Carbon Ion Irradiation Activates Anti-Cancer Immunity.

Carbon ion beams have the unique property of higher linear energy transfer, which causes clustered damage of DNA, impacting the cell repair system. This sometimes triggers apoptosis and the release in the cytoplasm of damaged DNA, leading to type I interferon (IFN) secretion via the activation of the cyclic GMP-AMP synthase-stimulator of interferon genes pathway. Dendritic cells phagocytize dead cancer cells and damaged DNA derived from injured cancer cells, which together activate dendritic cells to present cancer-derived antigens to antigen-specific T cells in the lymph nodes. Thus, carbon ion radiation therapy (CIRT) activates anti-cancer immunity. However, cancer is protected by the tumor microenvironment (TME), which consists of pro-cancerous immune cells, such as regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. The TME is too robust to be destroyed by the CIRT-mediated anti-cancer immunity. Various modalities targeting regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages have been developed. Preclinical studies have shown that CIRT-mediated anti-cancer immunity exerts its effects in the presence of these modalities. In this review article, we provide an overview of CIRT-mediated anti-cancer immunity, with a particular focus on recently identified means of targeting the TME.

Autophagy Inhibition Increased Sensitivity of Pancreatic Cancer Cells to Carbon Ion Radiotherapy.

BACKGROUND/AIMS: Pancreatic cancer has the poorest survival rate among all cancer types. Therefore, it is essential to develop an effective treatment strategy for this cancer. METHODS: We performed carbon ion radiotherapy (CIRT) in human pancreatic cancer cell lines and analyzed their survival, apoptosis, necrosis, and autophagy. To investigate the role of CIRT-induced autophagy, autophagy inhibitors were added to cells prior to CIRT. To evaluate tumor formation, we inoculated CIRT-treated murine pancreatic cancer cells on the flank of syngeneic mice and measured tumor weight. We immunohistochemically measured autophagy levels in surgical sections from patients with pancreatic cancer who received neoadjuvant chemotherapy (NAC) plus CIRT or NAC alone. RESULTS: CIRT reduced the survival fraction of pancreatic cancer cells and induced apoptotic and necrotic alterations, along with autophagy. Preincubation with an autophagy inhibitor accelerated cell death. Mice inoculated with control pancreatic cancer cells developed tumors, while those inoculated with CIRT/autophagy inhibitor-treated cells showed significant evasion. Surgical specimens of NAC-treated patients expressed autophagy comparable to control patients, while those in the NAC plus CIRT group expressed little autophagy and nuclear staining. CONCLUSION: CIRT effectively killed the pancreatic cancer cells by inhibiting their autophagy-inducing abilities.

Prognostic impact of lymph node micrometastasis in patients with gastric cancer.

PURPOSE: The clinical significance of lymph node micrometastasis (LNMM) remains controversial in gastric cancer (GC). In this study, we investigated the prognostic impact of LNMM in patients with GC. METHODS: A total of 624 patients with pathologically lymph node metastasis-negative (pN0) and N1 status (pN1) who underwent gastrectomy between 2004 and 2018 were enrolled in this retrospective study. The diameter of tumor cell clusters in metastatic lymph nodes was measured in 120 patients with pN1 GC. RESULTS: Patients with lymph node tumors < 1500 µm in diameter (LNMM) had a significantly better prognosis than those with tumors ≥ 1500 µm in diameter (p = 0.012; log-rank test). Cox's proportional hazards model revealed that LNMM (p = 0.016), several dissected lymph nodes (p = 0.049), and the provision of adjuvant chemotherapy (p = 0.002) were independent prognostic factors for the overall survival of patients with pN1 GC. There was no significant difference in the overall survival between patients with LNMM who received chemotherapy and those who did not (p = 0.332). CONCLUSIONS: LNMM is associated with a favorable prognosis and maybe an independent prognostic marker in patients with pN1 GC. LNMM in GC may be considered a factor preventing adjuvant chemotherapy.

Platelets enhance malignant behaviours of gastric cancer cells via direct contacts.

In this study, we aimed to analyse human cancer cell-platelet interactions in functional cell analyses and explore the molecular mechanisms behind tumour progression. Various functional analyses of gastric cancer (GC) cells were performed after direct/indirect co-incubation with platelets derived from GC patients. Further detailed expression and signalling analyses were performed after co-culture with direct and indirect GC cells-platelet contact. Malignant behaviours of cancer cells, such as proliferation, migration, invasion and adhesion, were significantly enhanced after direct co-incubation with platelets. Microarray analyses demonstrated changes in multiple genes, including epithelial-mesenchymal transition (EMT)-related genes. Among them, matrix metalloproteinase 9 was notably upregulated, which was validated by quantitative reverse transcription-polymerase chain reaction and western blot. Further, this change was only observed after direct co-incubation with platelets. This study demonstrated that platelets from GC patients promote malignant behaviours of GC cells through EMT-related signalling, especially by direct contact with tumour cells.

Antithrombin Together with NETs Inhibitor Protected Against Postoperative Adhesion Formation in Mice.

BACKGROUND/AIMS: Postoperative adhesions may induce adverse outcomes in patients. Adhesion formation is initiated by fibrin accumulation at the surgical site which is followed by local neutrophilia and the establishment of neutrophil extracellular traps (NET). Previous reports have suggested that the preventive efficacy of reagents designed to reduce postoperative adhesion is inversely correlated with neutrophilia and NET production. Antithrombin (AT) is a natural inhibitor of thrombin, a key factor in coagulation. Here, we evaluate whether treatment with AT and/or NET inhibitors prevent or reduce postoperative adhesion formation in mice. METHODS: Mice were treated with AT and/or NET inhibitors before and/or after cecum cauterization and their adhesion scores were evaluated on day 7 post-operation. Immunochemistry/ immunofluorescence analyses were also performed and we used GSK484, an inhibitor of peptidyl arginine deiminase 4 (PAD4), as the NET inhibitor. RESULTS: AT or GSK484 partially rescued postoperative adhesion formation in mice. AT prevented thrombin-induced plasminogen activator inhibitor 1 and interleukin-6 expression in mesothelial cells in vitro. However, AT could not prevent neutrophilia or NETs formation around the injured serosa. Finally, we investigated a combination of AT and a PAD4 inhibitor and found that this could inhibit almost all adhesion formation in these animals. Since AT-inactivating proteases are liberated following NET release, they might dampen the biological action of the AT treatment. This suggests that NET inhibitors might allow AT to exert its full action in the surgically injured serosa. CONCLUSION: Combined treatment with AT and GSK484 may effectively attenuate postoperative adhesion production in mice.

Platelet C-Type Lectin-Like Receptor 2 Reduces Cholestatic Liver Injury in Mice.

Cholestatic liver injury leads to liver dysfunction. The available evidence suggests that platelets can either promote or reduce liver injury and fibrosis. This study focused on the functions of the C-type lectin-like receptor 2 (CLEC-2), a new special platelet receptor that binds with podoplanin-activating platelets. The role of CLEC-2 and podoplanin in cholestatic liver injury was investigated. Mice were injected intraperitoneally with weekly doses of anti-CLEC-2 antibody (2A2B10) to achieve effective CLEC-2 inhibition in their platelets. Next, left and middle hepatic bile duct ligation (BDL) procedures were performed, and mice were euthanized 1 week later (2A2B10-BDL group). In addition, mice were prepared for control groups, and relevant histological and laboratory variables were compared among these groups. The inhibition of CLEC-2 resulted in increasing hepatocellular necrosis, hepatic inflammation, and liver fibrosis. In addition, podoplanin was strongly expressed in hepatic sinusoidal endothelial cells in BDL-treated mice. Moreover, in 2A2B10-BDL mice, total plasma bile acid levels were significantly increased. In summary, podoplanin is expressed on hepatic sinusoidal endothelial cells upon BDL. Platelets bind with podoplanin via CLEC-2 and become activated. As a result, the total bile acid pool is decreased. Therefore, the CLEC-2-podoplanin interaction promotes liver protection and inhibits liver fibrosis after cholestatic liver injury.

Exposure to Blood Components and Inflammation Contribute to Pancreatic Cancer Progression.

BACKGROUND: Pancreatectomy is a highly invasive procedure with extensive intraoperative blood loss (IBL) and high risk of postoperative pancreatic fistula (POPF). We conducted an experimental and retrospective clinical study to determine whether the malignant behaviors of pancreatic cancer cells were enhanced by exposure to blood components in vitro and to evaluate the oncological significance of high IBL and POPF in pancreatic cancer. METHODS: This study included 107 patients undergoing radical pancreatectomy in the University of Yamanashi Hospital between 2011 and 2017, classified into high (n = 29) and low (n = 78) IBL groups. In vitro experiments included functional analyses of Panc-1 pancreatic cancer and normal mesothelial cells exposed to patient blood components, and clinical data were used to assess the contribution of IBL and POPF to patient outcomes. RESULTS: The migration (p = 0.007), invasion (p < 0.001), and proliferation (p < 0.01) of Panc-1 cells were enhanced with platelet coculture. The ability of Panc-1 cells to adhere mesothelial cells was enhanced by plasma coincubation, especially in the presence of inflammation (p < 0.001). High IBL was associated with worse overall survival (p = 0.007) and increased locoregional recurrence (p = 0.003) in patients. POPF enhanced the negative prognostic significance of high IBL (p < 0.001 for overall survival, p = 0.001 for locoregional recurrence), indicating the oncological negative effects of high IBL and POPF. CONCLUSIONS: Blood components, especially platelets, and inflammation enhance the malignant behaviors of pancreatic cancer cells, potentially contributing to poor prognosis for pancreatic cancer patients.

Liquid biopsy as a perioperative biomarker of digestive tract cancers: review of the literature.

Tissue biopsies are the gold-standard for investigating the molecular characterization of tumors. However, a "solid" biopsy is an invasive procedure that cannot capture real-time tumor dynamics and may yield inaccurate information because of intratumoral heterogeneity. In this review, we summarize the current state of knowledge about surgical treatment-associated "liquid" biopsy for patients with digestive organ tumors. A liquid biopsy is a technique involving the sampling and testing of non-solid biological materials, including blood, urine, saliva, and ascites. Previous studies have reported the potential value of blood-based biomarkers, circulating tumor cells, and cell-free nucleic acids as facilitators of cancer treatment. The applications of a liquid biopsy in a cancer treatment setting include screening and early diagnosis, prognostication, and outcome and recurrence monitoring of cancer. This technique has also been suggested as a useful tool in personalized medicine. The transition to precision medicine is still in its early stages. Soon, however, liquid biopsy is likely to form the basis of patient selection for molecular targeted therapies, predictions regarding chemotherapy sensitivity, and real-time evaluations of therapeutic effects.

[Nab-Paclitaxel plus Gemcitabine for Patients with Recurrence after Resection for Adenocarcinoma of the Pancreas].

PURPOSE: The purpose of this study was to clarify the predictors of efficacy of nab-paclitaxel plus gemcitabine(GnP)for patients with recurrence after resection for adenocarcinoma of the pancreas. METHOD: Patients who had received GnP at our hospital were divided into 2 groups; effective group and non-effective group and we compared them. In addition, we compared the therapeutic effect of patients between well-differentiated adenocarcinoma and moderately differentiated adenocarcinoma. Furthermore, we compared the efficacy depending on the time of recurrence. RESULTS: In patients with well-differentiated adenocarcinoma, the disease control rate was 93.6% and progression free survival was 8.6 months, whereas those in patients with moderately differentiated adenocarcinoma were 57.1% and 4.4 months, respectively. Patients who recurred at 7 months or later, had a better therapeutic response than the patients who recurred within 6 months after surgery. CONCLUSIONS: GnP may be effective in patients with well-differentiated adenocarcinoma and in patients who recurred at 7 months or later.

Blockade of Tumor Necrosis Factor by Etanercept Prevents Postoperative Adhesion Formation in Mice.

BACKGROUND/AIMS: Although adhesion formation is a frequent adverse event following intraperitoneal surgery, efficient prophylactic interventions have not yet been established. We recently reported that blockade of interleukin (IL)-6 prevented postoperative adhesion after cecum cauterization. Intriguingly, this intervention dampened tumor necrosis factor (TNF) induction in the injured serosa. Herein, we addressed whether TNF might be a key target and, if so, how TNF blockade rescued adhesion formation. METHODS: Mice were administered an anti-TNF biologic (etanercept) on days -2 and -1 before and upon cecal cauterization. The adhesion scores were evaluated at day 7 postoperatively. Histological alterations were examined by immunochemistry/immunofluorescence studies. We incubated human neutrophils and mesothelial cell line cells with recombinant TNF in the presence of etanercept and measured transcript levels of cytokines and chemokines by quantitative reverse transcription-polymerase chain reaction (RT-qPCR). RESULTS: Etanercept rescued mice from adhesion formation, accompanied by a robust reduction of neutrophilia in the injured serosa. Immunofluorescence revealed a substantial formation of neutrophil extracellular traps (NETs) with the potential to induce tissue damage and profibrotic responses. In contrast, the etanercept-treated mice lacked NET formation. In addition, etanercept inhibited TNF-induced IL-6, TNF, and neutrophil-recruiting chemokines in neutrophils and mesothelial cells, a major cellular source of myofibroblasts in the adhesion band. CONCLUSION: Prophylactic administration of etanercept might be a potential strategy for preventing postoperative adhesion formation.

Postoperative Complications have Minimal Impact on Long-Term Prognosis in Immunodeficient Patients with Esophageal Cancer.

BACKGROUND: Postoperative complications have been recognized to have an adverse prognostic impact in various types of cancer. However, in a recent study, it has been reported that postoperative complications of total gastrectomy with splenectomy have little impact on the long-term outcomes of patients with gastric cancer. In addition, the mechanisms underlying the effect of postoperative complications on outcomes remain to be elucidated. We hypothesized that immunosuppression by postoperative complications may affect long-term outcomes in patients with esophageal cancer. METHODS: In this retrospective study, we assessed in 153 patients with esophageal cancer who underwent curative subtotal esophagectomy at our hospital and examined the correlation between postoperative complications, and multiple clinicopathological factors, and long-term outcomes with the patients stratified by total lymphocyte count (TLC). RESULTS: The median preoperative TLC was 1432. A total of 115 patients (75.2%) had a TLC of ≥ 1000/µL (high TLC group), and the remaining 38 patients (24.8%) had a TLC of < 1000/µL (low TLC group). Postoperative complications occurred in 39 of 153 cases (25.5%). There was no significant correlation between postoperative complications and any of the clinicopathological factors in either group. In the high TLC group, patients with postoperative complications had significantly lower overall and disease-free survival rates compared with those without complications (p < 0.001 and p < 0.01, respectively). In the low TLC group, no survival difference between patients with and without postoperative complications was observed. CONCLUSIONS: Postoperative complications may have a minimal impact on long-term outcomes in immunodeficient patients.

Prognostic Significance of Hiatal Hernia in Patients with Gastric Cancer Located within the Upper-Third of the Stomach.

BACKGROUND: Gastric cancers located within the upper-third of the stomach (UGC), especially the esophagogastric junction GC (EGJGC), have distinct clinicopathological features due to their potential for multidirectional lymphatic spread. In this study, we investigated the clinical significance of hiatal hernias (HH) in patients with UGC, including EGJGC. METHODS: In this retrospective study, we assessed status of HH in 147 patients with UGC who underwent curative resection at our hospital and examined the correlation between the presence of HH (+) and multiple clinicopathological factors. RESULTS: Thirty-four patients (23%) were HH (+). However, we found no significant correlation between HH (+) and clinicopathological factors. HH (+) patients frequently developed lymph node recurrences. Prognosis was significantly better in patients with UGC and HH (-), compared to those with UGC and HH (+). Similarly, EGJGC patients who were HH (-) showed superior survival compared to HH (+) patients. Multivariate analysis found that the HH (+) (p = 0.004), histological type (p = 0.029), and nodal stage (p = 0.034) were independent prognostic factors. CONCLUSIONS: The presence of HH might affect lymphatic spread of tumor cells, and consequently prognosis of patients with UGC. Therefore, special attention is needed in developing surgical and postoperative strategies for such patients with UGC who are HH (+).

Anastomosis technique for pancreatojejunostomy and early removal of drainage tubes may reduce postoperative pancreatic fistula.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most serious complications after pancreaticoduodenectomy (PD). Various factors have been reported as POPF risks, but the most serious of these is soft pancreas. To reduce POPF occurrences, many changes to the PD process have been proposed. This study evaluates short-term results of anastomosis technique for PD. METHODS: In total, 123 patients with soft pancreases who had undergone PD at Yamanashi University between January 2012 and August 2020 were retrospectively analyzed. We divided these patients into two groups depending on the time PD was performed: a conventional group (n = 67) and a modified group (n = 56). RESULTS: The rate of clinically relevant POPF was significantly lower in the modified group than that in the conventional group (5.4% vs 22.4%, p value < 0.001), with there being only one case of POPF in the modified group. There were no cases of POPF-related hemorrhaging in the modified group. On the third day after the operation, the amylase levels in the drainage fluid for the modified group became less than half (1696 vs 650 U/L). Multivariate analysis showed that the modified method was the independent predictors to prevent clinical POPF (p value = 0.002). CONCLUSIONS: Our novel anastomosis technique for pancreatojejunostomy reduced POPF in PD, especially in cases where the patient had a soft pancreas.

[Pathological Complete Response of Intrapelvic Recurrence of Rectal Cancer after Chemoradiotherapy-A Case Report].

50's man who have performed anterior pelvic exenteration with lateral lymph node dissection for rectal cancer with pT4bN0M0, pStage Ⅱc about 2 years ago, was admitted to our hospital for the treatment of intrapelvic recurrence of rectal cancer. No distant metastasis was found in the computed tomography examination but the tumor invaded the dorsal side of the pubis. Because radical excision was impossible with these findings, he received chemoradiotherapy(CRT). Post-CRT imaging showed that the tumor of intrapelvic recurrence region reduced the size, and invasion of pubis had disappeared and been markedly reduced. Thus, radical excision seemed possible at this point, and we decided to attempt operation after total 6 weeks of S-1(120 mg/day)regimen and radiation(40 Gy/20 Fr). We performed Miles' operation. The final pathological examination demonstrated that no viable tumor cells remained in the resected rectum specimen, confirming that a pathological complete response(pCR)had been achieved.

Indications for extrahepatic bile duct resection due to perineural invasion in patients with gallbladder cancer.

BACKGROUND: The indications for extrahepatic bile duct (EHBD) resection remain a major controversy in the surgical management of patients with gallbladder cancer. On the other hand, perineural invasion (PNI) was reported as an important factor in patients with gallbladder cancer because gallbladder cancer cells frequently spread to the tissues surrounding the EHBD via perineural routes. We assessed the correlation of PNI with clinicopathological factors in patients with gallbladder cancer to elucidate EHBD resection indications specifically in patients with PNI. METHODS: This retrospective study assessed the PNI status of 50 patients with gallbladder cancer who underwent curative resection and examined the correlation between the presence of PNI and clinicopathological factors. RESULTS: Thirteen patients (26%) were PNI positive. PNI was significantly correlated with male sex, proximal-type tumor, lymphatic and vascular invasion, and advanced T stage. Multivariate analysis found that PNI positivity (p < 0.001), lymphatic invasion (p = 0.007), and nodal stage (p < 0.001) were independent prognostic factors. PNI was never observed in patients with stage T1 cancer. Conversely, PNI was detected rarely in distal-type tumors, all of whom developed various types of recurrences. CONCLUSIONS: These results clearly demonstrated the prognostic impact of PNI in patients with gallbladder cancer. We suggest that EHBD resection in combination with cholecystectomy may not be useful for distal-type tumors from a perspective of PNI.

The impact of histological type on the accuracy of preoperative N staging in patients with gastric cancer.

BACKGROUND: The low accuracy of preoperative diagnosis of lymph node metastasis in gastric cancer (GC) complicates decisions on patient indication for neoadjuvant chemotherapy. METHODS: We investigated the use of preoperative clinical diagnosis of lymph node involvement (cN) in GC patients compared with postoperative pathological diagnosis. RESULTS: In a series of 265 patients enrolled at the University of Yamanashi Hospital, the overall sensitivity was 44.4% and specificity was 93.4% of CT for detecting lymph node metastasis. The positive and negative predictive values were 80.0% and 73.8%, respectively. The negative predictive value was lower for undifferentiated adenocarcinoma than that for differentiated adenocarcinoma (64.9% vs. 78.7%, p = 0.034). In cT2 ≤ and cN2 ≤ GC, overdiagnosis of lymph node metastasis was significantly more frequent in patients with differentiated (50.0%) than in undifferentiated (13.3%) adenocarcinoma (p = 0.046). CONCLUSIONS: Diagnostic accuracy of lymph node involvement depended on histological type and cT-stage. Thus, considering preoperative histological type in GC, it may be useful to decide treatment plan.

Long-term outcomes after surgical resection in patients with stage IV colorectal cancer: a retrospective study of 129 patients at a single institution.

BACKGROUND AND PURPOSE: Approximately 20% of all patients with colorectal cancer (CRC) are diagnosed at more advanced stages with synchronous distant metastasis, and the prognosis in these patients is usually poor. The aim of this study was to determine the factors that can identify subgroup(s) of patients with stage IV CRC who could benefit from curative (R0) resection of both primary and metastatic lesions. PATIENTS AND METHODS: A total of 126 patients with stage IV CRC who underwent surgical resection of primary tumor were retrospectively analyzed. Among these patients, 26 cases of R0 resection were further examined subsequently. Information on various clinicopathological factors of the patients were obtained from hospital records. Overall survival was estimated using the Kaplan-Meier method, and log-rank tests were used to compare survival distribution. All the factors with P < 0.05 in univariate analysis were analyzed in the Cox proportional hazards model. RESULTS: CEA negativity, left-sided tumor, R0 resection, differentiated histology, and nodal staging less than N1 were independent factors that predicted better prognosis in all the 126 patients with stage IV CRC. Tumor depth of T3 or less was significantly correlated with better survival in patients who had undergone R0 resection. CONCLUSION: Our findings demonstrate that it is possible to select patients in whom surgical resection would yield better prognosis, from a variety of patient subgroups with stage IV CRC.

[Investigation of Lateral Lymph Node Dissection for Rectal Cancer in Our Department].

No clear policy has been established in Japan for proper lymph node dissection for rectal cancer. In our department, we examined the frequency of lateral lymph node metastasis, its treatment outcomes, and whether lateral dissection can narrow down necessary cases. In 10 years from 2003 to 2013, 98 cases of lower rectal cancer surgically treated in our department were examined. The clinicopathological factors in these cases were examined, and the risk factors were examined based on their correlation with the presence or absence of lateral lymph node metastasis. Based on the postoperative prognostic analysis, the dissection effect index(metastasis positive rate×5-year survival rate in cases with positive metastases)was also examined. Forty-three lateral lymph node dissections were performed. Cases involving a circumferential resection margin (CRM)of 1mm or less had significantly more lateral lymph node metastases. In the prognostic analysis, the 5-year survival rate of lateral lymph node metastasis-positive cases was 19%, and the dissection effect index was 3.5. It was suggested that CRM-positive patients had a higher risk of lateral lymph node metastasis before surgery. However, considering the results of this study and the results of JCOG0212, the presence or absence of lateral lymph node metastasis may be a prognostic predictor, although the prognostic improvement effect by dissection is considered to be limited.

[Effects of Preoperative Skeletal Muscle Mass on the Prognosis of Stageâ ¡ and â ¢ Colorectal Cancer].

INTRODUCTION: Some studies reported that the decrease in skeletal muscle mass worsens the immune and nutritional status and related to the poor prognosis in colorectal cancer. We examined the relationship of skeletal muscle mass, immune and nutritional index, and outcome in patients with colorectal cancer at our hospital. SUBJECTS AND METHODS: We retrospectively analyzed 196 patients of cStageⅡ andⅢ colorectal cancer who underwent curative surgery in our institution between 2007 and 2013. The cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on preoperative computed tomography was assessed to calculate the psoas muscle index(PMI). Patients are divided into high PMIgroup(H-group)and low PMIgroup (L-group)with cut off value(6.36 cm / / 2/m2 for males and 3.92 cm2/m2 for females). Patient background, tumor factor, overall survival(OS), recurrence free survival(RFS)were examined retrospectively. RESULTS: There were 119 cases in H-group and 77 cases in L-group. Significant differences were recognized in gender, age, Alb value, BMI, and adjuvant chemotherapy between 2 groups. The 5-year survival rate was significantly different from 82.8% in H-group and 70.3% in L-group(p<0.01). The 5-year recurrence-free survival rate was 74.0%in the H-group, and 68.3%in the L-group (p=0.46). Univariate and multivariate analysis showed that age(OR: 1.90, p<0.01), high CEA(OR: 0.012, p<0.05), depth of invasion(OR: 2.19, p<0.05), lymph node metastasis(OR: 2.21, p<0.01), and preoperative low PMI(OR: 2.05, p<0.01), were significantly related to decrease of OS. CONCLUSION: Preoperative PMIsuggested to become prognostic factors in Stage Ⅱ and Ⅲ colorectal cancer.

[Effects of Preoperative Immune and Nutritional Indices on the Prognosis of pStage â ¡ and â ¢ Colorectal Cancer].

We examined the relationship between immune and nutritional indices and the outcome of colorectal cancer patients at our hospital. We retrospectively analyzed 196 patients with pStage Ⅱand Ⅲcolorectal cancer who underwent curative surgery in our institution between 2007 and 2013. The evaluation items were immune and nutritional indices, such as neutrophil/lym- phocyte ratio(NLR), platelet/lymphocyte ratio(PLR), lymphocyte/monocyte ratio(LMR), and the Onodera nutritional index (PNI). Moreover, we analyzed the relationship between immune and nutritional indices and outcome, overall survival(OS), and recurrence-free survival(RFS). Univariate and multivariate analyses showed that low LMR was significantly related to high mortality. Univariate analysis showed that high NLR, low LMR, and low PNIwere significantly related to a decrease in OS. Multivariate analysis showed that PNIwas an independent predictor of OS. LMR is suggested as a new predictor for postoperative complications. PNIis suggested as a new prognostic factor in pStageⅡand Ⅲcolorectal cancer.