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.

Potential of Direct Oral Anticoagulant in Bleeding After Gastric Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: An increasing number of patients are undergoing gastric endoscopic submucosal dissection (ESD) with active prescriptions of direct oral anticoagulants (DOACs). Only a few reports have described the effects of DOAC intake on postoperative bleeding. We aimed to investigate the bleeding risk associated with DOACs after gastric ESD. METHODS: Clinical studies published up to April 2022 showing bleeding rates after gastric ESD in patients taking DOACs were identified using electronic searches. The primary outcome was the rate of bleeding after gastric ESD in patients receiving DOACs compared to those not receiving antithrombotic therapy. In this meta-analysis, odds ratios (ORs) were calculated and pooled using a random effects model. The secondary outcome was the difference in the bleeding rate between patients treated with DOACs and those treated with warfarin and antiplatelet drugs. RESULTS: Seven studies were included in this meta-analysis. The pooled analysis showed that DOACs had a higher bleeding rate than non-thrombotic therapy (17.0% vs. 3.4%; OR 5.72; 95% confidence interval [CI], 4.33-7.54; I2 = 0%). The bleeding risk associated with DOAC administration was similar to that associated with warfarin (17.0% vs. 20.0%; OR 0.83; 95% CI 0.59-1.18; I2 = 0%), whereas it was higher than that associated with antiplatelet administration (16.9% vs. 11.0%; OR 1.63; 95% CI 1.14-2.34; I2 = 8%). CONCLUSIONS: This meta-analysis reveals that the bleeding risk of DOACs is higher than that of non-antithrombotics and antiplatelets, whereas it is comparable to that of warfarin. Gastric ESD in patients on anticoagulants requires careful postoperative management.

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.

Segmental or right hemi-colectomy? The optimal surgical procedure for transverse colon cancer: a propensity score-matched, multicenter, retrospective study.

PURPOSE: Extended colectomy is sometimes chosen for treatment of transverse colon cancer (TCC) because of concerns about short- and long-term outcomes. However, there is still a lack of evidence regarding the optimal surgical procedure. METHODS: We retrospectively collected and analyzed data of patients who underwent surgical treatment of pathological stage II/III TCC at four hospitals from January 2011 to June 2019. We excluded the patients with TCC located at distal transverse colon, and just evaluated and analyzed proximal and middle third TCC. Inverse probability treatment-weighted propensity score analyses was used to compare short- and long-term outcomes between patients who underwent segmental transverse colectomy (STC) and those who underwent right hemicolectomy (RHC). RESULTS: In total, 106 patients were enrolled in this study (STC group, n = 45; RHC group, n = 61). The patients' backgrounds were well balanced after matching. The incidence of major postoperative complications (Clavien-Dindo grade ≥ III) was not significantly different between the STC and RHC groups (4.5% vs. 5.6%, respectively; P = 0.53). The 3-year recurrence-free survival and overall survival rates were not significantly different between the STC and RHC groups (88.2% vs. 81.8%, P = 0.86 and 90.3% vs. 91.9%, P = 0.79, respectively). CONCLUSION: RHC has no significant benefits over STC with respect to either short- or long-term outcomes. STC with necessary lymphadenectomy could be an optimal procedure for proximal and middle TCC.

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.

Feeding gastrostomy and duodenostomy using the round ligament of the liver versus conventional feeding jejunostomy after esophagectomy: a meta-analysis.

Esophageal cancer patients require enteral nutritional support after esophagectomy. Conventional feeding enterostomy to the jejunum (FJ) is occasionally associated with small bowel obstruction because the jejunum is fixed to the abdominal wall. Feeding through an enteral feeding tube inserted through the reconstructed gastric tube (FG) or the duodenum (FD) using the round ligament of the liver have been suggested as alternatives. This meta-analysis aimed to compare short-term outcomes between FG/FD and FJ. Studies published prior to May 2022 that compared FG or FD with FJ in cancer patients who underwent esophagectomy were identified via electronic literature search. Meta-analysis was performed using the Mantel-Haenszel random-effects model to calculate Odds Ratios (ORs) with 95% confidence intervals (CIs). Five studies met inclusion criteria to yield a total of 1687 patients. Compared with the FJ group, the odds of small bowel obstruction (OR 0.09; 95% CI, 0.02-0.33), catheter site infection (OR 0.18; 95% CI, 0.06-0.51) and anastomotic leakage (OR 0.53; 95% CI, 0.32-0.89) were lower for the FG/FD group. Odds of pneumonia, recurrent laryngeal nerve palsy, chylothorax and hospital mortality did not significantly differ between the groups. The length of hospital stay was shorter for the FG/FD group (median difference, -10.83; 95% CI, -18.55 to -3.11). FG and FD using the round ligament of the liver were associated with lower odds of small bowel obstruction, catheter site infection and anastomotic leakage than FJ in esophageal cancer patients who underwent esophagectomy.

The T-CEA score: a useful prognostic indicator based on postoperative CEA and pathological T4 levels for patients with stage II-III colorectal cancer.

PURPOSE: To investigate a prognostic score for stage II-III colorectal cancer (CRC) based on post-CEA and pT4 levels. METHODS: Two cohorts of stage II-III CRC patients who underwent curative surgery between 2011 and 2017 were included. The prognostic score (T-CEA score) was calculated as follows: T-CEA-0, post-CEA ≤ 5 ng/mL and pT1-3; T-CEA-1, post-CEA > 5 ng/mL or pT4; T-CEA-2, post-CEA > 5 ng/mL and pT4. RESULTS: The T-CEA scores of the 587 patients were as follows: T-CEA-0 (n = 436; 74%), T-CEA-1 (n = 129; 22%), and T-CEA-2 (n = 10; 2%). The 5-year recurrence-free survival (RFS) rates of the T-CEA-0, 1, and 2 groups were 80.3%, 54.8%, and 0%, respectively (P < 0.01), and the 5-year overall survival (OS) rates were 90.9%, 74.2%, and 0%, respectively (T-CEA-0 vs T-CEA-1: P < 0.01, T-CEA-1 vs T-CEA-2: P = 0.04). Multivariate analysis revealed that an elevated T-CEA score of 1 or 2 was a significant risk factor for poor RFS (HR: 2.89, P < 0.01) and OS (HR: 2.85, P < 0.01). CONCLUSION: The T-CEA score is a reliable and convenient prognostic score for stage II-III CRC.

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.

The utility of serum osteopontin levels for predicting postoperative complications after colorectal cancer surgery.

BACKGROUND/AIM: Osteopontin (OPN) is a secretory glycoprotein, which is expressed not only in osteoblasts, but immune cells including macrophages and activated T cells. Its pleiotropic immune functions, such as bone remodeling, cancer progression, immune response, and inflammation have been reported previously. However, the association between OPN and postoperative complications (POC) after colorectal cancer (CRC) surgery has not been studied, so far. METHODS: Peripheral blood samples were collected before (pre) and immediately after surgery (post), and on postoperative days (POD) 1, 3, 5, and 7. Serum OPN levels were measured by ELISA. In total, 78 patients who underwent elective CRC surgery were divided into the No-POC (n = 54) and POC (n = 24) groups. RESULTS: The POC group had significantly higher OPN levels than the No-POC group throughout the postoperative observation period. The maximum OPN levels from pre- to postsurgical samples showed the best predictive potential for POCs (cut off: 20.75 ng/mL, area under the curve: 0.724) and were correlated with length of postoperative stays. OPN values were significantly correlated with C-reactive protein on POD3 and were identified as an independent predictive marker for POCs (odds ratio: 3.88, 95% CI: 1.175-12.798, P = 0.026). The severity of POCs was reflected in increased OPN levels. CONCLUSION: Increased postoperative OPN was associated with increased postoperative inflammatory host responses and POC after CRC surgery. Serum OPN level may be a useful biomarker for early prediction of POC and it may provide additional information for treatment decisions to prevent POC.

Biweekly TAS-102 and bevacizumab as third-line chemotherapy for advanced or recurrent colorectal cancer: a phase II, multicenter, clinical trial (TAS-CC4 study).

BACKGROUND: TAS-102 improves overall survival (OS) of patients with refractory colorectal cancer (CRC), resulting in median progression-free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, a combination of TAS-102 and bevacizumab was shown to extend median PFS by 3.7 months. However, approximately half of these patients experience grade 3/4 neutropenia. In this study, we evaluated whether biweekly TAS-102 and bevacizumab therapy has efficacy equal to that of conventional TAS-102 and bevacizumab therapy and whether it reduces adverse hematological effects. METHODS: This phase II, investigator-initiated, open-label, single-arm, multicenter study was conducted in Japan. Eligible patients had previously received first- and second-line chemotherapy for metastatic CRC. TAS-102 (35 mg/m2) was given twice daily on days 1-5 and days 15-19 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion for 30 min every 2 weeks. The primary end point was progression-free survival (PFS), and secondary end points were time-to-treatment failure (TTF), response rate (RR), OS, and safety. RESULTS: 44 patients with metastatic colorectal cancer were enrolled in this study. Median PFS was 4.6 months (95% confidence interval [95% CI] 3.6-5.3) and median OS was 10.5 months (95% CI 9.6-11.4). A partial response was observed in 2 patients (4.5%, 95% CI 0.4-16.0%). The most common adverse event above grade 3 was neutropenia (7 patients, 15.9%, 95% CI 7.6-29.7%). CONCLUSIONS: Biweekly TAS-102 and bevacizumab therapy as third-line chemotherapy appears as effective as conventional TAS-102 and bevacizumab therapy, and this approach reduces adverse hematological effects.

[Is Cell-Free DNA a Useful Biomarker for Predicting the Efficacy of Preoperative Chemotherapy for Advanced Colon Cancer?]

OBJECTIVE: To examine the potential of peripheral circulating cell-free DNA(cfDNA)as a predictor of response in patients undergoing neoadjuvant chemotherapy(NAC)for advanced colon cancer. METHODS: We compared histological response, background factors, and cfDNA molecular volume changes in cT4 and cT3N+ colon cancer patients. RESULTS: Six of 11 patients responded. The patients with muc and pap histology were non-responders. There was no relationship between CEA or cfDNA levels and response. Responders showed >50% change in DNA integrity index(=cfDNA long fragment/ short fragment ratio), while non-responders showed <50% change(p=0.015). CONCLUSION: Our results suggest that the variability rate in DNA integrity index of peripheral blood cfDNA may be useful in predicting the therapeutic efficacy of colon NAC.

[Long-Term Response to UFT/UZEL/Bevacizumab Therapy for Lung Metastasis after Surgery for Early-Stage Colon Cancer in a Late-Stage Elderly Patient].

Late-stage elderly patients have low tolerance to chemotherapy, and they have difficulties when they are treated with standard chemotherapy. We report a case of a late-stage elderly patient who had a long-term response to UFT/UZEL/bevacizumab( Bev)therapy for lung metastasis after surgery for early-stage colon cancer. He was 82-years-old and underwent laparoscopy-assisted sigmoid colectomy for sigmoid colon cancer at another hospital. The pathological diagnosis was pT1b, ly1, v0, N0, M0, pStage Ⅰ. Six months after the surgery, a small nodule was noted in the middle lobe of the right lung. It grew five months later and was definitely diagnosed as lung metastasis. Considering his physical condition and tumor size, we opted to introduce less invasive chemotherapy instead of standard chemotherapy. UFT/UZEL/Bev was started 14 months after surgery. Although he required dose reduction due to anorexia, he safely continued the treatment with partial response (PR), which was maintained for 2 years and 6 months. While UFT/UZEL/Bev has no convincing evidence, it may be an option for vulnerable patients, especially those with non-life-threatening disease.

Even a partial pathological response is associated with lower relapse rates in patients with operable rectal cancer undergoing neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy to treat locally advanced rectal cancer is an effective therapeutic strategy for the prevention of local recurrence and distant organ metastasis after surgery. OBJECTIVES: To assess the prognostic significance of histopathological tumor response in rectal cancer patients undergoing neoadjuvant chemotherapy. METHODS: This study included patients with operable rectal cancer who received neoadjuvant chemotherapy using the FOLFOX regimen (5-fluorouracil, l-leucovorin, and oxaliplatin) in a hospital between February 2012 and November 2017. The main outcome measure was disease-free survival with respect to histopathological response to neoadjuvant chemotherapy in resected specimens. RESULTS: The median follow-up was 32 months. Of 48 patients treated with neoadjuvant FOLFOX, 24 (50%) were classified as responders, which included two patients with pathological complete response and 22 patients with partial response. The remaining 24 patients (50%) were classified as nonresponders. Responders had a significantly better 3-year disease-free survival than nonresponders (86% vs. 62%, p = .02). CONCLUSIONS: Patients whose surgical specimens show a pathological complete response or partial response have good oncologic outcomes.

Combination of TAS-102 and bevacizumab as third-line treatment for metastatic colorectal cancer: TAS-CC3 study.

BACKGROUND: TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clinical impact beyond cytotoxic doublets. METHODS: This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRC patients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m2) was given orally twice daily on days 1-5 and 8-12 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion every 2 weeks. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety. RESULTS: Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 months; the median overall survival was 9.3 months. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematological adverse events above grade 3 and no treatment-related deaths occurred. CONCLUSIONS: This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC.

Does the diameter of colonic stent influence the outcomes in bridge-to-surgery patients with malignant large bowel obstruction?

PURPOSE: This study investigated the short- and long-term outcomes of 18- and 22-mm-diameter self-expandable metallic stent (SEMS) as a bridge to surgery (BTS) in patients with malignant large bowel obstruction (MLBO). METHODS: Sixty-nine pathological stage II and III colorectal cancer patients who underwent BTS were included in this multi-institutional retrospective study. Patients were divided into two groups regarding the diameter of SEMS: an 18-mm group (n = 30) and a 22-mm group (n = 39). RESULTS: There was no significant difference in the clinical success rate, but both of the two re-obstructions observed occurred in the 18-mm group. The 18-mm group showed a trend toward a higher incidence of overall postoperative complications (Clavien-Dindo grading ≥ II) than the 22-mm group (33.3% vs. 10.3%, P = 0.061). The 3-year disease-free and overall survival showed no significant differences between the 18- and 22-mm groups (78.2% vs. 68.8%, P = 0.753 and 92.8% vs. 82.1%, P = 0.471, respectively). CONCLUSION: SEMS of 18 and 22 mm diameter confer statistically equivalent short- and long-term outcomes as a BTS.

Preoperative lymphocyte-to-monocyte ratio predicts postoperative infectious complications after laparoscopic colorectal cancer surgery.

BACKGROUND AND AIM: Postoperative infectious complications (POI), which can increase length of hospital stay, medical cost, and worsen overall survival, are a concern in minimally invasive colorectal cancer (CRC) surgeries. Recent reports showed that relatively new inflammation-based score, lymphocyte-to-monocyte ratio (LMR) is an independent predictor of long-term outcomes after CRC surgeries. In this study, LMR was evaluated as a predictor of short-term postoperative outcomes. PATIENTS AND METHODS: This was a single-institutional retrospective study of 211 consecutive patients who had undergone laparoscopic CRC surgery with primary tumor resection from January 2014 to August 2015 at Nippon Medical School Chiba Hokusoh Hospital. The patients were divided into two groups (no POI; n = 176 and POI; n = 35). The associations between inflammation-based scores, namely neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and LMR, and the occurrence of POI were investigated. Receiving operator characteristic curve analysis was used to determine the cutoff point of preoperative LMR. RESULTS: Low LMR (cut-off 3.46), long operative time, and smoking were found to be independent predictors of POI in a multivariate analysis (LMR: Odds ratio 5.61, 95% confidence interval 1.98-15.9, P = 0.001). Patients with low LMR also appeared to have more advanced and aggressive tumours. CONCLUSION: This is the first study to report that the lower LMR is a predictive factor of POI after laparoscopic CRC surgery, and it may provide additional information for treatment decisions to prevent POI.

Emerging RAS, BRAF, and EGFR mutations in cell-free DNA of metastatic colorectal patients are associated with both primary and secondary resistance to first-line anti-EGFR therapy.

Oncogenic RAS mutations are negative biomarkers of response to epidermal growth factor receptor (EGFR) blockade. RAS mutations are usually detected in biopsies of primary colorectal tumors. However, the genomic profiles of primary tumors and metastases are not always concordant, and chemotherapeutic agents can alter the tumor molecular landscape. Cell-free DNA (cfDNA) is a novel tool to detect molecular heterogeneity. This study evaluated the clinical utility of cfDNA to predict primary or secondary resistance to EGFR blockade in patients with metastatic colorectal cancer. Thirty metastatic colorectal cancer patients without RAS and BRAF mutations were prospectively enrolled and treated with cytotoxic agents and EGFR blockade as first-line therapy. cfDNA was analyzed for the presence of RAS, BRAF, and EGFR (S492R) point mutations before initiating chemotherapy and every 2 months during chemotherapy. The analysis was performed in 223 plasma samples from all 30 patients. Of the 30 patients, five had RAS mutations in their cfDNA before starting chemotherapy and did not respond. Twenty-four of the remaining 25 patients without cfDNA RAS mutations had a response. Twenty of the 24 responders developed secondary resistance and cfDNA RAS mutations were found in 17 of the 20. cfDNA BRAF mutations were found in seven, and EGFR mutations were found in eight of the 20 patients. Emerging RAS, BRAF, and EGFR mutations occurred in patients with primary and secondary resistance to EGFR blockade. The detection of these mutations in cfDNA is a promising approach to predict treatment response and secondary resistance.

[Pathological Complete Response in Multiple Advanced Rectal Cancers with Neoadjuvant CapeOX plus BV Therapy-A Case Report].

A 70-year-old male with defecation difficulties was referred to our hospital. A colonoscopy and computed tomography revealed multiple advanced rectal cancers in the rectosigmoid and lower rectum with swollen lymph nodes. After 6 courses of neoadjuvant capecitabine and oxaliplatin and bevacizumab without radiotherapy(CapeOX plus BV therapy), a colonoscopy revealed that the tumors had significantly reduced. A low anterior laparoscopic resection with diverting ileostomy was performed. Histopathological examination showed no residual tumor cells or lymph node metastasis. A final diagnosis of pathological complete response was made. The patient has currently survived 1-year disease-free. Neoadjuvant CapeOX plus BV therapy can be a promising therapeutic option for locally advanced rectal cancer.

[A Case of Peritoneal Dissemination of Colorectal Cancer in Which Conversion Surgery Could Be Performed after Reduction with CAPOX/Bevacizumab].

A woman in her 60s underwent lower endoscopy due to a positive fecal occult blood test. A type 2 tumor was found in the cecum, and a biopsy resulted in the diagnosis of adenocarcinoma(tub2). Contrast-enhanced CT showed an enlarged paracolonic lymph node but no distant metastasis, so the patient underwent a laparoscopic-assisted ileocolic resection and D3 lymph node dissection for cecum cancer. The pathology was pT3, pN2b, pM0, pStage Ⅲc, and 12 courses of FOLFOX were administered as adjuvant chemotherapy. Twenty-four months after the completion of adjuvant chemotherapy, an elevated CEA was observed, and a PET-CT was performed, which showed multiple peritoneal disseminated nodules with FDG accumulation. Based on this finding, CAPOX/bevacizumab therapy was introduced, and on completion of 4 courses, the PET-CT showed a decrease in the size of the nodules and the disappearance of FDG accumulation. Based on this, the patient underwent resection. A peritoneal dissemination resection and bilateral ovariectomy were laparoscopically performed, and the patient is currently under observation. In patients with metastatic recurrence of peritoneal dissemination who underwent complete resection, treatment with CAPOX/bevacizumab may allow for disease control and provide a long-term prognosis.