Risk Factors for Lymph Node Metastasis of Rectal Neuroendocrine Tumor and Its Prognostic Impact: A Single-Center Retrospective Analysis of 195 Cases with Radical Resection.

PURPOSE: The incidence of rectal neuroendocrine tumors (NETs) has been steadily increasing. The risk factors for and prognostic impact of lymph node (LN) metastasis were analyzed in 195 patients with stage I-III rectal NET who underwent radical surgery. METHODS: This retrospective, single-center study analyzed risk factors for LN metastasis focusing on previously identified factors and a novel risk factor: multiple rectal NETs. The association between LN metastasis and the prognosis was also analyzed. RESULTS: Pathologically, the LN metastasis rate (also the rate of stage III disease) was 39%, which was higher than the clinical LN metastasis rate of 14%. Tumor size > 10 mm, presence of central depression, tumor grade G2, depth of invasion, LN swelling on preoperative imaging (cN1), venous invasion and multiple NETs were identified as risk factors for LN metastasis. As the tumor size and risk factors increased, the rate of LN metastasis increased. Among these 7 factors, venous invasion, cN1, and multiple NETs were identified as independent predictors of LN metastasis. LN metastasis of rectal NETs was associated with significantly poor disease-free and disease-specific survival. CONCLUSIONS: As risk factors increase, the potential for rectal NETs to metastasize to the LNs increases and LN metastasis is associated with a poor prognosis. This is the first study to report multiple NETs as a risk factor for LN metastasis. A future study examining the survival benefit of radical surgery accompanying LN dissection compared with local resection is warranted.

The impact of the advanced lung cancer inflammation index on the outcomes of patients with metastatic colorectal cancer who receive chemotherapy.

BACKGROUND: Advanced lung cancer inflammation index (ALI) is reported to be a prognosticator in various cancer patients with chemotherapy. However, the clinical impact of the ALI on treatment strategies in metastatic colorectal cancer (mCRC) patients remains unclear. METHODS: A total of 356 patients, who received first-line chemotherapy for mCRC between April 2005 and November 2019 in a single institution, were retrospectively enrolled. The association of pretreatment ALI (calculated as follows: BMI × albumin value/neutrophil-to-lymphocyte ratio) status with clinicopathological factors and patient survival outcome was analyzed, using subgroup analysis. RESULTS: The ALI-low cases were significantly associated with female sex, more synchronous metastasis, multiple metastatic sites, less primary tumor resection, less liver resection after chemotherapy, and poor overall survival (OS). A multivariate Cox proportional hazards analysis clarified that the ALI-low status was independently associated with poor OS (HR: 1.78, 95% CI 1.27-2.48, P = 0.001), in addition to right side tumor, multiple metastatic sites, and the non-performance of liver resection after chemotherapy. A subgroup analysis revealed that primary tumor resection and the resection of liver metastases after chemotherapy could not improve the prognosis of ALI-low cases in comparison with ALI-high cases, and the type of first-line chemotherapy did not significantly affect the association between the prognosis and the ALI status. CONCLUSION: ALI comprehensively evaluates the prognostic host status and is a reliable prognosticator for the mCRC patients with chemotherapy. Calculating pretreatment ALI may serve as a cost-effective and easily available tool for constructing treatment strategies.

Relationship between Fusobacterium nucleatum and antitumor immunity in colorectal cancer liver metastasis.

Fusobacterium nucleatum has been detected in 8%-13% of human colorectal cancer, and shown to inhibit immune responses against primary colorectal tumors in animal models. Thus, we hypothesized that the presence of F. nucleatum might be associated with reduced T cell density in colorectal cancer liver metastases (CRLM). We quantified F. nucleatum DNA in 181 CRLM specimens using quantitative PCR assay. The densities of CD8+ T cells, CD33+ cells (marker for myeloid-derived suppressor cells [MDSCs]), and CD163+ cells (marker for tumor-associated macrophages [TAMs]) in CRLM tissue were determined by immunohistochemical staining. Fusobacterium nucleatum was detected in eight (4.4%) of 181 CRLM specimens. Compared with F. nucleatum-negative CRLM, F. nucleatum-positive CRLM showed significantly lower density of CD8+ T cells (P = .033) and higher density of MDSCs (P = .001). The association of F. nucleatum with the density of TAMs was not statistically significant (P = .70). The presence of F. nucleatum is associated with a lower density of CD8+ T cells and a higher density of MDSCs in CRLM tissue. Upon validation, our findings could provide insights to develop strategies that involve targeting microbiota and immune cells for the prevention and treatment of CRLM.

The interplay of KRAS mutational status with tumor laterality in non-metastatic colorectal cancer: An international, multi-institutional study in patients with known KRAS, BRAF, and MSI status.

BACKGROUND: Although the prognostic relevance of KRAS status in metastatic colorectal cancer (CRC) depends on tumor laterality, this relationship is largely unknown in non-metastatic CRC. METHODS: Patients who underwent resection for non-metastatic CRC between 2000 and 2018 were identified from institutional databases at six academic tertiary centers in Europe and Japan. The prognostic relevance of KRAS status in patients with right-sided (RS), left-sided (LS), and rectal cancers was assessed. RESULTS: Of the 1093 eligible patients, 378 had right-sided tumors and 715 had left-sided tumors. Among patients with RS tumors, the 5-year overall (OS) and recurrence-free survival (RFS) for patients with KRASmut versus wild-type tumors was not shown to differ significantly (82.2% vs. 83.2% and 72.1% vs. 76.7%, respectively, all p > .05). Among those with LS tumors, KRAS mutation was associated with shorter 5-year OS and RFS on both the univariable (OS: 79.4% vs. 86.1%, p = .004; RFS: 68.8% vs. 77.3%, p = .005) and multivariable analysis (OS: HR: 1.52, p = .019; RFS: HR: 1.32, p = .05). CONCLUSIONS: KRAS mutation status was independently prognostic among patients with LS tumors, but this association failed to reach statistical significance in RS and rectal tumors. These findings confirm reports in metastatic CRC and underline the possible biologic importance of tumor location.

Fibrosis-4 Index, a Noninvasive Fibrosis Marker, Predicts Survival Outcomes After Hepatectomy for Colorectal Cancer Liver Metastases.

BACKGROUND: Liver fibrosis influences liver regeneration and surgical outcomes, and several noninvasive models based on laboratory data have been developed to predict liver fibrosis. This study was performed to determine whether the Fibrosis-4 (FIB-4) index, a noninvasive fibrosis marker, can predict the prognosis in patients with colorectal liver metastases (CRLM) undergoing hepatectomy. METHODS: This retrospective study involved 193 consecutive patients with CRLM who underwent hepatectomy. The FIB-4 index was calculated by laboratory data and age before hepatectomy and before preoperative chemotherapy. The FIB-4 cut-off was determined using survival classification and regression tree analysis. Patients were divided into two groups (high and low FIB-4 index), and post-hepatectomy overall survival (OS) and recurrence-free survival (RFS) were investigated. RESULTS: In total, 193 patients were evaluated. Chemotherapy before hepatectomy was performed in 105 (54.4%) patients. A high FIB-4 index (> 2.736) was found in 39 (20.2%) patients. OS was significantly shorter in patients with a high FIB-4 index than those with a low FIB-4 index in the univariate (45.9 vs. 74.4 months, log-rank p = 0.007) and multivariate analysis (hazard ratio 2.28, 95% confidence interval 1.39-3.74; p = 0.001). Among patients who received chemotherapy before hepatectomy, those with a high FIB-4 index had significantly shorter RFS (6.9 vs. 45.3 months, log-rank p = 0.047) and OS (23.9 vs. 55.0 months, log-rank p = 0.003) than those with a low FIB-4 index. This association was also confirmed by multivariate analysis (hazard ratio 4.28, 95% confidence interval 1.46-12.6; p = 0.008). CONCLUSION: Both the preoperative and prechemotherapy FIB-4 index can predict long-term outcomes after hepatectomy in patients with CRLM.

Postoperative complications are associated with poor survival outcome after curative resection for colorectal cancer: A propensity-score analysis.

OBJECTIVE: We retrospectively evaluated the impact of postoperative complications on long-term outcomes after curative resection for colorectal cancer (CRC), using propensity-score analysis (PSA). PATIENTS AND METHODS: We reviewed data from 673 consecutive patients with stage I to III CRC, who underwent curative resections between 2005 and 2017. Patients were divided into the complication group (Clavien-Dindo [CD] grade ≥ 3) and the control group (others). We performed PSA to obtain unbiased estimates of the effects of the oncological background on each outcome. RESULTS: We matched for sex, age, American Society of Anesthesiologists grade, location (right colon/left colon/rectum), histology (tub1/tub2/por), pathological tumor depth, and lymph node metastases. Eighty-five patients (12.6%) developed postoperative complications with CD grade ≥ 3. After PSA, 81 patients were included in each group. The complication group showed significantly worse relapse-free survival (RFS) than the control group (5-year RFS rate: 62% vs 77%; P = .047). In multivariate analysis with inverse probability of treatment weights, the complication group had a higher risk of relapse or death than the control group (hazard ratio: 2.08, 95% confidence interval:1.3-3.3; P = .018). CONCLUSIONS: Postoperative complications (CD grade ≥ 3) could cause poor long-term outcomes in patients with stage I to III CRC; their presence requires appropriate adjuvant chemotherapy and follow-up.

Prognostic significance of serum p53 antibody according to KRAS status in metastatic colorectal cancer patients.

BACKGROUND: Serum anti-p53 antibody is used clinically as a tumor marker of colorectal cancer. However, its prognostic significance in patients with metastatic colorectal cancer (mCRC) remains unclear. KRAS status may influence the host immune response against tumor progression. In the present study, we investigated the prognostic significance of serum anti-p53 in mCRC patients with wild-type KRAS and mutant KRAS treated with systemic chemotherapy. METHODS: A retrospective study of 150 mCRC patients in whom serum anti-p53 antibody was measured before first-line chemotherapy was conducted. The patients were divided into two groups, high p53 and low p53, based on their serum anti-p53 antibody levels. Associations between serum anti-p53 level and clinical outcomes were evaluated in conjunction with KRAS status. RESULTS: There were 97 (64.7%) patients with wild-type KRAS and 53 (35.3%) with mutant KRAS. In an analysis of all patients, there was no significant difference in overall survival (OS) between the high p53 and low p53 groups. In patients with mutant KRAS, those in the high p53 group exhibited significantly longer OS than those in the low p53 group (p = 0.017, log-rank test). In the multivariate analysis, serum p53 antibody level was an independent predictor of OS in mCRC patients (high vs. normal; hazard ratio 0.438, 95% confidence interval 0.178-0.974, p < 0.05). CONCLUSIONS: Serum anti-p53 antibody level may be an independent predictor of OS in mCRC patients with KRAS mutant tumors.

Long-term outcomes of colorectal cancer surgery for elderly patients: a propensity score-matched analysis.

PURPOSE: To investigate the effect of old age on the perioperative, short-term, and long-term surgical outcomes of elderly patients undergoing curative surgery for colorectal cancer (CRC). METHODS: The subjects of this retrospective study were 526 patients who underwent curative resections for stage I-III CRC between March 2005 and March 2016. We divided the patients into a young group (< 75 years old, n = 361) and an elderly group (≥ 75 years old, n = 165) and compared the clinicopathological factors and prognoses of the two groups. We performed a propensity score-matched (PSM) analysis with inverse probability of treatment weighting (IPTW) to avoid confounding bias. RESULTS: The elderly group had more right-sided tumors and more comorbidities than the young group. After PSM, there were 148 patients in each group. Although the elderly group had significantly shorter overall survival than the young group, the two groups did not differ significantly in cancer-specific survival (CSS; P = 0.136) or recurrence rate (RR; P = 0.317). Multivariate analysis with IPTW also revealed no significant difference in CSS (P = 0.171) or RR (P = 0.284) between the young and elderly groups. Our findings were limited by the study's retrospective single-institute conditions, and the inclusion of only patients who underwent radical resections. CONCLUSION: Primary tumor resection is appropriate for elderly patients with CRC.

Naples Prognostic Score Is a Useful Prognostic Marker in Patients With Metastatic Colorectal Cancer.

BACKGROUND: Systemic inflammation may influence the response to systemic chemotherapy or the prognosis in patients with various cancers. The Naples prognostic score, based on inflammatory and nutritional statuses, is a useful prognostic marker in patients undergoing surgery for colorectal cancer; however, its significance in patients with metastatic colorectal cancer remains unclear. OBJECTIVE: We aimed to evaluate the prognostic significance of the Naples prognostic factor in patients with metastatic colorectal cancer receiving first-line chemotherapy and to compare its prognostic accuracy with the neutrophil:lymphocyte ratio, platelet:lymphocyte ratio, and the systemic immune-inflammatory index. DESIGN: This was a retrospective study of prospectively collected data. SETTINGS: This study was conducted at a university hospital. PATIENTS: A total of 259 patients received first-line systemic chemotherapy for metastatic colorectal cancer. MAIN OUTCOME MEASURES: The Naples prognostic score was calculated by a composite score of albumin and cholesterol concentrations, lymphocyte:monocyte ratio, and neutrophil:lymphocyte ratio. The patients were divided into 3 groups based on increasing Naples scores (groups 0-2), and the associations of the Naples prognostic score with clinicopathologic features and overall survival were evaluated. RESULTS: Higher Naples prognostic score was positively associated with right-sided primary tumors and synchronous metastases and negatively with primary tumor resection. Patients in group 2 (high Naples prognostic score) had significantly shorter overall survival than those in groups 0 and 1 (p = 0.012 and 0.022). Multivariate Cox regression analysis identified the Naples prognostic score as an independent prognostic factor for overall survival (HR = 1.574; p = 0.004). Time-dependent receiver operating characteristic curve analysis showed that Naples prognostic score was more sensitive than other prognostic factors for predicting overall survival. LIMITATIONS: The main limitations are the sample size, single institutional feature, and treatment heterogeneity. CONCLUSIONS: The Naples prognostic score may be a useful prognostic marker in patients with metastatic colorectal cancer receiving systemic chemotherapy. See Video Abstract at http://links.lww.com/DCR/B72. LA PUNTUACIÓN PRONÓSTICA DE NÁPOLES ES UN MARCADOR PRONÓSTICO ÚTIL EN PACIENTES CON CÁNCER COLORRECTAL METASTÁSICO: La inflamación sistémica puede influir en la respuesta a la quimioterapia sistémica o el pronóstico en pacientes con varios tipos de cáncer. La puntuación pronóstica de Nápoles, basada en estados inflamatorios y nutricionales, es un marcador pronóstico útil en pacientes sometidos a cirugía por cáncer colorrectal; sin embargo, su importancia en pacientes con cáncer colorrectal metastásico sigue siendo incierta.El objetivo fue evaluar la importancia pronóstica del factor pronóstico de Nápoles en pacientes con cáncer colorrectal metastásico que reciben quimioterapia de primera línea y comparar su precisión pronóstica con la relación neutrófilos: linfocitos, plaquetas: linfocitos y el índice sistémico inmune-inflamatorio.Este estudio se realizó en un hospital universitario.Este fue un estudio retrospectivo de datos recolectados prospectivamente.Un total de 259 pacientes recibieron quimioterapia sistémica de primera línea para el cáncer colorrectal metastásico.La puntuación pronóstica de Nápoles se calculó mediante una puntuación compuesta de concentraciones de albúmina y colesterol, proporción de linfocitos: monocitos y proporción de neutrófilos: linfocitos. Los pacientes se dividieron en tres grupos basados en el aumento de las puntuaciones de Nápoles (grupos 0-2, respectivamente) y se evaluaron las asociaciones de la puntuación pronóstica de Nápoles con las características clínico-patológicas y la supervivencia general.La puntuación pronóstica de Nápoles es más alta se asoció positivamente con los tumores primarios del lado derecho y metástasis sincrónicas, y negativamente con la resección del tumor primario. Los pacientes del grupo 2 (alto puntaje pronóstico de Nápoles) tuvieron una supervivencia general significativamente menor que los de los grupos 0 y 1 (p = 0.012 y 0.022, respectivamente). El análisis de regresión de Cox multivariado identificó la puntuación pronóstica de Nápoles como un factor pronóstico independiente para la supervivencia global (índice de riesgo = 1.574; p = 0.004). El análisis de la curva característica de funcionamiento del receptor dependiente del tiempo mostró que la puntuación pronóstica de Nápoles era más sensible que otros factores pronósticos para predecir la supervivencia global.Las principales limitaciones son el tamaño de la muestra, la característica institucional única y la heterogeneidad del tratamiento.La puntuación pronóstica de Nápoles puede ser un marcador pronóstico útil en pacientes con cáncer colorrectal metastásico que reciben quimioterapia sistémica. Vea el Abstract del video en http://links.lww.com/DCR/B72.

Extracellular water to total body water ratio, a novel predictor of recurrence in patients with colorectal cancer.

Background: Total body water (TBW) fraction, which accounts for 60% of body weight, is an important indicator of body composition, and the extracellular water to TBW ratio (ECW/TBW) is reportedly useful in predicting clinical outcomes of patients with organ disorders. We aimed to clarify the clinical impact of preoperative ECW/TBW status on survival outcomes in cancer patients. Methods: We used a database of 320 colorectal cancer (CRC) patients who underwent potentially curative resections. Preoperative ECW/TBW was measured using a bioelectrical impedance analysis (BIA), and its correlation with patient survival outcomes, clinicopathological factors, laboratory data, and comorbidities were analyzed. Results: A high preoperative ECW/TBW was significantly associated with poorer relapse-free survival (RFS; p = 0.001) and overall survival (OS; p = 0.003). A high ECW/TBW ratio was significantly associated with older age (p < 0.001), low BMI (p = 0.009), and right-sided tumors (p = 0.03). In a multivariate analysis, a high ECW/TBW significantly predicted a higher RFS mortality (HR: 2.07, 95% CI: 1.10-3.88, p = 0.024) and OS mortality (HR: 3.23, 95% CI: 1.25-8.36, p = 0.016). Furthermore, a high ECW/TBW was significantly associated with lower hemoglobin (p < 0.001) and albumin levels (p < 0.001), but not comorbidities. Conclusions: A high preoperative ECW/TBW was a predictive factor for recurrence and poorer overall survival independent of the tumor, node, and metastasis (TNM) stage. Our data suggest that preoperative evaluation of ECW/TBW using BIA might serve as a novel tool for developing CRC treatment strategies.

Activin A promotes cell proliferation, invasion and migration and predicts poor prognosis in patients with colorectal cancer.

Activin A is a member of the transforming growth factor­ß superfamily of cytokines and displays various pathophysiological activities, including regulation of muscle catabolism and atrophy. Activin A expression is upregulated in several human cancer types and in certain pathologies, its expression is associated with poor prognosis. In the present study, activin A expression was assessed in colorectal cancer (CRC) tissue specimens from 157 patients with primary CRC and the relationship between activin A levels and clinicopathological characteristics, including skeletal muscle mass, and prognosis, was determined. Furthermore, the effects of knockdown of endogenous or exposure to exogenous activin A on the malignant behavior of human CRC cell lines were investigated in vitro. The results indicated that activin A mRNA was significantly upregulated in CRC tumor tissues compared with normal intestinal epithelium. High activin A expression was significantly associated with shorter cancer­specific survival (P=0.047) and overall survival (P=0.014). According to a multivariate analysis, tumor activin A levels were an independent prognostic factor for overall survival (P=0.001). However, activin A mRNA levels were not associated with the skeletal muscle index. The in vitro experiments demonstrated that exposure to exogenous activin A increased the proliferation, invasion and migration of CRC cell lines, whereas knockdown of endogenous activin A had the opposite effects. In conclusion, activin A is an autocrine and paracrine regulator of CRC cell proliferation and high tumor expression of activin A is associated with poor prognosis in patients with CRC.

The advanced lung cancer inflammation index is a novel independent prognosticator in colorectal cancer patients after curative resection.

BACKGROUND: The advanced lung cancer inflammation index (ALI), which comprehensively evaluates the patient body composition and inflammation/nutritional status, is reportedly associated with the patient outcome in lung cancer. However, the clinical significance in colorectal cancer (CRC) patients after curative resection remains unclear. METHODS: A total of 813 CRC patients after curative resection between April 2005 and June 2019 in a single institution were retrospectively enrolled. The association of the preoperative ALI (calculated as follows: body mass index × albumin value/neutrophil-to-lymphocyte ratio) with clinicopathological factors, postoperative complications, and survival was analyzed. RESULTS: A low ALI was significantly associated with male gender, older age, a higher depth of tumor invasion, progressed TNM stage, and preoperative carcinoembryonic antigen (CEA) positivity. Both postoperative complications and severe complications occurred more frequently in the ALI-low group than in the ALI-high group (P < .001 and P < .001, respectively), especially postoperative complications in stage III patients (P < .001) and severe complications in stages II and III patients (P = .024 and P = .004, respectively). In addition, a low ALI was an independent predictor of a poor overall survival (hazard ratio: 2.30, 95% confidence interval: 1.52-3.50, P < .001) and relapse-free survival (hazard ratio: 1.73, 95% confidence interval: 1.22-2.44, P = .002), especially in older patients, and in patients without lymph node metastasis or severe postoperative complications. CONCLUSION: This study suggests that preoperative ALI may serve as a novel independent predictive index for severe postoperative complications and recurrence in CRC patients after curative resection.

Preoperative skeletal muscle status is associated with tumor-infiltrating lymphocytes and prognosis in patients with colorectal cancer.

Background: Sarcopenia is associated with poor prognosis in patients with colorectal cancer (CRC), but the mechanisms contributing to this association remain unclear. We hypothesized that skeletal muscle status is associated with tumor-infiltrating lymphocytes (TILs) in patients with CRC. Therefore, this study investigated the clinical effect of sarcopenia and its relationship with the local immune system in CRC patients. Methods: A total of 256 consecutive patients with CRC who underwent curative resection between 2008 and 2014 were enrolled. Sarcopenia was determined according to the skeletal muscle index (SMI), which was assessed using L3 skeletal muscle mass on axial computed tomography images, and its relationship with patient clinicopathological characteristics and survival was evaluated. Additionally, TILs (CD3+, CD8+, CD4+, and FOXP3+ T cells) were assayed by immunohistochemistry. The relationship between TILs and skeletal muscle status was evaluated. Results: Patients with a lower SMI showed significantly shorter recurrence-free and overall survival compared with those with a higher SMI. Low expression of TILs was associated with significantly shorter recurrence-free survival. SMI was significantly correlated with the number of CD3+ and CD8+ cells in the ordinal logistic regression analysis. Patients with low skeletal muscle status and low CD3+ and CD8+ cells had an unfavorable prognosis compared with patients with high skeletal muscle status and high CD3+ and CD8+ cells. Conclusion: Our data showed an association between skeletal muscle status and local immune cells, and this association may play a pivotal role in the clinical outcome of patients with CRC.

Preoperative transferrin level is a novel prognostic marker for colorectal cancer.

AIM: This study investigated whether preoperative serum transferrin, a rapid-turnover protein, was associated with prognosis after colorectal cancer (CRC) resection. METHODS: We evaluated preoperative transferrin, which was calculated as iron and unsaturated iron-binding capacity, in 501 patients who underwent surgery for Stage I-III CRC. Transferrin level was directly proportional to total iron-binding capacity (TIBC), and TIBC < 250 µg/dl was defined as low transferrin. The associations between transferrin and prognosis were evaluated in univariate and multivariate Cox proportional hazards analyses. RESULTS: Fifty-eight of 501 patients (11.5%) had low transferrin. In these patients, low transferrin was significantly associated with high age, female gender, low body mass index (<18.5), high white blood cell count, low total protein, low albumin, high C-reactive protein, low hemoglobin, and low neutrophil/lymphocyte ratio. In the univariate analysis, low transferrin was associated with shorter relapse-free survival (RFS) (hazard ratio [HR] 2.180, 95% confidence interval [CI] 1.417-3.354, P < .001), overall survival (OS) (HR 2.930, 95% CI 1.784-4.811, P < .001), and cancer-specific survival (CSS) (HR 2.122, 95% CI 1.053-4.275, P = .035). In multivariate analysis, high age (P < .001), Glasgow Prognostic Score (P = .009), and low transferrin (HR 2.336, 95% CI 1.173-4.654, P = .011) were independently associated with shorter OS, and depth of invasion pT4 (P = .015), presence of lymph node metastasis (P = .001), low hemoglobin (P = .034), and low transferrin (HR 2.638, 95% CI 1.113-5.043, P = .025) were independently associated with shorter CSS. CONCLUSIONS: Preoperative serum transferrin in Stage I-III CRC patients was identified as a novel prognostic marker by univariate and multivariate analyses.

Time trial of dry box laparoscopic surgical training improves laparoscopic surgical skills and surgical outcomes.

INTRODUCTION: The present study assessed the utility of a dry box time trial during laparoscopic surgical training to improve laparoscopic surgical skills and surgical outcomes. METHODS: In a monthly time trial, surgeon trainees twice completed a set task that involved grasping a suture, aligning a needle with a needle holder, passing the suture, making three knots, and cutting the two tails of the suture. The mean suturing time was then analyzed. To assess the utility of this time trial, we analyzed the short-term outcomes of patients with stage I to III colon cancer who had undergone laparoscopic colectomy before and after the introduction of the time trial. RESULTS: The monthly time trial was introduced in October 2018, and 52 surgeon trainees participated in the trials examined in this study. Within 6 months of the program's introduction, the mean suturing time had significantly declined to less than 70% of the time trial, while the standard deviations had declined to less than 30%. In comparisons of the short-term outcomes of laparoscopic colon cancer surgery before (n = 49) and after (n = 46) the introduction of the time trial, the operative time tended to decline (P = .074) after the introduction of the time trial, and blood loss was significantly reduced (P = .018). The rate of postoperative complications was similar before and after the introduction. CONCLUSION: Regular time trials of laparoscopic surgical suture training using a dry box can be useful for improving laparoscopic surgical skills and surgical outcomes. Moreover, time trials can keep trainees motivated.

Preoperative C-reactive protein-to-albumin ratio and clinical outcomes after resection of colorectal liver metastases.

PURPOSE: Accumulating evidence suggests that the inflammatory tumor microenvironment can potentiate tumor progression and metastasis. The C-reactive protein-to-albumin ratio (CAR) is a novel inflammation-based prognostic score. This study was performed to examine the associations of the preoperative CAR with clinical outcomes in patients with colorectal liver metastases (CRLM) after curative resection. METHODS: We retrospectively assessed the preoperative CAR in 184 patients who underwent curative resection for CRLM from November 2001 to January 2018 at Kumamoto University (Kumamoto, Japan). The optimal cutoff level of the preoperative CAR was determined by survival classification and regression tree (CART) analysis. We compared clinicopathological factors and prognoses between the high-CAR and low-CAR groups. A Cox proportional hazards model was used to calculate hazard ratios (HRs), controlling for potential confounders. RESULTS: A higher preoperative CAR was associated with worse overall survival (OS) (p < 0.0001) and recurrence-free survival (RFS) (p = 0.003). Applying survival CART analysis, the high-CAR group comprised 33 patients (17.9%). In the multivariate analyses, a high CAR was independently associated with shorter OS (HR, 2.82; 95% confidence interval, 1.63-4.72; p = 0.0004) and RFS (HR, 1.62; 95% confidence interval, 1.02-2.49; p = 0.040). A high CAR was associated with a large tumor size, high serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels, high intraoperative blood loss, and more postoperative complications. CONCLUSION: A high preoperative CAR is associated with shorter OS and RFS and might serve as a prognostic marker for patients with CRLM after curative resection.

Controlling Nutritional Status (CONUT) Score Is a Prognostic Marker in Metastatic Colorectal Cancer Patients Receiving First-line Chemotherapy.

BACKGROUND/AIM: The Controlling Nutritional Status (CONUT) score is a useful nutritional evaluation, that is calculated from serum albumin, total cholesterol concentrations, and total lymphocyte count. This study aimed to investigate the association between the CONUT score and prognosis in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: The CONUT score was retrospectively calculated in 211 patients with mCRC receiving first-line chemotherapy. The patients were divided into three groups: the CONUT low-group (0-1), intermediate-group (2-4), and high-group (5-). The associations of the CONUT score with clinicopathological factors and survival outcomes were evaluated. RESULTS: The higher CONUT score was significantly associated with synchronous metastases, and no primary tumor resection. The higher CONUT score group showed a significant shorter progression-free survival (log-rank p<0.05) and overall survival (log-rank p<0.001). CONCLUSION: The CONUT score is a useful prognostic marker for predicting survival outcomes of patients with mCRC.

Hand-assisted laparoscopic spleen-preserving distal pancreatectomy combined with laparoscopic distal gastrectomy for the treatment of pancreatic neuroendocrine tumor with early gastric cancer: Report of a case.

INTRODUCTION: In a distal pancreatectomy combined with a distal gastrectomy, the splenic artery and vein must be conserved. However, it is not easy in pure laparoscopic surgery. We performed a hand-assisted laparoscopic spleen-preserving distal pancreatectomy (HALS-SPDP) combined with a laparoscopic distal gastrectomy (LDG) for the treatment of a pancreatic neuroendocrine tumor (NET) with early gastric cancer. PRESENTATION OF CASE: A 67-year-old male was hospitalized with no complaint. He was diagnosed with a pancreatic tail tumor (1.5cm in diameter) and early gastric cancer. He had undergone an endoscopic submucosal dissection (ESD). The pathohistology of the dissected tissue demonstrated that the histology was moderately differentiated adenocarcinoma, and the depth of the gastric cancer was pT1b2 (submucosal layer ∼1000µm). First, a pancreatectomy was performed extracorporeally under direct vision after detaching the spleen and the distal pancreas from the retroperitoneum under a hand-assisted laparoscopy. After the distal pancreatectomy, an LDG with a D1 lymphadenectomy was performed intracorporeally. The postoperative course was not eventful. Six months after surgery, an enhanced computed tomography (CT) scan revealed the patency of the splenic artery. CONCLUSION: An HALS-SPDP combined with an LDG is beneficial and safe for the patients who have a pancreatic benign or low-grade malignant tumor and gastric cancer.