Combined Comprehensive Risk Score of the Estimation of Physiologic Ability and Surgical Stress and C-Reactive Protein-to-Albumin Ratio Is a Strong Prognostic Indicator of Long-term Outcomes in Colorectal Cancer.

BACKGROUND: In patients with colorectal cancer, both C-reactive protein-to-albumin ratio and comprehensive risk score of the estimation of physiologic ability and surgical stress have demonstrated prognostic significance. OBJECTIVE: To assess the clinical value of the combined use of C-reactive protein-to-albumin ratio and comprehensive risk score for predicting prognosis in patients with colorectal cancer. DESIGN: Multicenter retrospective study. SETTINGS: The cohort was divided into 3 groups based on a combined score derived from the value of C-reactive protein-to-albumin ratio and comprehensive risk score (low/mid /high). PATIENTS: Patients who underwent curative resection between 2010 and 2019 at multiple institutions were enrolled in this study. MAIN OUTCOME MEASURES: Overall and recurrence-free survival. RESULTS: A total of 2207 patients (801 in low cohort, 817 in mid cohort, and 589 in high cohort) were included in this study. Multivariate analysis revealed that combined score was an independent prognostic factor for both overall and recurrence-free survival, irrespective of disease stage (p < 0.05). Furthermore, Harrell's C-Index indicated that the predictive power of combined score was significantly superior to that of C-reactive protein-to-albumin ratio or comprehensive risk score (p < 0.001). LIMITATIONS: This study had a retrospective design, and data on genetic markers were not included. CONCLUSION: The synergistic combination of C-reactive protein-to-albumin ratio and comprehensive risk score contributes to the robust definition of combined score, a potent prognostic factor, regardless of disease stage. This finding has the potential to provide novel insights into the management of patients with CRC who have undergone curative resection. See Video Abstract.

Stratification of Stage II Colon Cancer Using Recurrence Prediction Value: A Multi-institutional International Retrospective Study.

OBJECTIVE: To create a recurrence prediction value (RPV) of high-risk factor and identify the patients with high risk of cancer recurrence. SUMMARY BACKGROUND DATA: There are several high-risk factors known to lead to poor outcomes. Weighting each high-risk factor based on their association with increased risk of cancer recurrence can provide a more precise understanding of risk of recurrence. METHODS: We performed a multi-institutional international retrospective analysis of patients with Stage II colon cancer patients who underwent surgery from 2010 to 2020. Patient data from a multi-institutional database were used as the Training data, and data from a completely separate international database from two countries were used as the Validation data. The primary endpoint was recurrence-free survival (RFS). RESULTS: A total of 739 patients were included from Training data. To validate the feasibility of RPV, 467 patients were included from Validation data. Training data patients were divided into RPV low (n = 564) and RPV high (n = 175). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (Hazard ratio (HR) 2.628; 95% confidence interval (CI) 1.887-3.660; P < 0.001). Validation data patients were divided into two groups (RPV low, n = 420) and RPV high (n = 47). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (HR 3.053; 95% CI 1.962-4.750; P < 0.001). CONCLUSIONS: RPV can identify Stage II colon cancer patients with high risk of cancer recurrence world-wide.

Delayed-Onset Organ/Space Surgical Site Infection Worsens Prognosis in High-Risk Stage II and III Colorectal Cancer.

BACKGROUND: It is unclear how early- and delayed-onset organ/space surgical site infections (SSIs) affect the long-term prognosis of patients with colorectal cancer, who are potential candidates for adjuvant chemotherapy. This study aimed to investigate the association between the timing of SSI onset and clinical outcome. METHODS: This retrospective, multicenter cohort study evaluated patients who were diagnosed with high-risk stage II or III colorectal cancer and underwent elective surgery between 2010 and 2020. Five-year recurrence-free survival (RFS) was the primary endpoint and was compared between early SSI, delayed SSI (divided based on the median date of SSI onset), and non-SSI groups. RESULTS: A total of 2,065 patients were included. Organ/space SSI was diagnosed in 91 patients (4.4%), with a median onset of 6 days after surgery. The early-onset SSI group had a higher proportion of patients with Clavien-Dindo grade ≥IIIb SSI than the delayed-onset SSI. Patients who received adjuvant chemotherapy (AC) had earlier organ/space SSI onset than those who did not. The adjusted hazard ratio of 5-year RFS in the delayed-onset SSI was 2.58 (95% confidence interval: 1.43-4.65; p = 0.002): higher than that in the early-onset SSI, with the non-SSI as the reference. CONCLUSIONS: Delayed-onset organ/space SSI worsened long-term prognosis compared to early-onset, and this may be due to delayed initiation of AC. Patients who are clinically suspected of having lymph node metastasis might need additional intervention to prevent delays in commencing AC due to the delayed SSI.

Prognostic Impact of Main Lymph Node Metastasis in Patients with Colon Cancer.

BACKGROUND: Although extended lymph node dissection during colon cancer surgery is recommended in both Western and Eastern countries, the perception and clinical significance of main lymph node metastasis (MLNM) remains controversial. METHODS: In total, 1557 patients with colon cancer who underwent curative resection with D3 dissection were retrospectively analyzed. Clinicopathological factors associated with MLNM were analyzed. Kaplan-Meier survival analysis and log-rank tests were used to compare the prognosis between the MLNM and non-MLNM groups. RESULTS: Multivariate analysis showed that overall survival (OS) [hazard ratio, 2.117 (0.939-4.774), p = 0.071] and recurrence-free survival (RFS) [hazard ratio, 2.183 (1.182-4.031), p = 0.013] were affected by the MLNM status independent of the TNM stage. Survival analysis demonstrated that among patients with stage III disease, the OS and RFS rates were significantly different between patients with and without MLNM (OS: p = 0.0147, RFS: p = 0.0001). However, the OS and RFS rates were not significantly different between patients who had stage III disease with MLNM and patients who had stage IV disease (OS: p = 0.5901, RFS: p = 0.9610). CONCLUSIONS: MLNM is an independent prognostic factor for patients with colon cancer. The addition of the MLNM status to the current TNM classification may enhance the prognostic value of the TNM staging system and the clinical efficacy of adjuvant therapy in patients with colon cancer.

Comprehensive risk score of the E-PASS as a prognostic indicator for patients after elective and emergency curative colorectal cancer surgery: A multicenter retrospective study.

OBJECTIVE: To evaluate the prognostic value of the comprehensive risk score (CRS) of the Estimation of Physiologic Ability and Surgical Stress for managing patients with colorectal cancer (CRC) who underwent elective and emergency colorectal cancer surgery with curative intent. SUMMARY BACKGROUND DATA: CRS, which is calculated based on both clinical and surgical factors, is a good predictor of postoperative complications and mortality. However, the impact of CRS in CRC prognosis remains unclear. METHODS: Patients with CRC who underwent curative resection between 2010 and 2019 were retrospectively enrolled in this study. The cohort was divided into the low and high CRS groups. The prognostic value of CRS was evaluated via Cox regression and Kaplan-Meier analyses. The CRS cutoff value was obtained using the Youden index applied to OS curves and have not been validated by any validation cohorts. RESULTS: In total, 2407 patients, including 1359 and 1048 patients with low and high CRS, respectively, were enrolled in this study. Multivariate analysis revealed that a CRS was an independent prognostic factor of overall and recurrence-free survival regardless of disease stage. Furthermore, adjuvant chemotherapy was beneficial for the survival of patients with stage III CRC in both high and low CRS groups; however, the survival benefit was limited in elderly high CRS patients. CONCLUSIONS: CRS was a strong prognostic factor for CRC regardless of disease stage and might be considered as a biomarker for selecting elderly patients who are eligible for adjuvant chemotherapy.

Long-term and short-term outcomes of laparoscopic versus open resection following tube decompression for obstructive colorectal cancer: a single-center retrospective study.

PURPOSE: The benefits of laparoscopic surgery over open surgery are well documented; however, the suitability of laparoscopic surgery for obstructive colorectal cancer is still controversial. The aim of this retrospective study was to compare the clinical benefits of laparoscopic surgery vs. open surgery for obstructive colorectal cancer after tube decompression. METHODS: We analyzed the outcomes of patients who underwent laparoscopic surgery vs. open surgery for curative resection after tube decompression for obstructive colorectal cancer at our hospital between January, 2007 and March, 2018. RESULTS: This study comprised 67 patients: 29 patients who underwent open surgery and 38 patients who underwent laparoscopic surgery. The morbidity within 30 days after surgery was comparable between the groups. The 3-year overall survival rates of the open and laparoscopic groups were 83.3 and 79.4%, respectively (p = 0.6244), and the 3-year disease-free survival rates were 59.3 and 71.2%, respectively (p = 0.3200). Multivariate analysis showed that nodal stage (p = 0.021) was an independent prognostic factor for OS and sex (p = 0.010) and side-ness (p = 0.048) were independent prognostic factors for DFS. CONCLUSION: If adequate decompression is achieved, laparoscopic resection following tube decompression for obstructive colorectal cancer can be a safe alternative to open surgery.

Cost-effectiveness of TAS-102 plus bevacizumab versus TAS-102 monotherapy in patients with metastatic colorectal cancer.

BACKGROUND: TAS-102 plus bevacizumab is an anticipated combination regimen for patients who have metastatic colorectal cancer. However, evidence supporting its use for this indication is limited. We compared the cost-effectiveness of TAS-102 plus bevacizumab combination therapy with TAS-102 monotherapy for patients with chemorefractory metastatic colorectal cancer. METHOD: Markov decision modeling using treatment costs, disease-free survival, and overall survival was performed to examine the cost-effectiveness of TAS-102 plus bevacizumab combination therapy and TAS-102 monotherapy. The Japanese health care payer's perspective was adopted. The outcomes were modeled on the basis of published literature. The incremental cost-effectiveness ratio (ICER) between the two treatment regimens was the primary outcome. Sensitivity analysis was performed and the effect of uncertainty on the model parameters were investigated. RESULTS: TAS-102 plus bevacizumab had an ICER of $21,534 per quality-adjusted life-year (QALY) gained compared with TAS-102 monotherapy. Sensitivity analysis demonstrated that TAS-102 monotherapy was more cost-effective than TAS-102 and bevacizumab combination therapy at a willingness-to-pay of under $50,000 per QALY gained. CONCLUSIONS: TAS-102 and bevacizumab combination therapy is a cost-effective option for patients who have metastatic colorectal cancer in the Japanese health care system.

Bridge to Surgery for Obstructing Colonic Cancer: A Comparison between Right- and Left-sided Lesions.

OBJECTIVES: Few studies have compared management and outcomes of bridge to surgery (BTS) for obstructive colonic cancer according to the location of the tumor. Additional information is needed about this procedure's characteristics and short-term and long-term outcomes. We aimed to compare patient and tumor characteristics, and outcomes of BTS for obstructive right-sided versus left-sided colonic cancers. METHODS: This was a retrospective, single center, cohort study. The study cohort comprised 149 patients, including 48 with right-sided and 101 with left-sided obstructive colonic cancers, who were treated with BTS between January 2007 and December 2017. Data on medical history, investigations, treatments, and prognosis were collected from an electronic database of a single hospital. The primary end points were overall (OS) and disease-free (DFS) survival and short-term surgical outcomes. RESULTS: Significantly more patients with right-sided cancers had postoperative complications (29.2% vs. 14.9%, p = 0.039). Additionally, postoperative chemotherapy was administered to a marginally significantly greater proportion of patients with left-sided cancers (29.2% vs 45.5%, p = 0.057). The long-term outcomes were comparable between the two groups (the 5-year OS rates were 67.6% and 80.9% [p = 0.117] and the 5-year DFS rates were 62.2% and 58.6% [p = 0.671]). Multivariate analyses using all studied variables showed that lymphovascular invasion, advanced T stage, and adjuvant chemotherapy were independent poor prognostic factors. CONCLUSIONS: The long-term outcome was not different between the right- and left-sided groups. In a BTS setting, postoperative complications may reduce the compliance of adjuvant chemotherapy in right-sided cancers and affect long-term outcomes.

Comparison of decompression tubes with metallic stents for the management of right-sided malignant colonic obstruction.

BACKGROUND: Emergency surgical resection is a standard treatment for right-sided malignant colonic obstruction; however, the procedure is associated with high rates of mortality and morbidity. Although a bridge to surgery can be created to obviate the need for emergency surgery, its effects on long-term outcomes and the most practical management strategies for right-sided malignant colonic obstruction remain unclear. AIM: To determine the appropriate management approach for right-sided malignant colonic obstruction. METHODS: Forty patients with right-sided malignant colonic obstruction who underwent curative resection from January 2007 to April 2017 were included in the study. We compared the perioperative and long-term outcomes of patients who received bridges to surgery established using decompression tubes and those created using self-expandable metallic stents (SEMS). The primary outcome was the overall survival duration (OS) and the secondary endpoints were the disease-free survival (DFS) duration and the preoperative and postoperative morbidity rates. Analysis was performed on an intention-to-treat basis. RESULTS: There were 21 patients in the decompression tube group and 19 in the SEMS group. There were no significant differences in the perioperative morbidity rates of the two groups. The OS rate was significantly higher in the decompression tube group than in the SEMS group (5-year OS rate; decompression tube 79.5%, SEMS 32%, P = 0.043). Multivariate analysis revealed that the bridge to surgery using a decompression tube was significantly associated with the OS (hazard ratio, 17.41; P = 0.004). The 3-year DFS rate was significantly higher in the decompression tube group than in the SEMS group (68.9% vs 45.9%; log-rank test, P = 0.032). A propensity score-adjusted analysis also demonstrated that the prognosis was significantly better in the decompression tube group than in the SEMS group. CONCLUSION: The bridge to surgery using trans-nasal and trans-anal decompression tubes for right-sided malignant colonic obstruction is safe and may improve long-term outcomes.

Single-Port Totally Extraperitoneal Preperitoneal Hernia Repair: Procedure, Tips, and Our Experience.

Single-port laparoscopic surgery is gaining increased attention because of its superiority in terms of cosmesis. A 1.5 cm vertical transumbilical incision is used for the single port, which is created by the glove method. We began applying single-port surgery to hernia repair in 2010, at which time we used the transabdominal preperitoneal (TAPP) approach. We began applying the totally extraperitoneal peritoneal (TEP) approach in 2013. Single-port TEP repair is now our standard procedure for inguinal hernia repair, and we consider it to be indicated for all cases of inguinal hernia unless the hernia has occurred during pregnancy, the patient is assigned to American Society of Anesthesiologists (ASA) class 3/4, or ascites due to liver cirrhosis is present. Provided herein is a step-by-step description of our single glove-port TEP hernia repair procedure, tips that facilitate the procedure, and a brief summary of the 102 cases in which we have performed TEP repair.

Cetuximab-mediated ADCC activity is correlated with the cell surface expression level of EGFR but not with the KRAS/BRAF mutational status in colorectal cancer.

Cetuximab, an IgG1 monoclonal antibody against the epidermal growth factor receptor (EGFR), is widely used for the treatment of metastatic colorectal cancer (mCRC). One of the mechanisms of action is considered to be antibody-dependent cell-mediated cytotoxicity (ADCC) triggered by Fcγ-R on natural killer cells. However, whether ADCC is associated with EGFR expression and/or the mutational status of EGF downstream effectors (KRAS and BRAF) in colorectal cancer (CRC) remains unclear. The aim of the present study was to verify whether ADCC activities are associated with the cell surface expression levels of EGFR and/or the mutational status of KRAS and BRAF. Five human CRC cell lines with different cell surface expression levels of EGFR and different KRAS and BRAF mutational statuses were selected to evaluate ADCC activity using peripheral blood mononuclear cells (PBMCs) from healthy human donors. Furthermore, tumor cells from resected specimens of CRC patients were used to evaluate the cell surface expression level of EGFR using immunohistochemistry and the KRAS and BRAF mutational statuses using direct sequencing, while the ADCC activity was examined using PBMCs from the same CRC patients. A strong correlation was observed between the expression levels of EGFR and the ADCC activities in the cell lines (correlation coefficient: 0.949; P=0.003). Of the 13 resected specimens, a high ADCC activity level was significantly observed in tumor cells with high expression levels of cell surface EGFR, when compared with that in the tumor cells with low expression levels (P=0.027). In both CRC cell lines and tumor cells from CRC patients, the ADCC activities were significantly associated with the cell surface expression levels of EGFR [standard partial regression coefficients: 0.911 (P=0.017) and 0.660 (P=0.018), respectively], but not with the mutational status of KRAS and BRAF [standard partial regression coefficient: -0.101 (P=0.631) and 0.160 (P=0.510), respectively]. Cetuximab-mediated ADCC activity may be correlated with the cell surface expression level of EGFR, regardless of the mutational statuses of KRAS and BRAF, in CRC.

[FOLFIRI with bevacizumab chemotherapy for a patient with recurrence of rectal cancer under haemodialysis for chronic renal failure].

As pharmacokinetics in patients undergoing haemodialysis is different from patients with normal renal function, it remains unclear whether chemotherapy can be performed safely for patients with haemodialysis as well as those who have normal renal function. Here, we report a case with recurrence of rectal cancer who received FOLFIRI with bevacizumab chemotherapy under haemodialysis, and obtained good tumor control. A 47-year-old woman had undergone haemodialysis for 10 years due to chronic renal failure. At 45 years of age, she received abdominoperineal resection due to rectal cancer (pStage II). Four months after the surgery, liver metastasis was found, for which partial resection of the liver and adjuvant chemotherapy [UFT (400 mg/body)/UZEL (75 mg/body)] were performed. Eighteen months after the liver resection, multiple lung metastases were found. Therefore, intensive chemotherapy using FOLFIRI (CPT-11: 90 mg/m2) with bevacizumab (2.5 mg/m2) was performed. Severe neutropenia (grade 3, 4), but not non-hematologic adverse events such as diarrhea and bevacizumab-specific adverse events, was observed. As she did not recover easily from neutropenia in spite of treatment with G-CSF, a dose reduction of the FOLFIRI regimen was gradually performed. Although chemotherapy was conducted approximately monthly, the tumor response reflected a stable disease 8 months after 8 courses of chemotherapy. We suggest that it is important to investigate the pharmacokinetics of toxic agents such as CPT-11, (SN38) for dose modification, and for the safe and continuous chemotherapy of patients receiving haemodialysis.