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Resectability status is considered an important indicator for progression of pancreatic cancer. We verified the superior mesenteric artery (SMA) factors of resectability status by radiological and pathological analysis in patients who underwent pancreatoduodenectomy with combined resection of the SMA.We enrolled 22 patients who underwent pancreatoduodenectomy with combined resection of the SMA. Patients were divided into 3 groups according to the contact angle between the tumor and the SMA in preoperative computed tomography images (no contact, R-sma; contact within 180 degrees, BR-sma; contact more than 180 degrees, UR-sma). We pathologically evaluated cancer progression toward the SMA.There were 3 patients with R-sma, 12 with BR-sma, and 7 with UR-sma. The median distance (mm) between the cancer and the SMA was 7.0 with R-sma, 1.0 with BR-sma, and 0 with UR-sma (P = 0.0003). Invasion to the superior mesenteric nerve plexus was positive in none with R-sma, 11 with BR-sma, and 7 with UR-sma (P0.0001). Invasion to the SMA was positive in none with R-sma and BR-sma, and 7 with UR-sma (P0.0001).Superior mesenteric artery factors of resectability status are reliable indicator for cancer progression toward the SMA.

BACKGROUND Lymphatic basin dissection is a sentinel node biopsy method that is specific for gastric cancer. In this method, the dyed lymphatic system is dissected en bloc, and sentinel nodes are identified at the back table (ex vivo). Even with lymphatic basin dissection, blood flow to the residual stomach can be preserved, and function-preserving curative gastrectomy can be performed. The oncological safety of function-preserving curative gastrectomy combined with lymphatic basin dissection has not yet been fully investigated. We hypothesized that the oncological safety of sentinel node navigation surgery (SNNS) is not inferior to that of the guidelines. AIM To investigate the life prognosis of SNNS for gastric cancer in comparison with guidelines surgery. METHODS This was a retrospective cohort study. Patients were selected from gastric cancer patients who underwent sentinel node biopsy from April 1999 to March 2016. Patients from April 1999 to August 2008 were from the Department of Surgery II, Kanazawa University Hospital, and patients from August 2009 to March 2016 were from the Department of Surgical Oncology, Kanazawa Medical University Hospital. Patients who were diagnosed with gastric cancer, which was preoperatively diagnosed as superficial type (type 0), 5 cm or less in length, clinical T1-2 and node negative, and underwent various gastrectomies guided by sentinel node navigation were retrospectively collected. The overall survival (OS) and relapse-free survival (RFS) of these patients (SNNS group) were investigated. Patients with gastric cancer of the same stage and who underwent guidelines gastrectomy with standard nodal dissection were also selected as the control group. RESULTS A total of 239 patients in the SNNS group and 423 patients in the control group were included. Pathological nodal metastasis was observed in 10.5% and 10.4% of the SNNS and control groups, respectively. The diagnostic abilities of sentinel node biopsy were 84% and 98.6% for sensitivity and accuracy, respectively. In the SNNS group, 81.6% of patients underwent modified gastrectomy or function-preserving curative gastrectomy with lymphatic basin dissection, in which the extent of nodal dissection was further reduced compared to the guidelines. The OS rate in the SNNS group was 96.8% at 5 years and was significantly better than 91.3% in the control group (P = 0.0014). The RFS rates were equal in both groups. After propensity score matching, there were 231 patients in both groups, and the cumulative recurrence rate was 0.43% at 5 years in the SNNS group and 1.30% in the control group, which was not statistically different. CONCLUSION The oncological safety of patients who undergo gastrectomy guided by sentinel node navigation is not inferior to that of the guidelines surgery.

Chronic inflammation contributes to tumor development by creating a local microenvironment that facilitates neoplastic transformation and potentiates the progression of cancer. Esophageal cancer (EC) is an inflammation-associated malignancy with a poor prognosis. The nature of the switch between chronic inflammation of the esophagus and EC-related immunological changes remains unclear. Here, we examined the dynamic alterations of immune cells at different stages of chronic esophagitis, Barrett’s esophagus (BE) and EC using an esophageal spontaneous carcinogenesis rat model. We also investigated the anticancer effects of metformin. To stimulate EC carcinogenesis, chronic gastroduodenal reflux esophagitis via esophagojejunostomy was induced in 120 rats in metformin-treated and non-treated (control) groups. After 40 weeks, BE and EC developed in 96.7% and 63.3% of the control group, and in 66.7% and 23.3% of the metformin-treated group, respectively. Flow cytometric analysis demonstrated that the balance of M1/M2-polarized or phospho-Stat3-positive macrophages, regulatory T, cytotoxic T, natural killer (NK), NK T cells, and Th17 T cells was dynamically changed at each stage of the disease and were resolved by metformin treatment. These findings clarify the immunity in esophageal carcinogenesis and suggest that metformin could suppress this disease by improving the immunosuppressive tumor microenvironment and immune evasion.

Palliative chemotherapy with best supportive care is a mainstay for patients with gastric cancer (GC) and distant metastasis. However, with advances in GC chemotherapy, multimodal treatment, including perioperative chemotherapy plus conversion surgery, has attracted attention as a new strategy to improve the outcome of patients with stage IV disease. Conversion surgery is defined as surgical treatment aimed at R0 resection after a good response to induction chemotherapy for tumors originally considered unresectable or marginally resectable for technical and/or oncological reasons. Various biological characteristics differ, depending on each metastatic condition in stage IV GC. The main metastatic pathways of GC can be divided into three categories: lymphatic, hematogenous, and peritoneal. In each category, considerable historical data on conversion surgery have demonstrated the benefits of individualized approaches. However, owing to the diversity of these conditions, a common definition, including the choice of induction chemotherapy, optimal timing of resection, and eligibility for conversion surgery, has not been established among surgical oncologists. Thus, we explore the current and future treatment options by reviewing the literature on this controversial topic comprehensively.

Background The multidisciplinary treatment including induction chemotherapy plus conversion surgery (CS) has attracted attention as a new strategy to improve the outcome of metastatic gastric cancer (MGC). However, it is unclear which patients achieve a good response to chemotherapy and successful CS. Tumor-infiltrating immune cells (TIICs) have been reported to be both prognostic and predictive biomarkers not only in immunotherapy but also in chemotherapy in many cancer types. However, there have been no reports on the usefulness of TIICs as biomarkers in conversion surgery for MGC. The aim of the present study was to evaluate the association between the TIICs and treatment outcome for the multidisciplinary treatment in MGC. Methods We retrospectively analyzed 68 MGC patients who received docetaxel plus cisplatin plus S-1 (DCS) therapy between April 2006 and March 2019 in our institute. The number of tumor-infiltrating CD4+, CD8+, Foxp3+lymphocytes, CD68+, CD163+macrophages in pre-treatment endoscopic biopsy samples were evaluated to investigate their predictive value for multidisciplinary treatment. Results Fifty patients underwent CS following DCS therapy (CS group), whereas 18 patients underwent DCS therapy alone (non-CS group). The median survival time (MST) of CS group was 33.3 months, which was significantly longer than the MST of 9.0 months in non-CS group (p +macrophages was extracted as an independent prognostic factor for overall survival in all patients. There were more cases of high infiltration of CD163+macrophages in non-CS group than in CS group. Furthermore, in CS group, pathological responders to DCS therapy showed low infiltration of CD163+ macrophages, and high infiltration of CD8+lymphocyte. CD163 low group showed a significant prolonged survival compared with CD163 high group in patients who underwent CS (p = 0.02). Conclusions The pre-treatment CD163+macrophages infiltration would be a pivotal biomarker for predicting prognosis and pathological response to multidisciplinary treatment among TIICs in MGC. Thus, for patients with low CD163+macrophage infiltration in pre-treatment biopsy sample, diagnostic imaging should be performed frequently during chemotherapy to avoid missing the optimal timing for CS, and CS should be aggressively considered as a treatment option if curative resection is deemed feasible.

Background The lipid scavenger receptor cluster of differentiation 36 (CD36) has been shown to have a pro-metastatic function in several cancers. Adipose tissue, a favorable site for peritoneal metastasis (PM) from gastric cancer (GC), promotes this process by providing free fatty acids (FFAs); however, the role of CD36 in PM progression from GC remains to be elucidated. Materials and Methods We evaluated CD36 expression in the GC cells under various conditions. CD36 overexpressing (CD36OE) MKN45 cells were prepared and their migration and invasive properties were assessed. A PM mouse model was used to investigate the biological effects of palmitic acid (PA) and CD36. Furthermore, we examined the clinical role of CD36 expression in 82 human PM samples by immunohistochemical staining. Results Hypoxia markedly increased CD36 expression in GC cells. In normoxia, only CD36OE MKN45 cells treated with PA showed an increase in migration and invasion abilities. An increased expression of active Rac1 and Cdc42 was observed, which decreased following etomoxir treatment. Conversely, hypoxia increased those capacities of both vector and CD36OE MKN45 cells. In a mouse model transplanted with CD36OE MKN45 cells, more peritoneal tumors were observed in the high-fat diet group than those in the normal diet group. In clinical samples, 80% of PM lesions expressed CD36, consistent with hypoxic regions, indicating a significant association with prognosis. Conclusion Our findings indicate that a hypoxia in the peritoneal cavity induces CD36 expression in GC cells, which contributes to PM through the uptake of FFAs.

This prospective multicenter non-randomized phase III study aims to evaluate the long-term outcome of sentinel node navigation surgery for early gastric cancer compared with conventional distal or total gastrectomy. Clinically diagnosed primary T1N0M0 gastric cancer patients with a single lesion (≤40 mm) and without previous endoscopic treatment will be enrolled in this study. Sentinel nodes are identified by dye and radioisotope tracers and are subjected to intraoperative rapid pathology. For patients with negative sentinel node metastasis, individualized surgery consisting of limited stomach resection and sentinel node basin dissection is performed, while standard gastrectomy with D2 lymph node dissection is employed for the positive sentinel node patients. A total of 225 patients will be accrued from 13 hospitals that have experience in sentinel node mapping. The primary endpoint is 5-year relapse-free survival. The secondary endpoints are overall survival, sentinel node detection rate, diagnostic accuracy for sentinel node, distribution of sentinel nodes and metastatic sentinel node/non-sentinel node, and postoperative quality of life.

Objective Severe acute pancreatitis is a serious disease, but its detailed mechanism has not yet been elucidated. We aimed to clarify the interaction between neutrophils and platelets in the pathogenesis of acute pancreatitis. Methods We induced acute pancreatitis in rats by injection of sodium taurocholate into the biliopancreatic duct and killed them over time. We observed the histological changes in pancreatic tissue with special attention to the dynamics of neutrophils and platelets. We also measured the concentrations of neutrophil- and platelet-derived factors in pancreatic tissue and blood samples. Results Neutrophils and platelets in the pancreatic tissue showed a similar pattern of migration. They initially spread in the interlobular connective tissue and finally into the lobules. The concentration of myeloperoxidase gradually increased in the inflamed pancreas until 24 hours and the concentration of thromboxane B2, plasminogen activator inhibitor 1, and CD41 also increased with time. Finally, the concentration of serum myeloperoxidase, citrullinated histone H3, and high-mobility group box 1 increased over time. Conclusions The interaction between neutrophils and platelets in pancreatic tissue plays an important role in the mechanism of advancing severity in acute pancreatitis. Circulating damage-associated molecular patterns induced by excessive local inflammation may lead to other organ injuries.

Extravasated platelet aggregation (EPA) serves an important role in the cancer microenvironment during cancer progression, and has been demonstrated to interact with tumor cells in several types of cancer. EPA induces epithelial-mesenchymal transition (EMT) via transforming growth factor-β, and also recruits immunosuppressive cells, including regulatory T (Treg) cells and myeloid-derived suppressor cells (MDSCs). However, the role of EPA in gastric cancer with peritoneal metastasis remains unknown. The present study analyzed the association between EPA and prognosis in patients with gastric cancer with peritoneal metastasis. The present study evaluated 62 patients diagnosed with advanced gastric cancer with peritoneal metastasis between 2001 and 2016. EPA, EMT, Treg cells and MDSCs in peritoneal metastatic lesions were detected by immunohistochemical evaluation of CD42b, SNAIL, FOXP3 and CD33, respectively. CD42b expression was observed in 56.5% (35/62) of peritoneal metastatic lesions. CD42b expression in peritoneal metastatic lesions was associated with poor overall survival compared with lower frequencies (hazard ratio, 2.03; 95% confidence interval, 1.12–3.69; P=0.018). SNAIL, FOXP3 and CD33 expression were not associated with overall survival, but CD33 expression was markedly higher in CD42b-positive patients (P=0.022). These results indicated that EPA affects immunosuppression by recruiting MDSCs in the tumor microenvironment via the secretion of soluble factors, resulting in tumor progression. EPA may be a novel therapeutic target for gastric cancer with peritoneal metastasis.

Objectives Interleukin-17A (IL-17A) is pro-inflammatory cytokine and acts as profibrotic factor in the fibrosis of various organs. Fibrosis tumor-like peritoneal dissemination of gastric cancer interferes with drug delivery and immune cell infiltration because of its high internal pressure. In this study, we examined the relationship between IL-17A and tissue fibrosis in peritoneal dissemination and elucidated the mechanism of fibrosis induced by IL-17A using human peritoneal mesothelial cells (HPMCs) and a mouse xenograft model. Methods Seventy gastric cancer patients with peritoneal dissemination were evaluated. The correlation between IL-17A and fibrosis was examined by immunofluorescence and immunohistochemistry. A fibrosis tumor model was developed based on subcutaneous transplantation of co-cultured cells (HPMCs and human gastric cancer cell line MKN-45) into the dorsal side of nude mice. Mice were subsequently treated with or without IL-17A. We also examined the effect of IL-17A on HPMCs in vitro. Results There was a significant correlation between IL-17A expression, the number of mast cell tryptase (MCT)-positive cells, and the degree of fibrosis (r = 0.417, P Conclusions IL-17A derived from mast cells contributes to tumor fibrosis in peritoneal dissemination of gastric cancer. Inhibiting degranulation of mast cells might be a promising treatment strategy to control organ fibrosis.

Background Rhabdomyosarcoma (RMS), a malignant neoplasm that normally differentiates to form striated muscle, is the most common type of childhood soft tissue sarcoma. However, it infrequently occurs in adults and is uncommon in the liver. We herein report a case of RMS of the liver in an adult. Case presentation A 73-year-old woman was admitted to our institution for investigation of a hepatic mass. She had been followed for primary biliary cirrhosis for the past 20 years. A contrast-enhanced computed tomography scan of the abdomen showed a 12- × 10-cm heterogeneous low-density mass lesion containing cystic and solid components. A percutaneous liver biopsy was performed, and poorly differentiated cancer containing an RMS cell-like component was observed. The patient was diagnosed with RMS of the liver, and open surgery with right hepatic lobectomy was performed. Histopathological examination confirmed a diagnosis of pleomorphic RMS of the liver. The patient died of rapid progression of the tumor 6 months after the operation. Conclusions The tumor site in the present case is rare. The details of this case add to the current evidence base regarding establishment of the standard diagnosis and treatment of this rare condition. We recommend consideration of RMS as a differential diagnosis for hepatic tumors.

Introduction Platelets are one factor promoting tumor development. Conversely, lymphocytes are one factor for immune protection. The peripheral blood platelets-lymphocyte ratio (PLR) is useful as an inflammation/immune indicator to predict postoperative recurrence and prognosis of a variety of malignancies. The peripheral blood neutrophil-lymphocyte ratio (NLR) has also been reported as a useful inflammation/immune indicator. However, there are few studies evaluating the relationship between these peripheral blood indicators and the effectiveness of chemotherapy. Thus, we examined these relationships in gastric cancer patients. Patients and Methods Between 2005 and 2018, 41 gastric cancer patients treated with preoperative DCS therapy (docetaxel, cisplatin, and S-1) therapy followed by gastrectomy were evaluated. Data for peripheral blood tests prior to the initiation of chemotherapy were used. The effectiveness of chemotherapy was determined using Response Evaluation Criteria in Solid Tumors (RECIST) and the pathological response of primary lesions (Ef grade). The relationship between the blood test results and the effectiveness of chemotherapy was evaluated. Results Each optimal cut-off value of peripheral inflammation/immune indicators was calculated through ROC curves. Although the pathological responder (Ef grade 2 or 3) revealed significantly better prognosis than the non-responder (Ef grade 0-1b), no relationship was found between responder according to RECIST and prognosis (P=0.014, P=0.992). In univariate analysis, a low PLR (

Background: An artificial pancreas (AP) is useful for intensive insulin treatment (IIT). In this study, the safety and efficacy of an AP in the perioperative period of highly invasive hepato-biliary and pancreatic surgery (HBPS) was validated. Methods: Fifty patients underwent IIT with an AP during the HBPS perioperative period, including hepatectomy greater than two sectors (MH), pancreatoduodenectomy (PD), and liver transplantation (LT). The primary endpoint was occurrence of hypoglycemia (

Aim The present study aimed to examine the effects of prophylactic administration of recombinant human soluble thrombomodulin (rTM) for the prevention of sinusoidal obstruction syndrome (SOS). Materials and methods Crl:CD1 mice were allocated to the rTM, placebo, and control groups. The rTM group received an intraperitoneal administration of rTM, with intraperitoneal administration of monocrotaline (MCT) 1 h later. The placebo group received PBS instead of rTM, and the control group received PBS instead of rTM and MCT. Mice were sacrificed 48 h after MCT administration, and blood and liver tissues were evaluated. Immunostaining was performed using anti-CD42b and anti-SE-1 antibodies, and AZAN staining. Levels of plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS) in whole liver tissues were estimated using RT-PCR. Results Hematoxylin-eosin staining showed that SOS-related findings were markedly attenuated in the rTM group compared to the placebo group. CD42b immunostaining showed the presence of extravasated platelet activation (EPA) in the Disse space in the placebo group, but this was less noticeable in the rTM group. PAI-1 levels were significantly lower in the rTM group than in the placebo group in RT-PCR. However, eNOS levels were significantly higher in the rTM group than in the placebo group. Conclusion Administration of rTM may prevent SOS by protecting sinusoidal endothelial cells.

Peritoneal metastasis (PM) is one of the most common causes of noncurative surgery and the most frequent recurrence pattern in gastric cancer (GC). During the process of PM, GC cells detached from primary tumor interact with human peritoneal mesothelial cells (HPMC) overlapped with adipose tissues such as the omentum or mesentery. Although the interaction with HPMC promotes the malignancy of GC, the role of adipose tissues remains unclear.We aimed to clarify how adipose tissue are affected by adjacent primary tumors during the expression of adipokines and to elucidate whether GC cells transform adipocytes into CAFs in vitro. In addition, we investigated whether GC cells are affected by adipocytes in their ability to infiltrate.We investigated the phenotypic conversion of adipocytes during the malignant process of GC cells in vivo and in vitro. We evaluated the expression levels of adiponectin in the omental adipose tissue of gastric cancer patients by western blotting. Following adipocytes/gastric cancer cells coculture, adipocyte markers, adiponectin receptors, and inflammatory cytokine markers were detected by real-time PCR and/or western blotting in the single-cultured and co-cultured adipocytes; cancer-associated fibroblast (CAF) markers were detected by immunofluorescence and western blotting in the single-cultured and co-cultured adipocytes; invasion assays were performed in single cultured and co-cultured MKN45 and OCUM.In omental adipose tissues that are situated close to the primary tumors, the expression of adiponectin tended to decrease in patients with subserosal or serosal invasion. By co-culturing with GC cells, adipocytes were dedifferentiated and the expression levels of CAF marker FSP1 and inflammatory cytokines, PAI-1 and IL-6, significantly increased (p 0.05). Furthermore, GC cells co-cultured with adipocytes showed enhanced invasion ability.Our findings suggest that the phenotypic conversion of adipocytes may promote the malignancy of GC in the construction of the cancer microenvironment of PM.

Background The role of tumor–stroma interactions in tumor immune microenvironment (TME) is attracting attention. We have previously reported that cancer-associated fibroblasts (CAFs) contribute to the progression of peritoneal metastasis (PM) in gastric cancer (GC), and M2 macrophages and mast cells also contribute to TME of PM. To elucidate the role of CAFs in TME, we established an immunocompetent mouse PM model with fibrosis, which reflects clinical features of TME. However, the involvement of CAFs in the immunosuppressive microenvironment remains unclear. In this study, we investigated the efficacy of Tranilast at modifying this immune tolerance by suppressing CAFs. Methods The interaction between mouse myofibroblast cell line LmcMF and mouse GC cell line YTN16 on M2 macrophage migration was investigated, and the inhibitory effect of Tranilast was examined in vitro. Using C57BL/6J mouse PM model established using YTN16 with co-inoculation of LmcMF, TME of resected PM treated with or without Tranilast was analyzed by immunohistochemistry. Results The addition of YTN16 cell-conditioned medium to LmcMF cells enhanced CXCL12 expression and stimulated M2 macrophage migration, whereas Tranilast inhibited the migration ability of M2 macrophages by suppressing CXCL12 secretion from LmcMF. In PM model, Tranilast inhibited tumor growth and fibrosis, M2 macrophage, and mast cell infiltration and significantly promoted CD8 + lymphocyte infiltration into the tumor, leading to apoptosis of cancer cells by an immune response. Conclusion Tranilast improved the immunosuppressive microenvironment by inhibiting CAF function in a mouse PM model. Tranilast is thus a promising candidate for the treatment of PM.

Na+/H+exchanger 5 (NHE5) is enriched in neurons and cycles between recycling endosomes and plasma membranes and transports protons to the endosomal lumen as well as to the extracellular space. Although NHE5 expression is undetectable in normal astrocytes, C6 glioma cells express NHE5 at an elevated level. Using C6 cells as a model, here we demonstrate that NHE5 has an important role in tumor growth and tumor cell proliferation and invasion. Glioma xenografts originating fromNHE5-knockdown cells exhibited significantly slower growth than those fromNHE1-knockdown cells and control cells. Histological characterization of the migration front ofNHE5-knockdown tumors revealed a less invasive and less proliferative appearance thanNHE1-knockdown and control tumors.NHE5-knockdown but notNHE1-knockdown led to downregulation of fetal bovine serum (FBS)-induced MET and EGFR signaling. Moreover, depletion of NHE5 but not NHE1 reduced the ability of cells to spread on collagen. We found that NHE5 depletion greatly abrogated endocytic recycling and the protein stability of β1-integrin, which in part accounted for the defective cell adhesion, spreading, and invasion ofNHE5-knockdown cells.

Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model). The present study aimed to shed light on the mechanism by which bile acid stimulation causes cancer onset and progression. Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC‐DR, established from a metastatic thoracic lesion. ESCC‐DRtca2M was prepared by treating ESCC‐DR cells with taurocholic acid (TCA) to accelerate cancer progression. The lines were subjected to comprehensive genomic analyses. In addition, protein expression levels of glucose‐6‐phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF‐κB) (p65) and O‐linked N‐Acetylglucosamine (O‐GlcNAc) were compared among lines. Cancers developed in the reflux models exhibited greater hexosamine biosynthesis pathway (HBP) activation compared with the nonneoplastic tissues. Expression of O‐GlcNAc transferase (OGT) increased considerably in both ESCC and EAC compared with nonneoplastic squamous epithelium. Conversely, cell line‐based experiments revealed the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy. G6PD overexpression in response to TCA exposure was observed. Both NF‐κB (p65) and O‐GlcNAc were expressed more highly in ESCC‐DRtca2M than in the other cell lines. Moreover, ESCC‐DRtca2M cells had additional chromosomal abnormalities in excess of ESCC‐DR cells. Overall, glucose metabolism was upregulated in both esophageal cancer tissue and cell lines. While bile acids are not mutagenic, chronic exposure seems to trigger NF‐κB(p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression. Glucose metabolism was upregulated in both esophageal cancer tissue and cell lines, and the HBP was activated in the former. The cell line‐based experiments demonstrated upregulation of the pentose phosphate pathway (PPP) at higher degrees of malignancy. While bile acids are not mutagenic, chronic exposure seems to trigger G6PD overexpression and NF‐κB (p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.

Totally implantable vascular access devices (TIVADs) are often used to administer chemotherapy by prolonged intravenous infusion. The objective of the present study was to investigate the incidence of long-term complications and identify risk factors associated with TIVAD placement in patients with gastric cancer. A total of 121 patients with gastric cancer who had undergone 150 TIVAD placement procedures for chemotherapy or supportive care were enrolled in the present retrospective cohort study. A number of risk factors were analyzed, including age, sex, hypertension, diabetes mellitus, history of thrombosis, body mass index, disease stage, and site and purpose of TIVAD. In total, 40 TIVADs (26.7%) developed long-term complications, of which 27 (18.0%) were infections, seven (4.7%) were catheter-related deep vein thrombosis (CR-DVT), and six (4.0%) were obstructions. Chemotherapy was associated with an increased rate of infectious adverse events (odds ratio 2.925; 95% CI, 1.104-7.750; P=0.031) according to the multivariate analysis. CR-DVT occurred more frequently in upper arm ports than in chest wall ports; however, this difference was not statistically significant (7.5 vs. 0.0%; P=0.084) according to the univariable analysis. All CR-DVTs developed in the upper arm sites. Chemotherapy and the upper arm site were associated with long-term complications in patients with TIVAD. However, further studies are needed to confirm the findings of the present study and to determine the reasons for the high incidence of long-term complications in these patients.

A gastrointestinal-airway fistula (GAF) after esophagectomy is a very serious postoperative complication that can cause severe respiratory complications due to digestive juice inflow. Generally, GAF is managed by invasive surgical treatment; less-invasive treatment has yet to be established. We performed esophageal stent placement (ESP) in three cases of GAF after esophagectomy. We assessed the usefulness of ESP through our clinical experience. All GAFs were successfully managed by ESP procedures. After the procedure, the stent positioning and expansion were appropriately evaluated by radiological assessments over time. The stent was removed after endoscopic confirmation of fistula closure on days 8, 23, and 71. Only one patient with a long-term indwelling stent developed a manageable secondary gastrobronchial fistula as a procedure-related complication. In conclusion, ESP was shown to be a less-invasive and effective therapeutic modality for the treatment of GAF.

Background The embryonic stem cell-specific transcription factor, ZFP57, has been shown to play an important role in tumor formation. In this study, we examined if ZFP57 is involved in colorectal cancer metastasis. Materials and methods First, we used colorectal cancer cell lines to perform in vivo metastatic experiments with nude mice. Next, we carried out immunohistochemical analysis of clinical specimens of colorectal cancers. Results In liver metastatic experiments using human colorectal cancer HT29 and HCT116 cells, liver polymetastases occurred at high frequency in ZFP57-overexpressing HT29 and HCT116 cells, whereas both control cells only resulted in oligometastases. Next, we analyzed ZFP57 expression using clinical specimens. Liver metastasis-positive cases were more frequently associated with ZFP57 overexpression than negative cases in primary lesions of colorectal cancer, and the overexpression was particularly remarkable in tumor invasive lesions. Furthermore, ZFP57 overexpression was significantly correlated not only with liver metastasis but also with lymph node metastasis. In addition, the expression level of ZFP57 was significantly correlated with that of the metastasis-related gene NANOG. We also found that ZFP57 overexpression reduced the progression-free survival rate of patients with colorectal cancer. Conclusions This study demonstrated that ZFP57 plays an important role in the hematogenous metastasis of colorectal cancer, suggesting that it could be used as a novel treatment target.

The number of ABO-incompatible living donor liver transplantations (ABO-I LDLT) has increased owing to the use of preoperative rituximab for immunosuppression. However, controversy remains regarding adequate immunosuppression owing to rejection and infection. Here, we present 5 cases of our ABO-I LDLT experience, emphasizing rejection and infectious complications, retrospectively. The treatment protocol included prophylactic rituximab followed by plasma exchange prior to transplantation, splenectomy, and immunosuppressive and prophylactic antibiotic regimens after transplantation. Four of the 5 patients also received local infusion therapy via the portal vein. Neither hyperacute nor antibody-mediated rejection occurred. All grafts were functioning well at discharge. Rehospitalization was required for 2 patients due to severe infection within 6 months of transplantation. Invasive aspergillosis was successfully treated in 1 patient, but the other patient died from severe sepsis with overwhelming postsplenectomy infection syndrome. Our results confirm that, although improved immunosuppressive therapy markedly reduces rejection in ABO-I LDLT, it is also associated with an increased risk of various life-threatening infections.

Background Neutrophil extracellular traps (NETs) play a crucial role in host defense, but excess and prolonged interaction of NETs with platelets can cause severe inflammation and host organ damage. Modification of histone H3 by citrullination is involved in in vitro NET formation. The phosphodiesterase III inhibitor, cilostazol (Ciz), which has a protective effect on liver sinusoidal endothelial cells and inhibits platelet aggregation, may prevent organ damage caused by excess NETosis. In this study, we investigated whether citrullinated histone H3 (H3Cit) could serve as a biomarker for the detection of critical liver damage in sepsis and the efficacy of phosphodiesterase-III inhibition for preventing the liver dysfunction induced by NETosis. Materials and methods Mice injected with lipopolysaccharide (LPS; 1 mg/kg) were used as a sepsis model with or without treatment with Ciz (200 mg/kg). H3Cit, myeloperoxidase, and neutrophil elastase levels were measured by immunohistochemistry. We evaluated H3Cit-positive neutrophils in the peripheral blood by flow cytometry. Results Immunohistochemistry revealed that H3Cit-, neutrophil elastase-, and myeloperoxidase-positive cell numbers in the livers peaked at 12 h after LPS administration. However, flow cytometry showed a significant increase in H3Cit-positive neutrophils in the peripheral blood only 4 h after LPS injection. Treatment with Ciz significantly ameliorated all parameters. Conclusions H3Cit is a useful biomarker for early detection of NETosis or liver dysfunction, and Ciz may be an effective treatment for septic liver damage.

Chemotherapy, including preoperative chemotherapy, plays an important role in the treatment of esophageal cancer. However, although docetaxel, cisplatin, and fluorouracil (DCF) therapy has a powerful antitumor effect, the associated adverse events make it difficult to maintain the patient’s general condition. Oral mucositis is an important adverse effect of chemotherapy, and its severity, frequency, and impact on patient quality of life should not be underestimated. This study evaluated the role of oral cryotherapy for prophylaxis of oral mucositis caused by DCF therapy. We retrospectively examined the incidence and severity of adverse events, including mucositis, in 72 patients with esophageal cancer treated with DCF. Fifty-eight patients received cryotherapy during docetaxel administration and 14 received no cryotherapy. The incidence of mucositis of all grades and grade 3 was significantly lower in the cryotherapy group compared with the no-cryotherapy group (24.1% vs. 71.4%, P

Background The correlation between tumor location and lymphatic flow distribution in gastric cancer has been previously reported, and PTD (Proximal – Transitional – Distal) classification was proposed. Our group updated and developed the nPTD classification. Method We retrospectively studied gastric cancer patients who underwent the dye method sentinel node biopsy from 1993 to 2020. The inclusion criteria were a single lesion type 0 cancer of ≤5 cm in the long axis, clinically node-negative, and invasion within the proper muscle layer pathologically. In this study, the distribution of dyed lymphatic flow was evaluated for each occupied area of the tumor. Results We included 416 patients in this study. The tumors located in the watershed of the right and left gastroepiploic arteries near greater curvature had extensive lymphatic flow; therefore, a newly circular region with a diameter of 5 cm is set on the watershed of the greater curvature between P and T zone as the ‘n’ zone. In addition, for cancers located in the lesser P curvature, lymphatic flow to the greater curvature was not observed. Therefore, the P zone was divided into two: the lesser curvature side (PL) and the greater curvature side (PG). Conclusions The advantage of the nPTD classification is that it provides not only proper nodal dissection but also adequate function-preserving gastrectomy. If the tumor is localized within the PL, the proximal gastrectomy resection area can be further reduced. In contrast, for cancers located in the ‘n’ zone, near-total gastrectomy is required because of the extensive lymphatic flow.

The patient was a 61‒year‒old man who had an advanced gastric cancer with peritoneal dissemination. After chemotherapy, intraoperative findings during a total gastrectomy revealed the disappearance of the dissemination nodules. Although adjuvant chemotherapy was performed, the presence of massive ascites led to the recurrence of the peritoneal dissemination 5 months after the surgery. While the chemotherapy regimen was altered, we observed no reduction in malignant ascites. The patient complained of abdominal distention and was admitted to our hospital for symptom management. We performed a cell‒free and concentrated ascites reinfusion therapy(CART)several times. However, symptom management proved difficult; therefore, the patient underwent a peritoneovenous shunt(Denver shunt)placement. After the shunting, we observed no organ injury and improved abdominal distention; however, an asymptomatic coagulopathy was present in the course. Additionally, blood examinations showed increased FDP‒DD and thrombin‒antithrombin complex(TAT). However, 6 months after the shunting, coagulopathy improved and the patient reported the absence of abdominal distention. This report describes a patient with an asymptomatic coagulopathy after Denver shunt placement and evaluated the clinical course by using TAT values.

Although radiation therapy for pelvic cancer leads to improved outcomes, it may cause radiation enteritis. Radiation enteritis is classified as early and late reaction. Late reaction indicate progressive and irreversible changes caused by ischemic changes of the intestinal mucosa. Severe cases require a surgical treatment, which is challenging because of severe adhesions and a high risk of suture failure. In addition, the postoperative course may be unfavorable in some cases. We performed surgery for 4 radiation enteritis cases; however, the postoperative course was unfavorable in 2 cases because of impaired absorption and ileus of the remaining short bowel. These patients could not eat adequately after discharge; therefore, we needed to explain and make them understand the benefits and disadvantages of radiation therapy.

Background Tumor‐infiltrating lymphocytes (TILs) and other immune cells have been reported as a prognostic factor in several tumors, including gastric cancer, and they play an important role in antitumor effect at the primary site. There were few reports on the immune status in peritoneal metastatic lesions for gastric cancer. Aims The aims of this study were to assess the prognostic significance of TILs (CD4, CD8, CD19, regulatory T cells [Tregs]), and myeloid‐derived suppressor cells (MDSCs) in peritoneal metastatic lesions. Methods We retrospectively investigated 60 patients for gastric cancer with peritoneal metastasis who were treated between 2009 and 2016 in our institute. Immunohistochemistry for CD4, CD8, CD19, FOXP3, and CD33 was performed in the peritoneal metastatic lesions. The absolute numbers of immune cells and ratios were evaluated, and the relationship between immune‐related marker and overall survival (OS) was investigated. Results A high infiltration of CD8+ lymphocytes or high CD8/CD33 ratio was a better prognosis for OS in univariate analysis using all immunologic variables (P = .012, P = .001). In multivariate analysis for clinical and immunologic variables, high CD8/CD33 ratio was identified as an independent prognostic factor for OS (Hazard ratio: 0.291, 95% confidence interval: 0.126‐0.670, P = .004). Conclusion High CD8/CD33 ratio and high infiltration of CD8+ lymphocytes in peritoneal metastatic lesions were favorable prognoses for gastric cancer patients with peritoneal metastasis. It is necessary to modify the immune microenvironment result to increase the level of CD8+ lymphocytes in the peritoneal metastatic lesions.

We experienced 3 cases of upper gastric cancer who underwent BillrothⅠ reconstruction in laparoscopy assisted subtotal gastrectomy. Two cases were female and 1 was male. The postoperative course was uneventful in all cases without heartburn, and the surgical margin was negative. The body weight loss rate was 5.8-12.6%, and the short-term results were relatively acceptable. Although the number of cases in this study was small, reconstruction with BillrothⅠ/delta-shaped anastomosis after laparoscopy assisted subtotal gastrectomy were considered to be useful.