低酸素によって促進されるCD24の発現は胃癌細胞の運動・浸潤能亢進因子である

内容の要旨 , 審査の要旨広島大学(Hiroshima University)博士(医学)Doctor of Philosophy in Medical Sciencedoctora

Laparoscopic extra-abdominal suturing technique for the repair of Larrey’s diaphragmatic hernia using the port closure needle (Endo Close®): A case report

AbstractIntroductionMorgagni’s or Larrey’s diaphragmatic hernias are relatively uncommon. If the defect is too large for primary closure, the use of a mesh is inevitable. Although primary closure is adaptable for relatively small defects, it is difficult to suture the hernial orifice in which the anterior rim is absent. Herein, we present the case of a patient with Larrey’s diaphragmatic hernia that was easily and securely repaired using the recently developed laparoscopic extra-abdominal suturing technique via the port closure needle (Endo Close®; Medtronic, Minneapolis, USA).Presentation of caseAn 89-year-old woman complaining of vomiting was transferred to our hospital. Computed tomography scan showed Larrey’s diaphragmatic hernia. Laparoscopic repair was performed after gastric decompression. We diagnosed Larrey’s hernia on the left side of the falciform ligament. The transverse colon was herniated through the defect. Since the hernial defect was located below the substernal space, there was no tissue to stitch at the anterior rim of the hernial orifice. We performed the extra-abdominal suturing technique, suturing the posterior rim of the hernia to the full thickness of the anterior abdominal wall using the port closure needle (Endo Close®) without the need for a mesh. The patient was discharged on the 8th postoperative day. There was no evidence of recurrence at 8 months postoperatively.DiscussionThe recently developed extra-abdominal suturing technique using Endo Close® to suture the full thickness of the anterior abdominal wall achieved secure mattress suture and easy extra-abdominal tying.ConclusionThis method may be useful in terms of easiness and security of suture

Stimulation of natural killer cells with rhCD137 ligand enhances tumor-targeting antibody efficacy in gastric cancer.

Although many anticancer agents for gastric cancer have been developed, the prognosis for many patients remains poor. Recently, costimulatory immune molecules that reactivate antitumor immune responses by utilizing the host immune system have attracted attention as new therapeutic strategies. CD137 is a costimulatory molecule that reportedly potentiates the antitumor activity of tumor-targeting monoclonal antibodies (mAbs) by enhancing antibody-dependent cellular cytotoxicity. However, it remains unclear whether CD137 stimulates tumor-regulatory activity in gastric cancer. In this study, we investigated the antitumor effects of CD137 stimulation on gastric cancer cells administered tumor-targeting mAbs. Our results showed that human natural killer (NK) cells were activated by expressing CD137 after encountering trastuzumab-coated gastric cancer cells, and that stimulation of activated NK cells in the presence of trastuzumab and recombinant human CD137 ligand (rhCD137L) enhanced cytotoxicity and release of cytokines (IFN-γ, TNF, granzyme A, or granzyme B) as compared with activated NK cells with trastuzumab alone (p < 0.05). By combination treatment with rhCD137L, similar effects were obtained regarding cancer cell cytotoxicity in the presence of cetuximab (p < 0.01). Moreover, we revealed that CD137 expression was dependent upon the affinity between the Fc portion of the antibodies and FcγRIIIa of NK cells based on results indicating that human IgG1 and IgG3 subclasses enhanced CD137 expression (p < 0.001). These results confirmed that FcγRIIIA polymorphisms (158 V/V) enhanced CD137 expression to a greater degree than 158 F polymorphisms (p = 0.014). Our results suggested that CD137 stimulation could promote the effects of tumor-targeting mAbs in gastric cancer, and that further investigation of antibody binding affinity and in vivo activities might improve therapeutic strategies related to the treatment of gastric cancer patients

The influence of partial gastrectomy for gastric cancer on the spontaneous disappearance of Helicobacter pylori: A single‐center prospective study

Abstract Background/Aims Helicobacter pylori (HP) eradication is recommended after endoscopic treatment of early gastric cancer (EGC). Cases of spontaneous HP resolution after partial gastrectomy due to environmental changes have been reported; however, there is no evidence for the efficacy of HP eradication in suppressing carcinogenesis and also no reports on the natural history of HP after partial gastrectomy in gastric cancer (GC). To report the natural history of HP in patients with GC and HP infection after partial gastrectomy. Methods and Results We prospectively studied the rate of spontaneous disappearance of HP after partial gastrectomy in patients with GC. From April 2016 to May 2020, 80 patients underwent partial gastrectomy, including 9 cases of proximal gastrectomy (PG), and 71 cases of distal gastrectomy (DG). The presence of HP was confirmed in the stool antigen test 1 year after operation, HP infection persisted in 46 patients (57.5%) and disappeared in 34 patients (42.5%). In univariate analysis, only proton pump inhibitor (PPI) use was a significant contributing factor for the spontaneous resolution of HP infection, especially in the DG group. However, there was no difference in the rates of HP disappearance between Billroth‐I and Roux‐en‐Y reconstructions in the DG group. Conclusion The HP spontaneously disappeared in 42.5% of the GC patients within 1 year after partial gastrectomy. Further investigation in a larger cohort is needed to elucidate the underlying mechanisms

The gastric carcinosarcoma with severe venous invasion: a case report

Abstract Background Gastric carcinosarcoma with severe venous invasion is extremely rare, and to the best of our knowledge, this is the first reported case. Case presentation A 79-year-old man visited the Onomichi General Hospital following abnormal upper gastrointestinal series findings. Laboratory data demonstrated no anemia, and the serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were not elevated. Endoscopy identified a Borrmann type III lesion in the cardiac end of the stomach. Abdominal contrast-enhanced computerized tomography (CT) indicated that the lesser curvature of the stomach wall was modestly enhanced with bulky lymph nodes. Pathological biopsy examination identified a group 5, papillary adenocarcinoma. We diagnosed advanced gastric cancer with bulky lymph nodes (cT4aN3M0, cStage IIIC). Following neoadjuvant chemotherapy, the patient underwent open total gastrectomy with D2 lymph node dissection. Histopathologically, the tumor consisted of two components: a tubular adenocarcinoma and a sarcoma. The tumor cells were mainly intravenous and were not detected in the gastric wall stroma; this resulted in a venous invasion. Immunohistochemical analysis revealed that the tumor was positive for vimentin and partly positive for desmin and cytokeratin CAM5.2. We diagnosed a true gastric carcinosarcoma with severe venous invasion. Abdominal CT 2 months after surgery showed a low density area in the liver, suggesting metastasis. Conclusions Carcinosarcomas with lymph node metastasis are sometimes reported, but progression into the vasculature is very rare. We present a case of carcinosarcoma with unusual progression characteristics

Complete spontaneous necrosis of hepatocellular carcinoma confirmed on resection: A case report

Introduction: Complete spontaneous necrosis of hepatocellular carcinoma (HCC) without any pretreatment or angiography is rare. We present a rare case of spontaneous complete necrosis of HCC, as confirmed after hepatectomy. Presentation of case: The patient, a 74-year-old man with a history of alcoholic hepatitis, was referred to our hospital for confirmation of suspected HCC. In March 2015, abdominal ultrasonography detected a low echoic mass in segment 8 (S8) of the liver. Contrast-enhanced computed tomography (CT) imaging revealed interval growth of this tumor and showed that the tumor was well enhanced in the arterial phase and washed out in the portal and delayed phases. The serum alpha-fetoprotein level was elevated at 30.8 ng/mL and the percentage of the L3 isoform was 25.5%. Two months later, CT imaging showed that the tumor was of low density and had decreased in size; no contrast enhancement of the tumor was seen. Spontaneous necrosis of the HCC was considered; however, as we could not exclude viable malignant cells in the tumor, we performed S8 segmentectomy of the liver. The resected tumor specimen had a thick fibrous capsule. Histopathological findings showed only granulation and necrotic tissue accompanied by bleeding and hemosiderosis. No viable tumor cells were observed. The serum alpha-fetoprotein level returned to the normal range one month after surgery. Discussion: If spontaneous regression has occurred, there is a possibility of HCC recurrence and of remnant viable tumor cells. Conclusion: We present a rare case of complete spontaneous necrosis of HCC and strongly recommended surgical intervention

A Case of Gastric Cancer Following Living Donor Liver Transplantation

Only a few cases of de novo malignancy, especially gastric cancer after living donor liver transplantation (LDLT), have been reported. We report a case of gastric cancer following LDLT, after which immunosuppressants were minimized in accordance with the results of the mixed lymphocyte reaction (MLR) assay. A 65-year-old woman had previously undergone LDLT for hepatocellular carcinoma associated with hepatitis B virus infection. The liver graft had been donated by her son. During the course of postoperative surveillance with the MLR assay in order to minimize immunosuppressants, she was incidentally found to have gastric cancer during an endoscopic examination, 8 years after the liver transplantation. She underwent total gastrectomy with lymph node dissection. In this case, gastric cancer was detected 8 years after LDLT, which is longer than previously reported intervals between LDLT and malignancy detection. The number of patients undergoing LDLT is increasing, and the prognosis after liver transplantation has improved. Therefore, endoscopic surveillance programs are important for detecting malignancies in the early stages in liver transplant recipients