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1.
Int J Mol Sci ; 25(5)2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38474078

ABSTRACT

Carbon ion beams have the unique property of higher linear energy transfer, which causes clustered damage of DNA, impacting the cell repair system. This sometimes triggers apoptosis and the release in the cytoplasm of damaged DNA, leading to type I interferon (IFN) secretion via the activation of the cyclic GMP-AMP synthase-stimulator of interferon genes pathway. Dendritic cells phagocytize dead cancer cells and damaged DNA derived from injured cancer cells, which together activate dendritic cells to present cancer-derived antigens to antigen-specific T cells in the lymph nodes. Thus, carbon ion radiation therapy (CIRT) activates anti-cancer immunity. However, cancer is protected by the tumor microenvironment (TME), which consists of pro-cancerous immune cells, such as regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. The TME is too robust to be destroyed by the CIRT-mediated anti-cancer immunity. Various modalities targeting regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages have been developed. Preclinical studies have shown that CIRT-mediated anti-cancer immunity exerts its effects in the presence of these modalities. In this review article, we provide an overview of CIRT-mediated anti-cancer immunity, with a particular focus on recently identified means of targeting the TME.


Subject(s)
Heavy Ion Radiotherapy , Myeloid-Derived Suppressor Cells , Neoplasms , Humans , Neoplasms/pathology , T-Lymphocytes, Regulatory , DNA , Tumor Microenvironment
2.
In Vivo ; 37(6): 2808-2814, 2023.
Article in English | MEDLINE | ID: mdl-37905629

ABSTRACT

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 for 37 (47%) the therapeutic dose was reduced or switched from insulin to oral antidiabetic drugs. Total gastrectomy was an independent factor for remission of antidiabetic treatments after gastrectomy. Concerning HbA1c levels, only the absence of preoperative insulin use was an independent factor for improvement. However, reconstruction was not a significantly correlated factor for the improvement of postoperative HbA1c levels and reduction of antidiabetic medications after distal gastrectomy. CONCLUSION: Almost all patients discontinued or had their dose of antidiabetic medications reduced 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.


Subject(s)
Diabetes Mellitus, Type 2 , Obesity, Morbid , Stomach Neoplasms , Humans , Stomach Neoplasms/complications , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Glycated Hemoglobin , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/surgery , Treatment Outcome , Gastrectomy/adverse effects , Gastrectomy/methods , Hypoglycemic Agents/therapeutic use , Insulin , Postoperative Period , Obesity, Morbid/drug therapy , Obesity, Morbid/surgery , Retrospective Studies
3.
Cell Physiol Biochem ; 57(4): 212-225, 2023 Jul 19.
Article in English | MEDLINE | ID: mdl-37463410

ABSTRACT

BACKGROUND/AIMS: Pancreatic cancer has the poorest survival rate among all cancer types. Therefore, it is essential to develop an effective treatment strategy for this cancer. METHODS: We performed carbon ion radiotherapy (CIRT) in human pancreatic cancer cell lines and analyzed their survival, apoptosis, necrosis, and autophagy. To investigate the role of CIRT-induced autophagy, autophagy inhibitors were added to cells prior to CIRT. To evaluate tumor formation, we inoculated CIRT-treated murine pancreatic cancer cells on the flank of syngeneic mice and measured tumor weight. We immunohistochemically measured autophagy levels in surgical sections from patients with pancreatic cancer who received neoadjuvant chemotherapy (NAC) plus CIRT or NAC alone. RESULTS: CIRT reduced the survival fraction of pancreatic cancer cells and induced apoptotic and necrotic alterations, along with autophagy. Preincubation with an autophagy inhibitor accelerated cell death. Mice inoculated with control pancreatic cancer cells developed tumors, while those inoculated with CIRT/autophagy inhibitor-treated cells showed significant evasion. Surgical specimens of NAC-treated patients expressed autophagy comparable to control patients, while those in the NAC plus CIRT group expressed little autophagy and nuclear staining. CONCLUSION: CIRT effectively killed the pancreatic cancer cells by inhibiting their autophagy-inducing abilities.


Subject(s)
Heavy Ion Radiotherapy , Pancreatic Neoplasms , Humans , Animals , Mice , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/radiotherapy , Pancreatic Neoplasms/metabolism , Autophagy , Treatment Outcome , Pancreatic Neoplasms
4.
Surg Today ; 52(1): 61-68, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34023972

ABSTRACT

PURPOSE: The clinical significance of lymph node micrometastasis (LNMM) remains controversial in gastric cancer (GC). In this study, we investigated the prognostic impact of LNMM in patients with GC. METHODS: A total of 624 patients with pathologically lymph node metastasis-negative (pN0) and N1 status (pN1) who underwent gastrectomy between 2004 and 2018 were enrolled in this retrospective study. The diameter of tumor cell clusters in metastatic lymph nodes was measured in 120 patients with pN1 GC. RESULTS: Patients with lymph node tumors < 1500 µm in diameter (LNMM) had a significantly better prognosis than those with tumors ≥ 1500 µm in diameter (p = 0.012; log-rank test). Cox's proportional hazards model revealed that LNMM (p = 0.016), several dissected lymph nodes (p = 0.049), and the provision of adjuvant chemotherapy (p = 0.002) were independent prognostic factors for the overall survival of patients with pN1 GC. There was no significant difference in the overall survival between patients with LNMM who received chemotherapy and those who did not (p = 0.332). CONCLUSIONS: LNMM is associated with a favorable prognosis and maybe an independent prognostic marker in patients with pN1 GC. LNMM in GC may be considered a factor preventing adjuvant chemotherapy.


Subject(s)
Biomarkers, Tumor , Lymph Nodes/physiology , Lymphatic Metastasis/pathology , Neoplasm Micrometastasis/pathology , Stomach Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies
5.
Pancreas ; 50(7): 994-999, 2021 08 01.
Article in English | MEDLINE | ID: mdl-34629450

ABSTRACT

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.


Subject(s)
Carcinoma, Pancreatic Ductal/metabolism , Cytoglobin/biosynthesis , Pancreatic Neoplasms/metabolism , Vascular Endothelial Growth Factor A/biosynthesis , Aged , Aged, 80 and over , Carcinoma, Pancreatic Ductal/pathology , Female , Humans , Immunohistochemistry/methods , Interleukin-6/biosynthesis , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Pancreatic Neoplasms/pathology , Phosphatidylinositol 3-Kinases/biosynthesis , Prognosis , Proto-Oncogene Proteins c-akt/biosynthesis , Retrospective Studies
6.
Int J Oncol ; 59(2)2021 Aug.
Article in English | MEDLINE | ID: mdl-34278462

ABSTRACT

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 transcription­quantitative PCR was performed to determine the NOX5 expression levels of colon cancer cell lines. NOX5­knockdown 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 integrin­linked 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.


Subject(s)
Colonic Neoplasms/genetics , NADPH Oxidase 5/genetics , NADPH Oxidase 5/metabolism , Up-Regulation , Aged , Cell Line, Tumor , Cell Movement , Cell Proliferation , Colonic Neoplasms/metabolism , Disease Progression , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , HCT116 Cells , Humans , Male , Oligonucleotide Array Sequence Analysis , Signal Transduction
7.
Nutrition ; 91-92: 111362, 2021.
Article in English | MEDLINE | ID: mdl-34274653

ABSTRACT

OBJECTIVES: Nutritional status significantly influences postoperative prognosis in gastrointestinal cancers. It has been evaluated using sarcopenia before treatments such as surgery and chemotherapy, despite constant changes in nutritional status. We consider that nutritional status at cancer recurrence is one of the important factors that affect treatment choice and intensity. This study evaluated the prognostic effects of improved postoperative nutritional status for people with colorectal cancer recurrence. METHODS: We enrolled 209 participants with pathologically confirmed stage II or III colorectal cancer who underwent radical resection. Sarcopenia was diagnosed using the psoas muscle index obtained from analysis of three-dimensional computed tomographic images. We adopted the cutoff value that was proposed by Hamaguchi et al. (psoas muscle index < 6.36 cm2/m2 for men and < 3.92 cm2/m2 for women). Evaluation was performed before surgery and at the time of recurrence. Participants with preoperative sarcopenia who relapsed were divided into two groups at the time of recurrence: sarcopenia continuation and sarcopenia improvement. We compared the prognosis of the two groups and examined the effect of postoperative nutritional improvement. RESULTS: Among the 209 participants, 81 (38.8%) had preoperative sarcopenia; this group had significantly lower overall survival than those without sarcopenia (P = 0.028). Colorectal cancer recurred in 48 participants. Of those 46, sarcopenia was evaluated at the time of recurrence; 19 of those 46 had preoperative sarcopenia. Preoperative sarcopenia did not affect the cancer recurrence ratio (sarcopenia, 23.5%; non-sarcopenia, 21.3%; P = 0.893). The sarcopenia-improvement group had higher overall survival than the sarcopenia-continuation group (P = 0.042). CONCLUSIONS: Among participants with preoperative sarcopenia, the prognosis at the time of recurrence improved for the sarcopenia-improvement group compared to the sarcopenia-continuation group. In people with colorectal cancer and sarcopenia, nutritional management is important not only before but also after surgery.


Subject(s)
Colorectal Neoplasms , Sarcopenia , Colorectal Neoplasms/complications , Female , Humans , Male , Postoperative Complications/pathology , Prognosis , Psoas Muscles/pathology , Retrospective Studies , Sarcopenia/pathology
8.
Cell Physiol Biochem ; 55(4): 400-412, 2021 Jul 03.
Article in English | MEDLINE | ID: mdl-34214389

ABSTRACT

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.


Subject(s)
Antithrombins/pharmacology , Extracellular Traps/metabolism , Tissue Adhesions , Animals , Cecum/metabolism , Cecum/pathology , Cecum/surgery , Female , Interleukin-6/metabolism , Mice , Mice, Inbred BALB C , Protein-Arginine Deiminase Type 4/antagonists & inhibitors , Protein-Arginine Deiminase Type 4/metabolism , Serpin E2/metabolism , Tissue Adhesions/metabolism , Tissue Adhesions/pathology , Tissue Adhesions/prevention & control
9.
Ann Surg Oncol ; 28(13): 8263-8272, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34101067

ABSTRACT

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Blood components, especially platelets, and inflammation enhance the malignant behaviors of pancreatic cancer cells, potentially contributing to poor prognosis for pancreatic cancer patients.


Subject(s)
Pancreatic Fistula , Pancreatic Neoplasms , Humans , Inflammation , Pancreatectomy , Pancreatic Neoplasms/surgery , Postoperative Complications , Retrospective Studies , Risk Factors
10.
Surg Case Rep ; 7(1): 88, 2021 Apr 08.
Article in English | MEDLINE | ID: mdl-33834304

ABSTRACT

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.

11.
Shock ; 56(3): 374-383, 2021 09 01.
Article in English | MEDLINE | ID: mdl-33595258

ABSTRACT

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, were 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.


Subject(s)
Acute Lung Injury/prevention & control , Hemodiafiltration , Intestinal Perforation/therapy , Sepsis/complications , Sepsis/therapy , Thrombomodulin/therapeutic use , Acute Lung Injury/etiology , Aged , Aged, 80 and over , Animals , Cohort Studies , Disease Models, Animal , Female , Humans , Intestinal Perforation/etiology , Male , Middle Aged , Rats , Recombinant Proteins
12.
Anticancer Res ; 41(1): 317-326, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33419826

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/mortality , Diabetes Mellitus/drug therapy , Insulins/administration & dosage , Liver Neoplasms/complications , Liver Neoplasms/mortality , Postoperative Care , Adult , Aged , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/surgery , Diabetes Mellitus/diagnosis , Disease Susceptibility , Female , Hepatectomy , Humans , Liver Neoplasms/etiology , Liver Neoplasms/surgery , Male , Middle Aged , Prognosis , Survival
13.
Anticancer Res ; 41(1): 409-415, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33419838

ABSTRACT

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<0.001). Comparative analysis revealed that low-SVV was associated with a high incidence of postoperative complications and blood transfusion (p=0.018 and 0.037, respectively), and high-SVV was not related with postoperative complications. CONCLUSION: SVV-based management is a significant and feasible strategy to achieve safe and exact surgical resection of HCC.


Subject(s)
Blood Loss, Surgical , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Monitoring, Intraoperative , Stroke Volume , Aged , Biomarkers , Blood Loss, Surgical/prevention & control , Blood Transfusion , Carcinoma, Hepatocellular/diagnosis , Female , Heart Function Tests , Hepatectomy/adverse effects , Hepatectomy/methods , Humans , Liver Neoplasms/diagnosis , Male , Middle Aged , Monitoring, Intraoperative/methods , Postoperative Complications , Retrospective Studies
14.
Anticancer Res ; 41(1): 403-408, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33419837

ABSTRACT

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<0.001, respectively). CONCLUSION: Early drain removal regardless of DFA level may reduce the risk of developing POPF. CRP measured on POD 3 and POD 5 appeared to be a useful predictor of clinically relevant POPF.


Subject(s)
Amylases/metabolism , Device Removal , Drainage , Pancreatic Fistula/etiology , Pancreatic Fistula/prevention & control , Postoperative Complications , Biomarkers , Disease Management , Drainage/instrumentation , Drainage/methods , Humans , Incidence , Pancreatectomy/adverse effects , Pancreatectomy/methods , Pancreatic Fistula/diagnosis , Pancreatic Fistula/therapy , Postoperative Care , Postoperative Complications/prevention & control , ROC Curve , Risk Factors , Time Factors
15.
Anticancer Res ; 41(2): 1077-1082, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33517318

ABSTRACT

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<0.001). No recurrent cases were observed in the positive PH-BCS group. In the negative PH-BCS group, tumor and node status and chemotherapy were indicated as significant prognostic factors, and further step-wise multivariate analysis revealed only node status as a significant prognostic factor. CONCLUSION: Breast cancer screening at least every 2 years may improve the prognosis of TNBC.


Subject(s)
Early Detection of Cancer/methods , Triple Negative Breast Neoplasms/diagnosis , Triple Negative Breast Neoplasms/mortality , Adult , Aged , Drug Therapy , Female , Humans , Lymphatic Metastasis , Middle Aged , Prognosis , Survival Analysis , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology
16.
Gan To Kagaku Ryoho ; 48(1): 107-109, 2021 Jan.
Article in Japanese | MEDLINE | ID: mdl-33468736

ABSTRACT

PURPOSE: The purpose of this study was to clarify the predictors of efficacy of nab-paclitaxel plus gemcitabine(GnP)for patients with recurrence after resection for adenocarcinoma of the pancreas. METHOD: Patients who had received GnP at our hospital were divided into 2 groups; effective group and non-effective group and we compared them. In addition, we compared the therapeutic effect of patients between well-differentiated adenocarcinoma and moderately differentiated adenocarcinoma. Furthermore, we compared the efficacy depending on the time of recurrence. RESULTS: In patients with well-differentiated adenocarcinoma, the disease control rate was 93.6% and progression free survival was 8.6 months, whereas those in patients with moderately differentiated adenocarcinoma were 57.1% and 4.4 months, respectively. Patients who recurred at 7 months or later, had a better therapeutic response than the patients who recurred within 6 months after surgery. CONCLUSIONS: GnP may be effective in patients with well-differentiated adenocarcinoma and in patients who recurred at 7 months or later.


Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Albumins/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/analogs & derivatives , Humans , Neoplasm Recurrence, Local/drug therapy , Paclitaxel/therapeutic use , Pancreas , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/surgery , Gemcitabine
17.
Br J Cancer ; 124(3): 570-573, 2021 02.
Article in English | MEDLINE | ID: mdl-33110200

ABSTRACT

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.


Subject(s)
Blood Platelets/physiology , Cell Communication/physiology , Stomach Neoplasms/pathology , Cell Adhesion , Cell Movement , Cell Proliferation , Coculture Techniques , Disease Progression , Epithelial-Mesenchymal Transition/genetics , Humans , Matrix Metalloproteinase 9/metabolism , Neoplasm Invasiveness , Signal Transduction , Stomach Neoplasms/genetics , Tissue Array Analysis , Up-Regulation
18.
Surg Today ; 51(6): 849-861, 2021 Jun.
Article in English | MEDLINE | ID: mdl-32979121

ABSTRACT

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.


Subject(s)
Biomarkers, Tumor , Digestive System Neoplasms/diagnosis , Digestive System Neoplasms/pathology , Liquid Biopsy/methods , Body Fluids/chemistry , Body Fluids/cytology , Digestive System Neoplasms/therapy , Humans , Molecular Targeted Therapy , Monitoring, Physiologic , Neoplasm Recurrence, Local/diagnosis , Patient Selection , Perioperative Period , Precision Medicine , Prognosis
19.
Surg Case Rep ; 6(1): 315, 2020 Dec 09.
Article in English | MEDLINE | ID: mdl-33296059

ABSTRACT

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.

20.
World J Surg Oncol ; 18(1): 295, 2020 Nov 12.
Article in English | MEDLINE | ID: mdl-33183313

ABSTRACT

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 < 0.001), with there being only one case of POPF in the modified group. There were no cases of POPF-related hemorrhaging in the modified group. On the third day after the operation, the amylase levels in the drainage fluid for the modified group became less than half (1696 vs 650 U/L). Multivariate analysis showed that the modified method was the independent predictors to prevent clinical POPF (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.


Subject(s)
Pancreatic Fistula , Pancreaticojejunostomy , Amylases , Anastomosis, Surgical/adverse effects , Drainage , Humans , Pancreas/surgery , Pancreatic Fistula/etiology , Pancreatic Fistula/prevention & control , Pancreaticoduodenectomy/adverse effects , Pancreaticojejunostomy/adverse effects , Postoperative Complications/prevention & control , Prognosis , Retrospective Studies , Risk Factors
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