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BACKGROUND Oligometastasis, the presence of a small number of resectable metastatic tumors, usually has favorable outcomes. Here we examined whether the novel oligometastatic score (OLGS), which divides the number of colorectal liver metastases (CRLMs) by the time from colorectal resection to liver recurrence, better predicts CRLM patient survival than the commonly used clinical risk score. METHODS A total of 143 patients who underwent curative hepatectomy for CRLMs between 2007 and 2018 were analyzed. We investigated their clinical characteristics and outcomes using OLGS. RESULTS Of the 143 CRLM patients, 70 had synchronous CRLMs and 73 had metachronous CRLMs. Patients with metachronous CRLMs were divided into OLGS-low (n = 59) and OLGS-high (n = 14) subgroups. The 5-year overall survival (OS) rates after hepatectomy differed significantly between the subgroups (p

BACKGROUND/AIM The regulation of gene expression by miRNAs plays an important role in cancer progression. Here, we investigated the role of miR-3663-3p in gastric cancer. PATIENTS AND METHODS The relationship between miR-3663-3p expression, clinicopathological features and prognosis were retrospectively analyzed in 80 gastric cancer patients. RESULTS miR-3663-3p expression was significantly lower in gastric cancer tissue than adjacent non-cancerous tissue (p=0.002). Recurrence free survival was significantly lower in patients with low miR-3663-3p expression (p=0.016). Low miR-3663-3p expression was also an independent predictive factor for recurrence (p=0.029). Overexpression of miR-3663-3p in gastric cancer cell lines significantly suppressed cell proliferation, migration/invasion, and induced G0/G1 arrest (p

Background/aim This study aimed to investigate the impact of the inferior mesenteric artery (IMA) lymph node metastasis [IMALN (+)] on prognosis in left-sided colorectal cancer (LCRC). Patients and methods A total of 285 patients with stage III LCRC and 118 patients with stage IV LCRC who underwent resection of primary tumor between 2005 and 2016 were included. Results IMALN (+) patients (n=10) had worse overall survival (OS) than patients without IMA lymph node metastasis [IMALN (-); n=275] in stage III LCRC (p=0.007). Multivariate analysis revealed that IMALN (+) was a prognostic factor in stage III LCRC (OS, HR=3.09, p=0.043). Conversely, there was no difference between the OS of IMALN (+) and stage IV LCRC with distant lymph node metastasis only [stage IV LCRC (LYM); n=21; p=0.434]. Conclusion The prognosis of IMALN (+) was worse than that of IMALN (-); it was similar to that of stage IV LCRC (LYM).

The function of ANO9 in gastrointestinal cancer remains unclear. We investigated the biological behaviors and clinical prognostic values of ANO9 in gastric cancer (GC). Knockdown experiments were performed on human GC cell lines using ANO9 siRNA. Eighty‐four primary tissue samples from patients with advanced GC were examined immunohistochemically (IHC). Knockdown of ANO9 reduced the progression of cancer cells in MKN7 and MKN74 cells. A microarray analysis revealed that ANO9 regulated PD‐L2 via interferon (IFN)‐related genes. We confirmed using flow cytometry that the depletion of ANO9 reduced the binding ability to PD‐1 by downregulating the expression of PD‐L2 in MKN7 and MKN74 cells. IHC revealed a correlation between the expression of ANO9 and PD‐L2 and also that the strong expression of ANO9 was an independent poor prognostic factor in patients with advanced GC. The present results indicate that ANO9 regulates PD‐L2 and binding ability to PD‐1 via IFN‐related genes in GC. Therefore, ANO9 has potential as a biomarker and target of immune checkpoint blockage (ICB) for GC., The depletion of ANO9 reduced the binding ability to PD‐1 by downregulating the expression of PD‐L2 in GC cells. This is the first report to clarify the mechanism of ANO9 regulating the immune escape of cancer cells via PD‐L2.

Background/aim Ultrasonically activated surgical devices (USADs) have become indispensable instruments for gastrointestinal surgery. In this study, we investigated the oncological safety of the use of USADs. Materials and methods We harvested and cultivated the splashes and mist scattered from an USAD when cutting MKN45-derived cancer nodules. Seven days later, we observed viable cancer cells and the total number of cells was counted. The histopathology of the nodules cut by the USAD was also examined. Results The existence of viable cancer cells was confirmed by ex vivo cell culture. The number of viable cancer cells was reduced by slow grasping of the USAD. The surface of cancerous tissue cut by the USAD was partially heat-denatured, however, there were some parts in which cancerous tissue was exposed on the surface. Conclusion Surgeons should recognize the possibility that cancer cells may be scattered by USAD use.

Glucose fluctuation after gastrectomy represented by dumping syndrome is a well-known post-gastrectomy syndrome that negatively impacts patient quality of life. However, the current methods of post-gastrectomy glucose monitoring do not comprehensively capture the postoperative blood glucose fluctuations that characterize this. We used a continuous glucose monitoring (CGM) system to document the glycemic profiles of patients undergoing gastrectomy and compared these between patients undergoing distal gastrectomy (DG) and total gastrectomy (TG). To evaluate post-gastrectomy syndromes, including dumping syndrome, we used the Post-gastrectomy Syndrome Assessment Scale 37-item questionnaire. The glycemic profiles were also compared using this tool. We studied 57 patients who had undergone DG and 13 who had undergone TG between September 2017 and September 2019. Our results revealed larger diurnal glycemic variability and longer periods of nocturnal hypoglycemia after gastrectomy. The dumping score was worse in the TG than in the DG group (TG 2.4 ± 1.4 vs. DG 1.3 ± 1.2, P = 0.0061). Importantly, 30 of 57 DG patients (52.6%) and 5 of 13 TG patients (38.5%) experienced postprandial hypoglycemia following hyperglycemia without hypoglycemic symptoms. There was no correlation between the dumping symptom score and glycemic variability (ρ = 0.0545, P = 0.6662). CGM demonstrated diurnal glycemic variability and nocturnal hypoglycemia in patients undergoing gastrectomy. Because some hypoglycemic patients did not develop symptoms and glycemic variability was not necessarily associated with dumping symptom, dumping syndrome must only partially explain the postoperative glucose fluctuations.

The significance of spirometry as preoperative risk assessment for gastrointestinal surgery has been controversial. At the beginning of the COVID-19 pandemic, preoperative spirometry was temporarily suspended in our institute. This study was aimed to investigate the necessity of spirometry for gastrointestinal cancer surgery.We compared short-term postoperative outcomes between 318 patients who underwent surgery for colorectal or gastric cancer with (Spirometry group; n=272) or without spirometry (Non-spirometry group; n=46).Respiratory functional disorders were detected in 77 (28.3%) patients in the Spirometry group. No significant differences were noted in complications, including pneumonia, or the length of hospital stay between the two groups. An advanced age, male sex, comorbidities with respiratory diseases, and a smoking history significantly correlated with abnormal results in spirometry.Preoperative spirometry may be substituted with other clinical factors in patients with gastrointestinal cancer.

This retrospective study investigated the clinical significance of vertical location in gastric cancer (GC) and the optimal treatment strategy according to the vertical location.Between 1997 and 2018, 1,304 consecutive patients with GC who underwent curative surgical resection with lymphadenectomy were analyzed retrospectively.Patients with GC in the anterior wall (AW) had a significantly better prognosis compared to those in other sites of the lower third stomach (p=0.040). Multivariate analysis showed that tumor location in the AW was an independent prognostic factor and was associated with a lower incidence of lymph node metastasis (LNM) (p=0.023). The frequency of LNM in the area of D2 was lower in patients with AW GC than those with GC in other locations.Patients with AW GC had a favorable prognosis, with a lower incidence of LNM in lower-third GC.

Background: Breast cancer often metastasizes to the lungs, bones, liver, and brain, colon metastasis from breast cancer (CMBC) is extremely rare. Case Report: The patient was a 63-year-old female. Mastectomy had been performed for breast cancer (pStage IIB) 15 years earlier at another hospital. Metastasis to the lumbar spine had been detected 4 years prior to referral to us and the patient had undergone hormonal therapy with an aromatase inhibitor. Furthermore, early primary sigmoid colon cancer had been endoscopically resected 2 years before referral. The patient was diagnosed with cancer recurrence in the colon at follow-up examinations performed 2 years after that endoscopic resection. After referral to our hospital, laparoscopic sigmoidectomy was performed. Based on the histopathological examination and immunohistological staining results (positive for cytokeratin 7, GATA-binding protein 3, estrogen receptor and human epidermal growth factor receptor-related 2 (2+); negative for cytokeratin 20, progesterone receptor, E-cadherin, gross cystic disease fluid protein 15 and caudal-related homeobox 2) the final pathological diagnosis was CMBC. Conclusion: Although extremely rare, the possibility of CMBC should be considered in the case of colonic tumors in patients with a history of breast cancer.

Preoperative or induction chemotherapy with docetaxel, cisplatin, plus 5‐fluorouracil (DCF) is a promising regimen for advanced esophageal cancer. However, the DCF regimen is associated with a high risk of severe neutropenia or febrile neutropenia (FN). However, the current guidelines fail to recommend an optimal dosing schedule of pegfilgrastim along with the DCF regimen to prevent FN. In the present study, we assessed the efficacy and safety of giving pegfilgrastim early on day 3 during DCF therapy for esophageal cancer. In this single‐arm phase II study, patients with squamous cell carcinoma of the esophagus were recruited. They were treated with the DCF therapy on days 1‐5, with pegfilgrastim given on day 3. Primary endpoint was the occurrence of grade 4 neutropenia. Secondary endpoints included the incidence of FN, grade 3 neutropenia, dose delays/reductions, antitumor effect, and safety. Between July 2016 and December 2018, 23 patients were enrolled. The incidence of grade 4 neutropenia was 8.7% (95% confidence interval 1.1%‐28.0%). No patient experienced FN. Of the 19 patients who received two cycles of DCF, one required a dose reduction/treatment delay due to hematological toxicity in the second treatment cycle. No serious adverse events, considered relevant to pegfilgrastim, were observed. This is the first prospective study that showed an efficacious dosing schedule of pegfilgrastim for preventing hematological toxicity during DCF therapy. The results might be generalized to other similar regimens where continuous infusions of 5‐fluorouracil are used., This study is a prospective clinical trial showing that giving pegfilgrastim early, as primary prophylaxis in docetaxel, cisplatin, plus 5‐fluorouracil (DCF) therapy, is effective and safe in reducing the risk of severe neutropenia and FN. We believe that our study makes a significant contribution to the literature because this is the first study to provide supporting evidence on early dosing of pegfilgrastim during DCF therapy.

The volume-regulated anion channel is composed of leucine-rich repeat-containing protein A (LRRC8A) and is activated by hypotonic conditions to implement the process of regulatory volume decrease. The role of LRRC8A in regulating genes related to progression of esophageal squamous cell carcinoma (ESCC) was investigated, as well as the prognostic significance of LRRC8A expression in this tumor. Knockdown experiments were conducted using ESCC cell lines and LRRC8A siRNA to assess the influence of this protein on tumor function. In addition, the gene expression profile of ESCC was determined by microarray analysis. Immunohistochemistry was performed on 64 primary tumor samples from ESCC patients receiving radical esophagectomy. It was found that depletion of LRRC8A decreased cell proliferation and migration and also promoted apoptosis. Microarray data demonstrated G1/S checkpoint regulation and up-regulation or down-regulation of phosphatidylinositol 3-kinase/AKT signaling, matrix metalloproteinase, and integrin signaling-related genes (including p21, p27, MMP1, and ITGAV) in LRRC8A-depleted cells. Immunohistochemistry showed that LRRC8A expression was related to the pathologic N and T stage categories, and strong LRRC8A expression was correlated with a worse prognosis of ESCC. These findings indicate that LRRC8A modulates tumor progression by influencing cell cycle, apoptosis, and migration, providing new insights into its function as an effector or biomarker of ESCC.

Immunonutritional status is a known prognostic correlate in the context of gastric cancer (GC). In the present study, we investigated the prognostic relevance of a lipid profile-based immunonutritional score in patients with GC. Data pertaining to 224 patients with stage II and III GC who underwent curative gastrectomy were retrospectively analyzed. The total cholesterol-lymphocyte score (TL score) was defined as follows: patients with both low total cholesterol (TC) and total lymphocyte count were allocated a score of 2; patients with only one or none of these biochemical abnormalities were allocated a score of 1 or 0, respectively. Among the serum lipid indices, low TC was the strongest predictor of cancer-specific survival (CSS; p = 0.001). On multivariate analysis, both low prognostic nutritional index (PNI) (p

Background Robotic surgical systems have advantages over laparoscopic surgery. The object of this study was to assess patients' postoperative outcomes after robotic distal gastrectomy (RDG) compared to laparoscopic distal gastrectomy (LDG). Patients and methods We retrospectively evaluated 21 and 119 patients who underwent RDG and LDG, respectively, for stage I gastric cancer. Short-term outcomes were compared including drain amylase levels and quality of life using a post-gastrectomy syndrome questionnaire. Results No patients experienced pancreatic fistula or anastomosis-related complications following RDG. The rate of overall complications tended to be lower in patients undergoing RDG. In addition to drain amylase level, inflammatory findings were lower after RDG than LDG. Patients undergoing RDG experienced a better quality of life and less dissatisfaction in daily life. Conclusion RDG is feasible and produced highly-satisfactory results for early gastric cancer. We believe that the effective use of robotic surgery will increase safety and precision in minimally invasive surgery.

Background/aim This study examined whether functional outcomes of linear-stapled Billroth I (LS-BI) in totally laparoscopic distal gastrectomy (TLDG) are comparable to those of circular-stapled Billroth I (CS-BI) in laparoscopy-assisted distal gastrectomy (LADG). Patients and methods This was a retrospective study of patients with gastric cancer undergoing TLDG with LS-BI (n=50) or LADG with CS-BI (n=50). Postoperative endoscopic findings of the remnant stomach and nutritional status were evaluated. Results The occurrence of grade 2 or more severe remnant gastritis in the LS-BI group (46.0%) was significantly higher than that in the CS-BI group (18.0%) (p=0.005), whereas there was no significant difference in the incidence of residual food and bile reflux between the two groups. Postoperative changes in body weight, and serum albumin and total protein levels were similar between the two groups. Conclusion TLDG with LS-BI may be a good alternative to LADG with CS-BI because of its comparable nutritional outcomes, but with a higher occurrence of remnant gastritis.

The NaKnockdown experiments were conducted on human GC cell lines using ATP1A1 siRNA, and its effects on proliferation, the cell cycle, apoptosis, and cellular movement were examined. Gene expression profiling was performed by a microarray analysis. Primary tumor samples from 192 GC patients who underwent gastrectomy were subjected to an immunohistochemical analysis.High ATP1A1 expression levels were observed in NUGC4 and MKN74 cells. Cell proliferation was suppressed and apoptosis was induced by the siRNA-induced knockdown of ATP1A1. The microarray analysis showed that knockdown of ATP1A1 leads to the up-regulated expression of genes involved in the interferon (IFN) signaling pathway, such as STAT1, STAT2, IRF1, and IRF9. Furthermore, the depletion of ATP1A1 altered the phosphorylation of the MAPK pathway. The immunohistochemical analysis revealed that the expression of ATP1A1 was associated with the histological type, venous invasion, and the pathological T stage. Furthermore, the prognostic analysis showed a relationship between high ATP1A1 expression levels and poor postoperative survival.ATP1A1 appears to regulate tumor progression by altering IFN signaling, and high ATP1A1 expression levels were associated with poor postoperative survival in GC patients. The present results provide novel insights into the function of ATP1A1 as a mediator and/or biomarker of GC.

The significance of the duration of the recurrence-free survival after curative resection for colorectal cancer remains unclear. The purpose was to reveal the association between time to recurrence after surgery and the survival after recurrence. Patients with stage II and III colorectal cancer who underwent curative resection between 2007 and 2015 were retrospectively reviewed (n = 645). Patients with recurrence after surgery (n = 133) were divided into 2 groups: early recurrence (within 13 months after surgery, n = 63) and late recurrence (more than 13 months after surgery, n = 70). The overall survival after recurrence and clinicopathological features were compared between early recurrence, late recurrence, and without recurrence groups. The overall survival after recurrence was significantly shorter in patients with early recurrence occurring at less than 13 months (hazard ratio: 1.70, p = 0.03). A high preoperative CA19-9 level (odds ratio [OR]: 2.38, p = 0.03), venous invasion (OR: 2.26, p = 0.03), and the absence of adjuvant chemotherapy (OR: 2.08, p = 0.04) were independently correlated with early recurrence. Early recurrence was associated with a poor prognosis after recurrence. Venous invasion correlated with early recurrence. Adjuvant chemotherapy may reduce the risk of early recurrence. These results indicate the importance of prudent surveillance and the aggressive application of adjuvant chemotherapy.

Clinical significance of plasma urothelial carcinoma associated 1 (UCA1) in patients with colorectal cancer (CRC) remains unclear. This study investigated the usefulness of plasma UCA1 as a biomarker in patients with CRC.UCA1 levels were measured in the plasma and tissue from patients with CRC by quantitative polymerase chain reaction. Relationships between plasma UCA1 and clinicopathological features were examined.Plasma UCA1 levels were significantly lower in patients with CRC than in healthy volunteers. UCA1 expression in B-Raf proto-oncogene serine/threonine kinase (BRAF)-mutant CRC tissue was also lower than that in non-cancerous tissue, although it was higher in CRC with wild-type BRAF. In right-sided CRC, a lower plasma UCA1 level was associated with pT4 and BRAF mutation. In contrast, in left-sided CRC, higher plasma UCA1 was associated with pT4 and pStage 3b-4.Plasma UCA1 is a useful biomarker for CRC detection and predicting clinicopathological features, particularly BRAF mutation.

The targeting of membrane proteins that are activated in cancer stem cells (CSCs) represents one of the key recent strategies in cancer therapy. The present study analyzed ion channel expression profiles and functions in pancreatic CSCs (PCSCs). Cells strongly expressing aldehyde dehydrogenase 1 family member A1 (ALDH1A1) were isolated from the human pancreatic PK59 cell line using fluorescence‑activated cell sorting, and PCSCs were identified based on tumorsphere formation. Microarray analysis was performed to investigate the gene expression profiles in PCSCs. ALDH1A1 messenger RNA levels were higher in PCSCs compared with non‑PCSCs. PCSCs were resistant to 5‑fluorouracil and capable of redifferentiation. The results of the microarray analysis revealed that gene expression related to ion channels, including voltage‑gated potassium channels (Kv), was upregulated in PCSCs compared with non‑PCSCs. 4‑Aminopyridine (4‑AP), a potent Kv inhibitor, exhibited greater cytotoxicity in PCSCs compared with non‑PCSCs. In a xenograft model in nude mice, tumor volumes were significantly lower in mice inoculated with PK59 cells pre‑treated with 4‑AP compared with those in mice injected with non‑treated cells. The present results identified a role of Kv in the persistence of PCSCs and suggested that the Kv inhibitor 4‑AP may have potential as a therapeutic agent for pancreatic carcinoma.

Purpose The long-term prognostic impact of the hemoglobin A1c levels has not yet been evaluated in patients with gastric cancer. The present study investigated the clinical significance of the hemoglobin A1c levels in patients with gastric cancer. Methods We enrolled 294 patients with stage II, III, or IV gastric cancer who underwent gastrectomy. The patients were divided into high preoperative hemoglobin A1c (> 6.0%) and low preoperative hemoglobin A1c (≤ 6.0%) groups. Results In patients with stage III gastric cancer with severe postoperative complications, the high preoperative hemoglobin A1c group had a significantly worse prognosis than the low preoperative hemoglobin A1c group (p = 0.0409). In patients without severe postoperative complications, the high preoperative hemoglobin A1c group had a significantly favorable prognosis compared with the low preoperative hemoglobin A1c group (p = 0.0348). Conclusion The prognosis of patients with stage III gastric cancer having high preoperative hemoglobin A1c levels greatly depended on the presence or absence of postoperative complications. To avoid postoperative complications, optimal perioperative management and personalized treatments are critical, particularly for these patients.

Purpose Diagnosing early gastric cancer (EGC) or advanced gastric cancer (AGC) according to T-category is important for optimal GC treatment; however, the clinical and pathological diagnosis of tumor depths can sometimes vary. This study investigated the accuracy of clinical diagnosis of the tumor depth from the viewpoint of tumor localization and prognosis of patients with GC with discordance between clinical and pathological findings. Methods This study enrolled 741 patients with primary GC who underwent curative gastrectomy. Based on the clinical and pathological diagnosis of T-category, the patients were classified into four groups: Early-look EGC, Early-look AGC, Advanced-look EGC, and Advanced-look AGC. Tumor localization was classified longitudinally (the upper [U], middle [M], and lower [L] parts and cross-sectionally (the anterior [Ant] and posterior [Post] walls, and the lesser [Less] and greater [Gre] curvatures). Results Of the 462 clinical EGC cases, 52 were Early-look AGC cases that exhibited a significant association of tumor localization with the Post and Less in the U and M locations (UM-PL; p = 0.037). An Advanced-look EGC (p = 0.031) and Advanced-look AGC (p = 0.025) were independent prognostic factors for relapse-free survival each in pathological EGC and AGC, respectively. Conclusions Patients with clinically diagnosed EGC but with pathologically diagnosed AGC more frequently presented tumor in the UM-PL than in any other location. Selection of therapeutic strategy according to the clinical diagnosis might be critical; however, it should be also considered that the accuracy of preoperative assessments varies with tumor localization.

This study aimed to explore novel microRNAs in plasma for predicting chemoresistance in adjuvant chemotherapy for patients with gastric cancer (GC). We used the Toray 3D-Gene microRNA array-based approach to compare preoperative plasma microRNA levels between GC patients with and without recurrences after curative gastrectomy. All patients underwent adjuvant chemotherapy with S-1, an oral fluoropyrimidine. Of 2566 candidates, six candidate microRNAs (miR-1229-3p, 1249-5p, 762, 711, 1268a and 1260b), which were highly expressed in the preoperative plasma of patients with subsequent recurrences, were selected. In a large-scale validation analysis by quantitative RT-PCR, we focused on high plasma levels of miR-1229-3p, which was an independent poor prognostic factor for recurrence free survival (P = 0.009, HR = 3.71). Overexpression of miR-1229-3p in GC cells induced significant chemoresistance to 5-fluorouracil (5-FU), up-regulation of thymidylate synthase (TS) and dihydroprimidine dehydrogenase (DPD) and down-regulation of SLC22A7 both in vitro and in vivo. Intraperitoneal injection of miR-1229-3p in mice induced significant chemoresistance to 5-FU, accompanied by high levels of miR-1229-3p in plasma and tumor tissue. These findings suggest that plasma miR-1229-3p might be a clinically useful biomarker for predicting chemoresistance to S-1 and selecting other or combined intensive chemotherapy regimens in GC patients.

BACKGROUND/AIM Trans-hiatal and -cervical approach mediastinoscopic radical esophagectomy (TMrE) for esophageal cancers is a less-invasive procedure and does not require for trans-thoracic approach management. However, some patients suffer from pleural effusion after TMrE. In the present study, we investigated the clinicopathological factors of patients needing drainage of pleural effusion (DPE) after TMrE. PATIENTS AND METHODS This study included 118 patients who underwent TMrE between 2010 and 2016. RESULTS There were 43, 34 and 41 patients that underwent none, a single, and two or more DPEs respectively. Left-side DPE was significantly more frequent compared to right-side DPE. Change in the C-reactive protein (CRP) levels after surgery was significantly higher in patients with multiple DPEs than patients with none or a single DPE. The hospitalization days were significantly longer for patients with multiple DPEs. CONCLUSION Pleural effusion accumulates due to continuous inflammation. Although a temporary DPE is sometimes performed, post-operative chest drainage tubes are not necessarily needed.

Recent studies have described important roles for the sodium iodide symporter (NIS) in tumor behavior. The objectives of the present study were to investigate the role of NIS in the regulation of genes involved in tumor progression and the clinicopathological significance of its expression in gastric cancer (GC). In human GC cell lines, knockdown experiments were conducted using NIS siRNA, and the effects on proliferation, survival, and cellular movement were analyzed. The gene expression profiles of cells were examined using a microarray analysis. An immunohistochemical analysis was performed on 145 primary tumor samples obtained from GC patients. NIS was strongly expressed in MKN45 and MKN74 cells. The depletion of NIS inhibited cell proliferation, migration, and invasion and induced apoptosis. The results of the microarray analysis revealed that various interferon (IFN) signaling-related genes, such as STAT1, STAT2, IRF1, and IFIT1, were up-regulated in NIS-depleted MKN45 cells. Furthermore, the down-regulation of NIS affected the phosphorylation of MAPKs and NF-kB. Immunohistochemical staining showed that NIS was primarily located in the cytoplasm or cell membranes of carcinoma cells, and its expression was related to the histological type or venous invasion. Prognostic analyses revealed that the strong expression of NIS was associated with shorter postoperative survival. These results suggest that NIS regulates tumor progression by affecting IFN signaling, and that its strong expression is related to a worse prognosis in patients with GC. These results provide an insight into the role of NIS as a mediator and/or a biomarker for GC.

BACKGROUND/AIM A recent nationwide survey using the National Clinical Database in Japan identified a high proportion of low-weight patients, who are defined as low body mass index (BMI) patients, in comparison with Western countries. This study was designed to investigate the influence of low BMI on short- and long-term outcomes after curative gastrectomy for gastric cancer. PATIENTS AND METHODS Overall, 1,281 consecutive gastric cancer patients, who underwent curative gastrectomy with radical lymphadenectomy from 1997 through 2012 were retrospectively analyzed. Low BMI and non-low BMI were defined as a BMI 18.5 kg/m2, respectively. RESULTS Compared to patients with BMI higher than 18.5, those with BMI

5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is widely used for the intraoperative detection of malignant tumors. However, the fluorescence emission profiles of the accompanying necrotic regions of these tumors have yet to be determined. To address this, we performed fluorescence and high-performance liquid chromatography (HPLC) analyses of necrotic tissues of squamous cancer after 5-ALA administration. In resected human lymph nodes of metastatic squamous cell carcinoma, we found a fluorescence peak at approximately 620 nm in necrotic lesions, which was distinct from the PpIX fluorescence peak at 635 nm for viable cancer lesions. Necrotic lesions obtained from a subcutaneous xenograft model of human B88 oral squamous cancer also emitted the characteristic fluorescence peak at 620 nm after light irradiation: the fluorescence intensity ratio (620 nm/635 nm) increased with the energy of the irradiation light. HPLC analysis revealed a high content ratio of uroporphyrin I (UPI)/total porphyrins in the necrotic cores of murine tumors, indicating that UPI is responsible for the 620 nm peak. UPI accumulation in necrotic tissues after 5-ALA administration was possibly due to the failure of the heme biosynthetic pathway. Taken together, fluorescence imaging of UPI after 5-ALA administration may be applicable for the evaluation of tumor necrosis.

AIM To investigate the efficacy of thrombomodulin (TM)-α for treatment of disseminated intravascular coagulopathy (DIC) in the field of gastrointestinal surgery. METHODS Thirty-six peri-operative DIC patients in the field of gastrointestinal surgery who were treated with TM-α were retrospectively investigated. The relationships between patient demographics and the efficacy of TM-α were examined. Analysis of survival at 28 d was also performed on some parameters by means of the Kaplan-Meier method. Relationships between the initiation of TM-α and patient demographics were also evaluated. RESULTS Abscess formation or bacteremia was the most frequent cause of DIC (33%), followed by digestive tract perforation (31%). Twenty-six patients developed DIC after surgery, frequently within 1 wk (81%). TM-α was most often administered within 1 d of the DIC diagnosis (72%) and was continued for more than 3 d (64%). Although bleeding tendency was observed in 7 patients (19%), a hemostatic procedure was not needed. DIC scores, systemic inflammatory response syndrome (SIRS) scores, quick-sequential organ failure assessment (qSOFA) scores, platelet counts, and prothrombin time ratios significantly improved after 1 wk (P < 0.05, for all). The overall survival rate at 28 d was 71%. The duration of TM-α administration (≥ 4 , ≤ 6) and improvements in DIC-associated scores (DIC, SIRS and qSOFA) at 1 wk were significantly better prognostic factors for 28-d survival (P < 0.05, for all). TM-α was administered significantly earlier to patients with severe clinical symptoms, such as high qSOFA scores, sepsis, shock or high lactate values (P < 0.05, for all). CONCLUSION Early administration of TM-α and improvements in each parameter were essential for treatment of DIC. The diagnosis of patients with mild symptoms requires further study.

// Katsutoshi Shoda 1 , Daisuke Ichikawa 1 , Yuji Fujita 1, 2 , Kiyoshi Masuda 2 , Hidekazu Hiramoto 1 , Junichi Hamada 1 , Tomohiro Arita 1 , Hirotaka Konishi 1 , Toshiyuki Kosuga 1 , Shuhei Komatsu 1 , Atsushi Shiozaki 1 , Kazuma Okamoto 1 , Issei Imoto 2 , Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan 2 Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan Correspondence to: Daisuke Ichikawa, email: ichikawa@koto.kpu-m.ac.jp Issei Imoto, email: issehgen@tokushima-u.ac.jp Keywords: gastric cancer, Epstein–Barr virus, liquid biopsy Received: October 29, 2016 Accepted: February 6, 2017 Published: February 24, 2017 ABSTRACT Recent comprehensive molecular subtyping of gastric cancer (GC) identified Epstein–Barr virus (EBV)-positive tumors as a subtype with distinct salient molecular and clinical features. In this study, we aimed to determine the potential utility of circulating cell-free EBV DNA as a biomarker for the detection and/or monitoring of therapeutic response in patients with EBV-associated gastric carcinoma (EBVaGC). The EBV genes-to-ribonuclease P RNA component H1 ratios (EBV ratios) in the GC tumors and plasma samples were determined by quantitative real-time polymerase chain reaction in 153 patients with GC, including 14 patients with EBVaGC diagnosed by the conventional method. Circulating cell-free EBV DNA was detected in 14 patients with GC: the sensitivity and specificity of detection were 71.4% (10/14) and 97.1% (135/139), respectively. Plasma EBV ratios were significantly correlated with the size of EBVaGC tumors, and the plasma EBV DNA detected before surgery in EBVaGC cases disappeared after surgery. Patients with EBVaGC may have a better prognosis, but circulating cell-free EBV DNA had no or little impact on prognosis. In addition, repeated assessment of the plasma EBV ratio in EBVaGC showed a decrease and increase in plasma EBV DNA after treatment and during tumor progression/recurrence, respectively. These results suggest the potential utility of circulating cell-free DNA to reveal EBV DNA for the identification of the EBVaGC subtype and/or for real-time monitoring of tumor progression as well as treatment response in patients with EBVaGC.

// Atsushi Shiozaki 1, * , Michihiro Kudou 1, * , Daisuke Ichikawa 1 , Hiroki Shimizu 1 , Tomohiro Arita 1 , Toshiyuki Kosuga 1 , Hirotaka Konishi 1 , Shuhei Komatsu 1 , Hitoshi Fujiwara 1 , Kazuma Okamoto 1 , Mitsuo Kishimoto 2 , Yoshinori Marunaka 3, 4 , Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan 2 Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan 3 Department of Molecular Cell Physiology and Bio-Ionomics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan 4 Japan Institute for Food Education and Health, St. Agnes’ University, Kyoto, 602-8013, Japan * These authors have contributed equally to this work Correspondence to: Atsushi Shiozaki, email: shiozaki@koto.kpu-m.ac.jp Keywords: AE1, esophageal squamous cell carcinoma, MAPK, Hedgehog signaling pathway, cellular physiology Received: April 20, 2016 Accepted: January 04, 2017 Published: January 30, 2017 ABSTRACT Recent studies have described important roles for the anion exchanger (AE) in epithelial carcinogenesis and tumor behavior. The objectives of the present study were to investigate the role of AE1 in the regulation of genes involved in tumor progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy. AE1 was primarily located in the cell membranes or cytoplasm of carcinoma cells, and its distribution pattern was related to the histological degree of the differentiation of SCC or the pT category. Among patients with pT2-3 ESCC, the 5-year survival rate of patients with diffuse AE1 expression (40.2%) was significantly lower than that of patients with focal expression (74.0%). AE1 was strongly expressed in KYSE150 and TE8 human ESCC cells. The depletion of AE1 using siRNA inhibited cell proliferation, migration, and invasion and induced apoptosis. The results of the microarray analysis revealed that MAPK and Hedgehog signaling pathway-related genes, such as DHH, and GLI1, were down-regulated in AE1-depleted KYSE150 cells. In conclusions, the results of the present study suggest that the diffuse expression of AE1 is related to a worse prognosis in patients with advanced ESCC, and that it regulates tumor progression by affecting MAPK and Hedgehog signaling pathways. These results provide an insight into the role of AE1 as a mediator of and/or a biomarker for ESCC.

Background Precise staging is indispensable to select the appropriate treatment strategy for gastric cancer (GC); however, the diagnostic accuracy of conventional modalities needs to be improved. This study investigated the clinical significance of the preoperative neutrophil-to-lymphocyte ratio (NLR) for the prediction of pathological lymph node metastasis (pN+) in GC. Methods This was a retrospective study of 429 patients with GC who underwent curative gastrectomy. The predictive ability of NLR for pN+ was examined in comparison with that of computed tomography. Results The preoperative NLR ranged from 0.6 to 10.8 (median, 2.0), and the optimal cut-off value for predicting pN+ was 1.6 according to the receiver operating characteristic curve with the maximal Youden index. Multivariate analysis identified a NLR ≥ 1.6 (odds ratio (OR) 3.171; 95% confidence interval (CI) 1.448–7.235, p = 0.004) and cN+ (OR 2.426; 95% CI 1.221–4.958, p = 0.011) to be independent factors associated with pN+ in advanced GC (cT2-T4). On the other hand, a NLR ≥ 1.6 was not useful for predicting pN+ in early GC (cT1). In advanced GC, a NLR ≥ 1.6 detected pN+ with a higher sensitivity (84.9%) and negative predictive value (NPV) (63.9%) than conventional modalities (50.0 and 51.7%, respectively). When the subjects were limited to those with advanced GC with cN0, the sensitivity and NPV of a NLR ≥ 1.6 for pN+ increased further (90.7 and 81.0%, respectively). Conclusion The preoperative NLR may be a useful complementary diagnostic tool for predicting pN+ in advanced GC because of its higher sensitivity and NPV than conventional modalities.

Background: Transient receptor potential vanilloid 2 (TRPV2) was recently shown to be involved in migrant potentials. The present study aimed to investigate its role in esophageal squamous cell carcinoma (ESCC). Methods: Knockdown experiments were conducted using TRPV2 siRNA in human ESCC cell lines, and anti-tumor effects were analyzed. The gene expression profiles of cells were analyzed using a microarray method. An immunohistochemical staining was performed on 62 primary tumor samples. Results: TRPV2 overexpression was observed in TE15 and KYSE170 cells. TRPV2 depletion suppressed proliferation, cell cycle progression, and invasion/migration ability, and induced apoptosis. A pathway analysis of microarray data showed that TRPV2 depletion down-regulated WNT/β-catenin signaling-related genes and basal cell carcinoma signaling-related genes. The suppression of tumor functions, such as proliferation, invasion, and angiogenesis, was predicted in the ontology analysis. Immunohistochemical analysis revealed a correlation between strong TRPV2 expression and a poor prognosis in ESCC patients. Conclusion: The present results suggest that TRPV2 regulates cancer progression by affecting WNT/β-catenin or basal cell carcinoma signaling, and that TRPV2 strong expression is associated with a worse prognosis in ESCC patients. These results provide an insight into the role of TRPV2 as a novel therapeutic target or biomarker for ESCC.

BACKGROUND/AIM This study examined whether the prognostic nutritional index (PNI) is a useful predictor of pathological lymph node metastasis (pN+) in gastric cancer (GC). PATIENTS AND METHODS This study retrospectively examined 167 patients with advanced GC (cT2-T4) undergoing curative gastrectomy. The predictive ability of PNI for pN+ was evaluated in comparison with that of clinical lymph node metastasis (cN+) determined by computed tomography (CT). RESULTS The optimal cut-off value of PNI for predicting pN+ was 46 according to the receiver operating characteristic curve analysis. Multivariate analysis revealed a PNI

The patient was a 69-year-old woman.Upper gastrointestinal endoscopy showed a protruding tumor in the mid-thoracic esophagus, and biopsy revealed small cell carcinoma in November 2012. Four courses of neoadjuvant chemotherapy comprising CDDP and CPT-11 were administered, and radical resection was performed in March 2013.I n March 2014, chest computed tomography revealed the recurrence of mediastinal lymph nodes; thus, we administered chemoradiotherapy comprising 5- FU and CDDP, and the size of the recurrent tumors decreased.However, in February 2015, positron emission tomographycomputed tomography revealed liver metastases.Therefore, we switched to a new chemotherapy regimen containing CDDP and VP-16.Although the treatment was very effective and the liver metastases significantly decreased in size, it was discontinued after 9 courses owing to neurotoxicity.Next, 7 courses of chemotherapy comprising amrubicin, which is administered for treating small cell lung carcinoma, were administered, which suppressed tumor growth for approximately 8 months.However, the tumor then re-grew.Chemotherapy comprising S-1 was administered; however, the tumor gradually progressed.The patient died 51 months after the initial treatment.

This study aimed to investigate the abilities of the modified Glasgow prognostic score (mGPS) and other inflammatory scores to predict recurrence-free survival (RFS) among patients with colon cancer (CC). In addition, we evaluated the abilities of the mGPS to predict recurrence of stage II disease and the efficacy of adjuvant chemotherapy (AC) for stage III disease. This retrospective study evaluated 477 patients with stage I–III CC who underwent curative surgery. These patients were categorized as having a low mGPS (mGPS 0) or a high mGPS (mGPS 1–2). Patients in the high mGPS group had significantly poorer RFS than patients in the low mGPS group (p

BACKGROUND/AIM Surgical therapy for stage IV gastric cancer patients is still debatable. The clinical outcomes were compared between gastrojejunal bypass and gastrectomy for metastatic gastric cancer patients. PATIENTS AND METHODS A total of 110 patients with metastatic gastric cancer who underwent surgery were retrospectively analyzed. Twenty-nine patients underwent gastrojejunal bypass (group B) and 81 underwent gastrectomy (group G). RESULTS There was no significant difference in the 3-year overall survival between Group G patients with partial gastrectomy and total gastrectomy. However, patients in group G had a significantly better prognosis compared to patients in group B (p=0.01 and 0.03, respectively). The prognosis of patients with postoperative chemotherapy was significantly better in group G compared to group B (p=0.03), whereas it was not significantly different for the patients without postoperative chemotherapy (p=0.24). CONCLUSION Gastrectomy in patients with metastatic gastric cancer may improve survival when combined with postoperative chemotherapy.

Case 1 was that of a 65-year-old woman. Radical esophagectomy was performed after neoadjuvant chemotherapy(NAC) for lower thoracic esophageal cancer. Nineteen months after surgery, local recurrence was indicated on the dorsal side of the descending aorta. After chemoradiotherapy(CRT)and chemotherapy, residual cancer with aortic invasion was diagnosed. Case 2 was that of a 64-year-old man. Radical esophagectomy was performed after NAC for middle thoracic esophageal cancer. Five months after surgery, local recurrence was indicated between the descending aorta and left inferior pulmonary vein. After CRT and chemotherapy, residual cancer with invasion of the aorta and left lung was diagnosed. In both cases, we inserted an aortic stent and safely performed residual cancer resection including the aortic adventitia. In summary, aortic stent insertion enables safe resection of local recurrent tumors in the aorta after radical esophagectomy.

A 42-year-old woman with complaints of fever and abdominal pain, was diagnosed to have perforative appendicitis, for which emergency surgery was performed. Marked thickening and edema around the cecum, ileum, and the mesentery was observed. Ileocecal resection was performed, as malignant disease could not be excluded. Histopathological examination revealed abscess formation in the lining membrane of the intestine, inflammatory granulation and proliferation of the spindleshaped cells in the serosal membrane extensively, and an inflammatory pseudotumor(IPT)was diagnosed. It is generally difficult to clearly distinguish IPT from a malignant tumor before surgery. We thus report this case, along with a review of literature.

Recent studies identified that low levels of tumour suppressor microRNAs (miRNAs) in plasma/serum relate to tumour progression and poor outcomes in cancers. We selected six candidates (miR-126, 133b, 143, 203, 338-3p, 655) of tumour suppressor miRNAs in oesophageal squamous cell carcinoma (ESCC) by a systematic review of NCBI database. Of these, miR-655 levels were significantly down-regulated in plasma of ESCC patients compared to healthy volunteers by test- and validation-scale analyses. Low levels of plasma miR-655 were significantly associated with lymphatic invasion, lymph node metastasis and advanced stage. Univariate and multivariate analysis revealed that the low level of plasma miR-655 was an independent risk factor of lymphatic progression and a poor prognostic factor. Overexpression of miR-655 in ESCC cells inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition. Increased plasma miR-655 levels by the subcutaneous injection significantly inhibited lymph node metastasis in mice. Low levels of miR-655 in plasma relate to lymphatic progression and poor outcomes, and the restoration of the plasma miR-655 levels might inhibit tumour and lymphatic progression in ESCC. Electronic supplementary material The online version of this article (10.1186/s12943-018-0929-3) contains supplementary material, which is available to authorized users.

Undernutrition and sarcopenia are associated with a higher incidence of chemotherapy-related toxicity and a poor prognosis in several kinds of cancer, but the impact of sarcopenia on the outcomes of chemotherapy for esophageal cancer remains unclear. Thus, the purpose of this retrospective study was to investigate whether sarcopenia affects the efficacy and toxicities of chemotherapy for advanced esophageal cancer patients. Data were collected from 31 esophageal cancer patients who underwent neo-adjuvant chemotherapy followed by surgery. Body composition was assessed at the start of chemotherapy by bioelectrical impedance analysis, and outcomes of chemotherapy were compared between sarcopenic and non-sarcopenic groups. Of the 31 patients, sarcopenia was observed in 16 (51.6%). The incidence of toxicities was not different between the two groups. However, as for pathologic response, a good therapeutic effect (Grade 2 or higher) was more common in the non-sarcopenic group than in the sarcopenic group (53.3% vs. 25.0%). Multivariate analysis showed that sarcopenia was an independent predictor of poor pathological response (odds ratio 8.02; P = 0.037). The results of this study suggest the potential utility of sarcopenia assessment in neoadjuvant patient selection strategies.

Background: PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) is a serine–threonine kinase and overexpressed in various types of cancer by inhibiting the transactivation activities of p53 and PTEN. We tested whether PBK/TOPK acts as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). Methods: We analysed five GC cell lines and 144 primary tumours, which were curatively resected in our hospital between 2001 and 2003. Results: Overexpression of the PBK/TOPK protein was frequently detected in GC cell lines (4 out of 5 lines, 80.0%) was detected in primary tumour samples of GC (24 out of 144 cases, 16.6%) and was significantly correlated with venous invasion, tumour depth and recurrence rate. PDZ-binding kinase/T-LAK cell-originated protein kinase-overexpressing tumours had a worse survival rate than those with non-expressing tumours (P=0.0009, log-rank test). PDZ-binding kinase/T-LAK cell-originated protein kinase positivity was independently associated with a worse outcome in multivariate analysis (P

Aim The present study aimed to retrospectively investigate the utility of positron-emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (PET-CT) in regular follow-ups after esophageal cancer surgery.Clinical outcomes were retrospectively analyzed for 61 patients who were diagnosed with postoperative recurrence using PET-CT.A univariate analysis revealed that single recurrence, a low cytokeratin 19 fragment (CYFRA) value, chemoradiotherapy against recurrence, and recurrence over 6 months after surgery were significant prognostic factors. A low CYFRA level and single recurrence tended to be good prognostic factors in the multivariate analysis. The prognosis of cases with single recurrent tumor of size less than 10 mm was significantly better than those with tumors of 10 mm or more. PET-CT revealed small recurrent tumors, and contributed to the early detection of recurrence outside the body trunk.PET-CT contributes to the detection of single small recurrent tumors and those outside the body trunk. This follow-up method using PET-CT should be considered for patients after esophageal cancer surgery.

// Shuhei Komatsu 1, * , Daisuke Ichikawa 1 , Tsutomu Kawaguchi 1, * , Hiroki Takeshita 1 , Mahito Miyamae 1 , Takuma Ohashi 1 , Wataru Okajima 1 , Taisuke Imamura 1 , Jun Kiuchi 1 , Tomohiro Arita 1 , Hirotaka Konishi 1 , Atsushi Shiozaki 1 , Hitoshi Fujiwara 1 , Kazuma Okamoto 1 , Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan * These authors contributed equally to this work Correspondence to: Shuhei Komatsu, email: skomatsu@koto.kpu-m.ac.jp Keywords: plasma, microRNA, biomarker, prognosis, chemoresistance Received: March 27, 2016 Accepted: August 10, 2016 Published: August 22, 2016 ABSTRACT BACKGROUND: This study aims to explore novel microRNAs in plasma for predicting chemoresistance in preoperative chemotherapy of patients with esophageal squamous cell carcinoma (ESCC) using a microRNA array-based approach. RESULTS: (1) Four candidate microRNAs ( miR-223, 103a, 23b and 23a ), which were highly expressed in the pretreatment plasma of patients with a low histopathologic response, were selected. (2) In a large-scale validation analysis by quantitative RT–PCR, plasma levels of miR-223, miR-23b and miR-23a were significantly higher in patients with a low histopathologic response than in those with a high histopathologic response ( p = 0.0345, p = 0.0125 and p = 0.0114). (3) Of all candidate microRNAs, miR-23a expression of pretreatment ESCC tumor tissues was significantly higher in ESCC patients with a low histopathologic response than in those with a high histopathologic response ( p = 0.0278). (4) After overexpressing each candidate in ESCC cells, miR-23a induced significant chemoresistance to both 5-fluorouracil and cisplatin, and miR-223 to cisplatin in vitro . (5) A high level of plasma miR-23a , which tended to correlate with lymphatic invasion ( p = 0.0808) and deep depth of invasion ( p = 0.0658), was an independent risk factor for chemoresistance in ESCC ( p = 0.0222; odds ratio: 12.4; range 1.46–105). MATERIALS AND METHODS: We used the Toray ® 3D-Gene microRNA array-based approach to compare plasma microRNA levels between patients with a high or a low histopathologic response to chemotherapy. All patients underwent a preoperative chemotherapy regimen with cisplatin plus 5-fluorouracil. CONCLUSIONS: Plasma miR-23a might be a useful biomarker for predicting chemoresistance in ESCC patients.

// Wataru Okajima 1, * , Shuhei Komatsu 1, * , Daisuke Ichikawa 1 , Mahito Miyamae 1 , Tsutomu Kawaguchi 1 , Shoji Hirajima 1 , Takuma Ohashi 1 , Taisuke Imamura 1 , Jun Kiuchi 1 , Tomohiro Arita 1 , Hirotaka Konishi 1 , Atsushi Shiozaki 1 , Ryo Moriumura 1 , Hisashi Ikoma 1 , Kazuma Okamoto 1 , Hiroki Taniguchi 2 , Yoshito Itoh 3 , Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan 2 Department of Surgery, Kyoto Second Red Cross Hospital, Haruobicho, Kamigyo-ku, 602-8026, Kyoto, Japan 3 Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan * These authors contributed equally to this work Correspondence to: Shuhei Komatsu, email: skomatsu@koto.kpu-m.ac.jp Keywords: plasma, circulating microRNA, liquid biopsy, liver cirrhosis, tumor marker Received: February 17, 2016 Accepted: July 09, 2016 Published: July 22, 2016 ABSTRACT Aims: This study was designed to identify novel microRNAs (miRNAs) in plasma for detecting and monitoring hepatocellular carcinoma (HCC), independent of hepatic function and background liver diseases with different etiologies. Results: (1) Four oncogenic miRNAs (miR-151, 155, 191 and 224) with high expression in HCC tissues were selected as candidates. (2) Quantitative RT-PCR using plasma samples from 107 HCC patients and 75 healthy volunteers revealed a significantly higher level of plasma miR-224 in HCC patients than in healthy volunteers according to a small-scale analysis (P < 0.0001), two independent large-scale cohort analysis (P < 0.0001, AUC 0.908). (3) miR-224 expression was significantly higher in HCC tissues and HCC cell lines than in normal hepatic tissues and fibroblasts, respectively. (P = 0.0011, 0.0150) (4) Plasma miR-224 reflected tumor dynamics; preoperative plasma levels of miR-224 were significantly reduced in postoperative samples (P = 0.0058), and plasma miR-224 levels were significantly correlated with paired miR-224 levels in HCC tissues (P = 0.0005). (5) Furthermore, plasma miR-224 levels significantly discriminated HCC patients from patients with chronic liver disease (P = 0.0008). A high plasma miR-224 level was significantly correlated with larger tumor size (P = 0.0005) and recurrences (P = 0.0027). The plasma miR-224 level could accurately detect small tumors less than 18 mm preoperatively. Methods: We performed a systematic review of the NCBI database and selected candidate miRNAs reported as highly expressed in HCC tissue. Conclusions: Plasma miR-224 may be a sensitive biomarker for screening HCC and monitoring tumor dynamics.

Recent studies have shown that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was overexpressed in many human solid cancers, however, its roles in plasma of hepatocellular carcinoma (HCC) patients were unclear. The aim of this study was to investigate the significance of plasma MALAT1 levels in HCC patients. Plasma samples were collected from pre-operative HCC, hepatic disease patients, and healthy controls, and tissue samples from HCC patients and colorectal cancer patients with liver metastasis. Plasma and tissue MALAT1 levels were measured. Plasma MALAT1 levels were progressively and significantly higher in HCC patients than hepatic disease patients, and higher in hepatic disease patients than healthy controls. The expression of MALAT1 in HCC tissue was slightly higher than that in paired non-cancerous liver tissue, but not significant. The expression of MALAT1 in the non-cancerous liver tissue of 20 HCC patients was significantly higher than that in normal liver tissue of 13 colorectal cancer patients. In contrast, plasma MALAT1 levels were significantly low in HCC patients with hepatitis B infection, and significantly high in patients with liver damage B or liver cirrhosis. In a receiver-operator curve analysis of HCC and hepatic disease patients, the cut-off value of plasma MALAT1 was 1.60 and the area under the curve was 0.66. Plasma MALAT1 levels were not correlated with α-fetoprotein or protein induced by vitamin K absence II, whereas sensitivity and specificity for the detection of HCC with the combination of MALAT1, α-fetoprotein, and protein induced by vitamin K absence II were 88.6% and 75%, respectively. In conclusion, the plasma MALAT1 level is associated with liver damage, and has clinical utility for predicting development of HCC.

BACKGROUND/AIM The present study aimed to clarify an accurate diagnostic method for lymph node metastasis (LN+) in rectal neuroendocrine tumors (rNETs). PATIENTS AND METHODS This was a retrospective study of 14 rNETs and 45 rectal adenocarcinoma patients undergoing rectal resection. The short axis of LNs was measured using CT and pathological findings (43 paraffin-fixed LNs in rNETs and 786 LNs in adenocarcinoma). RESULTS The size of LN+ in CT and pathological findings was smaller in rNETs than adenocarcinoma (p=0.082 and p

Background/aim Few studies have examined postoperative CRP in esophageal cancer. We investigated the relationship between postoperative CRP values according to the postoperative period and prognosis in esophageal cancer. Patients and methods We performed a retrospective cohort study including 187 patients who underwent esophagectomy for esophageal squamous cell carcinoma (ESCC) between January 2008 and October 2016. Results CRP within 1 month of surgery was not related to overall survival (OS) or recurrence-free survival (RFS). In a univariate analysis, postoperative 2 months (2M)-CRP ≥0.15 ml/dl was associated with poorer OS (41.4 vs. 71.4%, p=0.0002) and RFS (28.9 vs. 51.3%, p=0.007). In a multivariate analysis, 2M-CRP ≥0.15 ml/dl was an independent factor for poorer OS (HR=2.27, 95%CI=1.03-3.34, p=0.005) and RFS (HR=1.65, 95%CI=1.08-2.52, p=0.020). The incidence of postoperative pneumonia was significantly higher in the 2M-CRP ≥0.15 ml/dl group (p=0.026). Conclusion 2M-CRP ≥0.15 ml/dl is an independent prognostic factor for ESCC. Furthermore, postoperative pneumonia may be associated with patient prognosis after esophagectomy.

Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy. However, there are few useful markers for diagnosis and treatment. Glutathione S-transferase Pi 1 (GSTP1) has been reported as a predictor of malignancy or anticancer drug resistance in some cancers. We investigated the association of GSTP1 expression with the malignancy or drug resistance in ESCC cell lines and clinical tissue samples. Proliferation and apoptosis assays regarding GSTP1 expression were examined in ESCC cell lines. Proliferation of GSTP1 knockdown cells was significantly decreased (P < .01), and the frequency of early apoptosis was increased (P < .05). Invasion capacity of GSTP1 knockdown cells was slightly decreased in transwell assay. These results suggest that GSTP1 plays an important role in malignant potential. To examine the effects of GSTP1 on drug resistance, chemosensitivity assay and apoptosis assay under cisplatin exposure were carried out. Viability of GSTP1 knockdown cells treated with cisplatin was lower than that of control cells (P < .01). Moreover, the frequency of early and late apoptosis in GSTP1 knockdown cells was markedly increased over that of control cells by cisplatin exposure (P < .01). In immunohistochemistry assay of resected tissue samples, GSTP1 expression was significantly associated with clinical downstaging (P = .04) in 72 ESCC patients with neoadjuvant chemotherapy. Furthermore, there was a significant association between GSTP1 expression in resected tissue and biopsy samples in 34 ESCC patients without neoadjuvant chemotherapy (P = .02). In summary, GSTP1 was related to malignant potential and may be a predictive marker of drug resistance in ESCC patients.

Jejunostomy is an essential route for nutritional support after esophageal cancer surgery. However, catheter-related complications may occur. This study compared the complications of feeding jejunostomy between gastric tube and jejunum after esophageal cancer surgery.The records of 215 patients with esophageal cancer who underwent radical esophagectomy with retrosternal gastric tube reconstruction between January 2010 and November 2016 were examined. One hundred and thirty-three patients underwent feeding jejunostomy via gastric tube and 82 patients underwent the procedure via the jejunum, and their records were reviewed for catheter-related complications.Catheter-related complications occurred in five patients in the gastric tube group and 12 in the jejunum group (3.8% vs. 14.6%, p=0.005). Mechanical bowel obstruction requiring surgical therapy occurred in three patients in the jejunum group, but in none in the gastric tube group (p=0.026).Feeding jejunostomy reconstruction via gastric tube appears to be a safe and useful procedure.

Background The standard treatment for superficial esophageal cancer (SEC) involving muscularis mucosal (T1a-MM) or submucosal (T1b) invasion has been the surgical resection of the esophagus. However, esophagectomy with extended lymph node dissection is highly invasive. Recent reports have shown that endoscopic submucosal dissection (ESD) followed by chemoradiotherapy (CRT) has promising results and might become a new therapeutic approach. This retrospective study aimed to elucidate the efficacy and safety of this new treatment. Methods Patients with clinical stage T1b tumor without apparent metastasis treated with ESD followed by CRT from 2014 to 2017 (the CRT group) were included. The outcomes on disease-free survival (DFS) of this group were compared with those of consecutive patients in a historical control group who underwent ESD followed by esophagectomy (the esophagectomy group) between 2008 and 2015. Results Of 32 patients analyzed, 16 were in the CRT group and 16 with similar stage cancer were in the esophagectomy group. Radiotherapy was completed in all patients, and the incidence of grade ≥ 3 nonhematologic adverse events was 6%. The 2-year overall survival rates were 100%, and locoregional control was achieved in all patients in the CRT group, and the 2-year DFS rates were 88 and 100% for the CRT and esophagectomy groups, respectively, without significant differences. Conclusions Our data confirmed our new approach as being safe and effective for locoregional control and may provide a nonsurgical treatment option for patients with clinical stage T1b tumors.

Aim This study was designed to investigate the clinical impact of postoperative serum albumin level on severe postoperative complications (SPCs) and prognosis. Materials and methods Data for a total of 728 consecutive patients who underwent curative gastrectomy for gastric cancer between 2004 and 2013 were retrospectively analyzed. From these patients, a propensity score-matched analysis was performed based on 14 clinicopathological and surgical factors. Results Short-term decrease in postoperative serum albumin level was not associated with the occurrence of SPCs. Regarding long-term decrease in serum albumin level, a decrease of ≥0.5 g/dl at 3 months did not affect the long-term survival of patients without SPCs, but was related to a significantly poorer prognosis in patients with SPCs. By multivariate analysis, long-term decrease of serum albumin level was an independent prognostic factor in patients with SPCs. Conclusion Long-term postoperative nutritional status as shown by a low level of albumin was related to prognosis in patients with SPCs.

A 39-year-old woman visited our hospital because of epigastric pain. Gastrointestinal endoscopy revealed a gastric submucosal tumor, 30mm in size, with ulcer locating near to the esophagogastric junction, and it was diagnosed with GIST by the endoscopic ultrasonography-guided fine needle aspiration. Then, she underwent laparoscopic surgery for the removal of gastric GIST. After peeling around the upper stomach, the local resection of the stomach was performed with linear staplers in the minor axis direction under the vision of the endoscope and laparoscope. Histopathological examinations confirmed that the tumor was GIST with an intermediate risk, and all surgical margins were free of GIST cells. Local resection with the laparoscopy endoscopy cooperative surgery(LECS)technique is a very useful way of the removal of gastric GISTs locating near to the esophagogastric junction in terms of the remnant gastric functions. Meanwhile, because the standard LECS requires the opening of the gastric lumen, there remains concerns about the intraperitoneal tumor dissemination for the gastric GIST with ulcer. We herein reported a case of laparoscopic local resection for a gastric GIST with ulcer locating near to the esophagogastric junction without gastric opening.