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Background Nicotinamide adenine dinucleotide phosphate (NADPH) Oxidases (NOXs) are transmembrane proteins that generate reactive oxygen species. Recent studies have reported that NOXs play important roles in the progression of various cancers. However, the expression and role of NOX2 in colon cancer is unclear. Therefore, this study aimed to investigate the expression of NOX2 and effects on the prognosis of patients with colon cancer, and also examined the pathophysiological role of NOX2 in cell proliferation and motility. Methods We used 116 primary colon cancer samples obtained from patients who underwent curative resection for stage II or III colon cancer for immunohistochemistry to assess the relationship between NOX2 expression and clinicopathological factors and evaluate the prognostic significance of NOX2 expression in colon cancer patients. The expression levels of NOX2 protein and mRNA in human colon cancer cell lines were analyzed and two highly NOX2 expressed cell lines (HCT116 and RKO) were used for further study. Knockdown experiments with NOX2 siRNA were performed, and the effects on cell proliferation, cell cycle progression, migration, and invasion were analyzed. Results Immunohistochemical staining revealed that NOX2 protein was scarcely expressed in noncancerous tissue compared to cancer tissue, and 45 samples (38.8%) had positive staining for NOX2 expression in cancer tissue. No clinicopathological factor was significantly associated with NOX2 expression. The 5-year recurrence-free survival rate of the NOX2 positive group was significantly lower than that of the NOX2 negative group (61.1% vs. 79.3%, p = 0.029). NOX2 depletion using siRNA significantly inhibited cell proliferation, G1 to S phase cell cycle progression, migration, and invasion in the two cell lines. Conclusions NOX2 expression affects the prognosis of colon cancer patients, as well as the tumorigenesis of colon cancer cells. NOX2 may be a novel biomarker and therapeutic target for colon cancer patients.

This study aimed to investigate the therapeutic effects of recombinant human thrombomodulin (rhTM) on acute lung injury (ALI) caused by sepsis in rats. Rats that underwent cecal ligation and puncture (CLP) were treated with or without rhTM, and then mortality was analyzed. In another set of experiments, ALI was assessed. Furthermore, microthrombosis in the lungs was investigated by immunohistochemistry. Moreover, plasma inflammatory and anti-inflammatory cytokines, such as TNF-α, high-mobility group box chromosomal protein 1 (HMGB-1), and IL-10, were evaluated by ELISA. Production of TNF-α and HMGB-1 by isolated tissue macrophages (Mφs) was assessed in vitro. Mortality after CLP was significantly improved by rhTM treatment. In addition, rhTM treatment improved the wet/dry weight ratio of the lungs, the pulmonary microvascular permeability, and the lung injury scores in animals that underwent CLP. Microthrombosis was detected in the lungs after CLP. These pathophysiological changes were blunted by rhTM treatment. Increased plasma TNF-α and HMGB-1 levels were blunted by rhTM treatment; however, the anti-inflammatory cytokine IL-10 was significantly greater in the rhTM(+) group than in the rhTM(−) group. Increased TNF-α and HMGB-1 production by the tissue Mφs stimulated with LPS were significantly blunted by rhTM treatment in vitro, but the production of IL-10 by the tissue Mφs was not changed in the cells incubated with rhTM. Overall, rhTM improved the mortality caused by septic peritonitis. The possible mechanisms are most likely anti-inflammatory and anticoagulant effects, which lead to the prevention of ALI.

Background/aim: We investigated the postoperative treatment status for diabetes mellitus and perioperative HbA1c levels in patients with diabetes mellitus and examined the effects of clinical factors on the remission of diabetes mellitus. Patients and methods: In this study, 126 patients with gastric cancer were considered to have diabetes mellitus preoperatively, of whom 79 were treated with oral antidiabetic drugs and/or insulin treatment. We compared diabetic treatment status and HbA1c values between the preoperative and postoperative periods in patients who underwent gastrectomy and examined the effects of clinical factors on improving diabetes mellitus. Results: Of the 79 patients treated preoperatively for diabetes mellitus, 34(43%) discontinued all medications for diabetes mellitus and 37 (47%) reduced the therapeutic dose or switched from insulin to oral antidiabetic drugs. Total gastrectomy was an independent factor for the remission of antidiabetic treatments after gastrectomy. Concerning the HbA1c level, only the absence of preoperative insulin use was an independent factor for the improvement. However, reconstruction was not a significant correlated factor for the improvement of postoperative HbA1c levels and the remission of antidiabetic medications after distal gastrectomy. Conclusions: Almost all patients discontinued or reduced the dose of antidiabetic medications after gastrectomy in clinical practice, and special attention should be paid in the management methods for diabetes mellitus in patients who underwent total gastrectomy for gastric cancer.

As the elderly population increases, the number of patients with gastric cancer has also been increasing. Elderly people have various preoperative problems such as malnutrition, high frequency of comorbidities, decreased performance status, and dementia. Furthermore, when surgery is performed, high postoperative complication rates and death from other diseases are also concerns. The goal of surgery in the elderly is that short-term outcomes are comparable to those in nonelderly, and long-term outcomes reach life expectancy. Perioperative problems in the elderly include: (1) Poor perioperative nutritional status; (2) Postoperative pneumonia; and (3) Psychological problems (dementia and postoperative delirium). Malnutrition in the elderly has been reported to be associated with increased postoperative complications and dementia, pointing out the importance of nutritional management. In addition, multidisciplinary team efforts, including perioperative respiratory rehabilitation, preoperative oral care, and early postoperative mobilization programs, are effective in preventing postoperative pneumonia. Furthermore, there are many reports on the usefulness of laparoscopic surgery for the elderly, and we considered that minimally invasive surgery would be the optimal treatment after assessing preoperative risk.

BACKGROUND/AIM This study examined the prognostic impact of the past history of breast cancer screening within the last 2 years (PH-BCS), for patients with triple negative breast cancer (TNBC), a subtype that carries extremely poor prognosis. PATIENTS AND METHODS Eighty-six consecutive cases with TNBC, who underwent surgery at our faculty from 2009 to 2015, were divided into two groups according to PH-BCS. Prognostic analyses for disease-free survival and overall survival between the two groups were performed. RESULTS The positive PH-BCS group (n=44) had a significantly better prognoses than the negative PH-BCS group (n=42) (p

Background/aim Several studies have reported that DM is closely associated with an increased incidence of hepatocellular carcinoma (HCC). To clarify the effects of diabetes mellitus (DM) and antidiabetic medications on the prognosis of patients with non-B non-C (NBNC) HCC following curative initial hepatectomy. Patients and methods HCC patients (n=156) were divided into three groups according to the presence or absence of chronic viral hepatitis: hepatitis B virus (HBV) group, hepatitis C virus (HCV) group, and NBNC group. The clinical characteristics and survival outcomes were compared. In the NBNC group, univariate and multivariate analyses were conducted to determine prognostic factors. Results The NBNC group had a higher incidence of DM, ethanol intake, and large nodules than the other groups. Disease-free survival (DFS) was significantly worse in the NBNC group than in the HBV group. In the NBNC group, insulin treatment was an independent prognostic factor for DFS and overall survival (OS). Conclusion Medications for DM that affect insulin resistance might be appropriate prognostic factors for NBNC-HCC.

BACKGROUND/AIM Drains are frequently placed at the time of distal pancreatectomy (DP) to evacuate pancreatic juice and intra-abdominal exudate and obtain information on abdominal cavity status. However, the timing of drain removal remains debatable. Meanwhile, prolonged drain placement might increase the risk of postoperative pancreatic fistula (POPF), with a prevalence of 5-40%. Therefore, we examined the effect of removing the drain within postoperative day (POD) 3 on the risk of POPF development. PATIENTS AND METHODS A total of 108 consecutive patients who underwent DP between April 2015 and March 2020 were examined and divided into two groups according to the day of drain removal; hence, for some patients, the drain was removed on POD 1 (POD 1 group) and for others on POD 3 (POD 3 group). Furthermore, risk factors, including drain fluid amylase (DFA) levels, for developing POPF were investigated. RESULTS The overall rate of clinically relevant POPF was 4.6% and did not significantly differ between the POD 1 and POD 3 groups [4.5% and 4.9%, respectively (p=0.924)]. DFA levels on POD 1 did not significantly differ between patients with and without POPF. On POD 3 and POD 5, C-reactive protein (CRP) levels were significantly higher in patients with POPF than in those without (p=0.03 and p

Background Nodular fasciitis (NF) is a type of rare and rapidly growing tumor that affects the muscular fascial layers. Due to its locally aggressive nature and rapid growth, NF can be mistaken as a malignant process on either clinical or histological grounds. Case presentation A 61-year-old man was affected by rectal cancer. We performed a robotic, high-anterior resection with lymph node dissection. According to the 8th edition of Union for International Cancer Control, the diagnosis was stage I pT2N0M0. During a routine follow-up 1.5 years after the robotic surgery, a computed tomography examination revealed a tumor in the upper right abdominal wall, at the site of the surgical port, that measured 45 mm. Magnetic resonance imaging indicated a hypo-intensive mass within the right straight muscle of the abdomen. Port site recurrence following the robotic surgery for rectal cancer was suspected, and an ultrasound-guided fine-needle aspiration was performed; it revealed a low-grade myofibroblastic tumor or benign neoplasm, but was inconclusive. We performed an excision of the lesion, and histopathology confirmed NF, seen as a solid, nodular, spindle-cell lesion. The patient was postoperatively followed for more than 1 year without any sign of recurrence of either cancer or NF. Conclusions NF is histologically benign, but local recurrence frequently occurs. We encountered a patient with NF at the port site after robotic surgery for rectal cancer.

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

BACKGROUND/AIM Elevated neutrophil-lymphocyte ratio (NLR) has been reported to be a poor prognostic factor in patients with colorectal cancer (CRC). However, no studies have focused on the dynamic change of preoperative NLR (pre-NLR) in CRC patients. We investigated the prognostic value of the change in NLR (ΔNLR) in CRC patients before and after surgery. PATIENTS AND METHODS We retrospectively analyzed the data from 307 patients with stage II or III CRC. We compared the clinicopathological factors, OS, and DFS among the various NLR factors. RESULTS The 5-year OS rate of the high ΔNLR group was significantly lower than that of the low ΔNLR group (p

Background/aim The high rate of recurrence and repetitive features of hepatocellular carcinoma (HCC) require specific treatment strategies. This study aimed to evaluate the long-term outcomes of recurrent HCC focusing on clinicopathological factors. Patients and methods A total of 104 patients who were treated with re-hepatectomy, radiofrequency ablation (RFA) or transcatheter arterial chemoembolization for recurrent HCC were analyzed. Post-recurrent prognoses were compared between each treatment group based on the presence of adverse prognostic factors (APFs) identified. Results In the hepatectomy group, the prognosis of patients with APFs was significantly worse compared to those without APFs. By contrast, the survival rate of patients who underwent RFA was not significantly different from those with and without APFs. Conclusion Our results demonstrate the heterogeneity that exists in terms of the long-term survival of patients with recurrent HCC. The treatment strategy for recurrent HCC should be based on the assessment of presence of APFs to improve long-term prognosis.

Background Rikkunshito (TJ-43) improves the gastrointestinal disorders by increasing levels of active ghrelin which is belonging to gastrointestinal hormones; however, effects of TJ-43 on other gastrointestinal hormones are still unknown. Accordingly, the purpose of this study was to investigate effects of TJ-43 on other gastrointestinal hormones and incretins including gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), which activate the islet cells in the pancreas. Methods Forty-one patients who underwent pylorus-preserving pancreatico-duodenectomy (PpPD) due to pancreato-biliary tumors were divided into two groups; patients were received TJ-43 (7.5 g daily dose) just after surgery [TJ-43(+) group, n = 21] or 3 weeks after surgery [TJ-43(−) group, n = 20]. Blood samples were collected for analysis of regular clinical blood tests at designated time points. In addition, active and inactive form of ghrelin, spexin, cholecystokinin (CCK), peptide YY (PYY), gastric inhibitory peptide (GIP), and glucagon-like peptide-1 (GLP-1) levels were assayed by ELISA. One week after surgery, meals were starting and oral calorie intake was assessed both in the two groups after starting meals. Insulin secretion was also assessed. Results Active form of ghrelin levels significantly increased in the TJ-43(+) group compared with the TJ-43(−) group. Reflecting this result, oral intake of staple food (carbohydrate) significantly increased in the in the TJ-43(+) group. Levels of spexin slightly decreased after PpPD in the TJ-43(−) group and were not changed in the TJ-43(+) group before and after surgery. Levels of CCK and PYY were not different before and after surgery in the TJ-43(−) group; however, these levels increased significantly in the TJ-43(+) group. Alternatively, GIP and GLP-1 levels decreased in the TJ-43(−) group after PpPD. Importantly, these levels significantly increased in the TJ-43(+) group compared with the TJ-43(−) group. Although there were no significant differences between the TJ-43(+) group and the TJ-43 (−) group, insulin secretion increased in the TJ-43(+) group. Conclusions TJ-43 treatment increased expression of incretins in addition to active ghrelin. Thus, it could have advantage for oral food intake and blood sugar control in patients after pancreatic surgery.

Background/aim The platelet-to-lymphocyte ratio (PLR) has recently been suggested as a new predictor of the prognosis in several carcinoma types. However, the clinical impact remains controversial in patients with ampullary carcinoma. Thus, the aim of this study was to investigate other useful biomarkers for identifying poor prognosis in patients with ampullary carcinoma. Patients and methods Forty-one patients with ampullary carcinoma underwent pancreaticoduodenectomy (PD) with curative resection between April 2000 and April 2017. Various clinicopathological findings of the patients and their tumors were evaluated as potential prognostic factors which might enable better stratification of prognosis. Results Platelet-to-lymphocyte ratio, as well as other markers, was found to be a prognostic factor in patients with ampullary carcinoma. The 2-year disease-free survival percentage was significantly higher in the group with low PLR than in the high PLR group (70.2% vs. 28.6%; p=0.005). Combinational analysis of the PLR and conventional TMs enabled us to stratify prognosis of the patients more clearly than by each marker alone. Conclusion PLR was a useful prognostic factor for patients with ampullary cancer. The combination of preoperative PLR and conventional TMs markers may be powerful predictive factors for postoperative prognosis in patients with ampullary carcinoma following PD.

Background/aim Basaloid squamous cell carcinoma of the oesophagus (BSCCE) has poorer prognosis than conventional oesophageal squamous cell carcinoma (ESCC). This study is the first report on highly expressed miRNAs in BSCCE and their target genes. Materials and methods BSCCE and ESCC patients who underwent esophagectomy were selected for this study. Total RNA was extracted from formalin-fixed paraffin-embedded blocks to examine expression of miRNAs and target genes. miRNA mimic or inhibitor transfected cells were used in validation experiments. miRNA and mRNA quantification were performed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results miRNA microarray analysis revealed four candidate miRNAs. Further investigations including cell line experiments demonstrated that miR-3687 was a candidate miRNA and progesterone receptor membrane component2 (PGRMC2) was its target gene. PGRMC2 was found to be related to cell proliferation and local progression. Conclusion miR-3687 may be a candidate miRNA conferring BSCCE aggressiveness, and PGRMC2 is one of its target genes.

Background/Aim: Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Esophageal squamous cell carcinoma (ESCC) is considered as one of the most aggressive carcinomas of the gastrointestinal tract. Basaloid squamous cell carcinoma of the esophagus (BSCCE) is reported to have a poorer prognosis compared to conventional ESCC. The current study aimed to elucidate molecular differences between BSCCE and ESCC, using miRNA profiling and predictive target gene searching. Methods Materials and Methods: Four BSCCE and 94 ESCC patients who underwent esophagectomy were selected for this study. Cell lines were used for target gene validation. Total RNA samples, extracted from formalin-fixed paraffin-embedded blocks, were used for microarray profiling and validation of the miRNAs, selecting the candidate target genes, and elucidating their clinicopathological features. Furthermore, total RNA samples, extracted from miRNA mimic- and inhibitor-transfected cells in cell line experiments, were used for target gene validation. Both miRNA and mRNA quantifications were performed by quantitative reverse transcription-polymerase chain reaction. Results The microarray analysis revealed seven highly expressed miRNAs (miR-205-5p, −4732-5p, −1246, −3687, −3175, −6087, and − 1587) in the BSCCE patients when compared with control. We selected miR-4732-5p and − 3687 for the validation study, and target gene investigations were conducted for miR-3687 ultimately. Several candidates were selected after searching for the target genes via TargetScan and in the literature. Through a pilot and a validation study, progesterone receptor membrane component 2 (PGRMC2) was identified as a target gene. Further investigations revealed that PGRMC2 was associated with tumor size clinicopathologically. Conclusion miR-3687 may constitute a candidate marker of aggressiveness in BSCCE, and PGRMC2 is one of its target genes. Moreover, the gene may play a role in cell proliferation and local progression. Although the current study included only a small number of samples, this is the first report regarding differentially expressed miRNAs and predictive target genes in BSCCE patients.

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

s Background Treatment guidelines for early gastric cancer (EGC) recommend additional gastrectomy for lesions which do not achieve curative resection after ESD, due to the potential risk of lymph node metastasis (LNM). However, many cases are found to have no LNMs, and additional gastrectomy itself can be a considerable risk especially in elderly patients. Methods We retrospectively stratified the risk of LNM according to the total number of four LNM risk factors (RFs) that resulted in non-curative resection for ESD in 861 EGC patients who underwent gastrectomy. Next, we compared this stratification risk to the surgical risk based on the National Clinical Database (NCD) risk calculator in 58 patients who underwent additional gastrectomy. Results As the total number of LNM RFs increased, the frequency of LNM also increased significantly (0/1RF 0.76%, 2RFs 15.08%, 3RFs 33.87%, 4RFs 50.00%; p

Background/aim Recent studies have reported the involvement of NADPH oxidases (NOXs) in tumor progression. However, the role of NOX5 in colon cancer is unclear. We examined the clinical significance of NOX5 expression in colon cancer. Patients and methods NOX5 expression was evaluated by immunohistochemistry in 119 patients with stage II or III colon cancer, and the relationship between NOX5 expression and clinicopathological data was analyzed. Results Of all tissues, 39.5% were negative and 60.5% were positive for NOX5 expression. Positive expression was significantly associated with undifferentiated histology (p=0.037) and lymph node metastasis (p=0.023). The 5-year progression-free survival rate of NOX5-positive patients was significantly worse than that of NOX5-negative patients (p=0.046). The rates of local recurrence observed in NOX5-positive patients were higher than that in NOX5-negative patients. Conclusion NOX5 expression may be related to poor prognostic factors and could be useful as a prognostic biomarker.

BACKGROUND/AIM Treatment algorithms for primary and recurrent hepatocellular carcinoma (HCC) are described in the current Japanese Clinical Practice Guidelines; however, primary and recurrent tumors exhibit several differences in oncological characteristics such as clinicopathological features and prognostic factors. This study aimed to investigate the prognostic factors for recurrent HCC including time of recurrence after primary hepatectomy, to elucidate appropriate treatment strategies in these patients. PATIENTS AND METHODS One hundred and nine patients who had undergone radical resection of primary HCC at our Hospital and had experienced intrahepatic recurrence were included in this study. Patients were categorized into the early-recurrence (ER

Background/aim The extent of lymph node (LN) dissection is defined according to the type of gastrectomy regardless of tumor location in recent Japanese gastric cancer treatment guidelines. However, lymphatic flow from lower-third stomach mainly drain to supra- and infra-pyloric nodes, as well as to partially lesser curvature nodes along the descending limb of the left gastric artery. In this study, we evaluated the prognostic impact of LN dissection of right paracardial (No. 1) and left greater curvature (No. 4sb) nodes in gastric cancer of lower-third stomach (LGC). Patients and methods A total of 239 patients with LGC who underwent distal gastrectomy at our hospital were retrospectively analyzed. The therapeutic value index (TVI) of each node was calculated by multiplying the incidence of LN metastasis by the 5-year survival rate of patients with metastasis to each nodal station. Results The incidence of No. 1 LN metastasis was 4.5% (positive/negative; 5/110 cases, unknown or no description; 129 cases). The 5-year survival rate of patients with metastasis to the node was 0%, and consequently the TVI of No. 1 LN station was "0". Similarly, the TVI of No. 4sb was found to be "0". Conclusion Survival benefit of dissection of No. 1 and No. 4sb LNs was presumed to be extremely low, suggesting that dissection of these two LNs could be omitted in LGC patients when undergoing distal gastrectomy.

Background/aim Basaloid squamous cell carcinoma of the oesophagus (BSCCE) is a variant of oesophageal squamous cell carcinoma (ESCC), that has a more aggressive biological behaviour than that of typical ESCC. miR-3687 has been previously identified to be highly expressed in BSCCE. This study aimed to evaluate the prognostic impact of miR-3687 in ESCC and determine the role of miR-3687 in ESCC motility. Materials and methods miR-3687 expression in human ESCC cell lines and in primary tumour samples obtained from patients with ESCC who underwent esophagectomy were analyzed via real-time polymerase chain reaction (PCR). Knockdown and over-expression experiments were conducted with miR-3687 siRNA and miRNA mimic, and the effect on cell proliferation, migration, and invasion was analyzed. Results A total of 92 samples were analyzed. High miR-3687 expression was correlated with poor prognosis. miR-3687 upregulation promoted cell migration and invasion. Conclusion miR-3687 expression negatively impacts the prognosis of patients with ESCC.

Background/aim Although perioperative management and operative techniques for pancreatic surgery have improved, postoperative pancreatic fistula (POPF) remains the major cause of morbidity and mortality following distal pancreatectomy (DP). The purpose of this study was to evaluate the superiority of the reinforced stapler compared to the bare triple row stapler. Patients and methods A total of 93 patients who underwent DP at the First Department of Surgery at Yamanashi University were examined. The patients were divided into two groups according to the closure method for the pancreatic stump; the bare triple-row stapler (BTRS) group and the reinforced triple-row stapler (RTRS) group. The postoperative outcomes were then compared in terms of several clinicopathological factors between the two groups. Results Seven patients were diagnosed with Grade B/C POPF in this series. The incidence of POPF in the RTRS group was lower than that in the BTRS group (3.6% vs. 13.5%), although there was no significant difference (p=0.077). Further detailed analysis demonstrated that RTRS significantly reduced POPF compared to BTRS in obese patients with a BMI >25.0 kg/m2 (p=0.038). Conclusion Reinforced triple-row staplers may reduce the incidence of severe POPF, especially in obese patients with a BMI >25 kg/m2.

Background/aim Nab-paclitaxel plus gemcitabine (nab-P+Gem) is one of most reliable and effective regimens for borderline or unresectable pancreatic cancer (PC). However, the feasibility and clinical benefits of this regimen have never been evaluated for patients with recurrent PC after pancreatectomy. The aim of this study was to investigate the feasibility of combination therapy with nab-paclitaxel plus gemcitabine (nab-P+Gem) for patients with recurrent PC. Patients and methods Twenty-two patients with recurrent PC received an intravenous infusion of nab-P (125 mg/m2) and Gem (1,000 mg/m2) on days 1, 8, and 15 of a 4-week cycle. The primary end-point of this study was completion of the 4 cycles. The secondary end-points were the safety, efficacy, and disease control rate. Results The treatment completion rate of the 4 cycles was 90.9%. The objective response rate was 13.6% and the disease control rate was 63.6%. The median progression-free survival was 7.2 months. The most common grade 3 or higher hematological toxicity was neutropenia (72.7%). There was no treatment-related death. Furthermore, the chemotherapeutic effects varied with the time of recurrence. Conclusion Combination nab-P+Gem therapy was well-tolerated and effective in patients with recurrent PC.

Background Traditionally, the surgery for simultaneous double cancer of the stomach and colon required a large incision to the upper and lower region of the abdomen. In this case, an artificial blood vessel was located under the skin after revascularization. Considering ischemia due to graft compression by incision retractor during laparotomy, this was difficult to do. This is a report on laparoscopic surgery for simultaneous double cancer of the stomach and colon after revascularization. Case presentation A 69-year-old man had early gastric cancer and advanced sigmoid colon cancer. He had suffered from thromboangitis obliterans and has undergone revascularization many times due to poor blood flow in his lower limbs. He had had some artificial blood vessels inserted under the skin, confirmed by blood vessel construction image by preoperative computed tomography (CT). There was a bypass vessel from the left axillary artery to the left femoral artery under the skin of the left thoracoabdominal. In addition, there were two bypass vessels from the left external iliac artery to the right femoral artery under the skin of the lower abdomen. One of the two bypasses was occluded. In the blood flow to the intestinal tract, the inferior mesenteric artery was already occluded. Peripheral blood flow in the common iliac artery depended on blood flow from the artificial blood vessel, and blood flow from the internal iliac artery to the rectum was poor. Laparoscopic Hartmann’s operation was performed for Stage II B (UICC 8th Edition) sigmoid colon cancer. Because the blood flow in the intestinal tract on the anal side was poor, we thought that anastomosis was at a high risk for leakage. Laparoscopic total gastrectomy was also performed simultaneously for two Stage I (UICC 8th edition) gastric cancers in the cardia and body. The location of the port site and stoma was carefully determined preoperatively to prevent damage and infection to the artificial blood vessels. Minimal invasive surgery was performed using laparoscopic surgery. Conclusions Laparoscopic surgery with small incisions is useful for patients with double cancer who need an approach to the upper and lower abdomen. Furthermore, laparoscopic surgery has less interference on graft in patients with artificial blood vessels under the skin by intraperitoneal approach.

Biomarkers may be of value for the early detection of gastric cancer (GC) and the preoperative identification of tumor characteristics to guide treatment strategies. The present study analyzed the expression levels of phospholipids in plasma from patients with GC using liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS) to detect reliable biomarkers for GC. Furthermore, combining the results with a machine learning strategy, the present study attempted to establish a diagnostic system for GC. A total of 20 plasma samples from preoperative patients with GC and 16 plasma samples from tumor-free patients (controls) were selected from our biobank named 'SHINGEN (Yamanashi Biobank of Gastroenterological Cancers)', which includes a total of 1,592 plasma samples, and were analyzed by LC/ESI-MS. The obtained data were discriminated using a machine learning-based diagnostic algorithm, whose discriminant ability was confirmed through leave-one-out cross-validation. Using LC/ESI-MS, the levels of 236 lipid molecules were determined. Biomarker analysis revealed that a few lipids that were downregulated in the GC group could discriminate between the GC and control groups. Whole lipid composition analysis using partial least squares regression revealed good discrimination ability between the GC and control groups. Integrative analysis of all molecules using the aforementioned machine learning method exhibited a diagnostic accuracy of 94.4% (specificity, 93.8%; sensitivity, 95.0%). In conclusion, the outcomes of the present study suggested the potential future application of the aforementioned system in clinical settings. By accumulating more reliable data, the present system will be able to detect early-stage cancer and will be capable of predicting the efficacy of each therapeutic strategy.

Background Disseminated intravascular coagulation (DIC) is associated with high mortality in patients with severe sepsis. The purpose of this study was to investigate the effects of recombinant human thrombomodulin (rhTM) in septic patients undergoing continuous hemodiafiltration (CHDF). Furthermore, effects of rhTM in acute lung injury, the first target organ in sepsis, was investigated using a sepsis model in rats. Methods Clinical laboratory data, and the DIC, Sequential Organ Failure Assessment (SOFA), and Acute Physiologic and Chronic Health Evaluation (APACHE) II scores were compared between patients undergoing CHDF alone (rhTM- group; n = 23 cases) and patients undergoing CHDF treated with rhTM (rhTM+ group; n = 21 cases). Rats underwent cecal ligation and puncture (CLP) treated with or without rhTM, and acute lung injury (ALI) was analyzed. Production of TNF-α by isolated tissue macrophages (Mfs) was assessed. Results The numbers of leukocytes, and C-reactive protein and D-dimer levels were significantly suppressed, and platelet counts recovered significantly faster in the rhTM+ group compared with the rhTM- group. The DIC score was reduced in both groups. The SOFA and APACHE II scores gradually reduced in the rhTM+ group. The CHDF treatment and ICU admission periods were shortened in the rhTM+ group compared with the rhTM- group. Treatment of rhTM was an independent factor for CHDF treatment period by multivariate analyses. CLP-induced ALI was significantly improved by rhTM. Increased TNF-α production by tissue Mfs was significantly suppressed by rhTM in vivo and in vitro. Conclusion Additive effects of rhTM treatment were observed in septic patients undergoing CHDF.

BACKGROUND/AIM We aimed to evaluate the correlation between stroke volume variation (SVV) and intraoperative blood loss (IBL) in hepatocellular carcinoma (HCC) resection and examine the perioperative utility of SVV-based management. PATIENTS AND METHODS Ninety-five patients who underwent partial or sub-segmental hepatectomy for HCC between 2013 and 2019 at the University of Yamanashi Hospital were retrospectively analyzed. A correlation analysis between IBL and SVV was performed, and then all cases were divided into three groups: high, middle, and low-SVV groups. Perioperative short-term outcomes based on SVV groups were analyzed. RESULTS There was a weak but significant negative correlation between SVV and IBL (ρ=-0.372, p

Recently, patients with esophageal squamous cell carcinoma (ESCC) have been treated with combination therapy, including surgical resection, chemotherapy, and/or radiation therapy. Therefore, the development of novel and useful biomarkers is expected because the malignant behavior of tumors and the treatment effect vary in each case. In this study, we examined the clinical significance of microRNA-X (miR-X) as a biomarker because it has been reported in studies that examined ESCC cell-lines in vitro. Methods In all, 81 consecutive patients who underwent radical esophagectomy without preoperative treatment for ESCC were examined. Total RNA was extracted from formalin-fixed paraffin-embedded samples and miR-X expression levels were evaluated. In this process, the miR-X levels were standardized against the RNU6B expression levels and were analyzed using the ΔΔCq method. Clinicopathological features between high and low expression groups of miR-X were compared using the median expression level as the cutoff value. Prognostic analyses were performed using several factors, including miR-X expression levels, to gage the cancer-specific (CSS) and recurrence-free survival (RFS) of these patients. Results High miR-X expression was found to be significantly related to deep invasion (p Conclusion The present study revealed that high miR-X expression was related to deep invasion and high vascular invasion in ESCC. It was also independent adverse prognostic factor for patients with ESCC. Detailed examination including in vitro re-verification is required because these results were inconsistent with previous reports and miR-X might play different roles in clinical settings. In any case, further detailed studies might establish the significance of miR-X as a novel and useful biomarker of ESCC.

sBackgroundThe number of elderly patients with gastric cancer has been increasing. Most elderly patients have associated reduced physiologic functions that can sometimes become an obstacle to safe surgical treatment. The National Clinical Database Risk Calculator, which based on a large Japanese surgical database, provides predicted mortality and morbidity in each case as the surgical-related risks. The purpose of this study was to investigate the clinical significance of the risk for operative mortality (NRC-mortality), as calculated by the National Clinical Database Risk Calculator, during long-term follow-up after gastrectomy for elderly patients with gastric cancer.MethodsWe enrolled 73 patients aged ≥ 80 years and underwent gastrectomy at our institution. Their surgical risk was evaluated based on the NRC-mortality. Several clinicopathologic factors, including NRC-mortality, were selected and analyzed as the possible prognostic factors for elderly patients who have undergone gastrectomy for gastric cancer. Statistical analysis was performed using the log-rank test and Cox proportional hazard model.ResultsNRC-mortality ranged from 0.5 to 10.6%, and the median value was 1.7%. Dividing the patients according to mortality, the overall survival was significantly worse in the high mortality group (≥ 1.7%,n= 38) than in the low mortality group (< 1.7%,n= 35), whereas disease-specific survival was not different between the two groups. In the Cox proportional hazard model, multivariate analysis revealed NRC-mortality, performance status, and surgical procedure as the independent prognostic factors for overall survival. For disease-specific survival, the independent prognostic factors were performance status and pathological stage but not NRC-mortality.ConclusionThe NRC-mortality might be clinically useful for predicting both surgical mortality and overall survival after gastrectomy in elderly patients with gastric cancer.

Background Postoperative pancreatic fistula (POPF) is one of the most serious complications after pancreaticoduodenectomy (PD). Various factors have been reported as POPF risks, but the most serious of these is soft pancreas. To reduce POPF occurrences, many changes to the PD process have been proposed. This study evaluates short-term results of anastomosis technique for PD. Methods In total, 123 patients with soft pancreases who had undergone PD at Yamanashi University between January 2012 and August 2020 were retrospectively analyzed. We divided these patients into two groups depending on the time PD was performed: a conventional group (n = 67) and a modified group (n = 56). Results The rate of clinically relevant POPF was significantly lower in the modified group than that in the conventional group (5.4% vs 22.4%, p value p value = 0.002). Conclusions Our novel anastomosis technique for pancreatojejunostomy reduced POPF in PD, especially in cases where the patient had a soft pancreas.

Background The number of elderly patients with gastric cancer (elderGC) has been increasing. Most of elderly patients were associated with reduced physiological functions, which sometimes constitute an obstacle to safe surgical treatments. The risk calculator of National Clinical Database (NRC), a Japanese surgical big database, provides mortality and morbidity as surgical-related risks. The purpose of this study is to investigate clinical significance of operative mortality calculated by NRC (NRC-mortality) during long-term follow-up after gastrectomy for elderGC.Methods We enrolled 73 patients aged 80 or over who underwent gastrectomy at our institution. Their surgical risk was evaluated based on the NRC-mortality. Several clinicopathological factors including NRC-mortality were selected and analyzed as possible prognostic factors for elderGC after gastrectomy. Statistical analysis was performing using the log-rank test and Cox proportional hazard model.Results NRC-mortality ranged 0.5 to 10.6%, and median value was 1.7%. Dividing elderGC into high- (1.7% or more, n=38) and low- (less than 1.7%, n=35) mortality groups, high-mortality group showed a significantly poor prognosis in overall survival (OS) than the low-mortality group, whereas there was no difference between the two groups in disease specific survival (DSS). In the analysis of Cox proportional hazard model, multivariate analysis revealed that NRC-mortality was an independent prognostic factor as well as neutrophil-lymphocyte ratio and surgical procedure in OS. In contrast, PS and pStage were independent prognostic factors in DSS, but not NRC-mortality.Conclusions The NRC-mortality might be clinical useful for not only predicting surgical mortality but also OS after gastrectomy in elderGC.

AIM To investigate the clinical utility of alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC)-specific microRNA (miRNA) for monitoring and prognostic prediction of patients. METHODS We performed a comprehensive miRNA array-based approach to compare miRNA expression levels between AFP-positive and AFP-negative cells in three patients with primary AFPGC. We next examined the expression levels of the selected miRNAs in five AFPGC and ten non-AFPGC tissue samples by quantitative reverse transcription-polymerase chain reaction to validate their utility. We also investigated the expression levels of the selected miRNA not only in tissue but also in plasma samples. Moreover, we investigated the relationship between plasma AFP levels and plasma selected miRNA expression levels, and also investigated the correlation of the selected miRNA expression levels and malignant potential. RESULTS Among the five miRNAs selected from the miRNA array results, the expression levels of miR-122-5p were significantly higher in the AFPGC patients than in the non-AFPGC patients (P < 0.05). In tissue samples, miR-122-5p expression level tended to be lower in the non-AFPGC tissue than the normal gastric mucosa. Conversely, in the AFPGC tissue, miR-122-5p expression level was significantly higher in the AFPGC tissue than both the normal gastric mucosa and the non-AFPGC tissue samples (P < 0.05). Plasma miR-122-5p expression levels were also significantly higher in the AFPGC patients than the health volunteers and the non-AFPGC patients (P < 0.05) and were strongly correlated with plasma AFP levels (r = 0.7975, P < 0.0001). Moreover, the correlation of miR-122-5p expression in tissue samples with malignant potential was stronger than that of plasma AFP level in the AFPGC patients. In contrast, no correlation was found between miR-122-5p expression levels and liver metastasis in the non-AFPGC patients. CONCLUSION miR-122-5p might be a useful biomarker for early detection and disease monitoring in AFPGC.

In this article, the current state of laparoscopic total gastrectomy (LTG) was reviewed, focusing on lymph node dissection and reconstruction. Lymph node dissection in LTG is technically similar to that in laparoscopic distal gastrectomy for early gastric cancer; however, LTG for advanced gastric cancer requires extended lymph node dissections including splenic hilar lymph nodes. Although a recent randomized controlled trial clearly indicated no survival benefit in prophylactic splenectomy for lymph node dissection at the splenic hilum, some patients may receive prognostic benefit from adequate splenic hilar lymph node dissection. Considering reconstruction, there are two major esophagojejunostomy (EJS) techniques, using a circular stapler (CS) or using a linear stapler (LS). A few studies have shown that the LS method has fewer complications; however, almost all studies have reported that morbidity (such as anastomotic leakage and stricture) is not significantly different for the two methods. As for CS, we grouped various studies addressing complications in LTG into categories according to the insertion procedure of the anvil and the insertion site in the abdominal wall for the CS. We compared the rate of complications, particularly for leakage and stricture. The rate of anastomotic leakage and stricture was the lowest when inserting the CS from the upper left abdomen and was significantly the highest when inserting the CS from the midline umbilical. Scrupulous attention to EJS techniques is required by surgeons with a clear understanding of the advantages and disadvantages of each anastomotic device and approach.

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

Aim The purpose of this study was to evaluate the clinical impact of histological heterogeneity in patients with node-positive colorectal cancer (CRC). Patients and methods One hundred and twenty-nine patients who underwent curative surgical resection for histological node-positive CRC were enrolled. Patients were divided according to the histological heterogeneity in the primary lesion into p-hetero and p-homo groups. The p-hetero group was further divided according to histological heterogeneity in the metastatic lymph nodes into n-hetero and n-homo groups. Results There were no significant differences between p-homo and p-hetero groups and between n-homo and n-hetero groups in prognosis. However, the recurrence-free survival rate of the n-homo group was significantly lower than that of the n-hetero group in the N2 category. Conclusion Histological heterogeneity in metastatic lymph nodes may be useful for predicting prognosis, and prognosis in those with histological heterogeneity in a metastatic lymph node is not necessarily poor, even in those of the N2 category.

Highlights • Gastric duplication cyst(GDC) contiguous with the stomach and pancreatic tail is extremely rare. • GDCs are usually diagnosed at a younger age. In adults, they are very rare disease and the diagnosis may be difficult. • Surgical resection is considered to be the best treatment due to the difficulty of diagnosis. • Laparoscopic surgery is less invasive and should be selected whenever possible., Introduction Gastrointestinal duplication cyst is a congenital rare disease that may occur in any region from mouth to anus. Among them, gastric duplication cysts are very rare. Case report Here we report A 23-year-old Japanese man who visited our hospital to evaluate an abdominal tumor. Abdominal computed tomography showed a well-circumscribed homogenous low-density mass measuring 6.2 × 6.0 cm between the pancreatic tail and the upper posterior wall on the gastric greater curvature, and the mass seemed to originate from the pancreatic tail. We found intraoperatively that the mass adhered to the stomach and pancreatic tail strongly, so we performed laparoscopic partial gastrectomy and spleen-preserving distal pancreatectomy. Pathological findings showed that the lining epithelium of the cystic mass consisted of the gastric foveolar epithelium with fundic glands. Furthermore, the pancreatic tissue of the pancreatic tail and the muscular layer of the cystic mass were intermingled. Discussion GDCs are usually diagnosed at a younger age and in adults, they are very rare. Therefore, surgical resection is considered to be the best treatment due to the difficulty of diagnosis, and also that it mimics a pancreatic cystic tumor, and malignant transformation. Complete resection of the cyst is the ideal technique and laparoscopic surgery should be selected whenever possible. Conclusion We experienced a case of GDC continuous to both stomach and pancreatic tail. Laparoscopic surgery is safety and useful even if GDC is continuous with both the stomach and the pancreas.

Basaloid squamous cell carcinoma of the oesophagus (BSCCE) has poorer prognosis than conventional oesophageal squamous cell carcinoma (ESCC). This study is the first report on highly expressed miRNAs in BSCCE and their target genes.BSCCE and ESCC patients who underwent esophagectomy were selected for this study. Total RNA was extracted from formalin-fixed paraffin-embedded blocks to examine expression of miRNAs and target genes. miRNA mimic or inhibitor transfected cells were used in validation experiments. miRNA and mRNA quantification were performed by quantitative reverse transcription polymerase chain reaction (qRT-PCR).miRNA microarray analysis revealed four candidate miRNAs. Further investigations including cell line experiments demonstrated that miR-3687 was a candidate miRNA and progesterone receptor membrane component2 (PGRMC2) was its target gene. PGRMC2 was found to be related to cell proliferation and local progression.miR-3687 may be a candidate miRNA conferring BSCCE aggressiveness, and PGRMC2 is one of its target genes.

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