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Background/aim: Trabectedin is used as a treatment for advanced-stage soft tissue sarcomas (STSs), particularly liposarcoma and leiomyosarcoma. Aside from its direct effect on tumor cells, trabectedin can affect the immune system in the tumor microenvironment. This study aimed to evaluate whether inflammatory biomarkers predict trabectedin efficacy in STSs., Patients and Methods: We retrospectively reviewed the clinical features and outcomes of patients with STS treated with trabectedin at our institution between 2016 and 2020. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation response index (SIRI=neutrophil × monocyte/lymphocyte) were calculated based on the blood samples obtained prior to trabectedin treatment initiation. Analyses of overall survival (OS) and progression-free survival (PFS) were performed according to various factors., Results: Of the 101 patients identified, 54 had L-sarcoma (leiomyosarcoma: 30; liposarcoma: 24), and 47 had other types of STSs. Elevated SIRI, NLR, PLR, LMR, and C-reactive protein (CRP) were associated with worse PFS (p<0.001, p=0.008, p=0.027, p=0.013, and p<0.001, respectively) according to the results of the univariate analysis. Multivariate analysis showed that elevated SIRI, other histology, and CRP were associated with poor PFS (p=0.007, p=0.008, and p=0.029, respectively). In addition, the multivariate analysis of OS showed that SIRI was an independent prognostic factor (hazard ratio=2.16, p=0.006)., Conclusion: Pretreatment SIRI can be considered a biomarker for the prognostic prediction of patients with STS treated with trabectedin., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The safety and efficacy of anti-angiogenic agents in patients with cancer with proteinuria and a history of proteinuria are not well established. This systematic review aimed to answer these questions., Materials and Methods: We searched three electronic databases for articles published until June 18, 2021. The main outcomes used were "death", "renal impairment", and "proteinuria impairment"., Results: After screening 303 references in the PubMed, Cochrane Library, and ICHUSHI-web databases, this review included five studies on renal cell carcinoma (RCC). In patients with metastatic RCC, the hazard ratio of the presence of (or having) proteinuria (1+ or higher) at baseline was 0.82 (0.23-2.97); thus, proteinuria was not significantly associated with the outcome of death. No significant deterioration in kidney function was observed in patients with proteinuria. Although proteinuria at baseline was a significant risk factor for proteinuria progression during and after treatment, most patients maintained grade 1 or 2 proteinuria and continued treatment without dose reduction or discontinuation., Conclusion: While weak evidence suggests that proteinuria at the start of treatment with anti-angiogenic agents might be a risk factor for worsening proteinuria, it was not significantly associated with death or renal impairment., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Recurrent laryngeal nerve paralysis (RLNP) induces aspiration pneumonia and reduces the patient's quality of life. To decrease the incidence of RLNP, we performed intraoperative neural monitoring (IONM) during thoracoscopic surgery for esophageal cancer and evaluated its usefulness., Patients and Methods: A total of 737 consecutive patients who underwent thoracoscopic surgery for esophageal cancer were enrolled in this study. Between May 1995 and March 2016, thoracoscopic esophagectomies were performed using video-assisted thoracoscopic surgery (VATS) with a small incision, whereas from April to June 2023, we used positive pressure pneumothorax with port placement only [minimum invasive esophagectomy (MIE)]. A total of 110 consecutive patients who underwent thoracoscopic surgery with IONM (IONM group) were retrospectively compared with those who underwent VATS or MIE without IONM (No-IONM group)., Results: The incidence of RLNP [Clavien-Dindo (CD) classification of ≥1] on postoperative day (POD) 5 was 13.9% in the IONM group, which was significantly lower than that of the no-IONM group (31.2%, p<0.001). Even when comparing only patients who underwent MIE, the incidence of RLNP on POD5 was 13.9% in the IONM group, which was significantly lower than that in the no-IONM group (26.2%, p=0.035). The incidence of postoperative pneumonia (CD ≥2) was 10.9% in the IONM group, which was significantly lower than that in the no-IONM group (26.1%, p=0.005). Bilateral RLNP did not occur in any of the IONM groups., Conclusion: IONM is a useful tool for reducing RLNP incidence and postoperative pneumonia after thoracoscopic surgery for esophageal cancer., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Chemotherapy is the standard treatment for patients with unresectable gastric cancer (UGC); however, the survival outcomes are poor. This study investigated the predictive values of skeletal muscle mass (SMM) index (SMI) before second-line chemotherapy and the survival outcomes of patients with UGC., Patients and Methods: A total of 79 patients diagnosed with UGC at our hospital who received at least second-line palliative chemotherapy were included. The cross-sectional SMM at the third lumbar vertebra was obtained before second-line chemotherapy. SMI was defined as the muscle area normalized by height squared (m 2 ), and SMI before second-line chemotherapy was defined as 2 nd SMI., Results: Using 2 nd SMI for men and women (35.4 and 31.7 cm 2 /m 2 , respectively) as the cutoff value, patients were divided into high (2 nd SMI High ; n=54) and low (2 nd SMI Low ; n=25) 2 nd SMI groups. The number of patients receiving fourth-line chemotherapy was significantly higher in the 2 nd SMI High group than in the 2 nd SMI Low group (p=0.039). The overall survival time after the start of second-line chemotherapy was significantly higher in the 2 nd SMI High group than in the 2 nd SMI Low group (p=0.008). The incidence of grade 3 or 4 side effects was significantly higher in the 2 nd SMI Low than in the 2 nd SMI High group (p=0.028). The multivariate analysis identified 2 nd SMI as independent prognostic factor after the start of second-line chemotherapy., Conclusion: The 2 nd SMI Low group had a significantly worse prognosis and significantly less conversion to fourth-line chemotherapy than the 2 nd SMI High group. Moreover, 2 nd SMI Low was associated with grade 3 or 4 side effects of second-line chemotherapy., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Persistent hyperglycemia caused by diabetes mellitus is a risk factor for pancreatic cancer (PC). We have previously reported that aberrant activation of atypical protein kinase C (aPKC) enhances PC cell progression. However, no reports have elucidated whether hyperglycemia promotes PC cell progression and whether aPKC activation is related to PC cell progression mechanisms., Materials and Methods: We examined whether high-glucose stimulation accelerates PC cell proliferation, migration, and invasion. Furthermore, to determine whether PC cells activate aPKC upon high-glucose stimulation, we measured the phosphorylation of aPKC at T560 in PC cells., Results: High-glucose stimulation accelerated PC cell proliferation, migration, and invasion. High-glucose treatment increased aPKC's activated form, with T560 phosphorylation, in PC cells. However, aPKC knockdown attenuated these effects. aPKC reportedly induces cell transformation through Yes-associated protein (YAP) activation. YAP expression was increased in high glucose-treated PC cells but not in aPKC-knockdown cells. aPKC interacts with partitioning defective 3 (Par-3), which aids in establishing cell polarity and inhibits aPKC by binding as a substrate. In Par-3-knockdown PC cells, YAP expression increased independently of high-glucose treatment. Over-expression of Par-3 and aPKC-dominant negative mutants prevented the high glucose-stimulated nuclear localization of YAP. YAP forms a complex with the zinc finger E-box binding homeobox 1 protein (ZEB1), an activator of epithelial-mesenchymal transition. ZEB1 expression was increased by high glucose treatment or Par-3 knockdown, but aPKC knockdown suppressed this increase., Conclusion: High glucose-induced aPKC activation promotes PC progression by enhancing the YAP signaling pathway., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Preoperative osteopenia, defined as low bone mineral density (BMD), has been reported as a prognostic factor in patients with digestive tract cancers. However, the correlation between preoperative osteopenia and the prognosis of gastric cancer (GC) remains unclear. The aim of this study was to reveal the importance of preoperative osteopenia as a prognostic factor in patients undergoing gastrectomy for GC., Patients and Methods: We enrolled 251 patients who had undergone curative surgery for histopathologically diagnosed gastric adenocarcinoma from January 2008 to December 2012. BMD was calculated as the average pixel density (Hounsfield units) within a circle of the mid-vertebral core at the bottom of the 11th thoracic vertebra on preoperative computed tomography., Results: Osteopenia had a high area under the curve and predictive value for both overall survival (OS) and disease-specific survival (DSS). The study cohort was categorized into an osteopenia group and non-osteopenia group based on the optimal BMD cutoff values for OS (157.5) and DSS (195) determined by receiver operating characteristic analysis. The multivariate analysis revealed that OS (hazard ratio=3.607, p<0.001) and DSS (hazard ratio=2.797, p=0.03) were significantly worse in patients with than without preoperative osteopenia., Conclusion: Preoperative osteopenia is associated with poor OS and DSS in patients undergoing gastrectomy for GC., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Laparoscopic distal gastrectomy for gastric cancer has become a common procedure in many institutions. As manual palpation is impossible, various methods have been developed to identify the location of the tumor and determine the proximal resection line. Intraoperative endoscopy requires manpower and is time-consuming. The authors take an intraoperative X-ray. Here, we demonstrate our methods and outcomes., Patients and Methods: We preoperatively applied metal clips just proximal to the tumor through esophagogastroduodenoscopy. During surgery, we applied metal vessel clips to the greater and lesser curvatures of the planned resection line of the stomach and took an intraoperative X-ray to examine the distance between the planned resection line and the tumor. If the distance was appropriate, the stomach was resected on the planned line, and if the distance was judged to be insufficient, the stomach was resected on the more proximal line, as appropriate. An intraoperative frozen section of the proximal resection margin was examined, as appropriate., Results: We performed this method for 71 patients. Tumors were successfully resected together with preoperative endoscopic clips in all patients. In five patients, intraoperative frozen section of the proximal resection margins was positive; however, additional resection confirmed negative margins. One patient underwent total gastrectomy, and the remaining 70 patients underwent distal gastrectomy., Conclusion: An intraoperative X-ray seems to be a simple and useful method for identifying the location of the tumor and determining the proximal resection line., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Poorly differentiated clusters (PDCs) have been reported to be a useful grading system for predicting prognosis in patients with colorectal cancer (CRC). We investigated the association between the number of PDCs and prognosis in patients with stage III CRC treated with oxaliplatin-based adjuvant chemotherapy., Patients and Methods: This is a retrospective study of 49 patients with stage III CRC who underwent curative surgery followed by oxaliplatin-based adjuvant chemotherapy. PDC was defined as a cluster of ≥5 cancer cells without glandular structure at the invasive front of the primary tumor., Results: During the observation period, 12 patients experienced relapse. The patients were divided into two groups (<7 and ≥7 PDC groups), and receiver operating characteristic (ROC) curves were calculated [area under the curve (AUC)=0.743]. Patients with ≥7 PDCs had a much shorter relapse-free survival (RFS) than those with <7 PDCs (p<0.0001). The overall survival (OS) was also significantly worse in patients with ≥7 PDCs than in those with <7 PDCs (p<0.0001). Multivariate analysis revealed that PDC was the only significant prognostic factor measured that could predict RFS (p=0.002) and OS (p=0.0047) in patients with stage III CRC treated with oxaliplatin-based adjuvant chemotherapy., Conclusion: In patients with stage III CRC treated with post-resection oxaliplatin-based adjuvant chemotherapeutic regimens, the presence of ≥7 PDCs at the invasive front of the primary tumor predicted unfavorable prognosis., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To ascertain whether preoperative neo-adjuvant nutritional therapy (NANT) using eicosapentaenoic acid (EPA) supplementation can provoke a rise in blood levels of EPA capable of restricting NF-B nuclear translocation in resected specimens., Patients and Methods: Patients were allocated to two groups depending on individual preference: Patients in the treatment group received 2 g of EPA daily for two weeks prior to surgery (NANT group, n=18). Patients in the control group had a normal diet (CONT group, n=26). NF-B translocation rate, in specimens collected, was investigated by histopathology. Five hundred malignant cells were counted, and tissues with 10% or higher NF-B nuclear translocation were determined to be positive., Results: The EPA blood concentration rose significantly in the NANT group (p<0.01). The positive rate of NF-B nuclear translocation in cancer cells was 11.1% in the NANT group compared with 50% in the CONT group. This difference was statistically significant (p<0.01)., Conclusion: Increased blood concentrations of EPA after preoperative supplementation was associated with suppression of NF-B nuclear translocation in malignant cells. These results suggest that intake of EPA-containing supplements before surgery can control NF-B activation and by extension, cancer aggressiveness., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Biliary fistulas (BFs) following hepatic resection are a complication of concern, and methods to completely prevent BFs after hepatic resection have yet to be developed. Our aim was to study the use of systemically administered indocyanine green (ICG) for preventing bile leakage (BL) from the cut surface of the liver., Patients and Methods: The study sample comprised 26 patients who underwent hepatectomy without ICG (conventional observation group; CO-G) and 23 hepatectomy patients who underwent intraoperative detection of BL using systemically administered ICG (ICG observation group; IO-G). We compared the bilirubin levels in drainage effluent between patients in whom BL from the resected liver was observed using conventional assessment with the naked eye and those in whom ICG leakage was used as an indicator of BL. In the IO-G, we also compared the number of BL spots on the resected plane visible to the naked eye with the number of visible spots on an ICG camera., Results: Three days after surgery, the bilirubin levels in the drainage fluid of the IO-G were significantly lower than those in the CO-G (1.3 vs. 1.9 mg/dl, p=0.019). Two cases (7.7%) of International Study Group of Liver Surgery (ISGLS) grade B biliary fistula occurred in the CO-G, but none in the IO-G. In the IO-G, the number of BL spots detected just after hepatectomy was significantly higher using ICG camera observation than the naked eye observation (0.22 vs. 0.91 spots, p<0.001)., Conclusion: Observation with systemically administered ICG can detect BLs with more sensitivity than conventional observation with the naked eye. This enables rapid repair and may prevent biliary fistula., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study investigated the influence of surgery for metasynchronous liver metastasis in gastric cancer on prognosis., Patients and Methods: A retrospective study was conducted involving 21 consecutive patients with gastric cancer with metasynchronous distant metastasis only in the liver after curative gastrectomy. The patients were divided into two groups: those who underwent hepatic resection and those who did not. The clinicopathological characteristics, recurrence-free survival (RFS), overall survival (OS), and disease-specific survival (DSS) were analysed., Results: Among 981 gastrectomies performed in Tottori University Hospital between 2005 and 2019, 930 were curative. Among 153 cases of recurrence during the follow-up, 21 consecutive cases involving the liver only and metasynchronous recurrent metastasis on imaging were included in this study. The study included 16 males and five females with a median age of 70 years. No statistical difference in RFS (237 vs. 201 days; p=0.788) was observed between the hepatectomy and non-hepatectomy groups; however, OS (1,564 vs. 608 days, p=0.008) and DSS (1,597 vs. 608 days, p=0.006) were significantly prolonged in the hepatectomy group. Univariate and multivariate analyses revealed that hepatectomy was the only independent prognostic factor (hazard ratio=0.33; p=0.042)., Conclusion: Hepatic resection of heterogeneous liver metastases in gastric cancer seems to be a useful option that can be expected to cure the disease, which cannot be achieved by chemotherapy alone., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Recent studies have indicated the clinical significance of tumor-associated macrophages (TAMs) in breast cancer; however, the detailed mechanisms of cell-cell interactions between TAMs and cancer cells remain unclear., Materials and Methods: In vitro cell culture studies using human monocyte-derived macrophages and breast cancer cell lines were performed to test which cytokines would be involved in cell-cell interactions between cancer cells and macrophages. In addition, studies using human resected samples and animal breast cancer models were performed to examine the significance of TAMs in cancer development., Results: Osteopontin, HB-EGF, and IL-6 were suggested to be macrophage-derived growth factors for breast cancer cells. FROUNT inhibitor significantly blocked TAM infiltration and subcutaneous tumor growth in an E0771 mouse breast cancer model., Conclusion: TAMs express growth factors, such as osteopontin, for cancer cells, and targeting of TAM infiltration might be a promising approach for anti-breast cancer therapy., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Maspin is a tumor-suppressor protein expressed in >90% of pancreatic ductal adenocarcinoma (PDAC) cases. We aimed to assess the prognostic value of subcellular localization of maspin., Patients and Methods: Ninety-two resected PDAC specimens were immunohistochemically analyzed. Cytoplasmic-only expression observed in >10% of the tumor was defined as maspin-positive., Results: The maspin-positive status (21.7%) was inversely correlated with well-differentiated histological type and indicated a shorter recurrence-free survival (RFS) and overall survival (OS). Cox's multivariate analysis showed that maspin-positive status was an independent factor for shorter RFS and OS. Maspin was localized to cytoplasm in AsPC-1 cells, but to both nucleus and cytoplasm in BxPC-3 cells. In AsPC-1 cells, cell invasion was significantly reduced in response to maspin suppression via transfection with siRNA targeting maspin, whereas no reduction was observed in BxPC-3 cells., Conclusion: Cytoplasmic-only expression of maspin could be an independent unfavorable prognostic indicator for patients with PDAC., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Despite improved treatment for gastric cancer (GC), the prognosis of advanced disease remains poor. Further investigation of the oncogenic sequence for GC is needed., Materials and Methods: The expression of TYRO3 protein tyrosine kinase in five GC cell lines was confirmed using western blotting. TYRO3 knockdown in GC cells, and bromodeoxyuridine and Transwell assays were used to examine the functions of TYRO3 in tumor proliferation and invasion. Finally, TYRO3 expression in 138 patients who underwent curative gastric resection for advanced GC (Union for International Cancer Control stage II/III) was tested by immunohistochemistry, and the association between prognosis and TYRO3 expression was analyzed., Results: TYRO3 was detected at various levels in all the tested GC cell lines. Deleting TYRO3 significantly suppressed proliferation and invasion. Immunohistochemistry revealed TYRO3 expression was an independent prognostic factor for overall survival in patients with GC., Conclusion: TYRO3 appears to mediate tumor progression and predict prognosis of patients with GC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The survival benefit of negative resection margins in patients who undergo gastrectomy with positive peritoneal lavage cytology (CY1) is unknown., Patients and Methods: We reviewed the medical records of 128 patients with CY1 but no other distant metastases who had undergone R1 gastrectomy, 21 of whom had positive margins. We compared overall survival (OS) according to margin status., Results: The positive-margin group had poorer performance status scores (p=0.02), higher number of patients had undergone limited lymphadenectomy (p=0.01), had type 4 tumors (p=0.01), and undifferentiated type (p=0.02). Median OS was 19.0 and 16.9 months in the groups with negative and positive margins, respectively (HR=1.26, 95%CI=0.75-2.12, p=0.39). An inverse probability of treatment weighted analysis showed an OS of 13.1 and 11.9 months for the groups with negative and positive margins, respectively (HR=0.83, 95%CI=0.43-1.63, p=0.59)., Conclusion: The prognoses of patients with CY1 and negative or positive margins may be equivalent., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The prognosis of pancreatic cancer remains poor with a high incidence of recurrence even after curative resection. The aim of this study was to investigate prognostic factors in patients with recurrent pancreatic cancer using the multicenter database., Patients and Methods: The subjects were 196 patients with recurrent pancreatic cancer who underwent resection between 2008 and 2015. We retrospectively investigated the relation between clinicopathological characteristics of the patients and overall survival from recurrence using univariate and multivariate analyses., Results: In univariate analysis, the positive lymphatic invasion (p=0.0240), time to recurrence from resection <1 year (p<0.0001), sites of recurrence except for local or lymph node (p=0.0273), liver recurrence (p=0.0389) and peritoneal recurrence (p<0.0001) were significantly associated with poor overall survival from recurrence. In multivariate analysis, time to recurrence from resection <1 year (p<0.0001) and peritoneal recurrence (p<0.0001) were independently associated with poor overall survival from recurrence., Conclusion: Time to recurrence from resection <1 year and peritoneal recurrence were significant independent predictors of poor overall survival from recurrence in patients with recurrent pancreatic cancer., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: We aimed to assess surgical outcome and long-term survival after elective hepatic resection for hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) in patients aged 80 years or older., Patients and Methods: This study included 100 patients aged 70 years or older, who underwent hepatic resection for HCC or CRLM between January 2000 and December 2012. Outcomes and clinicopathological data were compared between the elderly (aged 70-79 years; n=84) and extremely elderly groups (aged 80 years or older; n=16)., Results: Incidence of postoperative complications, in-hospital mortality, and postoperative OS in the extremely elderly group were comparable with those of the elderly group. In patients with HCC, the extremely elderly group was associated with shorter DFS (p=0.030) in univariate analysis, while multivariate analysis showed significant and independent factors of cancer recurrence., Conclusion: Hepatic resection for HCC and CRLM in patients aged 80 years and older may be safe and acceptable with appropriate selection. For HCC in patients aged 80 years and older, hepatic resection may be effective when negative surgical margins can be achieved., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The usefulness of C-reactive protein-to-albumin ratio (CAR) as a predictive indicator for clinically-relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD) is unclear. We performed a retrospective analysis to identify reliable inflammatory indicators for prediction of CR-POPF after PD., Patients and Methods: We enrolled 160 consecutive patients who underwent PD. Multivariate logistic regression analysis was performed. The areas under curves (AUCs) were compared with the discriminatory ability of inflammatory indicators, namely, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet count multiplied by C-reactive protein (P-CRP), and CAR., Results: The AUC for CAR on POD 3 to predict CR-POPF was 0.782 (p<0.001) and higher than that for CRP (0.773), NLR (0.652), PLR (0.504), and P-CRP (0.703). Multivariate analysis revealed that CAR on POD 3 was an independent predictive indicator of CR-POPF., Conclusion: CAR on POD 3 is a reliable predictor of CR-POPF after PD., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To evaluate the impact of DEPDC1 expression on patient prognosis after hepatic resection for hepatocellular carcinoma (HCC)., Patients and Methods: We reviewed data from 75 patients who underwent hepatic resection for HCC between 2004 and 2013. Recurrence at 2 years following resection, which mainly included metastatic recurrence, was defined as late recurrence., Results: DEPDC1 was up-regulated in HCC tissue and in non-tumor tissue of patients with HCC compared to normal liver (p<0.01 and p<0.01, respectively). High expression of DEPDC1 was associated with poor overall, disease-specific, and disease-free survival (p=0.02, p<0.01, and p<0.01, respectively). High DEPDC1 expression was an independent predictor of death and recurrence (p=0.03 and p<0.01, respectively). High expression of DEPDC1 in non-tumor liver was an independent risk factor for late recurrence (p=0.04)., Conclusion: High expression of DEPDC1 in tumor tissue appears to be associated with tumor progression and poor prognosis., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Although many prognostic indicators have been identified for resectable gastric cancer (GC), prognostic indicators for unresectable GC (urGC) have not been widely studied. The aim of the current study was to investigate prognostic indicators that could be determined through routine blood examinations in patients with urGC., Patients and Methods: We retrospectively analyzed clinicopathological factors in 92 patients with unresectable advanced and recurrent gastric adenocarcinoma., Results: Based on receiver operating curve analysis, neutrophil-to-lymphocyte ratio (NLR) had the highest area under curve for 1-year survival among patients with urGC. Among patients with urGC, NLR was significantly higher in those with advanced disease compared to those with recurrent disease (p=0.0051); and in those with peritoneal metastasis compared to those without peritoneal metastasis (p=0.041). Patients were divided into NLR High (NLR≥2.83) and NLR Low (NLR<2.83). Their median survival times were NLR High : 9.1 months and NLR Low : 17.1 months (p<0.0001). NLR was also inversely correlated with survival period (r=0.496, p<0.0001); and NLR measured one month after starting chemotherapy was significantly associated with the prognosis of both NLR Low and NLR High patients with urGC. Multivariate analysis showed NLR to be an independent predictor of overall survival in these patients., Conclusion: NLR is useful for predicting the prognosis of patients with unresectable GC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Prediction of local recurrence and distant metastasis is important for patients with pancreatic cancer following pancreatic resection. The aims of this study were to identify a novel prognostic score which combines distance from common hepatic artery (CHA) or superior mesenteric artery (SMA) and examine serum CA19-9 for predicting local recurrence in patients with pancreatic cancer following resection., Patients and Methods: This retrospective study comprised 149 patients who went through elective pancreatic resection for pancreatic cancer between June 2007 and December, 2017. We established new scores (CHA score and SMA score) using the distance between CHA or SMA and the tumor measured by preoperative CT scan in combination with preoperative serum CA19-9 values. We evaluated the relationship between the scores and local recurrence of pancreatic cancer. Finally, we investigated the relationship between the scores and local recurrence-free survival as well as the overall survival., Results: The optimal cut-off levels of the distance between CHA or SMA and the tumor, as determined by ROC analysis, were 20.55 and 10.9 mm, respectively. In a logistic progression model, demonstrated by multivariate analysis, lymphatic invasion (p=0.002), preoperative serum CA19-9 (p=0.007) and SMA score (p=0.004) were identified to be independent predictors of local recurrence in patients with pancreatic cancer following resection. In a Cox progression model, demonstrated by multivariate analysis, intraoperative blood loss (p=0.022), lymphatic invasion (p=0.001) and SMA score (p<0.001) were identified as independent factors of local recurrence. The independent predictors of poor overall survival by multivariate analysis consisted of intraoperative blood loss (p=0.045), intraoperative transfusion (p=0.026) and SMA score (p<0.001)., Conclusion: The SMA score may be an independent preoperative predictor of local recurrence and prognosis in patients with pancreatic cancer., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The albumin-bilirubin (ALBI) grade assesses the severity of liver dysfunction in patients with hepatocellular carcinoma. Herein we investigated the prognostic significance of the combination of the ALBI grade with serum carbohydrate antigen 19-9 (CA 19-9) concentration, the most frequently used tumor marker in pancreatic cancer (PC) in resected patients with PC., Materials and Methods: Included patients (n=100) had a histopathological diagnosis of pancreatic cancer and underwent pancreatectomy. Serum concentrations of albumin, bilirubin, and CA19-9 were measured within 5 days before surgery. Patients were divided into groups with high and low CA19-9 (cut-off ≥35 U/ml) and ALBI grade (2 and 3 vs. 1)., Results: The 5-year overall survival (OS) rates of the ALBI High and ALBI Low groups were 21.6% and 35.3%, respectively (p=0.015). The 5-year OS rates of the CA19-9 High and CA19-9 Low groups were 22.2% and 41.5%, respectively (p=0.017). Patients were divided into groups A (ALBI High and CA19-9 High ), B (ALBI High and CA19-9 Low or ALBI Low and CA19-9 High ), and C (ALBI Low and CA19-9 Low ). The 5-year OS rates of groups A, B, and C were 13.8%, 31.0%, and 43.3%, respectively (p=0.0006). Multivariate analysis revealed that the ALBI grade combined with the CA19-9 concentration, served as an independent prognostic indicator., Conclusion: The combination of ALBI grade and CA19-9 concentration predicted the prognosis of patients with PC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Nutritional status is strongly associated with cancer prognosis. The aim of this study was to identify the most useful combination of nutrition-related serum markers for predicting prognosis of patients with colorectal cancer (CRC)., Patients and Methods: A total of 523 patients who underwent proctocolectomies for CRC at our hospital were enrolled in this study. Serum concentrations of albumin, cholinesterase and total cholesterol, and total peripheral lymphocyte count (TLC) were used as nutrition-related markers., Results: In multivariate analysis of nutrition-related markers, serum albumin and cholinesterase levels were found to be independent prognostic indicators. Cut-off values from receiver operating characteristic analyses were used to sort patients as ChE High or ChE Low (serum cholinesterase level ≥ or <221.5), and as Alb High or Alb Low (serum albumin level ≥ or <3.85). We then sorted them into three groups: ChE High /Alb High (Group A); ChE High /Alb Low or ChE Low /Alb High (Group B); and ChE Low /Alb Low (Group C). Their 5-year overall survival rates differed significantly (Group A: 81.6%, Group B: 62.1%, Group C: 42.7%, p<0.0001); as did their 5-year disease-specific survival rates (Group A: 90.1%, Group B: 73.8%, Group C: 62.2%, p<0.0001)., Conclusion: The combination of serum cholinesterase and albumin levels is useful for predicting the prognosis of patients with CRC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Programmed death-1 (PD1) is an immunoinhibitory receptor, and PD1 overexpression on T-cells is involved in immune evasion in cancer. This study investigated the prognostic significance of PD1 expression on T-cells in gastric cancer., Materials and Methods: PD1 expression on CD4 + and CD8 + T-cells obtained from peripheral blood mononuclear cells was evaluated by multicolor flow cytometry., Results: Based on cutoff values from receiver operating characteristic analysis, patients were sub-grouped according to PD1 positivity as having high or low PD1 + CD4 + T-cell (cutoff ≥34.2%) and PD1 + CD8 + T-cell (cutoff ≥28.7%) frequencies. Five-year overall survival rates differed significantly between the groups with low and high frequency of PD1 + CD4 + T-cells (75.1% vs. 27.2%, respectively; p=0.0008). The 5-year overall survival rates were 78.3% and 37.2%, respectively, for the corresponding PD1 + CD8 + T-cell subgroups (p=0.0004). Multivariate analysis revealed that the frequency of PD1 + CD8 + T-cells was an independent prognostic indicator., Conclusion: The frequency of PD1 + CD8 + T-cells may predict the prognosis of patients with gastric cancer., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: Prognostic factors of recurrence and survival in various cancer types have been reported and include C-reactive protein (CRP)-based measures as evidenced by the Glasgow prognostic score (GPS), as well as peripheral blood cell-based prognostic values such as the prognostic index (PI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). The aim of this study was to identify significant prognostic values and compare them for suitability for use in patients after curative pancreatic resection for pancreatic cancer., Materials and Methods: Between 2000 and 2015, 188 patients were enrolled in this retrospective study. The relationship between clinicopathological variables including various prognostic values and disease-free (DFS) and overall (OS) survival was investigated by univariate analysis. The area under the receiver operating characteristics curve (AUC) was evaluated to compare the predictive ability of each of these scoring systems. Multivariate analysis was then performed to identify clinicopathological variables that associated DFS and OS., Results: In univariate analysis, GPS, modified GPS, CRP to albumin ratio and PI were significant risk factors for both DFS and OS. The AUC of CRP-based scores (GPS, modified GPS, and CRP to albumin ratio) were consistently larger in comparison with PI, which consists of both CRP and peripheral blood cell scores, at all time points for both DFS and OS. In multivariate analysis, GPS was the only independent risk factor of tumor recurrence and survival., Conclusion: CRP-based prognostic scores have an independent value for both tumor recurrence and prognosis in patients after curative resection for pancreatic cancer, and are superior to other peripheral blood cell count-based prognostic scores., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: We retrospectively investigated the relationship between prognosis and combined neutrophil-to-lymphocyte ratio (NLR) and serum carbohydrate antigen 19-9 (CA19-9) levels in patients with recurrent pancreatic cancer., Patients and Methods: We enrolled 66 patients whose pancreatic cancer recurred., Results: Based on ROC analysis results, the patients were divided into NLR High (NLR ≥1.69) or NLR Low (NLR <1.69), and into CA19-9 High (CA19-9 ≥107.95 U/ml) or CA19-9 Low (CA19-9 <107.95 U/ml). When the patients were grouped by combined NLR and CA19-9, their 2-year survival rates were NLR Low /CA19-9 Low : 58.7%; NLR Low /CA19-9 High or NLR High /CA19-9 Low (grouped together): 11.2%; and NLR High /CA19-9 High : 0% (p<0.0001). Finally, in multivariate analysis, the combination of NLR and serum CA19-9 level was an independent prognostic factor in patients with recurrent pancreatic cancer., Conclusion: The combination of NLR and serum CA19-9 level is a useful prognostic indicator for recurrent pancreatic cancer., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Probe-based confocal laser endomicroscopy (pCLE) is a novel diagnostic technique that can provide real-time imaging of tissues at the cellular level. In this study, pCLE was applied to liver tumors and its diagnostic value was evaluated., Patients and Methods: Ten patients who underwent hepatectomy for liver tumors were evaluated with pCLE from February to May 2017. Immediately after liver resection, pCLE evaluation was performed in the operating room as an ex vivo study. The newly-adopted "fluorescein-dripping method" was used for the observation., Results: First, the optimal fluorescein exposure time for the surface of liver was defined in the fluorescein-dripping method. Next, the distinctive findings in the cancerous region were investigated. The characteristic appearance of irregular arrangements of concentrated cells under fluorescein dripping was observed in six of seven hepatocellular carcinoma (HCC) tumors., Conclusion: In all HCC specimens, discrimination of the cancerous region from normal liver was possible with pCLE., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: A recent study demonstrated that immune-checkpoint molecules are associated with tumoral immune evasion., Materials and Methods: Programmed cell death protein 1 (PD-1) expression on CD4 + and CD8 + T-cells obtained from gastric cancer tissue was evaluated by multicolor flow cytometry. Immunohistochemical staining was also performed to evaluate programmed cell death ligand-1 (PD-L1) expression on gastric cancer cells., Results: There were statistically significant correlations between PD-L1 expression and age, histology, tumor size, depth of invasion, lymph node metastasis, lymphatic vessel invasion, venous invasion, and disease stage. The 5-year survival rates of patients with and without PD-L1-positive tumors were 48.9% and 80.7%, respectively, and the difference was statistically significant. Multivariate analysis indicated that PD-L1 expression was an independent prognostic indicator. The frequency of PD-1-positive CD4 + and CD8 + T-cells from gastric cancer tissue with PD-L1 expression was significantly more than that from gastric cancer tissue without PD-L1 expression., Conclusion: PD-L1 expression was related to a poor prognosis in patients with gastric cancer. Furthermore, PD-1 expression on T-cells was up-regulated in patients with tumors with PD-L1 expression., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Colorectal cancer (CRC) is one of the most malignant types of cancer worldwide. Recent studies suggest that a small subpopulation of cells, so-called cancer stem cells (CSCs), promote the high metastasis and relapse associated with CRC. WNT/β-catenin signaling plays a critical role in CSC maintenance. Therefore, its inhibitor may suppress CSCs and improve therapeutic effects on CRC., Materials and Methods: The effects of a derivative of WNT/β-catenin signaling inhibitor, IC-2, which we recently developed, on the CRC cell line DLD-1, were examined by luciferase reporter assay, WST assay, western blot, and sphere assay., Results: The reporter assay showed that IC-2 reduced WNT/β-catenin transcriptional activity in DLD-1 cells. Notably, IC-2 reduced expression levels of CSC marker proteins, as well as sphere formation. In addition, IC-2 increasesd cytotoxicity of 5-fluorouracil (5-FU) in DLD-1 cells., Conclusion: These results suggest that the combination treatment of IC-2 and 5-FU can stimulate tumor-suppressive effects on CRC., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: This prospective randomized study compared the survival of patients with stage IB-IIIA gastric cancer treated with surgery alone or surgery followed by adjuvant chemotherapy., Patients and Methods: Patients with pathological stage IB-IIIA disease were randomly assigned to the following groups: surgery alone (n=116), or surgery followed by adjuvant chemotherapy with 5-fluorouracil, doxifluridine, or uracil-tegafur for 12 months (n=113)., Results: The overall survival rate was 86.1% in the adjuvant group and 78.5% in the surgery-alone group. The overall survival rate did not significantly differ between the adjuvant-chemotherapy and surgery-only groups (p=0.163). In the subgroup analyses, patients with stage II disease and those receiving uracil-tegafur treatment in the adjuvant group showed significantly better prognosis than those in the surgery-alone group (p=0.036 and 0.005, respectively)., Conclusion: This study did not find a significant survival benefit to be associated with adjuvant chemotherapy with fluoropyrimidines in patients with stage IB-IIIA gastric cancer. However, it may be effective for patients with stage II disease. Additionally, uracil-tegafur is a promising agent for adjuvant chemotherapy of gastric cancer if S-1 is not available because of its toxicity., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: The aim of this study was to assess changes in body composition during neoadjuvant chemotherapy (NAC) and investigate whether chemotherapy-related toxicities affect body composition in patients with esophageal cancer., Patients and Methods: In ninety-four patients who underwent NAC for esophageal cancer, body composition was assessed before and after NAC. Associations between the incidence of toxicities and change in body composition during NAC were investigated., Results: Forty-four (46.8%) and 50 (53.2%) out of 94 patients were defined as having sarcopenia before and after NAC, respectively. There was no significant difference in the incidence of any toxicity pre-treatment between patients with sarcopenia and those without sarcopenia. No significant reduction in skeletal muscle mass or fat mass was observed in the patients during NAC (p=0.501 and p=0.072). However, patients who experienced grade 4 neutropenia or febrile neutropenia during NAC showed a significantly larger decrease in change of skeletal muscle mass compared to patients who did not experience those toxicities (p=0.013 and 0.036, respectively)., Conclusion: The incidence of serious adverse events such as febrile neutropenia and grade 4 neutropenia is associated with a significant reduction of skeletal muscle mass during NAC. We should make an effort to reduce the incidence of adverse events in order to maintain an appropriate body composition during NAC., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Preoperative biliary drainage (PBD) is often performed for jaundiced patients. However, the optimal duration of PBD remains unknown. The aim of this study was to investigate whether duration of PBD influenced the prognosis of patients after pancreaticoduodenectomy (PD) for pancreatic head cancer., Patients and Methods: Twenty-five patients who underwent PD for pancreatic head cancer with obstructive jaundice between 2007 and 2013 were included. Tumor and host factors were analyzed to evaluate their potential prognostic effects and patients' characteristics between the two groups according to the duration of PBD were analyzed., Results: In multivariate analysis, overall survival, duration of PBD ≥21 days and tumor-node-metastasis (TNM) stage III or IV were significant predictors. Duration of PBD ≥21 days was positively correlated with higher level of serum C-reactive protein (CRP), modified Glasgow prognostic score (mGPS) and neoadjuvant therapy., Conclusion: Duration of PBD is an independent prognostic factor after PD for pancreatic head cancer with obstructive jaundice., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The aim of this study was to evaluate a novel prognostic value of preoperative platelet-to-albumin ratio (PAR) in patients resected for pancreatic cancer., Patients and Methods: A total of 107 patients who underwent pancreatic resection for pancreatic cancer were studied. The patients were divided into two groups as PAR ≥46.4×10 3 or <46.4×10 3 Survival data were analyzed using the log-rank test for univariate analysis and Cox proportional hazards for multivariate analysis., Results: The PAR was a significant prognostic index on univariate analysis for disease-free survival (DFS) and overall survival (OS). The PAR retained its significance on multivariate analysis for OS (hazard ratio(HR)=2.344, 95% confidence interval(CI)=1.188-4.624, p=0.014) along with tumor differentiation and nodal involvement. PAR was a significant independent prognostic index for poor DFS on multivariate analysis (HR=1.971, 95% CI=1.128-3.444, p=0.017)., Conclusion: The preoperative PAR is a novel significant independent prognostic index for DFS and OS in patients after pancreatic resection with curative intent., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Angiogenesis is a known factor for the development of hepatocellular carcinoma (HCC). The aim of this study was to assess the property of iguratimod, that is an anti-inflammatory drug for rheumatoid arthritis, on anti-angiogenesis and anti-carcinogensis for HCC., Materials and Methods: In vitro, human umbilical vein endothelial cells were cultured under interleukin-8 (IL-8) with or without iguratimod. In vivo, a rat model with HCC received iguratimod or distilled water for 6 weeks. Diameter of the largest tumor, number of tumors and serum interleukin-8 concentration were compared between iguratimod and control groups., Results: By an in vitro angiogenesis assay, it was found angiogenesis in iguratimod group was significantly lower than that in control group (p=0.013). In vivo, largest tumor diameter (p=0.036), number of the tumor (p=0.011) and serum interleukin-8 concentration (p=0.036) in the iguratimod group were significantly smaller and lower than those in the control group., Conclusion: Iguratimod may inhibit hepatocellular carcinogensis by inhibition of interleukin-8 production in a rat model., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: No standard chemotherapy for adults with recurrent/refractory rhabdomyosarcoma (RMS) has yet been established. The present study aimed to assess the effect of ifosfamide and etoposide (IE) chemotherapy on previously treated RMS., Patients and Methods: Adults with recurrent/refractory RMS were treated with ifosfamide (1,800 g/m(2)/day), etoposide (100 mg/m(2)/day) and mesna (1,080 mg/m(2)/day) for 5 days. The effect and toxicity were evaluated by chart review., Results: Fifteen patients, with a median age of 33 years (range=25-67 years), were treated with IE chemotherapy. A median of six cycles of chemotherapy were administered and an objective response was obtained in eight patients. The median progression-free survival was 5.2 months (95% confidence interval=2.3-6.7 months) and overall survival was 14.4 months (95% confidence interval=4.6-28.3 months). Toxicity greater than grade 3 was as follows: neutropenia in all patients, anemia in seven, thrombocytopenia in seven and febrile neutropenia in eight., Conclusion: IE chemotherapy could be an alternative optional treatment method in adults with recurrent/refractory RMS., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Preoperative systemic inflammatory response is associated with a poor long-term prognosis after resection of malignant tumors. Several indicators of systemic inflammation have been reported to be predictive of outcomes, but have not been fully investigated. The aim of the present study was to evaluate the significance of the preoperative neutrophil to lymphocyte ratio (NLR) in therapeutic outcomes after pancreaticoduodenectomy for carcinoma of the ampulla of Vater., Patients and Methods: The study comprised of 37 patients who had undergone pancreaticoduodenectomy for carcinoma of the ampulla of Vater between January 2000 and December 2011. We retrospectively investigated the relation between preoperative NLR and disease-free as well as overall survival., Results: In multivariate analysis, preoperative biliary drainage (p=0.044) and pN2 or pN3 (p=0.027) status were independent and significant predictors of cancer recurrence, while significant predictors of overall survival consisted of pN2 or pN3 (p=0.025) and NLR ≥3 (p=0.026)., Conclusion: Preoperative NLR is an independent and significant indicator of long-term outcome in patients with carcinoma of the ampulla of Vater after pancreaticoduodenectomy. Measurement of NLR may help decision making in the postoperative management of patients with carcinoma of the ampulla of Vater., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: The prognosis for advanced gastric cancer with paraaortic lymph node (PALN) metastasis is very poor even after a curative resection. In the present study, induction chemotherapy followed by curative surgery was performed for advanced gastric cancer with PALN metastasis., Patients and Methods: Twenty patients with no non-curative factors except PALN metastasis who showed good clinical response for induction chemotherapy were enrolled in the study., Results: Combined S-1 plus cisplatin chemotherapy was administered to 10 patients; docetaxel, 5-FU plus cisplatin, to 5; S-1 plus paclitaxel to 3; and capecitabine plus cisplatin, to 2 patients. The overall response rate was 80% (16 out of 20 patients responded). All patients underwent curative gastrectomy with extended lymphadenectomy including the PALNs. Out of the 20 patients, 8 survived more than 5 years, and the 3- and 5-year survival rates were 72% and 65%, respectively. Female gender and residual PALN metastasis were significantly associated with worse prognosis and patients with a diffuse-type histology had a tendency to worse prognosis., Conclusion: Induction chemotherapy followed by curative surgery including extended PALN dissection seems a promising strategy for advanced gastric cancer with PALN metastasis as a sole distant metastasis, particularly for male patients and those with intestinal-type histology., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background/aim: The perioperative immunological response predicts long-term outcomes after resection for malignant tumors. The aim of the study was to evaluate the significance of perioperative change in the peripheral blood monocyte count regarding therapeutic outcome after pancreaticoduodenectomy for bile duct cancer., Patients and Methods: The study comprised of 51 patients who had undergone pancreaticoduodenectomy for bile duct cancer between January 2000 and December 2012. We retrospectively investigated the relation between perioperative change in peripheral blood monocyte count and disease-free as well as overall survival., Results: In multivariate analysis, advanced TNM stage, and decrease in monocyte count on postoperative day 1 in comparison with those before surgery were independent and significant predictors of poor disease-free survival and overall survival (p=0.014 and 0.004, and 0.010 and 0.006, respectively)., Conclusion: Perioperative change in peripheral blood monocyte count is an independent and significant indicator of therapeutic outcome after pancreaticoduodenectomy in patients with bile duct cancer., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background/aim: Patients with obstructive jaundice due to cancer of the pancreatic head often undergo preoperative endoscopic biliary drainage (EBD). The aim of the study was to evaluate the long-term impact of preoperative EBD following pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma., Patients and Methods: We studied 106 patients who underwent PD for pancreatic ductal adenocarcinoma between May 2000 and November 2013 at the Jikei University Hospital. We retrospectively examined perioperative findings as predictors of prognosis and the relationship between preoperative EBD and recurrence rate as well as overall survival., Results: In univariate analysis, significant factors associated with poor disease-free survival consisted of the presence of EBD (p=0.0213), poor tumor differentiation (p=0.0023) and tumor-node-metastasis (TNM) classification IV (p=0.0027), while significant factors associated with poor overall survival consisted of the presence of EBD (p=0.0047), poor tumor differentiation (p<0.0001), TNM classification IV (p=0.0031) and microscopic or macroscopic residual tumor (p=0.0184). In multivariate analysis, poor tumor differentiation (p=0.0033) and TNM classification IV (p=0.0020) were independent factors for poor disease-free survival, while the presence of EBD (p=0.0435), poor tumor differentiation (p=0.0009), TNM classification IV (p=0.0447) and microscopic or macroscopic residual tumor (p=0.0184) were independent factors for poor overall survival., Conclusion: Preoperative EBD may have a negative impact on prognosis after PD for pancreatic ductal adenocarcinoma., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objectives: Despite improvements in surgical techniques, instruments and perioperative management, postoperative pancreatic fistula (POPF) remains a serious complication after pancreaticoduodenectomy. The aim of the present study was to characterize a high-risk group for POPF after pancreaticoduodenectomy using perioperative clinical variables of patients., Patients and Methods: This retrospective study comprised of 247 patients who had undergone pancreaticoduodenectomy between May 2000 and May 2013. Perioperative risk factors pertinent to development of POPF were investigated using univariate and multivariate analyses., Results: POPF developed in 43 out of 247 patients (17.4 %). In univariate analysis, male gender (p=0.005), higher postoperative serum amylase (p=0.025) and lower postoperative serum albumin (p=0.041) were significant risk factors for POPF. In multivariate analysis, male gender (p=0.008) and lower postoperative serum albumin (p=0.010) were found to be independent risk factors., Conclusion: Male gender and postoperative lower serum albumin were associated with the development of POPF after pancreaticoduodenectomy., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: The aim of this study was to evaluate the significance of postoperative peripheral absolute blood lymphocyte-to-monocyte (ALC/AMC) ratio in pancreatic resections for pancreatic carcinoma., Patients and Methods: One hundred eleven patients who underwent pancreatic resection for pancreatic carcinoma were included in this study. We retrospectively examined perioperative findings as predictors of therapeutic outcome and the relation between postoperative ALC/AMC ratio and recurrence rate as well as overall survival of the patients with pancreatic carcinoma., Results: In univariate analysis, advanced tumor-node-metastasis (TNM) classification (p=0.0002), intraoperative flesh-frozen plasma (FFP) transfusion (p=0.0395), increased in preoperative serum carbohydrate antigen 19-9 (CA19-9) (p=0.0051) and lower postoperative ALC/AMC ratio (p=0.0007) were positively associated with poor disease-free survival. Advanced TNM classification (p=0.0008), intraoperative FFP transfusion (p=0.0343), elevated postoperative serum C-reactive protein (CRP) (p=0.0165) and lower postoperative ALC/AMC ratio (p=0.0029), as well as decreased preoperative lymphocyte counts (p=0.0248) were positively associated with poor overall survival. In multivariate analysis, advanced TNM classification (p=0.007), intraoperative FFP transfusion (p=0.0197), increase in preoperative serum CA19-9 (p=0.0075) and lower postoperative ALC/AMC ratio (p=0.0051) were independent factors for poor disease-free survival. Advanced TNM classification (p=0.0083), lower postoperative ALC/AMC ratio (p=0.0070) and elevated postoperative serum CRP (p=0.0094) were independent factors for poor overall survival., Conclusion: Lower postoperative peripheral ALC/AMC ratio may have a negative impact on recurrence and overall survival after pancreatic resection for pancreatic carcinoma., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: The aim of this study was to characterize a high-risk group of patients for pancreatic fistula (PF) after pancreatic resection using postoperative clinical variables of patients., Patients and Methods: The retrospective study included 297 patients who underwent pancreatic resection between January 2001 and December 2011. We examined the relationship between perioperative findings and the incidence of postoperative PF (POPF) among patients who underwent pancreatic resection between 2001 and 2009 (early period). Next, patients were stratified into three groups using serum albumin and CRP on postoperative day 1 (score 0: albumin ≥2.7 g/dl and CRP ≤10 mg/dl; score 1: albumin <2.7 g/dl or CRP >10 mg/dl; score 2: albumin <2.7 g/dl and CRP >10 mg/dl) as postoperative inflammatory score (PIS). We examined perioperative findings including PIS and POPF among patients who underwent pancreatic resection between 2010 and 2011 (late period)., Results: In univariate and multivariate analyses, male gender (p=0.032), serum albumin on postoperative day 1 (p=0.024) and serum CRP on postoperative day 1 were identified as independent risk factors for POPF in early-period patients. In univariate and multivariate analyses, postoperative hospital stay (p=0.009) and PIS (score 1: p=0.005, score 2: p=0.017) were identifical as independent risk factors for POPF in late-period patients., Conclusion: We found a novel PIS to indicate risk for PF after elective pancreatic resection.

Background: Excessive blood loss and blood transfusion may influence postoperative complications and prognosis of patients after pancreatic resection. We evaluated the influence of blood products use on postoperative recurrence and outcome of patients with pancreatic ductal adenocarcinoma., Patients and Methods: The study included 82 patients who underwent elective pancreatic resections for pancreatic ductal adenocarcinoma without distant metastasis or other malignancies between January 2001 and December 2010. We retrospectively investigated the influence of the use of perioperative blood products including red cell concentrate, fresh-frozen plasma (FFP), and albumin preparation, and clinical variables regarding disease-free and overall survival., Results: In disease-free survival, serum carcinoembryonic antigen more than 10 ng/ml (p=0.015), serum carbohydrate antigen 19-9 (CA19-9) more than 200 U/ml (p=0.0032), R1 resection (p=0.005), and FFP transfusion were independent risk factors for cancer recurrence in the Cox proportional regression model, pancreaticoduodenectomy (p=0.057) and advanced tumor stage (p=0.083) tended to associate with poor disease-free survival, but were not statistically significant. In overall survival, male gender (p=0.012), advanced tumor stage (p=0.005), serum CA19-9 more than 200 U/ml (p<0.001), and FFP transfusion (p=0.003) were positively associated with poor overall survival in the Cox proportional regression model., Conclusion: FFP transfusion is associated with poor therapeutic outcome after elective pancreatic resection for pancreatic ductal adenocarcinoma.

Background: Gallbladder carcinoma (GBC) is a cancer of the digestive tract with poor prognosis, for which surgical resection is the only potentially curative therapy. The prognostic value of postoperative peripheral blood leukocyte subset count in patients with cancer has not been fully investigated. Therefore, we retrospectively investigated the relation-ship between postoperative peripheral blood lymphocyte count and disease-free as well as overall survival after radical resection of GBC., Patients and Methods: The study subjects were 34 patients who underwent radical resection for GBC between January 2005 and April 2010. We retrospectively investigated the relation-ship between clinicopathological variables, including postoperative peripheral blood lymphocyte count, and disease-free as well as overall survival., Results: In univariate analysis, disease-free survival was worse in patients with intraoperative blood transfusion (p=0.0285), tumor node metastasis (TNM) stage ≥II (p<0.0001), and lymphocyte count of less than 1,000/μl (p=0.0002). Overall survival was worse in patients with TNM stage ≥II (p=0.0002) and lymphocyte count of less than 1,000/μl (p=0.0151). In multivariate analysis, TNM stage ≥II (p<0.0089) and peripheral blood lymphocyte count of less than 1,000/μl (p=0.0365) were independent predictors of poor disease-free survival. For overall survival, TNM stage ≥II (p=0.0230) was the only independent predictor. Moreover, lymphocyte counts of less than 1,000/μl correlated significantly with TNM stage ≥II, duration of operation, greater blood loss, and presence of intraoperative blood transfusion., Conclusion: Postoperative peripheral blood lymphocyte count correlates with outcome of patients with GBC treated by radical resection.

Background: In perioperative management of hepatic resection for colorectal cancer liver metastasis (CRLM), excessive blood loss and blood transfusion greatly influence postoperative complications and prognosis of the patients. We evaluated the influence of the use of blood products on prognosis of patients with CRLM., Patients and Methods: The subjects of this study were 65 patients who underwent elective hepatic resection between January 2001 and April 2011 for CRLM without distant metastasis or other malignancy. We retrospectively investigated the influence of the use of blood products, including red cell concentrate (RC) and fresh frozen plasma (FFP), and clinical variables on overall survival., Results: In univariate analysis, bilobar distribution (p=0.0332), more than four lymph node metastases of the primary cancer (p=0.0155), perioperative RC use (p=0.0205), and perioperative FFP use (p=0.0065) were positively associated with poor overall survival rate. In multivariate analysis, bilobar distribution (p=0.0012), more than four lymph node metastases of the primary cancer (p=0.0171), and perioperative FFP use (p=0.0091), were independent risk factors for poor overall survival rate., Conclusion: The use of FFP is associated with worse overall survival after elective hepatic resection for patients with CRLM.