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

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.

Behçet’s disease (BD) is a multisystem inflammatory disease of unknown origin. Rarely, BD occurs together with myelodysplastic syndrome (MDS). Interestingly, it is speculated that these are not simple coexistence but that the etiology of intestinal BD is at least partly derived from MDS itself. Furthermore, there is a relationship between MDS in patients with intestinal BD and trisomy 8. Immunosuppressive agents alone are insufficient to control MDS-associated BD, and many of these patients die of infection or hemorrhage. Surgery is considered for intestinal BD patients who are unresponsive to medical treatment or those with bowel complications such as perforation or persistent bleeding. We report a case of intestinal BD associated with MDS and trisomy 8. The patient was unresponsive to oral steroids and immunosuppressive treatment; the patient improved by surgical repair of a bowel perforation. Five years after the surgery, the patient is free of recurrence and not on medication. Our experience suggests that surgery may provide an effective therapeutic option for the treatment of MDS-related BD.

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

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

Objectives: Rectal stump washout has been widely performed to prevent the implantation of exfoliated cancer cells (ECCs) in patients with rectal cancer. However, it remains unclear whether intraluminal washout before transection is required in patients with sigmoid colon cancer. Therefore, this pilot study was conducted to elucidate the necessity of intraluminal washout for sigmoid colon cancer patients in comparison with rectal cancer patients by cytological assessments. Methods: A total of 16 patients with sigmoid colon cancer and 24 patients with rectal cancer who underwent sigmoidectomy or anterior resection with anastomosis using double-stapling technique were enrolled. A transanal washout sample was collected before washout and after irrigation with 500 and 1,000 mL of saline. Cytological assessments were conducted according to the Papanicolaou classification, and class IV and V cells were defined as malignant. Results: Before washout, exfoliated cancer cells were found in 15 of 24 (62.5%) patients with rectal cancer and in 1 of 16 (6.2%) patients with sigmoid colon cancer (p < 0.001). Distal-free margin from the tumor was significantly shorter in patients with cancer cells (p = 0.002), and the length of the distal-free margin was significantly associated with the tumor location. After irrigation with 500 and 1,000 mL of saline, no cancer cell was found in all patients with sigmoid colon cancer, whereas ECCs were still found in five patients with rectal cancer (20.8%). Conclusions: Intraluminal washout with 1,000 mL may be sufficient for sigmoid colon cancer patients with longer distal-free margin. A large-scale, randomized controlled study is necessary to confirm these results.

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

Postoperative complications have been recognized to have an adverse prognostic impact in various types of cancer. However, in a recent study, it has been reported that postoperative complications of total gastrectomy with splenectomy have little impact on the long-term outcomes of patients with gastric cancer. In addition, the mechanisms underlying the effect of postoperative complications on outcomes remain to be elucidated. We hypothesized that immunosuppression by postoperative complications may affect long-term outcomes in patients with esophageal cancer. In this retrospective study, we assessed in 153 patients with esophageal cancer who underwent curative subtotal esophagectomy at our hospital and examined the correlation between postoperative complications, and multiple clinicopathological factors, and long-term outcomes with the patients stratified by total lymphocyte count (TLC). The median preoperative TLC was 1432. A total of 115 patients (75.2%) had a TLC of ≥ 1000/μL (high TLC group), and the remaining 38 patients (24.8%) had a TLC of

Objectives The aim was to evaluate the relationship between cytoglobin (Cygb) expression and both clinicopathologic factors and prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). Methods Seventy-five patients with PDAC who underwent pancreatectomy between 2009 and 2014 at our department were included. Diagnosis was based on World Health Organization standards, with staging by TNM classification of Union for International Cancer Control. Expressions of Cygb, phosphoinositide-3 kinase, phosphorylated protein kinase B, interleukin-6, and vascular endothelial growth factor were evaluated by immunohistochemical staining of resected surgical specimens and densitometrical analysis. Results Elevated expression of Cygb was found mainly in carcinoma cells of PDAC. Patients with low expression of Cygb showed significantly shorter disease-free survival and disease-specific survival than those with high expression. There was also a significant negative correlation between Cygb expression and the expressions of phosphoinositide 3-kinase, phosphorylated protein kinase B, interleukin-6, and vascular endothelial growth factor. In univariate analysis, Cygb expression, clinical stage, histologic tumor grade, lymphatic invasion, and vascular invasion were prognostic factors. In multivariate analysis, Cygb expression and the clinical stage were independent prognostic factors. Conclusions Loss of Cygb may contribute to tumor recurrence and poor prognosis of PDAC by increases in angiogenic factor.

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/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/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.

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

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.

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.

NADPH oxidases (NOXs) are a family of transmembrane proteins that generate reactive oxygen species. It was previously reported that patients with colon cancer who had high NOX5 expression had poor prognosis. However, no studies have investigated the cellular functions of NOX5 in colon cancer. The present study aimed to clarify the relationship between NOX5 and cancer development using an in vitro model. Reverse transcription‑quantitative PCR was performed to determine the NOX5 expression levels of colon cancer cell lines. NOX5‑knockdown experiments were conducted, and the effect on cell proliferation, migration, and invasion were analyzed. In addition, mRNA microarray was conducted to assess changes in gene profile. NOX5 mRNA expression was high in HCT116 cells and moderate in SW48 cells. NOX5 knockdown significantly inhibited cell migration and invasion in both HCT116 and SW48 cells; however, NOX5 knockdown reduced cell proliferation in only HCT116 cells. mRNA microarrays revealed a strong relationship between NOX5 expression levels and integrin‑linked kinase signaling pathways. The NOX5 expression in colon cancer cells affected cancer progression, especially cell motility. NOX5 may be a novel therapeutic target for the future development of treatments for colon cancer.

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.

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

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.