Search

Background: A bridge to surgery (BTS) after self-expandable metallic stent (SEMS) placement is a widely recognized treatment strategy for obstructive colorectal cancer. However, there is still a lack of evidence for the efficacy and safety of laparoscopic surgery following SEMS placement. The aim of this systematic review and meta-analysis was to compare the short-term and long-term outcomes of laparoscopic surgery with those of open surgery following SEMS placement in patients with obstructive colorectal cancer. Methods: An electronic literature search through to December 2022 was performed to identify studies comparing short-term and long-term outcomes between laparoscopic and open surgery following SEMS placement for obstructive colorectal cancer. The main outcome measures were postoperative complication rates and mortality. Secondary outcome measures were the 3-year recurrence-free survival (RFS) and 3-year overall survival (OS) rates. The meta-analysis was performed using fixed-effect or random-effects methods to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: The meta-analysis included 15 studies and 883 patients, of whom 467 (52.9%) underwent laparoscopic surgery and 416 (47.1%) underwent open surgery following SEMS placement. The postoperative complication rate was significantly lower in the laparoscopic surgery group than in the open surgery group (OR 0.47, 95% CI 0.32–0.67, P < 0.001). There was no significant difference in the 3-year RFS rate or 3-year OS rate between the laparoscopic and open surgery groups (3-year RFS, OR 0.78, 95% CI 0.50–1.24, P = 0.30; 3-year OS, OR 0.68, 95% CI 0.41–1.12, P = 0.13). Conclusion: This meta-analysis found that the short-term outcome was better in patients who underwent laparoscopic surgery following SEMS placement than in those who underwent open surgery. Furthermore, there was no significant difference in long-term outcomes between the two groups. Laparoscopic surgery following SEMS placement may be a safe and effective treatment option for obstructive colorectal cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: To investigate the impact of postoperative infection (PI), surgical site infection, and remote infection (RI), on long‐term outcomes in patients with colorectal cancer (CRC). Methods: The Japan Society for Surgical Infection conducted a multicenter retrospective cohort study involving 1817 curative stage I/II/III CRC patients from April 2013 to March 2015. Patients were divided into the No‐PI group and the PI group. We examined the association between PI and oncological outcomes for cancer‐specific survival (CSS) and overall survival (OS) using Cox proportional hazards models and propensity score matching. Results: Two hundred and ninety‐nine patients (16.5%) had PIs. The 5‐year CSS and OS rates in the No‐PI and PI groups were 92.8% and 87.6%, and 87.4% and 83.8%, respectively. Both the Cox proportional hazards models and propensity score matching demonstrated a significantly worse prognosis in the PI group than that in the No‐PI group for CSS (hazard ratio: 1.60; 95% confidence interval: 1.10‐2.34; P =.015 and P =.031, respectively) but not for OS. RI and the PI severity were not associated with oncological outcomes. The presence of PI abolished the survival benefit of adjuvant chemotherapy. Conclusions: These results suggest that PI after curative CRC surgery is associated with impaired oncological outcomes. This survival disadvantage of PI was primarily derived from surgical site infection, not RI, and PI induced lower efficacy of adjuvant chemotherapy. Strategies to prevent PI and implement appropriate postoperative treatment may improve the quality of care and oncological outcomes in patients undergoing curative CRC surgery. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. [ABSTRACT FROM AUTHOR]

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. 482 patients with pathological stage II-III CRC were included. Univariate and multivariate analyses were performed to evaluate post-CEA levels. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Most patients with colorectal liver metastases, who undergo hepatectomy, experience recurrence. Although the prognosis is poorer for patients with early recurrence (within 6 months after hepatectomy) compared with later recurrence, no biomarker has been identified to predict early recurrence. Minimal residual disease (MRD) in patients who undergo curative surgery is the main cause of recurrence. In cancer patients, long fragment cell-free DNA is detected, and the presence of long fragments of cell-free DNA after surgery can indicate MRD. In this study, we developed a novel biomarker to predict early recurrence of colorectal liver metastases using cell-free DNA. Forty-one patients with colorectal liver metastases were enrolled. Peripheral blood samples were collected before and at 1 month after hepatectomy. Cell-free DNA was extracted from 1 ml plasma, and the long fragment/β-globin ratio, which can indicate MRD, was measured by real-time polymerase chain reaction. Three of 21 patients (14.3%) with decreases in the long cell-free DNA fragment/β-globin ratio after hepatectomy developed early recurrence compared with twelve of 20 patients (60.0%) with an increased ratio (P = 0.002). Patients with a decreased long fragment/β-globin ratio after hepatectomy had significantly longer recurrence-free survival compared with patients with an increased ratio (366 vs 102 days, P < 0.001). The cell-free DNA long fragment/β-globin ratio may serve as an effective biomarker of early recurrence in patients with colorectal liver metastases, who undergo hepatectomy. [ABSTRACT FROM AUTHOR]

The incidence of rare neuroendocrine tumors (NET) is rapidly increasing. Neuroendocrine carcinoma (NEC) is a NET with poorly differentiated histological features, high proliferative properties and associated poor prognoses. As these carcinomas are so rare and, thus, affect only a small number of patients allowing for few cell lines to be derived from patient biopsies, the histological, immunohistochemical, and clinical characteristics associated with colorectal NEC and NEC in other organs have yet to be clearly defined. Herein, we describe the establishment of a novel NEC cell line (SS‐2) derived from a tumor resection of the ascending colon from a 59‐year‐old Japanese woman. The histological, electron microscopic and immunohistochemical features of chromogranin A (CgA) as well as confirmation of synaptophysin positivity in this tumor were typical of those commonly observed in surgically resected colorectal NEC. Further, the Ki‐67 labeling index of the resected tumor was >20% and, thus, the tumor was diagnosed as an NEC of the ascending colon. The SS‐2 cell line maintained characteristic features to those of the resected tumor, which were further retained following implantation into subcutaneous tissues of nude mice. Additionally, when SS‐2 cells were seeded into ultra‐low attachment plates, they formed spheres that expressed higher levels of the cancer stem cell (CSC) marker CD133 compared to SS‐2 cells cultured under adherent conditions. SS‐2 cells may, therefore, contribute to the current knowledge on midgut NEC biological function while providing a novel platform for examining the effects of colorectal NEC drugs, including CSC. [ABSTRACT FROM AUTHOR]

Background The short-term safety and efficacy of a self-expandable metallic colonic stent (SEMS) insertion followed by elective surgery, “bridge to surgery (BTS)”, for malignant large-bowel obstruction (MLBO) have been well described comparing with emergency surgery. The aim of this study was to compare short-term outcomes of endoscopic decompression using a SEMS versus a transanal decompression tube (TDT). Materials and methods From January 2005 to November 2014, a total of 101 patients with MLBO underwent surgery at our single institution were retrospectively identified. Among them, 73 patients who underwent preoperative complete insertion of a decompression device (TDT, n = 45; SEMS, n = 28) were finally included in this study. Six patients with incomplete insertion of a decompression device (TDT, n = 5; SEMS, n = 1) were also excluded. The primary endpoints of this study were the postoperative morbidity and mortality rates. The secondary endpoints were decompression-related outcomes. Additionally, propensity score matched (PSM) analysis was conducted in short-term outcomes between the groups. Results The SEMS group had significantly higher proportion of right-sided tumor and bigger tumor size compared with those of the TDT group. The SEMS group had a significantly higher proportion of patients who underwent laparoscopic surgery, and consequently, a longer surgical duration than did the TDT group. Higher rates of insertion failure and perforation were recognized in the TDT group than in the SEMS group (10.0% versus 3.6% and 8.9% versus 0.0%, respectively), although these differences were not statistically significant ( P = 0.406 and 0.291, respectively). The two groups showed similar occurrences of anastomotic leakage, bowel obstruction, overall complications, and mortality. Compared with the TDT group, the SEMS group had a significantly lower rate of surgical site infection (24.4% versus 3.6%, respectively; P = 0.023 and P = 0.025 after PSM) and a shorter length of hospital stay (median, 21 d [interquartile range, 18-29 d] versus 38 d [interquartile range, 28-45 d], respectively; P = 0.015 and P = 0.003 after PSM). Solid food intake after decompression and preoperative temporary discharge occurred only in the SEMS group. Conclusions Preoperative SEMS insertion for MLBO is effective with at least equivalent short-term outcomes and superior preoperative quality of life compared with decompression using TDT. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that the Th1/Th2 balance shifts toward Th2 dominance in cancer-bearing state or under surgical stress. This study was designed to investigate whether perioperative impaired Th1/Th2 balance is associated with the occurrence of postoperative infection following colorectal cancer surgery. Methods: From 53 patients with colorectal cancer, peripheral blood samples were collected, before surgery, and on the 3rd, 7th, and 14th postoperative days. The proportions of CD4+ T-helper cells producing intracellular cytokines including interferon-γ (Th1 cells) and interleukin-4 (Th2 cells) were measured by flow cytometry. The patients were divided into two groups according to the presence (infected group) and absence (noninfected group) of postoperative infection. Results: The infected group showed serum hypoalbuminemia and higher frequency of blood transfusion compared with the noninfected group. No significant difference in the proportion of Th1 cells was observed between the two groups. In contrast, the infected group showed significantly higher proportions of Th2 cells than the noninfected group (1.9 ± 0.9% for noninfected group and 2.8 ± 1.3% for infected group; P < 0.05). Regarding Th1/Th2 ratio, the infected group showed a lower ratio than the noninfected group (14.7 ± 8.8 for noninfected group and 9.0 ± 3.2 for infected group; P < 0.05). Throughout the postoperative period, the Th1/Th2 ratio in the infected group was significantly lower than that in the noninfected group. Conclusions: This study demonstrated that perioperative Th2 dominance in addition to hypoalbuminemia and blood transfusion is associated with the occurrence of infection following colorectal cancer surgery. These results provide further information that may direct future treatments based on the Th1/Th2 concept focusing on decreasing the risk of postoperative infection. [Copyright &y& Elsevier]