Maternal immunoglobulins are distributed in the offspring's brain to support the maintenance of cortical interneurons in the postnatal period.

It is known that maternal immunoglobulins (Igs) are transferred to the offspring across the placenta. However, receiving maternal Igs, especially before the blood-brain barrier (BBB) is formed in the offspring's brain, carries the risk of transferring some brain-reactive Igs. It is thus hypothesized that there may be some unknown benefit to the offspring's brain that overweighs this risk. In this study, we show that the Ig detected in the embryonic/perinatal mouse brain is IgG not produced by the pups themselves, but is basically transferred from the mother across the placenta using the neonatal Fc receptor (FcRn) during embryonic stages. The amount of IgG in the brain gradually decreases after birth, and almost disappears within 3 weeks postnatally. IgG is detected on axon bundles, microglia, and some meningeal cells, including border-associated macrophages (BAMs), endothelial cells, and fibroblasts. Using Fcer1g knock-out (KO) mice, we show that BAMs and microglia receive maternal IgG in an Fc receptor γ chain (FcRγ)-dependent manner, but IgG on other meningeal cells and axon bundles is received independently of the FcRγ. These results suggest that maternal IgG may be used in multiple ways by different mechanisms. In maternal IgG-deficient mice, the number of interneurons in the cerebral cortex is not altered around birth but is reduced postnatally, suggesting that receipt of maternal IgG is necessary for the maintenance of cortical interneurons in the postnatal period. These data suggest that maternal IgG has an important function in the developing brain, where neither obvious inflammation nor infection is observed.

The benefits of interval appendectomy and risk factors for nonoperative management failure in the therapeutic strategy for complicated appendicitis.

PURPOSE: Emergency surgery (ES) for complicated appendicitis (CA) is associated with high morbidity. Interval appendectomy (IA) decreases this rate; however, nonoperative management (NOM) is not always successful. Some patients require unplanned ES due to NOM failure (IA failure: IA-F). This study aimed to verify the benefits of IA and to evaluate the risk factors for NOM failure. METHODS: Patients diagnosed with CA who underwent surgery between January 2012 and December 2021 were included in this study. We compared the surgical outcomes of the ES group with those of the IA success (IA-S) and IA-F groups. We also analyzed 14 factors that predicted NOM failure. RESULTS: Among 302 patients, the rate of severe complications (Clavien-Dindo grade ≥ III) was significantly higher in the ES group (N = 165) than in the IA-S group (N = 102). The rates were equal between the ES (N = 165) and IA-F (N = 35) groups. NOM was successful in 110 patients and failed in 27. Lack of abscesses, comorbidities, high WBC count, and free air were independent risk factors for NOM failure. CONCLUSIONS: Considering the benefits of IA and the non-inferior surgical outcomes of IA-F compared to ES, IA is a good therapeutic strategy for CA. However, in patients exhibiting four independent risk factors for NOM failure, careful monitoring of unplanned ES is necessary.

Oncologic investigation of the interval from stent placement to surgery in patients with obstructive colorectal cancer.

PURPOSE: Self-expandable metallic stent (SEMS) placement is widely used as a bridge to surgery (BTS) procedure for obstructive colorectal cancer. However, evidence regarding the optimal interval between SEMS placement and elective surgery is lacking. METHODS: We retrospectively collected data from patients with BTS between January 2013 and October 2021. Inverse probability treatment-weighted propensity score analyses were used to compare short- and long-term outcomes between the short-interval (SI) and long-interval (LI) groups, using a cutoff of 20 days. RESULTS: In total, 138 patients were enrolled in this study (SI group, n = 63; LI group, n = 75). In the matched cohort, the patients' backgrounds were well balanced. The incidence of Clavien-Dindo grade ≥ II postoperative complications was not significantly different between the SI and LI groups (19.0% vs. 14.0%, P = 0.47). There were no significant differences between the SI and LI groups in the 3-year recurrence-free survival (68.0% vs. 76.4%, P = 0.73) or 3-year overall survival rates (86.0% vs. 90.6%, P = 0.72). CONCLUSIONS: A longer interval did not deteriorate the oncological outcomes. Individual perioperative management with an appropriate interval to improve the patient's condition is required to ensure safe surgery.

Pks-positive Escherichia coli in tumor tissue and surrounding normal mucosal tissue of colorectal cancer patients.

A significant association exists between the gut microbiome and colorectal carcinogenesis, as well as cancer progression. It has been reported that Escherichia coli (E. coli) containing polyketide synthetase (pks) island contribute to colorectal carcinogenesis by producing colibactin, a polyketide-peptide genotoxin. However, the functions of pks+ E. coli in initiation, proliferation, and metastasis of colorectal cancer (CRC) remain unclear. We investigated the clinical significance of pks+ E. coli to clarify its functions in CRC. This study included 413 patients with CRC. Pks+ E. coli of tumor tissue and normal mucosal tissue were quantified using droplet digital PCR. Pks+ E. coli was more abundant in Stages 0-I tumor tissue than in normal mucosal tissue or in Stages II-IV tumor tissue. High abundance of pks+ E. coli in tumor tissue was significantly associated with shallower tumor depth (hazard ratio [HR] = 5.0, 95% confidence interval [CI] = 2.3-11.3, p < 0.001) and absence of lymph node metastasis (HR = 3.0, 95% CI = 1.8-5.1, p < 0.001) in multivariable logistic analyses. Pks+ E. coli-low and -negative groups were significantly associated with shorter CRC-specific survival (HR = 6.4, 95% CI = 1.7-25.6, p = 0.005) and shorter relapse-free survival (HR = 3.1, 95% CI = 1.3-7.3, p = 0.01) compared to the pks+ E. coli-high group. Pks+ E. coli was abundant in Stages 0-I CRC and associated with CRC prognosis. These results suggest that pks+ E. coli might contribute to carcinogenesis of CRC but might not be associated with tumor progression.

Successful management of malignant colovesical fistula using covered colonic self-expanding metallic stent: a case report.

BACKGROUND: A colovesical fistula (CVF) is commonly treated by resection of the intestine containing the fistula or creation of a defunctioning stoma. We herein report a case of successful fistula closure and avoidance of colostomy after placement of a covered colonic self-expanding metallic stent (SEMS) as a palliative treatment for a malignant CVF. CASE PRESENTATION: A 75-year-old man undergoing infusional 5-fluorouracil and irinotecan chemotherapy plus bevacizumab for recurrent peritoneal dissemination of rectal cancer was admitted to our hospital because of fecaluria with a high-grade fever. Blood tests showed a moderate inflammatory reaction (white blood cell count, 9200/mm3; C-reactive protein, 11.03 mg/dL; procalcitonin, 1.33 ng/mL). Urinary sediment examination showed severe bacteriuria. Abdominal contrast-enhanced computed tomography showed intravesical gas, thickening of the posterior wall of the bladder, and irregular thickening of the sigmoid colon wall contiguous with the posterior bladder wall. Magnetic resonance imaging (MRI) clearly showed a fistula between the bladder and sigmoid colon. Colonoscopy revealed a circumferential malignant stricture 15 cm from the anal verge, and a fistula to the bladder was identified by water-soluble contrast medium. We diagnosed a complicated urinary tract infection (UTI) associated with a CVF due to peritoneal dissemination and started empirical treatment with sulbactam/ampicillin. Given the absence of active inflammatory findings around the fistula on MRI and the patient's physical frailty, we decided to place a covered SEMS to close the fistula. Under fluoroscopic and endoscopic guidance, a covered colonic SEMS of 80-mm length and 20-mm diameter was successfully deployed, and the fistula was sealed immediately after placement. Urine culture on day 3 after stenting was negative for bacteria, and a contrast study on day 5 showed no fistula. The patient was discharged home on day 6 with no complications. The UTI did not recur for 4 months after discharge. CONCLUSIONS: A covered colonic SEMS was useful for sealing a malignant CVF in a patient unfit for surgery, and MRI was valuable to determine the status of the fistula. A covered colonic SEMS could be an alternative to surgical treatment for CVFs in patients who require palliative care.

Long-term outcomes between self-expandable metallic stent and transanal decompression tube for malignant large bowel obstruction: A multicenter retrospective study and meta-analysis.

Aim: To compare the oncological outcomes between self-expandable metallic stent (SEMS) as a bridge to surgery and transanal decompression tube (TDT) placement for malignant large bowel obstruction (MLBO). Methods: A total of 287 MLBO patients who underwent SEMS (n = 137) or TDT placement (n = 150) were enrolled in this multicenter retrospective study. Overall survival (OS) and disease-free survival (DFS) between the two groups were compared. A meta-analysis was performed using random-effects models to calculate odd ratios (OR) with 95% confidence intervals (CIs). Results: Postoperative complications of Clavien-Dindo grade ≥II and ≥III occurred frequently in the TDT group compared with the SEMS group (P = 0.002 and 0.005, respectively). The 3-y OS in the overall cohort and 3-y DFS in the pathological stage II/III cohort in the SEMS and TDT groups were 68.6% and 71.4%, and 71.0% and 72.6%, respectively. The survival differences were not significantly different in the OS and DFS analyses (P = 0.819 and P = 0.892, respectively). A meta-analysis of nine studies (including our cohort data) demonstrated no significant difference between the SEMS and TDT groups for 3-y OS and DFS (OR = 0.96, 95% CI = 0.57-1.62, P = 0.89 and OR = 0.69, 95% CI = 0.46-1.04, P = 0.07, respectively). Conclusion: Our study demonstrated that SEMS placement had no inferiority regarding long-term outcomes, including OS and DFS, compared with TDT placement. Considering the short-term benefits of SEMS placement, this could be a preferable preoperative decompression method for MLBO.

Postoperative infectious complications have a negative oncological impact in patients after stent placement with malignant large bowel obstruction.

PURPOSE: In this study, we aimed to investigate the oncological impact of postoperative infection in patients with malignant large bowel obstruction managed by self-expandable metallic stent placement as a bridge to surgery. METHODS: The cohort of this multicenter retrospective study comprised 129 patients with pathological stage II/III malignant large bowel obstruction who had undergone bridge to surgery. Patients were allocated to no-postoperative infection (n = 116) and postoperative infection groups (n = 13). RESULTS: The postoperative infection group had a significantly greater proportion of men, fewer harvested lymph nodes, and longer postoperative hospital stays than did the no-postoperative infection group. Self-expandable metallic stent-related variables, including clinical failure, were not associated with postoperative infection. Male sex and low body mass index were identified as risk factors for postoperative infection by multivariate logistic regression. Three-year relapse-free survival rates were 75.5% and 30.8% in the no-postoperative infection and postoperative infection groups, respectively; this difference is statistically significant. Male sex, postoperative infection, and T4 were identified as independent prognostic factors by multivariate Cox proportional hazard analysis. The postoperative infection group had a significantly higher total recurrence rate and shorter interval to recurrence than did the no-postoperative infection group. CONCLUSION: To the best of our knowledge, this is the first study to show that postoperative infection in bridge to surgery patients has a negative oncological impact. This finding indicates that further improvement in perioperative management of bridge to surgery patients is required to minimize postoperative infection and that patient-risk stratification and additional therapy would contribute to improving oncological outcomes.

Biomarkers for anti-vascular endothelial growth factor drugs.

Angiogenesis is regulated by interactions between vascular endothelial growth factors (VEGFs) and VEGF receptors. VEGF-A, VEGF-D, placental growth factor (PlGF) and plasminogen activator inhibitor-1 (PAI-1) have tumor angiogenic activity. VEGF-A and PAI-1 levels in the blood may impact the activity of bevacizumab, and VEGF-D levels may similarly diminish the efficacy of ramucirumab. However, the dynamics of these angiogenic biomarkers for anti-VEGF therapy have not been well established; therefore, they were evaluated in this retrospective study, which included two cohorts. Cohort 1 included patients who were treated with cytotoxic agents and bevacizumab as first-line chemotherapy, and Cohort 2 comprised patients who were treated with cytotoxic agents and anti-VEGF drugs (bevacizumab, ramucirumab or aflibercept) as second-line chemotherapy. VEGF-A, VEGF-D, PlGF and PAI-1 levels were measured before starting chemotherapy and were re-assessed every 1-2 months until disease progression. Bevacizumab had reduced benefit as a first-line chemotherapeutant in patients with very low or very high levels of VEGF-A. Bevacizumab increased VEGF-A and PlGF levels, but not VEGF-D or PAI-1. Anti-VEGF drugs offered the greatest benefit to patients with high PAI-1 before first- and second-line chemotherapy. PAI-1 levels were not affected by anti-VEGF drugs. Since ramucirumab increased VEGF-D, it offered less benefit to patients with high VEGF-D in second-line chemotherapy. Conversely, aflibercept offered greater benefits to patients with high VEGF-D, without increasing VEGF-D. These biomarkers may be useful for the prediction of drug efficacy and may predict resistance to anti-VEGF drugs.

TGF-ß1 increases cellular invasion of colorectal neuroendocrine carcinoma cell line through partial epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) plays a pivotal role in cancer progression and metastasis in many types of malignancies, including colorectal cancer. Although the importance of EMT is also considered in colorectal neuroendocrine carcinoma (NEC), its regulatory mechanisms have not been elucidated. We recently established a human colorectal NEC cell line, SS-2. In this study, we aimed to clarify whether these cells were sensitive to transforming growth factor beta 1 (TGF-ß1) and whether EMT could be induced through TGF-ß1/Smad signaling, with the corresponding NEC cell-specific changes in invasiveness. In SS-2 cells, activation of TGF-ß1 signaling, as indicated by phosphorylation of Smad2/3, was dose-dependent, demonstrating that SS-2 cells were responsive to TGF-ß1. Analysis of EMT markers showed that mRNA levels changed with TGF-ß1 treatment and that E-cadherin, an EMT marker, was expressed in cell-cell junctions even after TGF-ß1 treatment. Invasion assays showed that TGF-ß1-treated SS-2 cells invaded more rapidly than non-treated cells, and these cells demonstrated increased metalloproteinase activity and cell adhesion. Among integrins involved in cell-to-matrix adhesion, α2-integrin was exclusively upregulated in TGF-ß1-treated SS-2 cells, but not in other colon cancer cell lines, and adhesion and invasion were inhibited by an anti-α2-integrin blocking antibody. Our findings suggest that α2-integrin may represent a novel therapeutic target for the metastasis of colorectal NEC cells.

Clostridium perfringens sepsis after pancreatoduodenectomy: a case report.

BACKGROUND: Clostridium perfringens sepsis associated with massive intravascular hemolysis has an extremely poor prognosis. We here report a case of C. perfringens sepsis associated with massive intravascular hemolysis that developed secondary to a post-pancreaticoduodenectomy (PD) hepatic abscess. CASE PRESENTATION: A 70-year-old man with Type 2 diabetes underwent PD for an ampulla of Vater carcinoma. His postoperative course was uneventful. He was discharged on the 16th post-operative day (POD 16) after confirming no major abnormalities on abdominal contrast computed tomography (CT) on POD 14 or laboratory results on POD 16. Two days after discharge, he was readmitted because of fever and chills. Laboratory tests showed only a mild inflammatory reaction (white blood cell count, 11,980/mm3; C-reactive protein, 2.07 mg/dL). Abdominal CT showed an irregular, approximately 20-mm diameter, low-density area in the liver S6 region that had not been seen on a recent previous scan. We initially suspected postoperative cholangitis associated with biliary reconstruction and started empirical treatment with sulbactam/ampicillin after drawing blood for culture. Eight hours after admission, he developed septic shock with body temperature 40.0 â„ƒ and blood pressure 70/40 mm Hg. Laboratory findings showed a severe inflammatory reaction, severe anemia, and massive hemolysis (white blood cell count, 37,400/mm3; hemoglobin, 7.7 g/dL; total bilirubin, 8.05 mg/dL; direct bilirubin, 2.66 mg/dL; and lactate dehydrogenase, 1686 U/L). Hemoglobinuria was noted in the urinary catheter output. Repeat CT 9 h after admission showed the low-density area in S6 had become a gas-forming abscess. C. perfringens sepsis was strongly suspected on the basis of these findings and the abscess was drained percutaneously immediately after its diagnosis. His vital signs improved dramatically and he recovered within 24 h. Blood and abscess cultures grew C. perfringens 4 days after admission, leading to a definitive diagnosis of C. perfringens sepsis associated with massive intravascular hemolysis. He was discharged 18 days after admission. His sepsis has not recurred. CONCLUSIONS: Clostridium perfringens infection should be considered in patients who have undergone PD and present with gas-forming hepatic abscesses and/or sepsis associated with intravascular hemolysis. Prompt aggressive treatment is crucial, because C. perfringens infections can cause death within hours.

BRAF V600E mutations in right-side colon cancer: Heterogeneity detected by liquid biopsy.

INTRODUCTION: The prognosis for metastatic colorectal cancer patients (mCRC) with the BRAFV600E mutation is poor. BRAFV600E mutation frequency is reportedly low among Asians; however, the frequency of the BRAFV600E mutation in right-side colon cancer may not be low, even among Asians. In addition, spatial heterogeneity of BRAFV600E mutations also exists, as for RAS mutations. In this prospective observational study, we evaluated BRAFV600E mutations in cancer tissue and plasma of Japanese right-side colon cancer patients. METHOD: 215 patients with right-side colon cancer were included. BRAFV600E mutations of cancer tissue and plasma were detected using droplet digital PCR. Blood plasma of patients with BRAFV600E mutations in cancer tissue or plasma was drawn at intervals throughout chemotherapy, and BRAFV600E mutations were evaluated. RESULTS: BRAFV600E mutations were detected in tissue samples from 35 of 215 patients (16.3%, cecum; 22.4%, ascending colon; 17.8%, and transverse colon; 9.0%). BRAFV600E mutations were detected in plasma of 10 of 215 (4.7%) patients. Eight of the ten patients had BRAFV600E mutations in their primary tumours, but two (both were Stage IV) patients did not. Sensitivity of liquid biopsy to detect BRAFV600E mutations was 10.3% (3/29) in Stage I-III patients and 83.3% (5/6) in Stage IV patients. CONCLUSION: BRAFV600E mutations are observed in right-side colon cancer at high frequency, especially in the cecum. BRAFV600E mutations can be detected in plasma and the detection rate is high in patients with advanced cancer. Spatial heterogeneity was observed using liquid biopsy.

Colonic stent as a bridge to surgery versus emergency resection for right-sided malignant large bowel obstruction: a meta-analysis.

BACKGROUND: Preoperative colonic stenting for malignant large bowel obstruction (MLBO), also called bridge to surgery (BTS), is considered a great substitute treatment for emergency resection (ER) in the left-sided colon. However, its efficacy in the right-sided colon remains controversial. This systematic review and meta-analysis aimed to compare the postoperative short-term outcomes between BTS and ER for right-sided MLBO. METHODS: A comprehensive electronic literature search throughout December 2020 was performed to identify studies comparing short-term outcomes between BTS and ER for right-side MLBO. The main outcome measures were postoperative complications and mortality rates. A meta-analysis was performed using a fixed-effect or a random-effect method to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: Seven studies were included in this meta-analysis, comprising 5136 patients, of whom 1662 (32.4%) underwent BTS and 3474 (67.6%) underwent ER. This meta-analysis demonstrated that BTS resulted in reductions in postoperative complications (OR = 0.78; 95% CI: 0.66-0.92) and mortality (OR = 0.51; 95% CI: 0.28-0.92) than ER. CONCLUSION: The results of this meta-analysis indicate that BTS for right-sided MLBO confers preferable short-term outcomes as well as for left-sided. This suggests that BTS results in a reduction of postoperative complications and mortality for right-sided MLBO than ER.

A New Anorectal Melanoma Cell Line Derived from a Primary Human Rectal Tumor.

BACKGROUND: Anorectal melanoma is a rare disease with a poor prognosis. Symptoms are often nonspecific, which complicates preoperative diagnosis. Here, we describe the establishment of MELS, a new anorectal melanoma cell line derived from resection of a rectal tumor in a 40-year-old Japanese man. METHODS: Histological, electron microscopic, and immunohistochemical features of S-100, HMB-45, Melan-A, and NSE positivity of the tumor were typical of surgically resected anorectal melanoma. RESULTS: MELS cells are round or oval and have sharp thorn-like protrusions on some or all cell membranes. The cells form irregular attached colonies with numerous floating cells in two-dimensional culture. Transmission electron microscopy revealed that some MELS cells have cytoplasmic melanosomes. Immunocytochemically, MELS cells and surgical tissues had the same staining pattern. MELS cells had lower growth rates than Caco-2 (a colon adenocarcinoma cell line) and A375 (a cutaneous melanoma cell line) cells. Oxaliplatin and irinotecan were more effective in MELS cells than in Caco-2 and A375 cells. CONCLUSIONS: No previous report provided detailed clinical information on an anorectal melanoma cell line. Thus, MELS cells should improve our understanding of the biological characteristics of anorectal melanoma and provide a novel platform for examining the effects of therapies for anorectal melanoma.

Use of Liquid Biopsy to Detect PIK3CA Mutation in Metastatic Breast Cancer.

BACKGROUND: PIK3CA is associated with tumor progression, and the prevalence of PIK3CA mutation is high in breast cancer. Liquid biopsy offers convenient, noninvasive, and real-time insight into genetic alteration. In this study, we used liquid biopsy to detect PIK3CA mutations in patients with breast cancer. METHODS: We recruited patients with histologically confirmed breast cancer and distant metastases between April 2020 and September 2020. Circulating DNA was extracted from plasma (ctDNA) and exosomes (exoDNA). PIK3CA mutations (exons 9 and 20) were analyzed by droplet digital PCR. RESULTS: Of the 52 patients recruited, 16 had PIK3CA mutations in tumor tissue or blood: 9 had exon 9 mutations (E542K and E545K) and 8 had exon 20 mutations (H1047 L and H1047R). In 8 (15%) of the 52 patients, PIK3CA mutations were detected by liquid biopsies using ctDNA in 5 (9%), exoDNA in 6 (11%), and both ctDNA and exoDNA in 3 (6%). Of the 8 patients with PIK3CA mutations detected by liquid biopsies, 3 had no PIK3CA mutations in the primary tumors. CONCLUSIONS: PIK3CA mutations can be detected by liquid biopsy even in patients with no PIK3CA mutations in their primary tumors; thus, combination analysis using tissue and liquid biopsies can provide clinically useful information for patients with breast cancer.

Successful multidisciplinary management of vascular Ehlers-Danlos syndrome.

Vascular Ehlers-Danlos syndrome is a rare connective tissue disease with a high risk of severe complications. Because of these complications, the median life expectancy for patients with vascular Ehlers-Danlos syndrome is estimated at 48 years. However, the optimal management of these complications remains unclear. A 25-year-old man with abdominal pain was transported to our hospital by ambulance. He had undergone Hartmann's operation at 22 years of age for a first-time colonic perforation. At that time, a genetic test revealed germline variants in COL3A1, which encodes type III procollagen; therefore, the patient was diagnosed with vascular Ehlers-Danlos syndrome. When the patient presented to our hospital, we suspected another colonic perforation and thus performed an emergency operation. Open abdominal management, transcatheter arterial embolization, and negative-pressure wound therapy were performed as life-saving measures. Notably, these procedures should initially be avoided in patients with vascular Ehlers-Danlos syndrome because of tissue fragility. Open abdominal management, transcatheter arterial embolization, and negative-pressure wound therapy may be useful for patients with vascular Ehlers-Danlos syndrome who develop panperitonitis and massive intra-abdominal bleeding.

A Rapidly Growing Small-Intestinal Metastasis from Lung Cancer.

Small-intestinal metastasis from lung cancer, although relatively rare, often causes intestinal obstruction, gastrointestinal perforation, and gastrointestinal bleeding, making it an oncological emergency. Many patients have undergone emergency surgery for treatment of rapid progression of an intestinal metastatic lesion; however, information on changes in such metastases is lacking. We analyzed data from 4 patients with small-intestinal metastases from lung cancer who were treated during a 10-year period (January 2011 to December 2020) and for whom data on change in tumor diameter were available. The average rate of growth in tumor volume was 1.48-fold (range, 1.31- to 1.78-fold) during a median observation period of 22 (4-39) days, a rapid increase. Histopathological analysis showed that, in patients with a high degree of primary tumor atypia, rapid tumor growth may be caused by intratumoral hemorrhage, which was the reason for the rapid increase in tumor volume.

Detection of KRAS mutations in circulating tumour DNA from plasma and urine of patients with colorectal cancer.

BACKGROUND: Circulating tumour DNA (ctDNA) is very useful for purposes of cancer genetics; however, it has some limitations. Recently, ctDNA in body fluids, such as urine, sputum, and pleural effusion, has been investigated. The aim of this study was to evaluate the quantity of ctDNA derived from urine (trans-renal ctDNA) and the accuracy of KRAS mutation detection in relation to disease stage in colorectal cancer. METHODS: Urine, plasma, and tissue samples were collected from consecutively resected colorectal cancer patients. DNA was extracted from each sample and the quantity was determined. From each DNA sample, KRAS mutations were detected using droplet digital PCR. RESULTS: 200 patients participated and KRAS mutations were detected in 84 patients (42.0%) from tumour tissue. The concentration of trans-renal ctDNA (trtDNA) was significantly lower than that of plasma; however, there was no significant difference between the sensitivity using ctDNA and that using trtDNA (29.8% VS 33.3%, p = 0.62). Concordance between these two tests was only 17.5%. Combination analysis (ctDNA + trtDNA) improved the sensitivity to 53.6%, and sensitivity was significantly higher than that of corresponding single assays (p = 0.003). In early cancer stages, trtDNA had greater sensitivity for detecting KRAS mutations than ctDNA (37.7% vs. 21.3%, p = 0.047). Conversely, it was less useful for advanced cancer stages (21.7% vs. 52.2%, p = 0.07). Notably, KRAS mutations were detected using ctDNA or trtDNA in 12 of 116 (10.3%) patients who had no KRAS mutations in their tissue samples. CONCLUSIONS: trtDNA and ctDNA have equal potential and combination analysis significantly improved the sensitivity.

Elevated serum carcinoembryonic antigen level after curative surgery is a prognostic biomarker of stage II-III colorectal cancer.

BACKGROUND: High preoperative carcinoembryonic antigen (CEA) is a well-known risk factor for stage II-III colorectal cancer (CRC); however, in most cases, cancer does not recur. Conversely, postoperative CEA (post-CEA) is occasionally measured, and high post-CEA patients often develop recurrence; however, the clinical significance of post-CEA testing is unknown. The purpose of this study was to determine whether post-CEA elevation might indicate a poor prognosis for stage II-III CRC patients who underwent curative surgery. PATIENTS AND METHODS: 482 patients with pathological stage II-III CRC were included. Univariate and multivariate analyses were performed to evaluate post-CEA levels. RESULTS: Multivariate analysis showed that elevated post-CEA (hazard ratio (HR): 3.14, P < 0.001), pathological lymph node metastasis (pN+), and pathological T4 (pT4) are associated with poor recurrence-free survival (RFS), and that elevated post-CEA (HR: 3.12; P = 0.002), pN+, pT4, age >70, and smoking are independently associated with poor overall survival. Subgroup analysis among stage III patients, in combination with the risk classification of the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) study, showed that elevated post-CEA is a significant indicator of poor prognosis for RFS in both low-risk (73.8% vs. 21.2%, P < 0.001) and high-risk (49.9% vs. 25.0%, P = 0.04) groups. CONCLUSIONS: Post-surgical CEA elevation is independently associated with poor prognosis in stage II-III CRC. Adding post-CEA levels to the IDEA risk classification may provide a more reliable indicator of the need for individualized surveillance and adjuvant chemotherapeutic strategies.