, the AYA group still had a longer survival in months (median: 21.00, IQR: 5.00-64.50) than the older group (median: 18.00, IQR: 6.00-53.00) (P < 0.001). The Cox proportional hazards regression model showed that advanced age (hazard ratio [HR] = 1.405, 95%CI: 1.218-1.621, P < 0.001) was a risk factor for OS of HCC patients. In the subgroup analysis, the Cox proportional hazards regression model showed that in AJCC I/II HCC patients, advanced age (HR = 1.749, 95%CI: 1.352-2.263, P < 0.001) was a risk factor for OS, while it was not a risk factor in AJCC III/IV HCC patients (HR = 1.186, 95%CI: 0.997-1.410, P = 0.054) before PSM. After PSM, advanced age (HR = 1.891, 95%CI: 1.356-2.637, P < 0.001) was still a risk factor for OS in AJCC I/II HCC patients, but was not a risk factor for OS in AJCC III/IV HCC patients (HR = 1.192, 95%CI: 0.934-1.521, P = 0.157) after PSM.CONCLUSIONAYA patients with HCC have different clinical characteristics from older adults. In different AJCC stages, the two groups of patients have different OS: In AJCC I/II HCC patients, advanced age is a risk factor for OS, but it is not a risk factor for OS in the AJCC III/IV HCC patient group.     

Identification of serum angiopoietin-2 as a biomarker for clinical outcome of colorectal cancer patients treated with bevacizumab-containing therapy

Background:

The combination of chemotherapy with the vascular endothelial growth factor (VEGF) antibody bevacizumab is a standard of care in advanced colorectal cancer (CRC). However, biomarkers predicting outcome of bevacizumab-containing treatment are lacking. As angiopoietin-2 (Ang-2) is a key regulator of vascular remodelling in concert with VEGF, we investigated its role as a biomarker in metastatic CRC.

Methods:

Serum Ang-2 levels were measured in 33 healthy volunteers and 90 patients with CRC. Of these, 34 had metastatic disease and received bevacizumab-containing therapy. To determine the tissue of origin of Ang-2, quantitative real-time PCR was performed on microdissected cryosections of human CRC and in a murine xenograft model of CRC using species-specific amplification.

Results:

Ang-2 originated from the stromal compartment of CRC tissues. Serum Ang-2 levels were significantly elevated in patients with metastatic CRC compared with healthy controls. Amongst patients receiving bevacizumab-containing treatment, low pre-therapeutic serum Ang-2 levels were associated with a significant better response rate (82 vs 31% P<0.01), a prolonged median progression-free survival (14.1 vs 8.5 months; P<0.01) and a reduction of 91% in the hazard of death (P<0.05).

Conclusion:

Serum Ang-2 is a candidate biomarker for outcome of patients with metastatic CRC treated with bevacizumab-containing therapy, and it should be further validated to customise combined chemotherapeutic and anti-angiogenic treatment.     

Outcomes of neoadjuvant chemoradiotherapy followed by radical resection for T4 colorectal cancer

BACKGROUNDPatients with clinical T4 colorectal cancer (CRC) have a poor prognosis because of compromised surgical margins. Neoadjuvant therapy may be effective in downstaging tumors, thereby rendering possible radical resection with clear margins. AIMTo evaluate tumor downsizing and resection with clear margins in T4 CRC patients undergoing neoadjuvant concurrent chemoradiotherapy followed by surgery.METHODSThis study retrospectively included 86 eligible patients with clinical T4 CRC who underwent neoadjuvant concurrent chemoradiotherapy followed by radical resection. Neoadjuvant therapy consisted of radiation therapy at a dose of 45-50.4 Gy and chemotherapy agents, either FOLFOX or capecitabine. A circumferential resection margin (CRM) of < 1 mm was considered to be a positive margin. We defined pathological complete response (pCR) as the absence of any malignant cells in a specimen, including the primary tumor and lymph nodes. A multivariate logistic regression model was used to identify independent predictive factors for pCR.RESULTSFor 86 patients who underwent neoadjuvant chemoradiotherapy and surgery, the rate of pCR was 14%, and the R0 resection rate was 91.9%. Of the 61 patients with rectal cancer, 7 (11.5%) achieved pCR and 5 (8.2%) had positive CRMs. Of the 25 patients with colon cancer, 5 (20%) achieved pCR and 2 (8%) had positive CRMs. We observed that the FOLFOX regimen was an independent predictor of pCR (P = 0.046). After a median follow-up of 47 mo, the estimated 5-year overall survival (OS) and disease-free survival (DFS) rates were 70.8% and 61.4%, respectively. Multivariate analysis revealed that a tumor with a negative resection margin was associated with improved DFS (P = 0.014) and OS (P = 0.001). Patients who achieved pCR exhibited longer DFS (P = 0.042) and OS (P = 0.003) than those who did not.CONCLUSIONNeoadjuvant concurrent chemoradiotherapy engenders favorable pCR and R0 resection rates among patients with T4 CRC. The R0 resection rate and pCR are independent prognostic factors for patients with T4 CRC.     

Plasma MMP-2 and MMP-7 levels are elevated first month after surgery and may promote growth of residual metastases

BACKGROUNDMMP-2 also known as gelatinase A and MMP-7 (matrilysin) are members of the zinc-dependent family of MMPs (Matrix metalloproteinase). MMP-2 and MMP-7 are remodeling enzymes that digest extracellular matrix; MMP-2 is extensively expressed during development and is upregulated at sites of tissue damage, inflammation, and in stromal cells of metastatic tumors. MMP-7 is expressed in the epithelial cells and in a variety of cancers including colon tumors. Plasma MMP-2 and MMP-7 levels were assessed before and after minimally invasive colorectal resection for cancer pathology.AIMTo determine plasma MMP-2 and MMP-7 levels before and after minimally invasive colorectal resection for cancer pathology.METHODSPatients enrolled in a plasma bank for whom plasma was available were eligible. Plasma obtained from preoperative (Preop) and postoperative blood samples was used. Only colorectal cancer (CRC) patients who underwent elective minimally invasive cancer resection with preop, post-operative day (POD) 1, 3 and at least 1 late postop sample (POD 7-34) were included. Late samples were bundled into 7 d blocks (POD 7-13, 14-20, etc.) and treated as single time points. Plasma MMP-2 and MMP-7 levels were determined via enzyme-linked immunosorbent assay in duplicate.RESULTSTotal 88 minimally invasive CRC resection CRC patients were studied (right colectomy, 37%; sigmoid, 24%; and LAR/AR 18%). Cancer stages were: 1, 31%; 2, 30%; 3, 34%; and 4, 5%. Mean Preop MMP-2 plasma level (ng/mL) was 179.3 ± 40.9 (n = 88). Elevated mean levels were noted on POD1 (214.3 ± 51.2, n = 87, P < 0.001), POD3 (258.0 ± 63.9, n = 80, P < 0.001), POD7-13 (229.9 ± 62.3, n = 65, P < 0.001), POD 14-20 (234.9 ± 47.5, n = 25, P < 0.001), POD 21-27 (237.0 ± 63.5, n = 17, P < 0.001,) and POD 28-34 (255.4 ± 59.7, n = 15, P < 0.001). Mean Preop MMP-7 level was 3.9 ± 1.9 (n = 88). No significant differences were noted on POD 1 or 3, however, significantly elevated levels were noted on POD 7-13 (5.7 ± 2.5, n = 65, P < 0.001), POD 14-20 (5.9 ± 2.5, n = 25, P < 0.001), POD 21-27 (6.1 ± 3.6, n = 17, P = 0.002) and on POD 28-34 (6.8 ± 3.3, n = 15 P < 0.001,) vs preop levels.CONCLUSIONMMP-2 levels are elevated for 5 wk and MMP-7 levels elevated for weeks 2-6. The etiology of these changes in unclear, trauma and wound healing likely play a role. These changes may promote residual tumor growth and metastasis.     

Anatomic resection improved the long-term outcome of hepatocellular carcinoma patients with microvascular invasion: A prospective cohort study

BACKGROUNDThe long-term effect of anatomic resection (AR) is better than that of non-anatomic resection (NAR). At present, there is no study on microvascular invasion (MVI) and liver resection types.AIMTo explore whether AR improves long-term survival in patients with hepatocellular carcinoma (HCC) by removing the peritumoral MVI.METHODSA total of 217 patients diagnosed with HCC were enrolled in the study. The surgical margin was routinely measured. According to the stratification of different tumor diameters, patients were divided into the following groups: ≤ 2 cm group, 2-5 cm group, and > 5 cm group.RESULTSIn the 2-5 cm diameter group, the overall survival (OS) of MVI positive patients was significantly better than that of MVI negative patients (P = 0.031). For the MVI positive patients, there was a statistically significant difference between AR and NAR (P = 0.027). AR leads to a wider surgical margin than NAR (2.0 ± 2.3 cm vs 0.7 ± 0.5 cm, P < 0.001). In the groups with tumor diameters < 2 cm, both AR and NAR can obtain a wide surgical margin, and the surgical margins of AR are wider than that of NAR (3.5 ± 5.8 cm vs 1.6 ± 0.5 cm, P = 0.048). In the groups with tumor diameters > 5 cm, both AR and NAR fail to obtain wide surgical margin (0.6 ± 1.0 cm vs 0.7 ± 0.4 cm, P = 0.491). CONCLUSIONFor patients with a tumor diameter of 2-5 cm, AR can achieve the removal of peritumoral MVI by obtaining a wide incision margin, reduce postoperative recurrence, and improve prognosis.     

Impact of Obesity on Quality of Life,Psychological Distress,and Coping on Patients with Colon Cancer

BackgroundDespite the causal relationship between obesity and colon cancer being firmly established, the effect of obesity on the course of cancer calls for further elucidation. The objective of this study was to assess differences in clinical‐pathological and psychosocial variables between obese and nonobese individuals with colon cancer.Materials and MethodsThis was a prospective, multicentric, observational study conducted from 2015–2018. The sample comprised patients with stage II–III, resected colon cancer about to initiate adjuvant chemotherapy with fluoropyrimidine in monotherapy or associated with oxaliplatin and grouped into nonobese (body mass index <30 kg/m²) or obese (≥30 kg/m²). Subjects completed questionnaires appraising quality of life (European Organization for Research and Treatment of Cancer Quality of Life Core questionnaire), coping (Mini‐Mental Adjustment to Cancer), psychological distress (Brief Symptom Inventory 18), perceived social support (Multidimensional Scale of Perceived Social Support), personality (Big Five Inventory 10), and pain (Brief Pain Inventory). Toxicity, chemotherapy compliance, 12‐month recurrence, and mortality rate data were recorded.ResultsSeventy‐nine of the 402 individuals recruited (19.7%) were obese. Obese subjects exhibited more comorbidities (≥2 comorbidities, 46.8% vs. 30.3%, p = .001) and expressed feeling slightly more postoperative pain (small size‐effect). There was more depression, greater helplessness, less perceived social support from friends, and greater extraversion among the obese versus nonobese subjects (all p < .04). The nonobese group treated with fluoropyrimidine and oxaliplatin suffered more grade 3–4 hematological toxicity (p = .035), whereas the obese had higher rates of treatment withdrawal (17.7% vs. 7.7%, p = .033) and more recurrences (10.1% vs. 3.7%, p = .025). No differences in sociodemographic, quality of life, or 12‐month survival variables were detected.ConclusionObesity appears to affect how people confront cancer, as well as their tolerance to oncological treatment and relapse.Implications for PracticeObesity is a causal factor and affects prognosis in colorectal cancer. Obese patients displayed more comorbidities, more pain after cancer surgery, worse coping, and more depression and perceived less social support than nonobese patients. Severe hematological toxicity was more frequent among nonobese patients, whereas rates of withdrawal from adjuvant chemotherapy were higher in the obese cohort, and during follow‐up, obese patients presented greater 12‐month recurrence rates. With the growing and maintained increase of obesity and the cancers associated with it, including colorectal cancer, the approach to these more fragile cases that have a worse prognosis must be adapted to improve outcomes.     

Effect of the systemic immune-inflammation index on postoperative complications and the long-term prognosis of patients with colorectal cancer: a retrospective cohort study

BackgroundColorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract. Surgery is the main way to cure CRC, but the postoperative complication rate and recurrence rate remain high. The systemic immune-inflammation (SII) index reflects a patient’s systemic inflammatory state and immune state. Postoperative recurrence and the occurrence of complications are closely related to the inflammatory state and immune state. Thus, the SII index may have some value in predicting postoperative complications and the long-term prognosis of CRC patients, but relevant studies are currently lacking. The present study sought to examine the effect of the SII index on the postoperative complications and long-term prognosis of patients with CRC.MethodsFrom January 2014 to January 2017, the data of 440 patients with CRC who had been admitted to the Affiliated Hospital of Guangdong Medical University were retrospectively collected, and the patients were equally divided into the high and the low SII groups according to their preoperative SII index levels. The postoperative complication rate and postoperative progression-free survival (PFS) and mortality between the 2 groups were compared.ResultsCompared to the low SII group, the incidence of postoperative infection in the high SII group was significantly increased (15.45% vs. 9.09%, P=0.042), mortality was significantly increased at 5 years postoperatively (20.91% vs. 7.27%, P<0.001), and PFS was significantly shortened (P<0.001). The SII index had certain predictive value for postoperative infection in CRC patients, and the area under the curve (AUC) was 0.645 [95% confidence interval (CI): 0.559–0.731, P=0.001]. The SII index also had certain predictive value for the progression of CRC patients within 5 years of surgery, and the AUC was 0.670 (95% CI: 0.610–0.729, P<0.001). Additionally, the SII index had certain predictive value for death within 5 years of surgery in patients with CRC, and the AUC was 0.660 (95% CI: 0.593–0.726, P<0.001). CRC patients with postoperative infection had a significantly shorter PFS period than those who did not develop postoperative infection (P=0.029).ConclusionsThe SII index has certain predictive value for the diagnosis of postoperative infectious complications and the long-term prognosis of CRC patients.     

Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure

BACKGROUNDFor locally advanced rectal cancer (LARC), standard therapy [consisting of neoadjuvant chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (ChT)] achieves excellent local control. Unfortunately, survival is still poor due to distant metastases, which remains the leading cause of death among these patients. In recent years, the concept of total neoadjuvant treatment (TNT) has been developed, whereby all systemic ChT-mainly affecting micrometastases-is applied prior to surgery.AIMTo compare standard therapy and total neoadjuvant therapy for LARC patients with high-risk factors for failure.METHODSIn a retrospective study, we compared LARC patients with high-risk factors for failure who were treated with standard therapy or with TNT. High-risk for failure was defined according to the presence of at least one of the following factors: T4 stage; N2 stage; positive mesorectal fascia; extramural vascular invasion; positive lateral lymph node. TNT consisted of 12 wk of induction ChT with capecitabine and oxaliplatin or folinic acid, fluorouracil and oxaliplatin, CRT with capecitabine, and 6-8 wk of consolidation ChT with capecitabine and oxaliplatin or folinic acid, fluorouracil and oxaliplatin prior to surgery. The primary endpoint was pathological complete response (pCR). In total, 72 patients treated with standard therapy and 89 patients treated with TNT were included in the analysis.RESULTSCompared to standard therapy, TNT showed a higher proportion of pCR (23% vs 7%; P = 0.01), a lower neoadjuvant rectal score (median: 8.43 vs 14.98; P < 0.05), higher T-and N-downstaging (70% and 94% vs 51% and 86%), equivalent R0 resection (95% vs 93%), shorter time to stoma closure (mean: 20 vs 33 wk; P < 0.05), higher compliance during systemic ChT (completed all cycles 87% vs 76%; P < 0.05), lower proportion of acute toxicity grade ≥ 3 during ChT (3% vs 14%, P < 0.05), and equivalent acute toxicity and compliance during CRT and in the postoperative period. The pCR rate in patients treated with TNT was significantly higher in patients irradiated with intensity-modulated radiotherapy/volumetric-modulated arc radiotherapy than with 3D conformal radiotherapy (32% vs 9%; P < 0.05).CONCLUSIONCompared to standard therapy, TNT provides better outcome for LARC patients with high-risk factors for failure, in terms of pCR and neoadjuvant rectal score.     

Estimating prognosis and palliation based on tumour marker CA 19-9 and quality of life indicators in patients with advanced pancreatic cancer receiving chemotherapy

Background:

To investigate the prognostic value of quality of life (QOL) relative to tumour marker carbohydrate antigen (CA) 19-9, and the role of CA 19-9 in estimating palliation in patients with advanced pancreatic cancer receiving chemotherapy.

Methods:

CA 19-9 serum concentration was measured at baseline and every 3 weeks in a phase III trial (SAKK 44/00–CECOG/PAN.1.3.001). Patients scored QOL indicators at baseline, and before each administration of chemotherapy (weekly or bi-weekly) for 24 weeks or until progression. Prognostic factors were investigated by Cox models, QOL during chemotherapy by mixed-effect models.

Results:

Patient-rated pain (P<0.02) and tiredness (P<0.03) were independent predictors for survival, although less prognostic than CA 19-9 (P<0.001). Baseline CA 19-9 did not predict QOL during chemotherapy, except for a marginal effect on pain (P<0.05). Mean changes in physical domains across the whole observation period were marginally correlated with the maximum CA 19-9 decrease. Patients in a better health status reported the most improvement in QOL within 20 days before maximum CA 19-9 decrease. They indicated substantially less pain and better physical well-being, already, early on during chemotherapy with a maximum CA 19-9 decrease of ⩾50% vs <50%.

Conclusion:

In advanced pancreatic cancer, pain and tiredness are independent prognostic factors for survival, although less prognostic than CA 19-9. Quality of life improves before best CA 19-9 response but the maximum CA 19-9 decrease has no impact on subsequent QOL. To estimate palliation by chemotherapy, patient''s perception needs to be taken into account.     

MutL homolog 1 methylation and microsatellite instability in sporadic colorectal tumors among Filipinos

BACKGROUNDColorectal cancer (CRC) ranks third in terms of incidence and second in mortality worldwide. In CRC, the silencing of mismatch repair genes, including the mutL homolog 1 (hMLH1) has been linked to microsatellite instability (MSI), the lengthening or shortening of microsatellite repeats. Very limited data have been presented so far on the link of hMLH1 methylation and MSI in Southeast Asia populations with sporadic CRC, and on its clinical significance.AIMTo investigate the significance of the MSI status and hMLH1 methylation in CRC Filipino patients.METHODSFifty-four sporadic CRC patients with complete clinical data were included in this study. Genomic DNA from CRC tumor biopsies and their normal tissue counterparts were profiled for MSI by high resolution melting (HRM) analysis using the Bethesda Panel of Markers (BAT25, BAT26, D2S123, D5S346, and D17S250). hMLH1 methylation screening was performed using bisulfite conversion and methylation specific polymerase chain reaction. Statistical analysis was conducted to calculate their associations to clinicopathological characteristics and survival relevance (Kaplan-Meier curves and the log-rank test).RESULTS hMLH1 methylation was observed in 9% and 35% of CRC and normal samples, respectively. Higher incidence of consistently methylated hMLH1 found in both normal and CRC was noticed for relation to location of tumor (P < 0.05). As for MSI status, D2S123 the most common unstable microsatellite and MSI-high (MSI-H) was the most common MSI profile, counted for 46% and 50% of normal and CRC tissues, respectively. The presence of MSI-low (MSI-L) and microsatellite stable (MSS) was 43% and 11% for normal, and 31% and 19% for CRC samples. The mean month of patients’ survival was shorter in patients whose normal and tumor tissues had methylated compared to those with unmethylated hMLH1 and with MSI-H compared to those with MSI-L/MSS (P < 0.05). This was supported by significant difference in Kaplan-Meier with log-rank analysis. This data indicated that hMLH1 methylation and high MSI status have prognostic value.CONCLUSIONThis study showed the clinical significance of hMLH1 methylation and MSI status in sporadic CRC Filipino patients, especially in the normal part of the tumor.     

Outcomes of curative liver resection for hepatocellular carcinoma in patients with cirrhosis

BACKGROUNDGiven the poor synthetic function of cirrhotic liver, successful resection for patients with hepatocellular carcinoma (HCC) necessitates the ability to achieve resections with tumor free margins.AIMTo validate post hepatectomy liver failure score (PHLF), compare it to other established systems and to stratify risks in patients with cirrhosis who underwent curative liver resection for HCC. METHODSBetween December 2010 and January 2017, 120 patients underwent curative resection for HCC in patients with cirrhosis were included, the pre-operative, operative and post-operative factors were recorded to stratify patients'' risks of decompensation, survival, and PHLF.RESULTSThe preoperative model for end-stage liver disease (MELD) score [odds ratio (OR) = 2.7, 95%CI: 1.2-5.7, P = 0.013], tumor diameter (OR = 5.4, 95%CI: 2-14.8, P = 0.001) and duration of hospital stay (OR = 2.5, 95%CI: 1.5-4.2, P = 0.001) were significant independent predictors of hepatic decompensation after resection. While the preoperative MELD score [hazard ratio (HR) = 1.37, 95%CI: 1.16-1.62, P < 0.001] and different grades of PHLF (grade A: HR = 2.33, 95%CI: 0.59-9.24; Grade B: HR = 3.15, 95%CI: 1.11-8.95; Grade C: HR = 373.41, 95%CI: 66.23-2105.43; P < 0.001) and HCC recurrence (HR = 11.67, 95%CI: 4.19-32.52, P < 0.001) were significant independent predictors for survival.CONCLUSIONPreoperative MELD score and tumor diameter can independently predict hepatic decompensation. While, preoperative MELD score, different grades of PHLF and HCC recurrence can precisely predict survival.     

Laparoscopic vs. open surgery for gastrointestinal stromal tumors of esophagogastric junction: A multicenter,retrospective cohort analysis with propensity score weighting

Objective:Laparoscopic resection is increasingly performed for gastrointestinal stromal tumors(GISTs).However,the laparoscopic approach for GISTs located in the esophagogastric junction(EGJ-GIST)is surgically challenging.This study compares the efficacy of laparoscopic surgery and the open procedure for EGJ-GIST through the propensity score weighting(PSW)method.Methods:Between April 2006 and April 2018,1,824 surgical patients were diagnosed with primary gastric GIST at four medical centers in South China.Of these patients,228 were identified as EGJ-GISTs and retrospectively reviewed clinicopathological characteristics,operative information,and long-term outcomes.PSW was used to create the balanced cohorts.Results:PSW was carried out in laparoscopic and open-surgery cohorts according to year of surgery,sex,age,body mass index(BMI),tumor size,mitotic rates and recurrence risk.After PSW,438 patients consisting of 213 laparoscopic(L group)and 225 open surgery(O group)patients were enrolled.After PSW,the following measures in the L group were superior to those in the O group:median operative time[interquartile range(IQR)]:100.0(64.5-141.5)vs.149.0(104.0-197.5)min,P<0.001;median blood loss(IQR):30.0(10.0-50.0)vs.50.0(20.0-100.0)mL,P=0.002;median time to liquid intake(IQR):3.0(2.0-4.0)vs.4.0(3.0-5.0)d,P<0.001;median hospital stay(IQR):6.0(4.0-8.0)vs.7.0(5.0-12.0)d,P<0.001;and postoperative complications(10.3%vs.22.7%,P=0.001).The median follow-up was 55(range,2-153)months in the entire cohort.No significant differences were detected in either relapse-free survival(RFS)[hazard ratio(HR):0.372,95%confidence interval(95%CI):0.072-1.910,P=0.236]or overall survival(OS)(HR:0.400,95%CI:0.119-1.343,P=0.138)between the two groups.Conclusions:Laparoscopic surgery for EGJ-GIST is associated with the advantages of shorter operative time,reduced blood loss,shorter time to liquid intake,and shorter length of stay,all without compromising postoperative outcomes and long-term survival.     

Nuclear oxidative damage correlates with poor survival in colorectal cancer

Oxidative DNA damage results from DNA adducts such as 8-oxo-7, 8 dihydro-2′-deoxyguanosine (8-oxo-dG), which is a pro-mutagenic lesion. No known association between 8-oxo-dG, disease progression and survival exists in colorectal cancer (CRC). We examined levels of 8-oxo-dG in sporadic CRC to determine its relationship with pathological stage and outcome. A total of 143 CRC patients and 105 non-cancer patients were studied. Nuclear and cytoplasmic 8-oxo-dG was assessed using immunohistochemistry. Double immunofluorescence using 8-oxo-dG and manganese superoxide dismutase (MnSOD) antibodies localised cytoplasmic 8-oxo-dG. Apoptosis was detected using TUNEL. Nuclear staining levels were similar in tumour tissue and matched normal mucosa in both epithelial (P=0.22) and stromal (P=0.85) cells. Epithelial cytoplasmic staining was greater in tumour tissue (P<0.001). Double immunofluorescence localised cytoplasmic 8-oxo-dG to mitochondria. Epithelial and stromal nuclear 8-oxo-dG decreased with local disease spread, but highest levels were found in distant disease (P<0.01). Survival was related to epithelial nuclear and stromal staining in normal mucosa (P<0.001) and tumour (P<0.01) but was unrelated to cytoplasmic staining. Normal control cells in tissue from cancer patients with high levels of 8-oxo-dG failed to undergo cell death. 8-oxo-dG may be an important biomarker of disease risk, progression and survival for CRC patients.     

A Pilot Randomized Controlled Trial of Brief Cognitive‐Behavioral Therapy for Anxiety in Patients with Terminal Cancer

Introduction.

Patients with terminal cancer often experience marked anxiety that is associated with poor quality of life. Although cognitive-behavioral therapy (CBT) is an evidence-based treatment for anxiety disorders, the approach needs to be adapted to address realistic concerns related to having cancer, such as worries about disease progression, disability, and death. In this pilot randomized controlled trial (clinicaltrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT00706290","term_id":"NCT00706290"}}NCT00706290), we examined the feasibility and potential efficacy of brief CBT to reduce anxiety in patients with terminal cancer.

Methods.

We adapted CBT by developing treatment modules targeting skills for relaxation, coping with cancer worries, and activity pacing. Adults with incurable malignancies and elevated anxiety based on the Hamilton Anxiety Rating Scale (HAM-A) were randomly assigned to individual CBT or a waitlist control group. Primary outcomes included the number of completed CBT visits and the change in HAM-A scores from baseline to 8-week follow-up per a treatment-blind evaluator. The feasibility criterion was 75% adherence to the intervention.

Results.

We randomized 40 patients with terminal cancers to CBT (n = 20) or waitlist control (n = 20) groups; 70% completed posttreatment assessments. Most patients who received CBT (80%) participated in at least five of the required six therapy sessions. Analysis of covariance models, adjusted for baseline scores, showed that those assigned to CBT had greater improvements in HAM-A scores compared to the control group, with an adjusted mean difference of –5.41 (95% confidence interval: –10.78 to –0.04) and a large effect size for the intervention (Cohen''s d = 0.80).

Conclusion.

Providing brief CBT tailored to the concerns of patients with terminal cancer was not only feasible but also led to significant improvements in anxiety.     

Efficacy and safety of camrelizumab plus chemotherapy versus chemotherapy alone in patients with untreated,HER2-negative,unresectable locally advanced,or metastatic gastric cancer or gastroesophageal junction cancer: a retrospective comparative cohort study

BackgroundNivolumab combined with chemotherapy has been shown to improve prognosis in patients with untreated, human epidermal growth factor receptor 2 (HER2)-negative advanced gastric cancer (GC) and programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥5. However, the available first-line treatment options for advanced GC are limited. Analysis of efficacy and safety of other programmed cell death protein 1 (PD-1) antibodies combined with chemotherapy may provide alternative treatment options.MethodsThis retrospective study included patients with untreated, HER2-negative, unresectable locally advanced, or metastatic GC or gastroesophageal junction (GEJ) cancer who received either camrelizumab combined with oxaliplatin plus S-1 (SOX)/capecitabine plus oxaliplatin (CapeOX) or SOX/CapOX alone between November 2020 and April 2022. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety were evaluated.ResultsThis study included 49 patients in camrelizumab plus chemotherapy group and 54 in chemotherapy group. The baseline clinical characteristics beyond Epstein-Barr virus (EBV) status and PD-L1 CPS had no difference between combination group and chemotherapy group. ORR and DCR were significantly higher in combination therapy group than in chemotherapy group (59.18% vs. 38.89%, P=0.048; 83.67% vs. 62.96%, P=0.018). The median PFS in combination group was significantly longer than chemotherapy group [10.03 vs. 6.24 months, hazard ratio (HR) 0.603, 95% confidence interval (CI): 0.368–0.989, P=0.045]. The OS was not mature at the time of the OS analysis, with 40% patients died. Subgroup analyses showed that PFS was longer in patients with PD-L1 CPS ≥1 compared with CPS <1 and in patients with a neutrophil-lymphocyte ratio (NLR) <2.38 compared with ≥2.38. The most common grade 3–4 treatment-related adverse events (TRAEs) were granulocytopenia (57% in combination group vs. 54% in chemotherapy group), anemia (39% vs. 33%, respectively), and thrombocytopenia (39% vs. 33%, respectively). The proportion of reactive cutaneous capillary endothelial proliferation (RCCEP, 73% vs. 0%) was higher in combination group relative to chemotherapy group; all were grades 1–2.ConclusionsAmong patients treated with camrelizumab combined with chemotherapy, the clinical outcomes were superior to those patients treated with chemotherapy. However, these promising findings need to be confirmed in future clinical trials.