Publications by authors named "Hiroyuki Takamura"

181 Publications

Correction to: Dynamic switch of immunity and antitumor effects of metformin in rat spontaneous esophageal carcinogenesis.

Cancer Immunol Immunother 2021 Sep 7. Epub 2021 Sep 7.

Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, 920-8640, Japan.

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http://dx.doi.org/10.1007/s00262-021-03039-7DOI Listing
September 2021

Risk Factors for Overall Complications and Remote Infection After Gastrectomy in Elderly Gastric Cancer Patients.

In Vivo 2021 Sep-Oct;35(5):2917-2921

Department of Surgical Oncology, Kanazawa Medical University Hospital, Ishikawa, Japan.

Background/aim: A significant predictive factor for the occurrence of complications after gastrectomy in elderly gastric cancer patients is yet to be determined. We aimed to evaluate the clinical factors associated with overall complications including remote infection after gastrectomy in elderly gastric cancer patients.

Patients And Methods: We retrospectively analyzed data of 101 patients aged over 80 years, who underwent curative gastrectomy. We analyzed the clinicopathological factors that were independently associated with the occurrence of overall complications or remote infection by a logistic regression model.

Results: The overall complication rate was 24.8%. We identified pneumonia as a remote infection, and the occurrence rate of remote infections was 5.9%. On multivariate analysis, hemoglobin (<11 g/dl) and operation time (>240 min) were significantly correlated with the occurrence of overall complications. Regarding the occurrence of remote infection, performing total gastrectomy and a hemoglobin level <11 g/dl were identified as significant risk factors.

Conclusion: Preoperative anemia and intraoperative factors, including the surgical procedure, could affect the occurrence of postoperative complications in elderly patients.
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http://dx.doi.org/10.21873/invivo.12582DOI Listing
August 2021

Dynamic switch of immunity and antitumor effects of metformin in rat spontaneous esophageal carcinogenesis.

Cancer Immunol Immunother 2021 Aug 16. Epub 2021 Aug 16.

Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, 920-8640, Japan.

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.
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http://dx.doi.org/10.1007/s00262-021-03027-xDOI Listing
August 2021

Relationship between fatty liver change and nutritional status after total gastrectomy in gastric cancer patients: a retrospective study.

BMC Surg 2021 Aug 14;21(1):325. Epub 2021 Aug 14.

Department of Surgical Oncology, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan.

Background: The relationship between chronological nutritional changes and development of fatty liver after total gastrectomy (TG) in gastric cancer (GC) patients is still unclear. This study aimed to evaluate relationship between development of fatty liver and chronological changes of nutritional parameters during 12 months after TG.

Methods: We retrospectively analyzed medical records of 59 patients with GC who underwent TG at the Kanazawa Medical University Hospital between January 2009 and December 2017. We defined fatty liver change as a mean liver-to-spleen attenuation ratio (L/S ratio) of less than 1.2 in the computed tomography images at 12 months after TG and divided the patients into fatty liver (FL) and non-FL groups from the L/S ratio. We analyzed serum levels of total protein and albumin, and psoas muscle index (PMI) before TG and at 6 and 12 months after TG in the non-FL and FL groups.

Results: Six patients showed an L/S ratio of less than 1.2 at 12 months after TG and were included into FL group. There was no significant difference between the groups in serum parameters, L/S ratio, and PMI before TG. In the FL group, the mean levels of total protein and albumin decreased after TG and were significant lower at 6 months, compared with the non-FL group. And then, these levels in the FL group recovered at 12 months. In contrast, the mean levels of total protein and albumin in the non-FL group did not decrease below the preoperative levels throughout the year after surgery. As with laboratory parameters, all patients in the FL group showed decrease of PMI at 6 months after TG. This proportion was significantly higher than that in the non-FL group (100% vs. 40.8%, P = 0.006).

Conclusions: We evaluated that the patients with fatty liver occurring after TG had significantly lower levels of serum nutritional parameters and skeletal muscle index at 6 months, not but 12 months, after TG.
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http://dx.doi.org/10.1186/s12893-021-01324-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364078PMC
August 2021

Dissection and removal of bile duct plastic stents penetrating the duodenal papilla: report of three rare cases.

Clin J Gastroenterol 2021 Aug 18;14(4):1255-1262. Epub 2021 May 18.

Department of Gastroenterology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa, 920-0293, Japan.

We encountered three cases with incidental penetration of a straight Amsterdam-type bile duct plastic stent into the duodenal papilla. All patients had undergone insertion of a biliary plastic stent due to common bile duct stones. However, in all three cases, we observed penetration of the biliary plastic stent into the duodenal papilla just before the elective surgery or at the time of plastic stent replacement. We, therefore, performed stent dissection using a bipolar snare and were able to safely remove the plastic stents in all three cases. We believe that this is the first report of plastic stent dissection using a bipolar snare.
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http://dx.doi.org/10.1007/s12328-021-01435-1DOI Listing
August 2021

Laparoscopic intraperitoneal mesh repair of a large incisional hernia in a kidney transplantation patient: A case report.

Asian J Endosc Surg 2021 May 16. Epub 2021 May 16.

Department of General and Digestive Surgery, Kanazawa Medical University Hospital, Kahoku, Japan.

A 73-year-old woman presented to our hospital because of painful bulging in the right lower abdomen, and developed a 17 × 12 cm incisional hernia after kidney transplantation using right oblique incision. Laparoscopic intraperitoneal onlay mesh (IPOM) repair was performed. Since a transplanted kidney is close to the abdominal wall defect, the space between the transplanted kidney and the abdominal wall was peeled off to secure enough space for the mesh to be place. After that the fascial defect was detected precisely, and the polypropylene-polyglycolic acid composite mesh was fixed with 3 cm overlapping of the hernia ring by non-absorbable tacks. The patient was discharged 9 days after surgery. In general, abdominal incisional hernias after kidney transplantation are relatively large with boundary defect of abdominal wall ensuing between the abdominal and allograft. However, laparoscopic IPOM repair of incisional hernia after kidney transplantation can be performed safely and effectively.
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http://dx.doi.org/10.1111/ases.12954DOI Listing
May 2021

Advanced gastric cancer with abdominal wall invasion treated with curative resection after chemotherapy: a case report.

J Med Case Rep 2021 May 9;15(1):230. Epub 2021 May 9.

Department of Surgical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan.

Introduction: In patients with gastric cancer, 6-27% of patients are diagnosed with T4b disease that invades adjacent organs, and curative resection can improve the prognosis of these patients.

Case Presentation: A 70-year-old Japanese man presented with an abdominal tumor and was diagnosed with advanced gastric cancer (L-Circ type 3 T4b N2 M0 H0 stage IVA, based on the 15th edition of the Japanese Classification of Gastric Carcinoma) with extensive abdominal wall invasion. We performed open gastrojejunal bypass for gastric obstruction and initiated a chemotherapeutic regimen comprising S-1 (120 mg/day) and oxaliplatin (100 mg/m). Upper gastrointestinal endoscopy performed after the administration of six courses of the S-1 and oxaliplatin regimen revealed a persistent primary lower gastric wall lesion; however, the diameter of the abdominal wall invasion and metastatic lymph nodes was significantly reduced, in addition to decreased serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels. Subsequently, the patient underwent distal gastrectomy with D2 lymphadenectomy combined with transverse colon and abdominal wall resection. We performed radical en bloc resection and achieved a tumor-free resection margin. Simple abdominal wall closure was performed without mesh or musculocutaneous flap placement. Histopathological examination of the resected tumor specimen showed direct invasion of the mesocolon and rectus abdominis muscle. The patient was postoperatively diagnosed with L Gre-Ant type5 T4b (SI: rectus abdominis muscle) N2 PM0 DM0 Stage IIIA R0 Grade 2a gastric cancer based on histopathological findings and received S-1 as adjuvant chemotherapy, 2 months postoperatively. No recurrence was detected 6 months postoperatively.

Conclusions: We report a case of advanced gastric cancer with extensive abdominal wall invasion that was successfully treated with gastrectomy combined with resection of adjacent organs showing tumor invasion after effective systemic chemotherapy. A therapeutic approach comprising curative surgery combined with perioperative chemotherapy is useful in patients with T4b gastric cancer.
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http://dx.doi.org/10.1186/s13256-021-02820-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106858PMC
May 2021

Analysis of perioperative glucose metabolism using an artificial pancreas.

Artif Organs 2021 Sep 16;45(9):998-1005. Epub 2021 May 16.

Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kanazawa University, Kanazawa, Japan.

Hyperglycemia associated with insulin resistance is common in surgical patients with and without diabetes and is associated with poor surgical outcomes. Several studies have recently shown that a closed-loop blood glucose monitoring system in the form of an artificial pancreas is safe and effective for surgical patients. In this study, we analyzed the risk factors for insulin resistance in patients using an artificial pancreas. We investigated 109 patients who underwent surgical management by an artificial pancreas for 24 hours from the start of surgery during either major hepatectomy (MH), defined as resection of more than two liver segments, or pancreaticoduodenectomy (PD). The target glucose range was from 80 to 110 mg/dL using an artificial pancreas. We analyzed the risk factors for and predictors of a high insulin dose, including sarcopenia markers, according to the median 24-hour total insulin infusion. The median total insulin dose and glycemic control rate (GCR), which is the rate of achieving the target blood glucose range, per 24 hours were 78.0 IU and 30.4% in the MH group and 82.6 IU and 23.5% in the PD group, respectively. The muscle volume was the only independent factor in the high-dose subgroup, and the GCR was significantly lower in the high-dose subgroup despite a high insulin dose in both the MH and PD groups. The results of this study suggest that preoperative sarcopenia is closely associated with insulin resistance in the perioperative period. Clinicians must effectively manage sarcopenia, which may result in improved perioperative glycemic control and reduced postoperative complications.
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http://dx.doi.org/10.1111/aor.13962DOI Listing
September 2021

[Role of Surgical Resection after Chemoradiotherapy in Locally Advanced Pancreatic Cancer].

Gan To Kagaku Ryoho 2021 Jan;48(1):124-126

Dept. of General and Digestive Surgery, Kanazawa Medical University.

We investigated 34 cases of preoperative chemoradiotherapy(CRT)for locally advanced pancreatic cancer including resectable pancreatic cancer in our department during the past 11 years. For resectable(R)or borderline resectable(BR)pancreatic cancer, survival curves were generally higher in the CRT plus S-1 group treated after CRT than in the CRT group treated with post-CRT chemotherapy, but there was no statistically significant difference. In non-resected cases, local exacerbation was observed, which was one of the causes of a decline in terminal QOL. From the above, at present, it is desirable to remove R or BR pancreatic cancer after CRT, but the significance of surgery may change in the future due to the improvement of multidisciplinary treatment.
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January 2021

Incidental intrahepatic cholangiocarcinoma in patients undergoing liver transplantation: A multi-center study in Japan.

J Hepatobiliary Pancreat Sci 2021 Apr 9;28(4):346-352. Epub 2021 Feb 9.

The Study Group of the Japanese Liver Transplantation Society, Tokyo, Japan.

Background: Intrahepatic cholangiocarcinoma had been considered a contraindication for liver transplantation because of poorer outcomes. However, incidental intrahepatic cholangiocarcinoma in the explanted liver has been reported because of the difficulty of obtaining an accurate diagnosis in cirrhotic livers on preoperative imaging.

Methods: We conducted a nationwide survey to analyze the incidence of incidental intrahepatic cholangiocarcinoma and outcomes after liver transplantation, in Japan.

Results: Forty-five of 64 institutions (70%) responded to our initial investigation. Between January 2001 and December 2015, 6627 liver transplantations were performed in these 45 institutions, with 19 cases (0.3%) of incidental intrahepatic cholangiocarcinoma reported from 12 transplant centers. Six cases were diagnosed as hepatocellular carcinoma preoperatively. The 1-, 3-, and 5-year recurrence-free survival rates were 79%, 45%, and 45%, respectively. Tumor recurrence after liver transplantation was found in 10 patients (53%). The 1-, 3-, and 5-year overall survival rates were 79%, 63%, and 46%, respectively.

Conclusions: Intrahepatic cholangiocarcinoma at liver transplantation is associated with a high risk of recurrence and poor prognosis, even these tumors are detected incidentally in the explanted liver.
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http://dx.doi.org/10.1002/jhbp.896DOI Listing
April 2021

Chronological Changes in Neutrophil/lymphocyte Ratio in Advanced Gastric Cancer Patients Treated with Nivolumab: a Report of Nine Cases.

Asian Pac J Cancer Prev 2020 Oct 1;21(10):2955-2960. Epub 2020 Oct 1.

Department of Surgical Oncology, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, Japan.

Background: Nivolumab has been approved for use in advanced gastric cancer (GC) after third-line chemotherapy in Japan. However, it remains difficult to predict favorable nivolumab response before treatment.

Methods: We evaluated the clinical course with a focus on the chronological changes in neutrophil/lymphocyte ratio (NLR) throughout the chemotherapy and assessed the relationship between nivolumab response and chronological changes in NLR before nivolumab administration.

Results: We experienced nine cases who received nivolumab monotherapy for unresectable advanced or postoperative recurrent GC. Nivolumab was used as third-line chemotherapy in all patients, and partial response (PR) and stable disease (SD) were observed in two patients each. Nivolumab treatment resulted in progressive disease (PD) in five patients. In patients with PR or SD, changes in the NLR tended to correspond to the response of target metastatic lymph nodes to first- and second-line chemotherapy. In the four cases with PR or SD following nivolumab, ∆NLRresponses that was the difference in the degree of decline during the most effective pretreatment chemotherapy were 1.39, 0.73, 1.62, and 1.22. However, the patients with PD showed lower ∆NLRresponses, at 0.66, 0.66, 0.25, 0.13, and -0.05 in the five cases. Mean ∆NLRresponses in the patients with PR or SD and patients with PD were 1.17 and 0.33, respectively (P = 0.0008).

Conclusions: We experienced nine GC cases treated with nivolumab and assessed the association between chronological NLR changes throughout chemotherapy and tumor response to nivolumab. Changes in NLR during pretreatment chemotherapy might predict tumor response to nivolumab monotherapy in patients with advanced GC.
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http://dx.doi.org/10.31557/APJCP.2020.21.10.2955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798180PMC
October 2020

Clinical features and diagnostic imaging of cholangiolocellular carcinoma compared with other primary liver cancers: a surgical perspective.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033820948141

General and Digestive Surgery, 12857Kanazawa Medical University, Kahoku, Ishikawa, Japan.

Background And Objectives: Although cholangiolocellular carcinoma is considered a combined hepatocellular and cholangiocarcinoma, we feel that this classification is not appropriate. Therefore, we compared the diagnostic imaging findings, surgical prognosis, and pathological features of cholangiolocellular carcinoma with those of other combined hepatocellular and cholangiocarcinoma subtypes, hepatocellular carcinoma, and cholangiocarcinoma.

Methods: The study patients included 7 with classical type combined hepatocellular and cholangiocarcinoma; 8 with stem cell feature, intermediate type combined hepatocellular and cholangiocarcinoma; 13 with cholangiolocellular carcinoma; 58 with cholangiocarcinoma; and 359 with hepatocellular carcinoma. All patients underwent hepatectomy or living-related donor liver transplantation from 2001 to 2014.

Results: cholangiolocellular carcinoma could be distinguished from hepatocellular carcinom, other combined hepatocellular and cholangiocarcinoma subtypes, and cholangiocarcinoma by the presence of intratumoral Glisson's pedicle, hepatic vein penetration, and tumor-staining pattern on angiography-assisted CT. Cholangiolocellular carcinoma was associated with a significantly lower SUV-max than that of cholangiocarcinoma on FDG-PET. Hepatocellular carcinoma, classical type, and cholangiolocellular carcinoma had significantly better prognoses than stem cell feature, intermediate type and cholangiocarcinoma. A cholangiocarcinoma component was detected in cholangiolocellular carcinoma that progressed to the hepatic hilum, and the cholangiocarcinoma component was found in perineural invasion and lymph node metastases.

Conclusions: From the viewpoint of surgeon, cholangiolocellular carcinoma should be classified as a good-prognosis subtype of biliary tract carcinoma because of its tendency to differentiate into cholangiocarcinoma during its progression, and its distinctive imaging and few recurrence rates different from other combined hepatocellular and cholangiocarcinoma subtypes.
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http://dx.doi.org/10.1177/1533033820948141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592326PMC
October 2020

Inhibitory Effects of Beraprost Sodium in Murine Hepatic Sinusoidal Obstruction Syndrome.

Anticancer Res 2020 Sep;40(9):5171-5180

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Background/aim: In this study, the liver sinusoidal endothelial cells (LSECs)-protective effects of beraprost sodium (BPS) were investigated using mice with monocrotaline (MCT)-induced sinusoidal obstruction syndrome (SOS).

Materials And Methods: The mice were divided into BPS, placebo and control groups. They were killed 48 h after MCT administration, and blood samples and liver tissues were evaluated. Immunostaining was performed using anti-SE-1 and anti-CD42b antibodies, whereas plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS) levels were evaluated using western blot or real-time RT-PCR.

Results: On pathological examination, SOS-related findings were observed in zone 3 in the placebo group; however, these were significantly suppressed in the BPS group. SE-1 staining showed a consistent number of LSECs in the BPS group compared with that in the placebo group, while CD42b staining showed a significant decrease in the number of extravasated platelet aggregation (EPA) in the BPS group. PAI-1 expression was significantly lower in the BPS group than in the placebo group; however, eNOS expression was significantly higher in the BPS group than in the placebo group.

Conclusion: Prophylactic administration of BPS is useful for suppressing the development of SOS through the protective effects of LSEC.
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http://dx.doi.org/10.21873/anticanres.14520DOI Listing
September 2020

[A Case of Effective Disease Control of Advanced Gastric Cancer with Distant Lymph Node Metastases Following Nivolumab Treatment].

Gan To Kagaku Ryoho 2020 Aug;47(8):1258-1260

Dept. of Surgical Oncology, Kanazawa Medical University Hospital.

A 66-year-old man was diagnosed with advanced gastric cancer(L, Less, Type 2, T4a[SE], N2, M1[LYM], H0, P0, cStage Ⅳ)and received treatment with S-1/cisplatin as first-line chemotherapy. This treatment resulted in partial response(PR) after 3 months, with reduction in the sizes of metastatic lymph nodes surrounding the pancreatic head and paraaortic lesion. However, the sizes of metastatic lymph nodes increased after 7 months of chemotherapy. Ramucirumab/nab-paclitaxel was then administered as second-line chemotherapy, and the diameter of the metastatic lymph nodes subsequently decreased after 4 months of the regimen. However, progressive disease was observed at 7 months, and blood transfusion was required because of bleeding from the primary gastric tumor. Therefore, nivolumab was initiated as third-line chemotherapy 14 months after the first treatment. After nivolumab administration, a 28% reduction in metastatic lymph nodes was achieved within 3 months, together with the regression of the primary gastric tumor and improvement in anemia within 6 months. PR was achieved after 12 months of nivolumab administration, and effective disease control was maintained for 16 months without any adverse reaction to nivolumab.
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August 2020

Efficacy of the fat-dissociation method for nodal harvesting in gastric cancer.

World J Gastrointest Surg 2020 Jun;12(6):277-286

Department of Surgical Oncology, Kanazawa Medical University, Kahoku-gun, Ishikawa, 920-0293, Japan.

Background: There is an increased need for accurate staging for gastric cancer treatment. Consequently, it is necessary to carefully examine all dissected lymph nodes for precise staging. Recently, the fat-dissociation method has been developed as a quick and accurate method for harvesting dissected lymph nodes of colorectal cancer cases.

Aim: To investigate the usefulness of the fat-dissociation method for harvesting dissected lymph nodes of gastric cancer cases.

Methods: Fifty-six resected specimens from gastric cancer patients who underwent standard curative gastrectomy and lymph node dissection at our hospital were used. Group 2 lymph nodes were separated from each specimen, and the remaining adipose tissue containing the group 1 lymph nodes was used. Some resected specimens were subjected to the fat-dissociation method. One vial of Imofully was dissolved in 50 mL of saline and injected into the tissue. The tissue was incubated for 1 h and the dissolved fat was removed. Subsequently, the nodes were identified, picked up with scissors, and mapped. The number of nodes in each lymphatic compartment and duration of lymph node harvest and mapping were compared.

Results: The fat-dissociation method was used for 24 samples, while the conventional dissection method was used for 32 samples. The total number of harvested lymph nodes was 45.9 in the fat dissociation group and 44.3 in the control group, and there was no significant difference between the two groups. There were also no significant differences in the number of lymph nodes between the two groups based on a comparison of the lymphatic compartments. However, the total median duration of the fat-dissociation method was 38.2 min, reflecting a reduced duration of approximately 60 min compared to the control group.

Conclusion: Based on our results, the fat-dissociation method is effective in shortening the duration of lymph node harvest in gastric cancer surgery.
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http://dx.doi.org/10.4240/wjgs.v12.i6.277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385510PMC
June 2020

A Case of Advanced Gastroesophageal Junction Cancer with Bulky Lymph Node Metastases Treated with Nivolumab.

Case Rep Oncol 2020 May-Aug;13(2):702-707. Epub 2020 Jun 23.

Department of Surgical Oncology, Kanazawa Medical University, Kahoku, Japan.

A 71-year-old woman was diagnosed with advanced gastroesophageal junction cancer with bulky lymph nodes along the cardiac region and the lower mediastinum (GE-Circ type 3 T3 N3 M0 H0 stage III) and received treatment with S-1 and oxaliplatin (SOX) as first-line chemotherapy. After 3 cycles of SOX, severe anorexia and diarrhea were observed. We converted from this regimen of systemic chemotherapy to ramucirumab (RAM) monotherapy as second-line chemotherapy. This treatment resulted in a reduction in size of the metastatic lymph nodes along the cardiac region and the lower mediastinum. However, progression of lymph node metastasis and the primary tumor was observed following 7 months of RAM monotherapy. Therefore, nivolumab was initiated as third-line chemotherapy 14 months after the initial treatment. After 3 months of nivolumab administration, a 47% reduction in metastatic lymph nodes was achieved and a regression of the primary gastric tumor as seen on an enhanced computed tomography scan. After 7 months of nivolumab monotherapy, the diameter of the target lymph nodes had reduced by 81% from baseline, and there was no evidence of malignancy upon pathological assessment of the primary tumor site biopsy. The patient survived with nivolumab monotherapy for approximately 2 years after her first visit, without any adverse reaction to nivolumab.
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http://dx.doi.org/10.1159/000507955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383216PMC
June 2020

Extravasated platelet aggregation contributes to tumor progression via the accumulation of myeloid-derived suppressor cells in gastric cancer with peritoneal metastasis.

Oncol Lett 2020 Aug 10;20(2):1879-1887. Epub 2020 Jun 10.

Department of Gastroenterological Surgery, Division of Cancer Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa 920-8641, Japan.

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.
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http://dx.doi.org/10.3892/ol.2020.11722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377031PMC
August 2020

Severity of postgastrectomy syndrome and quality of life after advanced gastric cancer radical gastrectomy.

Mol Clin Oncol 2020 Aug 3;13(2):133-140. Epub 2020 Jun 3.

Department of Surgical Oncology, Kanazawa Medical University, Kahoku, Ishikawa 920-0293, Japan.

It has previously been suggested that postgastrectomy syndrome (PGS) is more severe in patients after surgery for advanced gastric cancer than in patients with early gastric cancer. Using the postgastrectomy syndrome assessment scale-45 (PGSAS-45), the present study aimed to determine whether PGS for postgastrectomy patients, in Kanazawa Medical University Hospital, with advanced gastric cancer was more severe than for patients with early gastric cancer. A questionnaire survey was conducted using PGSAS-45 for curative gastric cancer gastrectomy cases at Kanazawa Medical University Hospital. The questionnaire data were combined with patient background data, anonymized and moved to an unlinked file for patient privacy. Using this dataset, non-recurrent cases of distal partial gastrectomy were extracted and divided into two groups, stage IA or IB patients (group E), and stage IIA or higher (group A). The main outcome measures (MOMs) of PGSAS-45 were compared between the two groups. The participants in the present study included 35 cases in group E and 22 cases in group A. The results of a univariate analysis to compare the MOMs between the two groups showed that only the dumping subscale was significantly different in group A and was judged to be caused by the underlying bias of the background factor. There were no MOMs with significant differences in the pathological stage based on multiple regression analyses. In cases of distal partial gastrectomy, the PGS and quality of life (QoL) of patients following advanced gastric cancer surgery were similar to those of patients with early gastric cancer. The standardized treatment for advanced gastric cancer did not induce notable postoperative failures, and QoL was not impaired. In contrast, for early-stage gastric cancer cases, the present study suggests that it is necessary to distinguish metastasis-negative cases to indicate an appropriate, function-preserving curative gastrectomy.
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http://dx.doi.org/10.3892/mco.2020.2061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366243PMC
August 2020

Predictive factors for developing acute cholangitis and/or cholecystitis in patients undergoing delayed cholecystectomy: A retrospective study.

Asian J Surg 2021 Jan 21;44(1):280-285. Epub 2020 Jul 21.

Department of Surgery, Japanese Red Cross Kanazawa Hospital, Kanazawa, Ishikawa, 921-8162, Japan; Department of General and Digestive Surgery, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan.

Background: /Objective: We evaluated the risk of acute cholangitis and/or cholecystitis while waiting for cholecystectomy for gallstones.

Methods: We retrospectively enrolled 168 patients who underwent cholecystectomy for gallstones after conservative therapy. We compared clinical data of 20 patients who developed acute cholangitis and/or cholecystitis while waiting for cholecystectomy (group A) with 148 patients who did not develop (group B). We investigated surgical outcomes and risk factors for developing acute cholangitis and/or cholecystitis.

Results: Preoperatively, significant numbers of patients with previous history of acute grade II or III cholecystitis (55.0% vs 10.8%; p < 0.001) and biliary drainage (20.0% vs 2.0%; p = 0.004) were observed between groups A and B. White blood cell counts (13500/μL vs 8155/μL; p < 0.001) and C-reactive protein levels (12.6 vs 5.1 mg/dL; p < 0.001) were significantly higher in group A than in group B; albumin levels (3.2 vs 4.0 g/dL; p < 0.001) were significantly lower in group A. Gallbladder wall thickening (≥5 mm) (45.0% vs 18.9%; p = 0.018), incarcerated gallbladder neck stones (55.0% vs 22.3%; p = 0.005), and peri-gallbladder abscess (20.0% vs 1.4%; p = 0.002) were significantly more frequent in group A than in group B. A higher conversion rate to open surgery (20.0% vs 2.0%; p = 0.004), longer operation time (137 vs 102 min; p < 0.001), and higher incidence of intraoperative complications (10.0% vs 0%; p = 0.014) were observed in group A, compared with group B.

Conclusion: A history of severe cholecystitis may be a risk factor for acute cholangitis and/or cholecystitis in patients waiting for surgery; it may also contribute to increased surgical difficulty.
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http://dx.doi.org/10.1016/j.asjsur.2020.07.002DOI Listing
January 2021

Pancreatic neuroendocrine tumor featuring growth into the main pancreatic duct and tumor thrombus within the splenic vein: a case report.

J Surg Case Rep 2020 Jul 14;2020(7):rjaa155. Epub 2020 Jul 14.

Department of General and Digestive Surgery, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, Japan.

A 48-year-old woman was admitted to our hospital because of upper abdominal pain. Computer tomography showed an enhancing mass in the pancreatic body, dilation of the main pancreatic duct (MPD) and a filling defect within the splenic vein. On the basis of the preoperative diagnosis of pancreatic body cancer, distal pancreatectomy was scheduled. The pancreas was divided along the left edge of the gastroduodenal artery; however, frozen pathological examination of the pancreatic stump was tumor positive, and therefore a total pancreatectomy was performed. The lesion was a white expansive nodular mass that had spread into the MPD and protruded into the splenic vein. A pathological diagnosis of non-functioning neuroendocrine tumor (NET) was made. In general, imaging findings of disruption of the MPD and tumor vein thrombus are characteristics of pancreatic ductal adenocarcinoma, but are uncommon in NET. However, NET should be included in the differential diagnosis for such patients.
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http://dx.doi.org/10.1093/jscr/rjaa155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365031PMC
July 2020

Pretreatment with a Phosphodiesterase-3 Inhibitor, Milrinone, Reduces Hepatic Ischemia-Reperfusion Injury, Minimizing Pericentral Zone-Based Liver and Small Intestinal Injury in Rats.

Ann Transplant 2020 Jul 14;25:e922306. Epub 2020 Jul 14.

Department of Gastroenterologic Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.

BACKGROUND Severe pericentral zone (zone 3)-based liver injury (LI) may become intractable, with allograft dysfunction after liver transplantation. The phosphodiesterase-3 inhibitor, milrinone, has been reported to attenuate hepatic ischemia-reperfusion injury (IRI). This study clarified how hepatic IRI involved zone 3-based LI, in which zone milrinone was effective, and whether milrinone could improve small intestinal injury (SII) with hepatic IRI. MATERIAL AND METHODS Rats were divided into sham, ischemia-reperfusion (IR), or IR+milrinone groups (n=13 per group). Milrinone was administered intraportally via intrasplenic injection, and whole hepatic ischemia was induced for 30 min. Five hours after reperfusion, serum chemistry and histopathological findings were compared. Expression of CD34 for the detection of altered sinusoidal endothelium as sinusoidal capillarization and cleaved caspase-3 as an apoptosis marker were analyzed via immunohistochemistry. Survival rates were examined after 45 min of whole hepatic ischemia. RESULTS Serum aspartate aminotransferase and direct bilirubin levels were significantly decreased in the IR+milrinone group compared with those of the IR group. The degree of LI, sinusoidal capillarization and apoptosis at zone 3 in the IR group was significantly increased compared with those at the periportal zone (zone 1). These findings at zone 3 in the IR group were improved in the IR+milrinone group. SII with villus congestion and apoptosis in the IR group was significantly attenuated in the IR+milrinone group. The 7-day survival rate was significantly elevated in the IR+milrinone group as compared with that of the IR group. CONCLUSIONS A hepatic IRI model caused zone 3-based LI and SII, which were attenuated by intraportal administration of milrinone.
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http://dx.doi.org/10.12659/AOT.922306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380127PMC
July 2020

Spleen Volume as a Predictive Biomarker for Thrombocytopenia and Liver Dysfunction After Oxaliplatin-based Chemotherapy.

Anticancer Res 2020 Jun;40(6):3361-3370

Department of General and Digestive Surgery, Kanazawa Medical University Hospital, Ishikawa, Japan.

Background/aim: We evaluated whether splenic volume (SV) predicts sinusoidal obstruction syndrome (SOS) in colorectal cancer (CRC) patients receiving capecitabine plus oxaliplatin (CapeOX) therapy.

Patients And Methods: In this retrospective study, we measured SV in 41 patients receiving adjuvant CapeOX for CRC at five different time points. We compared the clinical data of the 18 patients who experienced ≥30% increases in SV immediately after vs. before CapeOX (group A) with data for the remaining 23 patients (group B).

Results: Platelet numbers decreased and the levels of hepatobiliary enzymes increased significantly 1 year after CapeOX compared with before CapeOX in group A. However, in group B, significantly decreased platelet numbers and significantly increased aspartate transaminase levels were confirmed only immediately after CapeOX, with no significant subsequent changes.

Conclusion: SV was significantly associated with thrombocytopenia and liver dysfunction in CRC patients, and predicted SOS.
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http://dx.doi.org/10.21873/anticanres.14319DOI Listing
June 2020

Diagnostic ability of multi-detector spiral computed tomography for pathological lymph node metastasis of advanced gastric cancer.

World J Gastrointest Oncol 2020 Apr;12(4):435-446

Department of Surgical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa 920-0293, Japan.

Background: The reliability of preoperative nodal diagnosis of advanced gastric cancer by multi-detector spiral computed tomography (MDCT) is still unclear.

Aim: To examine the diagnostic ability of MDCT more precisely by using data on intranodal pathological metastatic patterns.

Methods: A total of 108 patients with advanced gastric cancer who underwent MDCT and curative gastrectomy at Kanazawa Medical University Hospital were enrolled in this study. The nodal sizes measured on computed tomography (CT) images were compared with the pathology results. A receiver-operating characteristic curve was constructed, from which the critical value (CV) was calculated by using the data of the first 69 patients retrospectively. By using the CV, sensitivity and specificity were calculated with prospectively collected data from 39 consecutive patients. This enabled a more precise one-to-one correspondence of lymph nodes between CT and pathological examination by using the size data of lymph node mapping. The intranodal pathological metastatic patterns were classified into the following four types: Small nodular, peripheral, large nodular, and diffuse.

Results: Although all the cases were clinically suspected as having metastasis, 81 had lymph node metastasis and 27 had no metastasis. The number of dissected, detected on CT, and metastatic nodes were, 4241, 897, and 801, respectively. The CV obtained from the receiver-operating characteristic was 7.6 mm for the long axis. The sensitivity was 91.4% and the specificity was 47.3% in the prospective phase. The large nodular and diffuse metastases were easy to diagnose because metastatic nodes with a large axis often exhibit these forms.

Conclusion: The ability of MDCT to contribute to a nodal diagnosis of advanced gastric cancer was examined prospectively with precise size data from node mapping, using a CV of 7.6 mm for the long axis that was calculated from the retrospectively collected data. The sensitivity was as high as 91%, and would be improved when referring to the enhanced patterns. However, its specificity was as low as 47%, because most of metastatic nodes in gastric cancer being small in size. The small nodular or peripheral type metastatic nodes were often small and considered difficult to diagnose.
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http://dx.doi.org/10.4251/wjgo.v12.i4.435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191330PMC
April 2020

Differences in 18F-FDG Uptake and Expression of Glucose Transporter Between 2 Distinct Subtypes of Mass-Forming Intrahepatic Cholangiocarcinomas.

Clin Nucl Med 2020 Jun;45(6):e267-e273

From the Department of Radiology, Kanazawa University Graduate School of Medical Sciences.

Purpose: Recently, intrahepatic cholangiocarcinoma (iCCA) has been classified into small duct cholangiocarcinoma (SDC) and large duct cholangiocarcinoma (LDC) according to the origin of the biliary tree. Although the usefulness of F-FDG PET/CT in iCCA is well known, there are no reports evaluating differences in accumulation of F-FDG according to the recently described iCCA subtypes. The aim of this study was therefore to assess F-FDG accumulation and the expression of glucose transporters in SDC and LDC.

Methods: Our institutional review board approved this retrospective study and waived the requirement for informed consent. Fourteen consecutive surgically resected mass-forming iCCA (7 SDCs, 23 ± 6.7 mm; 7 LDCs, 44 ± 26 mm) were enrolled. The SUVmax on F-FDG PET/CT and the expression of glucose transporter 1 (Glut-1), Glut-2, hexokinase 2 (HK2), and glucose-6-phosphatase by immunohistochemistry were evaluated and compared between SDC and LDC.

Results: The SUVmax in SDC was significantly lower than that in LDC (3.2 ± 0.8 vs 7.6 ± 3.2, P < 0.01). The staining scores of Glut-1 and HK2 were significantly lower in SDC than in LDC (0 vs 3 ± 1.4, P = 0.0034; 1.6 ± 1.1 vs 3.4 ± 1.1, P = 0.014, respectively). Expression levels of Glut-2 and glucose-6-phosphatase were variable and did not show a significant difference between SDC and LDC. Overall survival was significantly worse in LDC than in SDC (P = 0.01).

Conclusions: F-FDG accumulation and Glut-1 and HK2 expression were significantly higher in LDC than in SDC. A low-glycolytic feature may be one of the characteristic findings of SDC.
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http://dx.doi.org/10.1097/RLU.0000000000003055DOI Listing
June 2020

Prophylactic Effect of Recombinant Human Soluble Thrombomodulin for Hepatic Sinusoidal Obstruction Syndrome Model Mice.

In Vivo 2020 May-Jun;34(3):1037-1045

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

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.
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http://dx.doi.org/10.21873/invivo.11873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279798PMC
February 2021

The neutrophil/lymphocyte ratio as a predictor of successful conversion surgery for stage IV gastric cancer: a retrospective study.

BMC Cancer 2020 Apr 29;20(1):363. Epub 2020 Apr 29.

Department of Surgical Oncology, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan.

Background: Conversion surgery (CS) following a response to chemotherapy occasionally leads to prolonged survival in patients with stage IV gastric cancer (GC). This study aimed to evaluate the predictive value of the neutrophil/lymphocyte ratio (NLR) for the success of CS in patients with stage IV GC.

Methods: We retrospectively analyzed data of 50 patients with stage IV GC who received systemic chemotherapy between January 2009 and December 2017 at the Kanazawa Medical University Hospital. The successful CS group included the patients who underwent R0 or R1 resection with CS, and the failed CS group included the patients who did not undergo CS after chemotherapy or those who, despite undergoing CS, had to additionally undergo R2 resection. Clinicopathological characteristics were examined in both groups. Univariate and multivariate analyses were performed to identify pretherapeutic parameters that were independently associated with the achievement of successful CS.

Results: The number of patients in the successful and failed CS groups were 12 and 38, respectively. On univariate analysis, gender (P = 0.01), NLR (P = 0.003), albumin levels (P = 0.004), and absence of peritoneal metastasis (P = 0.004) were found to be significantly correlated with a successful CS. On multivariate analysis, NLR < 4 and absence of peritoneal metastasis were independently correlated with a successful CS (P = 0.02 and P = 0.002, respectively). In patients without peritoneal metastasis, successful CS rates in patients with NLR < 4 were significantly higher than those in patients with NLR ≥ 4 (61.1% vs. 10.0%, P = 0.005).

Conclusions: The NLR was a significant independent predictor of the achievement of successful CS in stage IV GC patients, especially among the patients without peritoneal metastasis. Patients with a low NLR could have higher possibility of achieving successful CS.
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http://dx.doi.org/10.1186/s12885-020-06884-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191721PMC
April 2020

Inactivation of Transcriptional Repressor Capicua Confers Sorafenib Resistance in Human Hepatocellular Carcinoma.

Cell Mol Gastroenterol Hepatol 2020 10;10(2):269-285. Epub 2020 Mar 10.

Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan.

Background & Aims: Sorafenib is a multireceptor tyrosine kinase inhibitor that can prolong overall survival in patients with advanced hepatocellular carcinoma (HCC). Although most HCC patients who receive sorafenib ultimately show disease progression, it still is unclear whether and how HCC cells acquire chemoresistance during sorafenib treatment in human beings.

Methods: We analyzed surgically resected HCC tissues from a patient who received sorafenib for prevention of HCC recurrence after surgery (Adjuvant Sorafenib for Hepatocellular Carcinoma after Resection or Ablation trial) and established patient-derived HCC cells. Whole-exome sequence analysis was performed to detect mutations in sorafenib-resistant clones. We examined 30 advanced HCC cases immunohistochemically and 140 HCC cases enrolled in the Adjuvant Sorafenib for Hepatocellular Carcinoma after Resection or Ablation trial using microarray analysis to evaluate the association of Capicua Transcriptional Repressor (CIC) status with sorafenib treatment response.

Results: We found a CIC mutation in recurrent HCC specimens after sorafenib. CIC encodes Capicua, a general sensor of receptor tyrosine kinase signaling. HCC cells established from the recurrent tumor specimen showed chemoresistance to sorafenib in vitro and in vivo. Established sorafenib-resistant Huh1 and Huh7 cell lines showed reduced expression of Capicua without mutations. Immunohistochemical analysis showed that HCC patients with low Capicua expression showed poor overall survival. Microarray analysis showed that the CIC gene signature could predict the preventive effect of adjuvant sorafenib treatment on HCC recurrence. Intriguingly, although CIC knockdown induced sorafenib resistance in HCC cell lines, regorafenib suppressed growth of sorafenib-resistant, Capicua-inactivated HCC cells and inhibited extracellular signal-regulated kinase phosphorylation.

Conclusions: Evaluation of Capicua status may be pivotal to predict response to sorafenib, and regorafenib treatment could be effective to treat HCC with functional Capicua impairment.
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http://dx.doi.org/10.1016/j.jcmgh.2020.02.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305345PMC
July 2021

Impact of Extravasated Platelet Activation and Podoplanin-positive Cancer-associated Fibroblasts in Pancreatic Cancer Stroma.

Anticancer Res 2019 Oct;39(10):5565-5572

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Background/aim: The aim of the study was to evaluate the status of extravasated platelet activation (EPA) surrounding podoplanin (PDPN)-positive cancer-associated fibroblasts (CAFs) in pancreatic cancer stroma by neoadjuvant chemotherapy.

Patients And Methods: A total of 74 patients were enrolled in this study. We investigated CD42b and PDPN expression in the groups of untreated, gemcitabine (GEM) alone, GEM plus S-1 (GS) and GEM plus nab-paclitaxel (GnP).

Results: CD42b expression in surrounding CAFs was observed in 58% patients. CD42b expression was significantly correlated with PDPN expression. CD42b-positive cases were significantly lower in the group treated with GnP than in the untreated group and groups treated with GEM alone or GS. PDPN expression was reduced in the GnP group, as revealed by markedly disorganized collagen and a low density of PDPN-positive fibroblasts. There was a significantly lower CD42b expression and fewer PDPN-positive fibroblasts in the GnP group than in untreated, GEM alone, and GS groups, but there was no significant difference between the latter three groups.

Conclusion: There is a significant association between EPA and PDPN-positive CAFs in pancreatic cancer stroma. Our data suggest that the GnP regimen decreases EPA through PDPN-positive CAF depletion.
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http://dx.doi.org/10.21873/anticanres.13750DOI Listing
October 2019

Monitoring of Heat Shock Response and Phenotypic Changes in Hepatocellular Carcinoma After Heat Treatment.

Anticancer Res 2019 Oct;39(10):5393-5401

Department of Human Pathology, Kanazawa University Hospital, Kanazawa, Japan.

Background/aim: Local recurrence of hepatocellular carcinoma (HCC) after thermal coagulation therapy may be associated with an aggressive phenotypic change. This study focused on the thermal effects on HCC cells and evaluated the heat shock response and phenotypic changes after heat treatment.

Materials And Methods: HepG2 and HuH7 cells were used. After heat treatment at 37-50°C for 5-30 min, we assessed their survival rate, induction of heat shock protein (HSP)70 promoter, proliferation rate, induction of the epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-related markers.

Results: Induction of HSP70 promoter per surviving cell was maximized after 10 min of heat treatment at 48°C. Induction of EMT and CSC-related markers was also observed.

Conclusion: Sub-lethal heat treatment causes large heat shock response to surviving HCC cells and induce EMT-like and CSC-like phenotypic changes that might contribute to increased aggressiveness.
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http://dx.doi.org/10.21873/anticanres.13733DOI Listing
October 2019

Incidence of and risk factors for totally implantable vascular access device complications in patients with gastric cancer: A retrospective analysis.

Mol Clin Oncol 2019 Oct 15;11(4):343-348. Epub 2019 Jul 15.

Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.

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.
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http://dx.doi.org/10.3892/mco.2019.1897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713938PMC
October 2019
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