Angucyclinones with IDO and TDO inhibitory activities isolated from the actinomycetes Umezawaea beigongshangensis.

Four previously undescribed angucyclinones umezawaones A-D (1-4) were isolated from the liquid cultures of Umezawaea beigongshangensis. Their structures were determined by spectroscopic analyses, single crystal X-ray diffraction, quantum chemical 13C NMR and electronic circular dichroism calculations. All compounds displayed strong inhibitory activities against indoleamine 2,3-dioxygenase and tryptophan-2,3-dioxygenase in enzymatic assay, especially compound 2.

Jackstone in the renal calyx: A rare case report.

BACKGROUND: Jackstone is a rare entity of calculi in urinary tracts and has the characteristic appearance resembling toy jacks. They are nearly always reported to occur in the urinary bladder, we first report a rare case of jackstone located in the obstructed renal calyx. CASE SUMMARY: We report a 46-year-old man presenting with intermittent, painless gross hematuria and left flank pain. Urinary computed tomography revealed staghorn stones and secondary hydronephrosis. A jackstone with radiating branches was found in one of the dilated renal calyx. Percutaneous nephrolithotomy was performed and endoscopic images were recorded during the operation. Postoperative stone composition analysis revealed it as calcium oxalate monohydrate stones. CONCLUSION: Jackstones can occur in the renal collecting system besides the bladder. The unique appearance and imaging manifestations are the most important factors in the diagnosis of jackstones, and further exploration of the formation mechanism is required.

Endoscopic treatment of urothelial encrusted pyelo-ureteritis disease: A case series.

BACKGROUND: Urothelial encrusted pyelo-ureteritis disease is an infrequent condition and there is no unified surgical treatment and reference standard to consult. We have used a minimally invasive endoscopic method to treat three such cases, which yielded excellent results. CASE SUMMARY: The first case was a 45-year-old man who had unilateral ureteropelvic junction (UPJ) atresia and contralateral stenosis and was treated by double endoscopic surgery using an anterograde percutaneous nephroscope coupled with a rigid retrograde ureteroscope. The second case was a 12-year-old boy who received a percutaneous nephroscopy on one side and a percutaneous nephroscopy with a rigid ureteroscope on the other side due to the presence of bilateral UPJ stenosis. The third case was a 32-year-old woman with bilateral lower ureteral stricture treated using a rigid retrograde ureteroscope. Endoscopic surgeries were successfully performed on all the three patients. Varying degrees of encrustation and erosion of the urothelium were observed during the operation. The calcified layer composition analysis showed magnesium ammonium phosphate or carbonate apatite. Two patients achieved a good prognosis. CONCLUSION: Minimally invasive endoscopic treatment for urothelial encrusted pyelo-ureteritis disease can yield better results.

Diet high in branched-chain amino acid promotes PDAC development by USP1-mediated BCAT2 stabilization.

BCAT2-mediated branched-chain amino acid (BCAA) catabolism is critical for pancreatic ductal adenocarcinoma (PDAC) development, especially at an early stage. However, whether a high-BCAA diet promotes PDAC development in vivo, and the underlying mechanism of BCAT2 upregulation, remain undefined. Here, we find that a high-BCAA diet promotes pancreatic intraepithelial neoplasia (PanIN) progression in LSL-KrasG12D/+ ; Pdx1-Cre (KC) mice. Moreover, we screened with an available deubiquitylase library which contains 31 members of USP family and identified that USP1 deubiquitylates BCAT2 at the K229 site. Furthermore, BCAA increases USP1 protein at the translational level via the GCN2-eIF2α pathway both in vitro and in vivo. More importantly, USP1 inhibition recedes cell proliferation and clone formation in PDAC cells and attenuates pancreas tumor growth in an orthotopic transplanted mice model. Consistently, a positive correlation between USP1 and BCAT2 is found in KC; LSL-KrasG12D/+ ; p53flox/+ ; Pdx1-Cre mice and clinical samples. Thus, a therapeutic targeting USP1-BCAT2-BCAA metabolic axis could be considered as a rational strategy for treatment of PDAC and precisive dietary intervention of BCAA has potentially translational significance.

Long-Term Cardiac Disease- and Cancer-Associated Mortalities in Patients With Non-Metastatic Stomach Adenocarcinoma Receiving Resection and Chemotherapy: A Large Competing-Risk Population-Based Cohort Study.

Background: The survival of patients with non-metastatic gastric adenocarcinoma (nmGaC), who are receiving more and more frequently chemotherapy, has improved throughout the last decades, while treatment-caused cardiotoxicity remains a major concern. This study aimed to investigate competing causes of mortality and prognostic factors within a large cohort of patients with resected nmGaC, and to describe the heart-specific mortalities of patients undergoing resection and chemotherapy and of all resected patients. Methods: In this population-based cohort study, data on patients diagnosed with nmGaC from 2004 through 2016, managed with resection with or without chemotherapy, followed up until the end of 2016, and surviving ≥ 1 month were retrieved from the US Surveillance, Epidemiology, and End Results-18 Program. Cumulative mortality functions were calculated. Prognostic factors for heart- and cancer-specific mortalities were evaluated using both multivariable-adjusted Fine-Gray subdistribution and cause-specific hazard functions. Results: Together 21,257 patients with resected nmGaC were eligible for analysis with an accumulated follow-up of 73,711 person-years, where 10,718 (50%) also underwent chemotherapy. Mortalities were overestimated when using the Kaplan-Meier method. Heart diseases were the most common non-cancer cause of mortality. Compared with all resected patients, heart-specific mortality of those also receiving chemotherapy was lower overall and especially at older ages. In the total group of patients, the 8-year cumulative mortalities from heart diseases were 4.4% and 2.0% in resected patients and those also receiving chemotherapy, respectively; in patients ≥ 80 years, the heart disease-specific mortalities were as high as 11.1% and 6.5%, respectively. In overall patients undergoing resection, older ages, black ethnicity, and location at gastric antrum/pylorus were associated with increased heart-specific mortality, while more recent period, female sex, Asian/Pacific Islanders, invasion of serosa, and more positive lymph nodes were associated with lower heart-specific mortality; among those further receiving chemotherapy, only the associations with period of diagnosis, age, and ethnicity were significant. Associations with older ages were stronger for heart-specific mortality than for cancer-associated mortality. Conclusions: Among survivors with resected nmGaC receiving chemotherapy, heart-specific mortality, the most common one among non-cancer causes of mortality, is not higher compared to overall resected patients in this observational study, suggesting that chemotherapy may be relatively safely administered to selected patients under strict indications. Age and ethnicity were major factors associated with heart-specific mortality in both overall resected patients and those further receiving chemotherapy. Overall and stratified cause-specific cumulative incidences of mortality are provided, which can be more clinically useful than the Kaplan-Meier estimates. Our study provides clinically useful evidence for tailored patient management.

Day-by-day blood pressure variability in hospitalized patients with COVID-19.

In a retrospective analysis, the authors investigated day-by-day blood pressure variability (BPV) and its association with clinical outcomes (critical vs. severe and discharged) in hospitalized patients with COVID-19. The study participants were hospitalized in Tongji Hospital, Guanggu Branch, Wuhan, China, between February 1 and April 1, 2020. BPV was assessed as standard derivation (SD), coefficient of variation (CV), and variability independent of mean (VIM). The 79 participants included 60 (75.9%) severe patients discharged from the hospital after up to 47 days of hospitalization, and 19 (24.1%) critically ill patients transferred to other hospitals for further treatment (n = 13), admitted to ICU (n = 3) or died (n=3). Despite similar use of antihypertensive medication (47.4% vs. 41.7%) and mean levels of systolic/diastolic blood pressure (131.3/75.2 vs. 125.4/77.3 mmHg), critically ill patients, compared with severe and discharged patients, had a significantly (p ≤ .04) greater variability of systolic (SD 14.92 vs. 10.84 mmHg, CV 11.39% vs. 8.56%, and VIM 15.15 vs. 10.75 units) and diastolic blood pressure (SD 9.38 vs. 7.50 mmHg, CV 12.66% vs. 9.80%, and VIM 9.33 vs. 7.50 units). After adjustment for confounding factors, the odds ratios for critical versus severe and discharged patients for systolic BPV were 3.41 (95% confidence interval [CI] 1.20-9.66, p = .02), 4.09 (95% CI 1.14-14.67, p = .03), and 2.81 (95% CI 1.12-7.05, p = .03) for each 5-mmHg increment in SD, 5% increment in CV, and 5-unit increment in VIM, respectively. Similar trends were observed for diastolic BPV indices (p ≤ .08). In conclusion, in patients with COVID-19, BPV was greater and associated with worse clinical outcomes.

1H NMR-based metabolomics analyses in children with Helicobacter pylori infection and the alteration of serum metabolites after treatment.

BACKGROUND AND AIMS: Helicobacter pylori (H. pylori) infection can occur in early childhood, without eradication therapies such infection can persist throughout life and cause many different diseases. This study investigated the metabolic characteristics and explored the underlying mechanism of children with H. pylori infection, and identified potential biomarkers for evaluating the efficacy of H. pylori eradication therapies. METHODS: We performed 1H NMR-based metabonomics coupled with multivariate analysis to investigate the metabolic profiling of serum samples between Children with and without H. pylori infection. In the same manner, we compared the alternations of metabolites in H. pylori-infected children before and after H. pylori eradication therapies. RESULTS: 21 metabolites from serum in H. pylori-infected and H. pylori-uninfected children were identified, which were mainly involved in energy, amino acid, lipid and microbial metabolism. We found that the serum levels of trimethylamine N-oxide and alanine were significantly higher in H. pylori-infected children compared to uninfected sera, whereas lactate was significantly lower. We also found that the levels of trimethylamine N-oxide and creatine in H. pylori-infected children was significantly decreased after H. pylori eradication therapies, whereas lactate and low-density lipoprotein/very low-density lipoprotein was significantly increased. CONCLUSIONS: This is the first study using 1H NMR-based metabolomics approach to explore the effects of H. pylori infection in children. Our results demonstrated that the disturbances of metabolism in energy, amino acids, lipids and microbiota could play an important role in the pathogenesis of gastrointestinal and extragastric diseases caused by H. pylori infection. Trimethylamine N-oxide and lactate might serve as potential serum biomarkers for evaluating the efficacy of H. pylori eradication therapies.

Effect of oral nutritional supplementation on the post-discharge nutritional status and quality of life of gastrointestinal cancer patients after surgery: a multi-center study.

BACKGROUND AND OBJECTIVES: To evaluate the effect of oral nutritional supplementation (ONS) on the postdischarge nutritional status and quality of life (QoL) of gastrointestinal cancer patients after surgery. METHODS AND STUDY DESIGN: A multi-center study was conducted on gastrointestinal cancer patients who received surgical treatment from 2013-2015. All patients were screened using the Nutrition Risk Screening 2002 (NRS 2002) to assess nutritional risk. Patients with nutritional risk were randomized into two groups: patients in the study group (n=55) were given dietary guidance and ONS, control group (n=59) received only dietary guidance. Anthropometric measurements, nutrition-related laboratory tests, and gastrointestinal function scores were also collected and analyzed using Student's t test and analysis of variance (ANOVA). In addition, the EQ-5D was used to evaluate patients' QoL. RESULTS: Compared with baseline measurements, the body weight of patients in the study group increased by 1.35±0.53 kg and 1.35±0.73 kg at 60 and 90 days, which were significantly higher than those in the control group (-1.01±0.54 kg, and -1.60±0.81 kg at 60 and 90 days). The results from ANOVA showed that only weight and BMI differed significantly between the study and control groups and also between different measurement times (p<0.01). No differences were found for the other indicators or QoL between the study groups. CONCLUSIONS: ONS may improve the weight and BMI of surgically treated gastrointestinal cancer patients postdischarge. However, these effects had little impact on patients' QoL.

Long-term Outcomes of Laparoscopy-assisted Gastrectomy for T4a Advanced Gastric Cancer: A Single-center Retrospective Study.

BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) has been proven to be feasible and oncologically safe for early gastric cancer. Despite the rapid increase in the number of LAG cases, there are few reports on the long-term outcomes of T4a (serosalinvasion) gastric cancer after LAG. The aim of the present study was to evaluate the long-term clinical outcomes in patients with stage T4a gastric cancer after laparoscopic gastrectomy. MATERIALS AND METHODS: A total of 578 patients with gastric cancer were treated with LAG between February 2004 and December 2014. Among these patients, 224 patients were pathologically confirmed with T4a advanced gastric cancer. The clinical and follow-up data were retrospectively analyzed, the survival rates were estimated using the Kaplan-Meier method, and the risk factors for overall and disease-free survival (DFS) were evaluated by Cox regression. RESULTS: Among these 224 patients, 129 patients were above 60 years old, and the male-to-female ratio was 157:67. Furthermore, among these patients, 125 patients received laparoscopy-assisted distal gastrectomy, whereas 99 patients received laparoscopy-assisted total gastrectomy. Forty (17.90%) patients experienced postoperative complications according to the Clavien-Dindo classification. Median follow-up time was 32 months. Recurrence was observed in 99 (44.20%) patients. The cumulative 5-year overall survival (OS) and DFS rates were 47.20% and 43.60%, respectively. The 5-year OS and DFS rates were 72.50% and 70.00% for stage N0, 57.00% and 53.90% for stage N1, 41.60% and 37.00% for stage N2, and 23.30% and 21.30% for stage N3, respectively. In the univariate analysis, tumor size, tumor location, N stage and metastatic lymph node ratio (MLR) were correlated with OS and DFS. The MLR was identified as an independent predictor for OS (P<0.05; hazard ratio=1.828; 95% confidence interval, 1.353-2.469) and DFS (P<0.05; hazard ratio=1.197; 95% confidence interval, 0.945-1.516). CONCLUSIONS: The long-term outcomes of LAG for T4a (M0) gastric cancer were acceptable, compared with previous reports. Therefore, this treatment could be considered as an alternative operative approach for T4a gastric cancer. The MLR was an independent predictor for OS and DFS.

Next-generation-sequencing technology used for the detection of Mycoplasma hominis in renal cyst fluid: a case report.

Background: Mycoplasma is an opportunistic pathogen causing both urogenital and extragenital infections. The lack of cell wall renders Mycoplasma difficult to culture and identify with ordinary methods. Next-generation sequencing (NGS) is a new technology helping a lot in the diagnosis of infective diseases. In this case, NGS played a key role in the diagnosis of Mycoplasma infection. Case presentation: A mid-aged man suffering from renal cyst underwent cyst incision followed by invasive treatments to eliminate hematoma caused by renal artery hemorrhage. After the cyst incision operation, the patient had a persistent high temperature. The persistent increase of blood neutrophile granulocyte count and C-reaction protein suggested an unresolved infection. The empirically chosen anti-infective agents were meropenem and linezolid since the ordinary bacterial cultures of surgical site drainage and blood yielded a negative result. At postoperation day (POD) 17, NGS result of his drainage clearly indicated the pathogen was Mycoplasma hominis. At POD 24, the drug sensitivity test showed resistance to quinolones, clarithromycin and erythromycin, but intermediate to azithromycin. Since then, the antimicrobial agents were changed into azithromycin and kept unchanged until the patient was fully recovered and discharged at POD 39. Conclusion: When the ordinary laboratory diagnostic methods failed, NGS diagnosis could reduce the hospitalization expenses and shorten the lengths of hospital stay.

Evaluation of perioperative prophylaxis with fosfomycin tromethamine in ureteroscopic stone removal: an investigator-driven prospective, multicenter, randomized, controlled study.

PURPOSE: To compare efficacy, safety, and cost-effectiveness of fosfomycin tromethamine with other standard-of-care antibiotics in patients undergoing ureteroscopic lithotripsy. METHODS: This study was a prospective, multicenter, randomized, controlled trial. Eligible patients scheduled for ureteroscopic lithotripsy were randomly assigned to receive either fosfomycin (fosfomycin group, N = 101 patients) or standard-of-care antibiotic therapy as prophylaxis (control group, N = 115 patients). The incidence of infectious complications and adverse events was analyzed between the two groups, as well as the cost-benefit analysis. RESULTS: The incidence of infections following lithotripsy was 3.0% in the fosfomycin group and 6.1% in the control group (p > 0.05). Only asymptomatic bacteriuria was reported in fosfomycin group. In the control group was reported asymptomatic bacteriuria (3.5%), fever (0.9%), bacteremia (0.9%), and genitourinary infection (0.9%). The rate of adverse events was very low, with no adverse event reported in the fosfomycin group and only one in the control group (forearm phlebitis). The average cost per patient of antibiotic therapy with fosfomycin was 151.45 ± 8.62 yuan (22.7 ± 1.3 USD), significantly lower compared to the average cost per patient of antibiotics used in the control group 305.10 ± 245.95 yuan (45.7 ± 36.9 USD; p < 0.001). CONCLUSIONS: Two oral doses of 3 g fosfomycin tromethamine showed good efficacy and safety and low cost in perioperative prophylaxis of infections following ureteroscopic stone removal.

Apatinib in refractory radiation-induced brain edema: A case report.

RATIONALE: Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has observed to be effective and safe in refractory radiation-induced brain edema, like Avastin did. Till now, there is no case report after apatinib came in the market. PATIENT CONCERNS: Two patients who received brain radiotherapy developed clinical manifestations of brain edema, including dizziness, headache, limb activity disorder, and so on. DIAGNOSES: Two patients were both diagnosed as refractory radiation-induced brain edema. INTERVENTIONS: Two patients received apatinib (500 mg/day) for 2 and 4 weeks. OUTCOMES: Two patients got symptomatic improvements from apatinib in different degrees. Magnetic resonance imaging after apatinib treatments showed that compared with pre-treatment imaging, the perilesional edema reduced dramatically. However, the toxicity of apatinib was controllable and tolerable. LESSONS: Apatinib can obviously relieve the symptoms of refractory radiation-induced brain edema and improve the quality of life, which offers a new method for refractory radiation-induced brain edema in clinical practices. But that still warrants further investigation in the prospective study.

A modified uncut Roux-en-Y anastomosis in totally laparoscopic distal gastrectomy: preliminary results and initial experience.

OBJECTIVE: To investigate the safety and feasibility of totally laparoscopic uncut Roux-en-Y anastomosis in the distal gastrectomy with D2 dissection for gastric cancer. We also summarized the preliminary experience of totally laparoscopic uncut Roux-en-Y anastomosis. METHODS: A retrospective analysis was done in 51 cases of total laparoscopic uncut Roux-en-Y anastomosis in the distant gastrectomy with D2 dissection for gastric cancer in our hospital from September 2014 to December 2015. RESULTS: All of 51 cases underwent total laparoscopic uncut Roux-en-Y anastomosis. All the procedures were performed successfully. There were neither conversions to open surgery nor intraoperative complications in all 51 cases. In this study, the median operative time was 170 (135-210) min and the median time of anastomosis was 27 (24-41) min. The blood loss was 60 (30-110) ml. The time to flatus and length of postoperative hospital stay were 2 (1-3) days, and 8 (7-12) days, respectively. The mean lymph node harvest was 34 (18-49). One anastomotic bleeding occurred postoperatively which was cured by conservative treatment. No major postoperative complication occurred, such as anastomotic leak, anastomotic stenosis, and Roux stasis syndrome. After a short-term follow-up, no recanalization or reflux gastritis was encountered by endoscopy. CONCLUSION: The totally laparoscopic uncut Roux-en-Y anastomosis in distal gastrectomy with lymph node dissection for gastric cancer is safe and feasible, with a very low rate of recanalization and reflux gastritis.

Comprehensive transcriptome analysis identifies novel molecular subtypes and subtype-specific RNAs of triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly heterogeneous group of cancers, and molecular subtyping is necessary to better identify molecular-based therapies. While some classifiers have been established, no one has integrated the expression profiles of long noncoding RNAs (lncRNAs) into such subtyping criterions. Considering the emerging important role of lncRNAs in cellular processes, a novel classification integrating transcriptome profiles of both messenger RNA (mRNA) and lncRNA would help us better understand the heterogeneity of TNBC. METHODS: Using human transcriptome microarrays, we analyzed the transcriptome profiles of 165 TNBC samples. We used k-means clustering and empirical cumulative distribution function to determine optimal number of TNBC subtypes. Gene Ontology (GO) and pathway analyses were applied to determine the main function of the subtype-specific genes and pathways. We conducted co-expression network analyses to identify interactions between mRNAs and lncRNAs. RESULTS: All of the 165 TNBC tumors were classified into four distinct clusters, including an immunomodulatory subtype (IM), a luminal androgen receptor subtype (LAR), a mesenchymal-like subtype (MES) and a basal-like and immune suppressed (BLIS) subtype. The IM subtype had high expressions of immune cell signaling and cytokine signaling genes. The LAR subtype was characterized by androgen receptor signaling. The MES subtype was enriched with growth factor signaling pathways. The BLIS subtype was characterized by down-regulation of immune response genes, activation of cell cycle, and DNA repair. Patients in this subtype experienced worse recurrence-free survival than others (log rank test, P = 0.045). Subtype-specific lncRNAs were identified, and their possible biological functions were predicted using co-expression network analyses. CONCLUSIONS: We developed a novel TNBC classification system integrating the expression profiles of both mRNAs and lncRNAs and determined subtype-specific lncRNAs that are potential biomarkers and targets. If further validated in a larger population, our novel classification system could facilitate patient counseling and individualize treatment of TNBC.

Mini-percutaneous Nephrolithotomy Under Total Ultrasonography in Patients Aged Less Than 3 Years: A Single-center Initial Experience from China.

BACKGROUND: Urolithiasis in pediatric population is a serious problem with the incidence increased these years. In the management of larger stones (diameters >2 cm), percutaneous nephrolithotomy (PCNL) is considered to be the gold standard. This study aimed to investigate the efficacy and safety of mini-PCNL under total ultrasonography in patients aged <3 years. METHODS: We reviewed 68 patients (80 renal units) aged <3 years between August 2006 and December 2014 in Peking University People's Hospital and Beijing Tsinghua Changung Hospital, including 36 renal units with a single stone, 6 with staghorn stones, 14 with upper ureteral stones, and 24 with multiple stones. The mean age of the patients was 24.2 months (range 6-36 months), and the mean maximum stone diameter was 19.2 mm (range 10-35 mm). The puncture site selection and tract dilation were guided by Doppler ultrasonography solely. All procedures were performed using 12-16 Fr tracts. Stones were fragmented using pneumatic lithotripsy and a holmium laser with an 8/9.8 Fr rigid ureteroscope. RESULTS: Fifty-six patients with unilateral stones underwent a single session procedure, and 12 patients with bilateral stones underwent two procedures. The mean time to establish access was 2.8 min (range 1.8-5.0 min), the mean operative time was 36.5 min (range 20-88 min), the mean decrease in hemoglobin concentration was 8.9 g/L (2-15 g/L), and the stone-free rate (SFR) at hospital discharge was 94.0%. The mean postoperative hospital stay was 7.1 days (range 3-13 days). Postprocedure complications included fever (>38.5°C) in five patients and reactive pleural effusion in one patient. Blood loss requiring transfusion, sepsis, adjacent organ injury, and kidney loss were not observed. CONCLUSIONS: This study indicated that ultrasound-guided mini-PCNL is feasible and safe in patients aged <3 years, without major complications or radiation exposure.

Anti-epidermal growth factor receptor monoclonal antibodies in metastatic colorectal cancer: a meta-analysis.

AIM: To investigate the correlation between Kirsten rat sarcoma viral oncogene homolog (KRAS) status and the therapeutic effects of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) in metastatic colorectal cancer (mCRC). METHODS: Randomized controlled trials (RCTs) were identified and the association between KRAS mutation and clinical outcome in mCRC patients treated with anti-EGFR MoAbs was investigated. Ten RCTs were included in this meta-analysis. Progression-free survival and overall survival were used to assess the strength of the relationship between KRAS mutation and clinical outcome. RESULTS: In first-line treatment, survival benefit was confined to patients with wild-type KRAS. Chemotherapy regimens and angiogenesis inhibitor treatment influenced the results of the analysis. Wild-type KRAS mCRC patients did not seem to benefit from oxaliplatin-based chemotherapy (PFS: HR = 0.88, 95%CI: 0.70-1.10; OS: HR = 0.93, 95%CI: 0.82-1.04). Clinical benefit in mCRC patients was limited to therapeutic regimens which included anti-EGFR MoAbs and fluorouracil-based therapy (PFS: HR = 0.77, 95%CI: 0.69-0.86; OS: HR = 0.85, 95%CI: 0.75-0.95). When anti-EGFR MoAbs were used as second- or further-line treatment, clinical benefit was still confined to patients with wild-type KRAS. CONCLUSION: KRAS status is a potential predictive marker of clinical benefit due to anti-EGFR MoAb therapy in mCRC patients.