肺癌の免疫療法に関する研究: 特に腫瘍局所における抗腫瘍活性の誘導とその応用に関する研究

取得学位 : 博士（医学）, 学位授与番号 : 医博乙第1055号, 学位授与年月日：平成1年5月17日,学位授与年：198

Preliminary results of phase I trial of oral uracil/tegafur (UFT), leucovorin plus irinotecan and radiation therapy for patients with locally recurrent rectal cancer

BACKGROUND: Surgical attempts for locally recurrent rectal cancer often fail due to local re-recurrence and distant metastasis. Preoperative chemoradiation may enhance better local control and survival. The aim of this study was to assess the safety of oral uracil and tegafur (UFT) plus leucovorin (LV), and irinotecan combined with radiation and determine the maximum-tolerated dose (MTD) and dose limiting toxicity (DLT) of the triple drug regimen. PATIENTS AND METHODS: Patients with locally recurrent rectal cancer received escalating doses of irinotecan on days 1, 8, 15, and 22 (starting at 30 mg/m(2), with 10 mg increments between consecutive cohorts) and fixed doses of UFT (300 mg/m(2)) plus LV (75 mg/day) on days 3 to 7, 10 to 14, 17 to 21, and 24 to 28. Radiation was given 5 days per week totaling 40 to 50 Gy (2Gy/day). RESULTS: Six patients were treated at the starting dose, and 2 received the full scheduled chemoradiotherapy. The other 4 patients had grade 3 diarrhea and diarrhea was the DLT. One patient had partial response and he had subsequently radical surgical resection. Median progression free survival for local recurrence was 320 days. CONCLUSION: Irinotecan plus UFT/LV with concomitant radiotherapy in patients with locally recurrent rectal cancer was not feasible due to diarrhea in this setting. Modification of the treatment is needed

Laparoscopic Resection of a Jejunal Inflammatory Fibroid Polyp that Caused Occult Gastrointestinal Bleeding, Diagnosed via Capsule Endoscopy and Double-Balloon Enteroscopy: A Case Report

An inflammatory fibroid polyp (IFP) is a mesenchymal tumor of the gastrointestinal tract. IFPs in the small intestine are the most frequently detected with symptoms, such as abdominal pain and tarry stool due to intussusception. Accordingly, few studies have reported jejunal IFP as a cause of occult gastrointestinal bleeding (OGIB) diagnosed via both of capsule endoscopy (CE) and double-balloon enteroscopy (DBE). A 68-year-old woman presented with a progression of anemia and a positive fecal occult blood test result. Esophagogastroduodenoscopy and total colonoscopy findings were unremarkable. CE revealed a tumor with bleeding in the jejunum. DBE also revealed a jejunal polypoid tumor. Bleeding from the tumor seemed to have caused anemia. The patient underwent partial laparoscopic resection of the jejunum, including resection of the tumor. The tumor was histopathologically diagnosed as IFP. To our knowledge, this is the first reported case of laparoscopic resection of jejunal IFP with OGIB diagnosed via CE and DBE preoperatively

KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation

Kato K., Noda T., Kobayashi S., et al. KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation. Cancer Science , (2024); https://doi.org/10.1111/cas.16144.Tumor endothelial cells (TECs), which are thought to be structurally and functionally different from normal endothelial cells (NECs), are increasingly attracting attention as a therapeutic target in hypervascular malignancies. Although colorectal liver metastasis (CRLM) tumors are hypovascular, inhibitors of angiogenesis are a key drug in multidisciplinary therapy, and TECs might be involved in the development and progression of cancer. Here, we analyzed the function of TEC in the CRLM tumor microenvironment. We used a murine colon cancer cell line (CT26) and isolated TECs from CRLM tumors. TECs showed higher proliferation and migration than NECs. Coinjection of CT26 and TECs yielded rapid tumor formation in vivo. Immunofluorescence analysis showed that coinjection of CT26 and TECs increased vessel formation and Ki-67+ cells. Transcriptome analysis identified kallikrein-related peptide 10 (KLK10) as a candidate target. Coinjection of CT26 and TECs after KLK10 downregulation with siRNA suppressed tumor formation in vivo. TEC secretion of KLK10 decreased after KLK10 downregulation, and conditioned medium after KLK10 knockdown in TECs suppressed CT26 proliferative activity. Double immunofluorescence staining of KLK10 and CD31 in CRLM tissues revealed a significant correlation between poor prognosis and positive KLK10 expression in TECs and tumor cells. On multivariate analysis, KLK10 expression was an independent prognostic factor in disease-free survival. In conclusion, KLK10 derived from TECs accelerates colon cancer cell proliferation and hematogenous liver metastasis formation. KLK10 in TECs might offer a promising therapeutic target in CRLM

Results of a Randomized Clinical Study of Gemcitabine Plus Nab-Paclitaxel Versus Gemcitabine Plus S-1 as Neoadjuvant Chemotherapy for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma (RCT, CSGO-HBP-015)

The version of record of this article, first published in Annals of Surgical Oncology, is available online at Publisher’s website: https://doi.org/10.1245/s10434-024-15199-8.Background: The optimal neoadjuvant chemotherapy (NAC) regimen for patients with localized pancreatic ductal adenocarcinoma (PDAC) remains uncertain. This trial aimed to evaluate the efficacy and safety of two neoadjuvant chemotherapy (NAC) regimens, gemcitabine plus nab-paclitaxel (GA) and gemcitabine plus S-1 (GS), in patients with resectable/borderline-resectable (R/BR) PDAC. Patients and Methods: Treatment-naïve patients with R/BR-PDAC were enrolled and randomly allocated. They received two cycles (2 months) of each standard protocol, followed by radical surgery for those without tumor progression in general hospitals belonging to our intergroup. The primary endpoint was to determine the superior regimen on the basis of achieving a 10% increase in the rate of patients with progression-free survival (PFS) at 2 years from allocation. Results: A total of 100 patients were enrolled, with 94 patients randomly assigned to the GS arm (N = 46) or GA arm (N = 48). The 2-year PFS rates did not show the stipulated difference [GA, 31% (24–38%)/GS, 26% (18–33%)], but the Kaplan–Myer analysis showed significance (median PFS, GA/GS 14 months/9 months, P = 0.048; HR 0.71). Secondary endpoint comparisons yielded the following results (GA/GS arm, P-value): rates of severe adverse events during NAC, 73%/78%, P = 0.55; completion rates of the stipulated NAC, 92%/83%, P = 0.71; resection rates, 85%/72%, P = 0.10; average tumor marker (CA19-9) reduction rates, −50%/−21%, P = 0.01; average numbers of lymph node metastasis, 1.7/3.2, P = 0.04; and median overall survival times, 42/22 months, P = 0.26. Conclusions: This study found that GA and GS are viable neoadjuvant treatment regimens in R/BR-PDAC. Although the GA group exhibited a favorable PFS outcome, the primary endpoint was not achieved

手術成績からみた小型進行肺癌の手術適応の検討

This report analyzes the operative indication for the small lesion of advanced lung cancer. The subjects consisted of 25 patients with T1N2 lung cancer, one T1N3, four T1M1 and five small lung cancer lesion with dissemination, which was regarded as the small lesion of advanced lung cancer. The cumulative 5-year survival rate after operation for 25 patients with T1N2 lesion was 30.6%. Of 25 patients, 18 were selected patients who underwent a curative operation with a 5-year survival of 37.0%. In the remaining 7 patients, who underwent a non-curative operation, 5-year survival was 0%. As to mediastinal lymph node involvement, it is possible that metastasis to more than two levels of mediastinal lymph nodes or to the upper mediastinal lymph nodes (#1-3) are poor prognostic factors in T1N2 lesion. Another group except T1N2 could not be the comparative materials because they were much fewer in number. But T4 cases associated with small lung cancer lesion with dissemination and T1M1 cases associated with intrapulmonary metastasis encountered at thoracotomy could be expected to have a long-term survival. We conclude that T1N2 patients with metastasis to within one level of mediastinal lymph node, which will possibly have a curative operation, is a proper operative indication for the small lesion of advanced lung cancer

中間気管支幹に発生した気管支平滑筋腫の1切除例

Leiomyoma of the trachea and bronchus is a rare tumor. Only 45 cases have been reported in the Japanese literature. We report here a case of leiomyoma of the intermediate bronchus which was successfully operated on. A 45-year-old man suffered from a repeated episode of pneumonia in the right lower lobe. Bronchoscopy revealed a polypoid mass on the intermediate bronchus. The diagnosis of leiomyoma was made by bronchoscopic biopsy. Sleeve resection of the intermediate bronchus including the tumor and end-to-end anastomosis was performed. His postoperative course was uneventful and bronchoscopic findings showed clear healing of the anastomotic site. The resected specimen contained a tumor with smooth surface having protrusion into the bronchial lumen with 6 x 5 x 4 mm in size. The final pathological diagnosis was leiomyoma of the intermediate bronchus with no evidence of malignancy

管状左上区切除＋左下葉分画肺切除により肺機能を温存した肺門部早期肺癌症例

金沢大学医薬保健研究域医学系A 59-year-old man complained of fever due to infection in the intralobar pulmonary sequestration. On bronchoscopic examination, squamous cell carcinoma was found out at orifice of the left upper division bronchus. His pre-operative pulmonary function test showed low pulmonary reserve because of myelopathy. He underwent left S1 + 2 + S3 sleeve segmentectomy and S9 + 10 segmentectomy for intralobar pulmonary sequestration. He is well without any evidence of recurrence 10 months after surgery

Sleeve Lobectomy 10年後の再発に対し Completion Pneumonectomy を施行した腺様嚢胞癌の1例

A 62-year-old woman with adenoid cystic carcinoma which recurred 10 years after sleeve middle lobectomy was reported. Completion pneumonectomy was performed and her postoperative course was uneventful. If pulmonary function permits, reoperation for recurrent lung cancer should be attempted

アンスロンチューブを用いて大動脈合併切除術を施行した肺癌の1例

金沢大学医薬保健研究域医学系A 63-year-old male had squamous cell carcinoma in the left upper lobe. CT scan suggested the invasion of the tumor into the vertebral body and the descending aorta. Left pneumonectomy and combined aortic resection under the temporary bypass using Anthron tube was performed. The bypass using Anthron tube provides us no systemic heparinization and the procedure is easy. So the danger of massive bleeding during and after the operation can be decreased and the operative time can also be shortened. This procedure may be a great help for carrying out the operation with combined aortic resection more safely and speedily