Estimation of the physiologic ability and surgical stress scoring system as a useful predictor of postoperative recurrence in patients with stage II colorectal cancer: a multicenter study.

PURPOSE: We determined the usefulness of the estimation of physiologic ability and surgical stress (E-PASS), initially reported as a predictive factor for postoperative morbidity and mortality, as a prognostic indicator in stage II colorectal cancer (CRC). METHODS: Overall, 739 patients who underwent proctocolectomy for CRC at Tottori University Hospital and affiliated hospitals and histologically diagnosed with stage II CRC were included in the current study. RESULTS: A receiver operating characteristic (ROC) analysis of the five-year recurrence-free survival indicated that the comprehensive risk score (CRS) of E-PASS predicted postoperative recurrence. A multivariate analysis revealed that the presence of preoperative perforation, T4, v ≥ 2, and CRSHigh (≥ 0.2267) were independent predictors of postoperative recurrence. Patients were assigned a score using these factors, as follows: the presence of perforation = 1, the absence of preoperative perforation = 0, T4 = 1, T3 = 0, v2/3 = 1, v0/1 = 0, CRSHigh = 1, and CRSLow = 0 (total score: 0-4). Accordingly, the respective 5-year relapse-free survival rates were 91.0%, 83.6%, 70.3%, and 52.0% among those with scores of 0, 1, 2, and both 3 and 4 (P < 0.001). CONCLUSIONS: The CRS predicts postoperative recurrence in patients with stage II CRC.

Risk factors for recurrence in elderly patients with stage II colorectal cancer: a multicenter retrospective study.

BACKGROUND: Adjuvant chemotherapy for stage II colorectal cancer (CRC) is considered appropriate for patients with risk factors for recurrence, rather than for all patients uniformly. However, the risk factors for recurrence remain controversial, and there is limited information, especially for elderly patients. The Geriatric Nutritional Risk Index (GNRI) is widely used as a simple nutritional screening tool in the elderly and is associated with cancer prognosis and recurrence. This study aimed to investigate the risk factors for recurrence in the elderly with stage II CRC, focusing on the GNRI. METHODS: We enrolled 348 elderly patients (≥ 75 years) with stage II CRC who underwent curative resection at the Department of Surgery, Tottori University and our 10 affiliated institutions. The patients were divided into GNRIhigh (≥ 93.465) and GNRIlow (< 93.465) groups. RESULTS: The GNRIlow group showed a significantly worse overall survival (OS), cancer-specific survival (CSS), and relapse-free survival (RFS) (P < 0.001, P < 0.001, and P < 0.001, respectively). In a multivariate analysis, GNRIlow (hazard ratio [HR]: 2.244, P < 0.001), pathologic T4 stage (HR: 1.658, P = 0.014), and moderate to severe lymphatic or venous invasion (HR: 1.460, P = 0.033) were independent factors affecting RFS. By using these three factors to score the risk of recurrence from 0 to 3 points, the prognosis was significantly stratified in terms of OS, CSS, and RFS (P < 0.001, P < 0.001, and P < 0.001, respectively). The recurrence rate for each score was as follows: 0 points, 9.8%; 1 point, 22.0%; 2 points, 37.3%; and 3 points, 61.9%. CONCLUSIONS: GNRIlow, pathologic T4 stage, and moderate to severe lymphatic or venous invasion are high-risk factors for recurrence in the elderly with stage II CRC. The scoring system using these three factors appropriately predicted their recurrence and outcome.

Circular stapling anastomosis with indocyanine green fluorescence imaging for cervical esophagogastric anastomosis after thoracoscopic esophagectomy: a propensity score-matched analysis.

BACKGROUND: Thoracoscopic esophagectomy has been extensively used worldwide as a curative surgery for patients with esophageal cancer; however, complications such as anastomotic leakage and stenosis remain a major concern. Therefore, the objective of this study was to evaluate the efficacy of circular stapling anastomosis with indocyanine green (ICG) fluorescence imaging, which was standardized for cervical esophagogastric anastomosis after thoracoscopic esophagectomy. METHODS: Altogether, 121 patients with esophageal cancer who underwent thoracoscopic esophagectomy with radical lymph node dissection and cervical esophagogastric anastomosis from November 2009 to December 2020 at Tottori University Hospital were enrolled in this study. Patients who underwent surgery before the anastomotic method was standardized were included in the classical group (n = 82) and patients who underwent surgery after the anastomotic method was standardized were included in the ICG circular group (n = 39). The short-term postoperative outcomes, including anastomotic complications, were compared between the two groups using propensity-matched analysis and the risk factors for anastomotic leakage were evaluated using logistic regression analyses. RESULTS: Of the 121 patients, 33 were included in each group after propensity score matching. The clinicopathological characteristics of patients did not differ between the two groups after propensity score matching. In terms of perioperative outcomes, a significantly higher proportion of patients who underwent surgery using the laparoscopic approach (P < 0.001) and narrow gastric tube (P = 0.003), as well as those who had a lower volume of blood loss (P = 0.009) in the ICG circular group were observed after matching. Moreover, the ICG circular group had a significantly lower incidence of anastomotic leakage (39% vs. 9%, P = 0.004) and anastomotic stenosis (46% vs. 21%, P = 0.037) and a shorter postoperative hospital stay (30 vs. 20 days, P < 0.001) than the classical group. According to the multivariate analysis, the anastomotic method was an independent risk factor for anastomotic leakage after thoracoscopic esophagectomy (P = 0.013). CONCLUSIONS: Circular stapling anastomosis with ICG fluorescence imaging is effective in reducing complications such as anastomotic leakage and stenosis.

Estimation of Physiological Ability and Surgical Stress Score Is a Useful Prognostic Indicator for Elderly Patients with Colorectal Cancer.

BACKGROUND: The incidence of colorectal cancer (CRC) among the elderly has been increasing. Therefore, determining postoperative prognosis factors in elderly CRC patients has clinical importance. This study retrospectively investigated the prognostic significance of the estimation of physiological ability and surgical stress (E-PASS) in elderly CRC patients. METHODS: This study enrolled 166 elderly patients aged 75 or more with a histopathological diagnosis of colorectal adenocarcinoma who underwent curative surgery. RESULTS: According to the results of receiver operating characteristic analysis, the patients were divided into the following 2 groups based on the comprehensive risk score (CRS): CRS of ≥0.05 (CRSHigh) and CRS of < 0.05 (CRSLow). The 5-year overall survival rates of CRSHigh group and CRSLow group were 51.1 and 89.6%, respectively, and the difference was statistically significant (p < 0.001). Furthermore, 5-year disease-specific survival rates of CRSHigh group and CRSLow group were 81.4 and 96.3%, respectively, and the difference was statistically significant (p = 0.017). Also, multivariate analysis indicated that CRS was an independent prognostic indicator in elderly CRC patients. With regard to the cause of death, both recurrence and cancer-unrelated deaths were observed significantly more in the CRSHigh group than in the CRSLow group. CONCLUSIONS: E-PASS was a useful prognostic indicator in elderly CRC patients.

Disinfection with single or double usage of new antiseptic olanexidine gluconate in general surgery: a randomized study.

PURPOSE: Olanexidine gluconate is a newly developed solution for skin disinfection that was recently approved in Japan. We aimed to compare single and double application of the solution in preventing surgical site infection (SSI) in patients undergoing general surgery. METHODS: This randomized study was conducted at the Tottori University Hospital. Patients scheduled to undergo gastrointestinal or hernia surgery were randomly assigned to one of two groups using either one or two Olanedine applicators for skin disinfection. The primary endpoint was the difference in SSI incidence between the two groups. The secondary endpoint was all adverse events related to olanexidine gluconate. RESULTS: A total of 393 patients qualified for the study protocol: 193 received a single application, and 200 received a double application of Olanedine. SSI occurred in 10 patients (2.5%) overall; nine were superficial incisional SSIs, and one patient had a deep incisional SSI. Of the 10 patients who developed SSI, six (3.1%) were in the group receiving a single application, and four (2.0%) were in the group receiving a double application; there was no statistically significant difference between the two groups (P = 0.537). Allergic reactions or skin disorders related to olanexidine gluconate were not observed. CONCLUSION: There was no difference in the SSI incidence between the use of one or two Olanedine applicators for skin preparation in elective general surgery. Therefore, a single application of Olanedine is sufficient and is recommended for general surgery as a standard disinfection precaution. TRIAL REGISTRATION NUMBER: UMIN000027319; 5/12/2017.

[A Case of Solitary Metastasis to the Small Intestine with Lymph Node Metastasis after Surgery in Rectal Cancer].

The patient was a 63-year-old man. He underwent laparoscopic anterior resection of a rectal cancer when he was 60 years. The tumor was diagnosed as T3N0M0, Stage Ⅱ, and he was followed up without adjuvant chemotherapy. Two years and 9 months after surgery, anemia and increased levels of tumor markers were observed. CT scan revealed a mass in the mesentery. We suspected rectal cancer recurrence and performed partial resection of the jejunum with regional lymph node dissection. As the tumor appearance and histological findings were similar to those of the previous rectal cancer, the tumor was diagnosed as hematogenous metastasis of rectal cancer with lymph nodes metastasis. The hematogenous metastasis of rectal cancer to the small intestine is rare; however, it may cause metastasis to regional lymph nodes. Therefore, lymph node dissection may be necessaryin surgical interventions for metastatic tumors of the small intestine.

Combined Pre- and Postoperative Lymphocyte Count Accurately Predicts Outcomes of Patients with Colorectal Cancer.

BACKGROUND: Although preoperative lymphopenia is reportedly a prognostic factor in cancer patients, the association between postoperative lymphopenia and patient prognosis has not been widely studied. METHODS: We enrolled 379 patients who underwent surgery for colorectal cancer (CRC) to analyze correlations among pre- and postoperative lymphocyte counts (LCs) and prognosis in patients with CRC. RESULTS: Pre- and postoperative LCs were significantly correlated (r = 0.615, p < 0.0001). Based on results of receiver operating characteristic analysis, patients were subgrouped as preoperative LC ≥1,280 (pre-LCHigh, n = 234), preoperative LC < 1,280 (pre-LCLow, n = 145); and as postoperative LC ≥680 (post-LCHigh, n = 246), and postoperative LC < 680 (post-LCLow, n = 133). Five-year disease-specific survival rates significantly differed between pre-LCHigh (88.6%) and pre-LCLow (72.5%) groups (p < 0.0001); and also between the post-LCHigh (88.5%) and post-LCLow (71.1%) groups (p < 0.0001). Five-year disease-specific survival rates of patients who were both pre-LCLow and post-LCLow was significantly lower than those for patients who were either pre-LCHigh or post-LCHigh or pre-LCHigh/post-LCHigh (p = 0.0003). Multivariate analysis indicated that the combination of pre- and postoperative LC was an independent prognostic indicator. CONCLUSIONS: The combination of pre- and postoperative LC is a predictive factor for prognosis in CRC patients.

A prognostic index for colorectal cancer based on preoperative absolute lymphocyte, monocyte, and neutrophil counts.

PURPOSE: Associations between the preoperative absolute neutrophil count (NC), lymphocyte count (LC), and monocyte count (MC) in the peripheral blood and the prognosis of colorectal cancer (CRC) patients have not been widely studied. METHODS: We enrolled 361 patients who underwent surgery for CRC between January 2007 and December 2013 to analyze correlations among the LC, MC, and NC and prognosis. RESULTS: Based on cut-off values determined by a receiver operating characteristic analysis, patients were subgrouped as LymphHigh or LymphLow (cut-off: LC = 1460 cells/µL); as MonoHigh or MonoLow (cut-off: MC = 421 cells/µL); and as NeutHigh or NeutLow (cut-off: NC = 3247 cells/µL). Patients were then given lymphocyte-monocyte-neutrophil (LMN) scores by adding the points of their different subgroups (1 point each for LymphLow, MonoHigh and NeutHigh; 0 points for LymphHigh, MonoLow and NeutLow). The 5-year overall survival rates significantly differed by the LMN score (0: 89.7%, 1: 80.6%, 2: 68.8%, and 3: 57.4%; P < 0.0001). In the multivariate analysis, the LMN score was found to be an independent prognostic indicator. CONCLUSIONS: The combination of the preoperative absolute number of lymphocytes, monocytes, and neutrophils is a useful prognostic indicator in CRC patients.

Prognostic value of the combination of pre- and postoperative C-reactive protein in colorectal cancer patients.

PURPOSE: Inflammation is closely related to cancer development and progression. This retrospective study investigated the prognostic value of the combination of pre- and postoperative C-reactive protein (CRP) levels in patients with colorectal cancer (CRC). METHODS: The subjects of this study were 406 patients who underwent surgery for CRC. RESULTS: Based on receiver-operating characteristic analysis, patients were divided into the following groups: those with a preoperative CRP of ≥ 0.5 mg/dL (pre-CRPHigh), those with a preoperative CRP of < 0.5 mg/dL (pre-CRPLow), those with a postoperative CRP of ≥ 17.0 mg/dL (post-CRPHigh), and those with a postoperative CRP of < 17.0 mg/dL (post-CRPLow). They were then allocated to one of the following three groups: Group A, comprised of those in the pre-CRPHigh and post-CRPHigh groups; Group B, comprised of those in either the pre-CRPHigh and post-CRPLow or pre-CRPLow and post-CRPHigh groups; and Group C, comprised of those in the pre-CRPLow and post-CRPLow groups. The disease-specific 5-year survival rates were 53.8%, 72.8%, and 87.2% in Groups A, B, and C, respectively, and these differences were significant. Finally, multivariate analysis revealed that the combination of pre- and postoperative CRP levels was an independent prognostic indicator. CONCLUSIONS: The combination of pre- and postoperative CRP was predictive of the prognosis of CRC patients.

The attenuation value of preoperative computed tomography as a novel predictor for pancreatic fistula after pancreaticoduodenectomy.

PURPOSE: Pancreatic fistula (PF) is the most serious complication following pancreaticoduodenectomy (PD). This study was performed to identify new clinical factors that may predict the development of PF after PD to improve perioperative management. METHODS: Seventy-five consecutive patients who underwent PD from 2012 to 2015 were evaluated. The patients' perioperative data including the computed tomography (CT) parameters were collected. The minimum, maximum, and mean CT attenuation values (HUmin, HUmax, and HUmean, respectively) were extracted from the pancreatic parenchyma (≥ 100 pixels), and the standard deviation of these values (HUSD) was determined from the slice in which the superior mesenteric and splenic veins were merged. PF was defined as grade B or C according to the International Study Group for Pancreatic Fistula criteria. RESULTS: The PF occurrence rate (grade B or C) was 25.3% in 75 patients. A multivariate analysis identified a larger HUSD (odds ratio 3.092; 95% CI 1.018-9.394) and higher amylase concentration in drainage fluid on postoperative day 1 (odds ratio 1.0001; 95% CI 1.00001-1.00022) as significant risk factors for PF. CONCLUSIONS: The HUSD of preoperative CT attenuation values in the pancreatic parenchyma was found to be an independent predictor for PF after PD and it might therefore positively contribute to the perioperative management of PD.

[Breast Cancer Patient with Bone Metastases Who Was Able to Return Home without Using Opioids after Administration of Strontium-89 Chloride].

A 46-year-old woman underwent mastectomy for right inflammatory breast cancer.Three years later, she was diagnosed with multiple bone metastases and was treated with systemic chemotherapy and zoledronic acid.Six years after the mastectomy, she complained of severe sacral pain, and 40 Gy external radiotherapy was applied to the sacral metastases.Oxycodone was also administered, but dose escalation was difficult because of severe nausea and fatigue.A bone scan showed increased uptake of Tc99m in an area consistent with the painful regions, and an injection of 89SrCl2 was administered.Five weeks after the injection, her severe pain was relieved and she was able to discontinue the use of opioids completely.She successfully lived at home for 100 days without using opioids.In this case, radionuclide therapy with 89SrCl2 led to remarkable pain relief with an improvement in the quality of life of the patient.

A Prospective Randomized Study of the Herbal Medicine Yokukansan for Preventing Delirium After Gastrointestinal Cancer Surgery.

Background: Yokukansan, the Chinese Herbal Medicine, may be effective for treating postoperative delirium. However, there is no sufficient evidence supporting this notion. This study aimed to investigate whether yokukansan was effective for preventing delirium after gastrointestinal cancer surgery by the prospective randomized study. Methods: This was a double-blind, randomized, controlled trial. Patients aged 75 years or older who underwent surgery between May 2017 and December 2019 were randomized to the yokukansan or anchusan (another Herbal Medicine) group. They received treatments with oral intake of assigned medicine from the day before surgery until postoperative day 3. Then, the incidence of postoperative delirium was compared. A psychiatrist diagnosed patients with postoperative delirium. Results: Seventy-seven patients were enrolled in this study, and the full analysis set comprised 68 patients. In total, 25 of 68 (36.8%) patients presented with postoperative delirium. Specifically, 13 (37.1%) patients in the control group and 12 (36.4%) in the yokukansan group were diagnosed with postoperative delirium. However, the results did not differ significantly in both groups. Moreover, there was no remarkable difference in terms of delirium severity, and adverse events correlated with the medications were not observed. Conclusion: Yokukansan was ineffective in preventing delirium after gastrointestinal cancer surgery.

GPX4 Regulates Tumor Cell Proliferation via Suppressing Ferroptosis and Exhibits Prognostic Significance in Gastric Cancer.

BACKGROUND/AIM: Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide. Glutathione peroxidase 4 (GPX4) is a glutathione-dependent antioxidant enzyme known to regulate ferroptosis, which is a non-apoptotic form of cell death accompanied by iron-dependent accumulation of reactive oxygen species (ROS). This study evaluated the expression and function of GPX4 in GC. MATERIALS AND METHODS: The expression of GPX4 was examined in five human GC cell lines (KATO-III, MKN-1, MKN-28, MKN-45, and MKN-74) using real-time quantitative PCR and western blotting. The role of GPX4 in GC was examined using small interference RNA and cell proliferation and ROS assays. Finally, we analyzed GPX4 expression in tumor tissues from 106 patients who underwent GC surgery using immunohistochemistry and evaluated the relationship between GPX4 levels and clinical outcomes of GC. RESULTS: GPX4 was expressed in all GC cell lines at various levels. GPX4 silencing and inhibition significantly reduced cell proliferation and increased ROS generation. Furthermore, the mRNA levels of prostaglandin-endoperoxide synthase 2, a known biomarker of ferroptosis, were increased after GPX4 silencing. GPX4 expression was found to be an independent prognostic factor for overall and disease-specific survival in GC patients. CONCLUSION: GPX4 can regulate cancer cell death via ferroptosis in GC cell lines and represents a significant risk factor for survival in patients with GC.

The Combination of Prognostic Nutritional Indicator and Serum Carcinoembryonic Antigen is Useful in Predicting Postoperative Recurrence in Stage II Colorectal Cancer.

BACKGROUND: The efficacy of adjuvant chemotherapy in stage II colorectal cancer (CRC) patients has not been clearly demonstrated. Therefore, identification of robust prognostic factors is crucial for the assessment of recurrence risk in stage II CRC and appropriate adjuvant treatment, in clinical practice. METHODS: We enrolled 135 colorectal adenocarcinoma patients who underwent proctocolectomies and had histologically diagnosed stage II CRC. RESULTS: Receiver operating characteristic (ROC) analysis, to evaluate the predictive ability of certain serum factors for CRC recurrence, indicated that the prognostic nutritional indicator (PNI), followed by serum carcinoembryonic antigen (CEA) level, were the strongest predictive metrics. Based on cutoff values from ROC analyses, patients were divided as follows; CEAHigh (≥ 4.55 ng/mL), CEALow (< 4.55 ng/mL), PNIHigh (≥ 47.72), and PNILow (< 47.72). The recurrence rates of patients with CEAHigh and PNILow, CEAHigh and PNIHigh, CEALow and PNILow, and CEALow and PNIHigh were 34.3%, 0%, 6.8%, and 2.6%, respectively (a significant difference at P < 0.0001). Logistic regression analysis revealed that the combination of serum CEA level and PNI was an independent predictive indicator of tumor recurrence after operation in stage II CRC patients. The 5-year disease specific survival rates of patients with CEALowPNIHigh, CEAHighPNIHigh, CEALowPNILow, CEAHighPNILow were 100%, 100%, 97.4%, and 77.5%, respectively (P < 0.0001). CONCLUSION: The combination of CEA and PNI was useful in predicting postoperative recurrence in stage II CRC patients.

Initial Experience in Rectal Cancer Surgery for the Next Generation of Robotic Surgeons Trained in a Dual Console System.

BACKGROUND: Robotic surgery for rectal cancer is used worldwide, with an increasing incidence of robotic surgeons. Therefore, the most appropriate educational system for next-generation robotic surgeons should be urgently established. METHODS: We analyzed 39 patients who underwent robotic rectal surgery performed by a next-generation surgeon with limited experienced in laparoscopic rectal cancer surgery. The dual console system was used in the initial 15 cases, and we assessed short-term outcomes and the learning curve on operative time using the cumulative sum method. RESULTS: The patients were divided into two groups: 15 cases in the early phase, and 24 cases in the late phase. The operative time and surgeon console time were significantly shorter in the late phase than the early phase (P < 0.001). Postoperative complications were more frequently observed in the early phase (P = 0.049); however, the estimated blood loss and length of hospital stay were not significantly different. In the initial 15 cases that using the dual console, the average operative time changing to the expert surgeon was 82 minutes in the first 5 cases, 19 minutes on average in the next 5 cases, and no change occurred in the last 5 cases. The learning curve peaked after 14 cases, plateaued from case number 15 to 23, and decreased in a linear fashion until the final case. CONCLUSION: Education of a next generation surgeon using a dual console system for robotic rectal cancer surgery was performed safely.

Infiltration of CD204-overexpressing Macrophages Contributes to the Progression of Stage II and III Colorectal Cancer.

BACKGROUND/AIM: M1 macrophages have antitumour effects, while M2 macrophages promote tumour proliferation and invasion. The clinical significance of the M2-specific marker CD204 has not been elucidated in colorectal cancer (CRC). We investigated the prognostic significance of CD204- and CD68-positivity in specimens from patients with CRC and examined the effects of M2 polarized-macrophages on the proliferative and invasive potentials of CRC cell lines in vitro. MATERIALS AND METHODS: Surgical tumour specimens from 206 patients with Stage II and III CRC were examined by immunohistochemistry. Proliferation and invasion assays and flow cytometry were used to investigate CD204 expression in macrophages co-cultured with three CRC cell lines. RESULTS: Infiltration of CD204-positive cells was significantly associated with shorter overall survival and relapse-free survival; no association was observed for CD68. M2-polarized macrophages significantly promoted proliferation and invasion of CRC cells. CONCLUSION: Higher infiltration of CD204-positive macrophages into the tumour-microenvironment might be prognostically important in CRC.

Prognostic Significance of the Number of Teeth in Patients with Colorectal Cancer.

OBJECTIVES: Fusobacterium nucleatum, which is the predominant subgingival microbial species found in chronic periodontitis, has been recently proposed as a risk factor for both the initiation and progression of colorectal cancer. We evaluated whether the number of teeth, which represents oral health, is a marker for the prognosis of patients with colorectal cancer. METHODS: This retrospective single-center study recruited 179 patients who underwent primary colorectal cancer resection with curative intent between 2015 and 2017. The baseline characteristics and survival were analyzed according to the number of teeth observed in dental panoramic radiographs taken before surgical resection as a part of the perioperative surveillance for oral function and hygiene. RESULTS: The median number of teeth was 20 (interquartile range: 6-25), including 28 patients with no teeth. Patients with 20 or more teeth had better overall survival (p = 0.002) and colorectal cancer-specific survival (p = 0.032) than those with less than 20 teeth. Multivariate analyses confirmed that the number of teeth was a significant prognostic factor for overall survival (p = 0.045) but not for colorectal cancer-specific survival (p = 0.258). We also took a propensity score-weighting approach using inverse probability weighting, and the p-values of the number of teeth were 0.032 for overall survival and 0.180 for colorectal cancer-specific survival. CONCLUSIONS: A low number of teeth, which can be easily and noninvasively assessed, has been a poor prognostic factor for overall survival in colorectal cancer patients who underwent surgery with curative intent.

AMIGO2 as a novel indicator of liver metastasis in patients with colorectal cancer.

Our previous study showed that adhesion molecule with immunoglobulin like domain 2 (AMIGO2) is a pivotal driver gene of liver metastasis via regulating tumor cell adhesion to liver endothelial cells in mouse models. The aim of the present study was to clarify the role of AMIGO2 in liver metastasis in patients the colorectal cancer (CRC). Two human CRC cell lines, Caco-2 (AMIGO2-low) and HCT116 (AMIGO2-high), were used in this study. AMIGO2-overexpressing Caco-2 and AMIGO2-knockdown HCT116 cells were generated by transfection with an AMIGO2 expression vector or AMIGO2 small interfering RNA, respectively. Cell proliferation, invasion and adhesion to human liver endothelial cells were examined in in vitro studies. Immunohistochemical analysis was also performed to evaluate the association between AMIGO2 expression and liver metastasis in patients with CRC. In vitro studies revealed that cell proliferation, invasion and adhesion to liver endothelial cells were accelerated by upregulation of AMIGO2 expression, but suppressed by downregulation of AMIGO2 expression in human CRC cells. Immunohistochemical analysis using clinical CRC specimens revealed that AMIGO2 expression was associated with the frequency of liver metastasis (P<0.01), but not that of pulmonary metastasis (P=0.611) and peritoneal dissemination (P=0.909). In addition, AMIGO2 expression levels in tumor cells were significantly higher in liver metastatic foci than primary lesions (P=0.012). In conclusion, the present results indicated that AMIGO2 expression may contribute to the formation of liver metastasis in CRC.

Platelet-to-Lymphocyte Ratio Multiplied by the Cytokeratin-19 Fragment Level as a Predictor of Pathological Response to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma.

BACKGROUND: The standard treatment for resectable advanced esophageal squamous cell carcinoma in Japan is surgery followed by neoadjuvant chemotherapy, and it is important to predict the effect of neoadjuvant chemotherapy before treatment. Therefore, this study aims to extract conventional blood examination data, such as tumor markers and/or inflammatory/nutritional index levels, that can predict the pathological response of patients with esophageal squamous cell carcinoma to neoadjuvant chemotherapy. METHODS: We retrospectively analyzed the medical records of 66 patients with thoracic esophageal squamous cell carcinoma who received neoadjuvant chemotherapy, followed by curative esophagectomy at Tottori University Hospital between June 2009 and December 2019. RESULTS: We demonstrated that the product of the platelet-to-lymphocyte ratio (PLR) multiplied by the cytokeratin-19 fragment (CYFRA) level, which was termed "PLR-CYFRA," is the most accurate indicator that predicts the pathological response to neoadjuvant chemotherapy, with the highest area under the curve [0.795 (95% confidence interval: 0.665-0.925), P < 0.001] in receiver operating characteristic analyses. Therefore, we divided patients into the PLR-CYFRALow (< 237.6, n = 21) and PLR-CYFRAHigh (≥ 237.6, n = 45) groups and found that the percentage of PLR-CYFRALow was significantly higher in patients with a better pathological response (P < 0.001). Furthermore, patients with good pathological response had significantly better prognoses in terms of disease-specific survival (P = 0.014), recurrence-free survival (P = 0.014), and overall survival (P = 0.032). In the multivariate analysis, PLR-CYFRA was an independent predictor of the pathological response of patients with esophageal squamous cell carcinoma to neoadjuvant chemotherapy (P = 0.002). CONCLUSION: Pretreatment PLR-CYFRA might be a useful and simple tool that predicts the pathological effect of neoadjuvant chemotherapy in esophageal squamous cell carcinoma.

Combination of C-reactive Protein and Monocyte Count Is a Useful Prognostic Indicator for Patients With Colorectal Cancer.

BACKGROUND/AIM: Several studies have demonstrated the usefulness of C-reactive protein (CRP) or cellular components obtained from complete blood count as prognostic indicators in colorectal cancer (CRC) patients. The aim of this study was to investigate the prognostic significance of the combination of CRP and blood cellular components in CRC patients. PATIENTS AND METHODS: A total of 463 patients who underwent curative surgery for CRC were enrolled in this study. RESULTS: ROC analysis revealed that the values of area under the curve of neutrophil, lymphocyte, platelet, and monocyte counts (MC) for overall survival (OS) were 0.594, 0.513, 0.553, and 0.625, respectively. Using cut-off values derived from ROC analysis, patients were divided into the following groups, CRPHigh, CRPLow, MCHigh, and MCLow The 5-year OS rates of CRPHigh and MCHigh, CRPHigh and MCLow, CRPLow and MCHigh, and CRPLow and MCLow patients were 60.2%, 75.7%, 82.1%, and 88.3%, respectively (p<0.0001). Multivariate analysis revealed that the combination of serum CRP levels and MC was an independent prognostic indicator. With regard to the cause of death, the combination of CRP and MC was significantly associated with both cancer-related and unrelated death. CONCLUSION: The combination of CRP and MC is useful in predicting the prognosis in CRC patients.