[Successful Endoscopic Submucosal Dissection of Early Gastric Cancer in a Patient after Azacitidine Therapy for the Treatment of Myelodysplastic Syndrome].

A 76‒year‒old man was introduced to our hospital after being suspected of having early gastric cancer with an upper gastrointestinal endoscope that was performed to find the cause of anemia. Two cancers were revealed: type 0‒Ⅱa+Ⅰ lesion in the lesser curvature of the upper body and type 0‒Ⅱa+Ⅱc lesion in the greater curvature of the middle body. The blood test showed abnormalities(hemoglobin, 6.8 g/dL; platelets, 26,000/µg). Thus, myelodysplastic syndrome(MDS) was suspected, and since this was prioritized over gastric cancer, the patient was transferred to the hematology department. As high risk MDS was diagnosed, azacitidine therapy was initiated. After 2 cycles of treatment, the blood abnormalities improved(hemoglobin, 11.3 g/dL; platelets, 254,000/µg). ESD was performed in our department for the 2 lesions. Histopathological examination showed that both lesions represented well‒differentiated adenocarcinoma, and so radical resection was performed. Since MDS occurs due to aging and is common among patients, we believe that timely treatment is necessary.

[A Case of Advanced Gastric Cancer Confirmed as Pathological Complete Response Following S-1 plus Oxaliplatin Chemotherapy and Gastric Resection].

A 69-year-old woman presented with persistent nauseous, underwent upper gastrointestinal endoscopy, and was diagnosed with type 2 advanced gastric cancer at the antrum. Abdominal contrast CT image data revealed that there was a large, swollen, pancreatic superior lymph node invading the common hepatic artery. We determined that the tumor was unresectable and systemic chemotherapy was performed using S-1 plus oxaliplatin(SOX)therapy. After 5 courses of chemotherapy, the abdominal contrast CT image data indicated reduction of both the primary lesion and lymph node metastasis. A laparotomy was performed. As the No. 8a lymph node was forming hard scar tissue, we could not dissected clearly it from the common hepatic artery wall. We strongly suspected that cancer tissue remained at the artery wall. A distal gastrectomy and Roux-en-Y reconstruction were performed. Histologically, the resected specimen was determined to be Grade 3, with a pathological complete response(pCR). The patient was administered S-1 for 6 months after the operation and has enjoyed 2.5 years of recurrence-free survival. SOX therapy for unresectable gastric cancer and surgical intervention as conversion surgery were effective. This case demonstrated the possibility of life prolongation using these therapies.

The usefulness of three-dimensional cell culture in induction of cancer stem cells from esophageal squamous cell carcinoma cell lines.

In recent years, research on resistance to chemotherapy and radiotherapy in cancer treatment has come under the spotlight, and researchers have also begun investigating the relationship between resistance and cancer stem cells. Cancer stem cells are assumed to be present in esophageal cancer, but experimental methods for identification and culture of these cells have not yet been established. To solve this problem, we created spheroids using a NanoCulture® Plate (NCP) for 3-dimensional (3-D) cell culture, which was designed as a means for experimentally reproducing the 3-D structures found in the body. We investigated the potential for induction of cancer stem cells from esophageal cancer cells. Using flow cytometry we analyzed the expression of surface antigen markers CD44, CD133, CD338 (ABCG2), CD318 (CDCP1), and CD326 (EpCAM), which are known cancer stem cell markers. None of these surface antigen markers showed enhanced expression in 3-D cultured cells. We then analyzed aldehyde dehydrogenase (ALDH) enzymatic activity using the ALDEFLUOR reagent, which can identify immature cells such as stem cells and precursor cells. 3-D-cultured cells were strongly positive for ALDH enzyme activity. We also analyzed the expression of the stem cell-related genes Sox-2, Nanog, Oct3/4, and Lin28 using RT-PCR. Expression of Sox-2, Nanog, and Lin28 was enhanced. Analysis of expression of the hypoxic surface antigen marker carbonic anhydrase-9 (CA-9), which is an indicator of cancer stem cell induction and maintenance, revealed that CA-9 expression was enhanced, suggesting that hypoxia had been induced. Comparison of cancer drug resistance using cisplatin and doxorubicin in 3-D-cultured esophageal cancer cells showed that cancer drug resistance had increased. These results indicate that 3-D culture of esophageal squamous cell carcinoma lines is a useful method for inducing cancer stem cells.

Aminopeptidase N (APN/CD13) as a target molecule for scirrhous gastric cancer.

BACKGROUND: Scirrhous gastric cancer is associated with peritoneal dissemination and advanced lymph node metastasis from an early stage, and the prognosis is still poor. In this study, we aimed to analyze candidate molecules for targeted therapy of scirrhous gastric cancer. We searched for molecules/metabolic activity that might be predominantly expressed in a subpopulation of scirrhous gastric cancer cells and might function as cancer stem cell markers. RESULTS: For this purpose, we investigated the expression of various cell surface markers and of aldehyde dehydrogenase (ALDH) activity. These analyses showed that the scirrhous gastric cancer cell lines HSC-58 and HSC-44PE heterogeneously expressed CD13, while CD44, CDCP1, EpCAM and ABCG2 were expressed uniformly. Moreover, 10% of the total HSC-58 cell population expressed ALDH enzyme activity. A subpopulation of cells strongly positive for ALDH also expressed high levels of CD13, both of which are known as cancer stem cell markers. HSC-58 cells expressing high levels of CD13 showed lower sensitivity to a cancer drug cisplatin than cells with low levels of CD13. In contrast, CD13(-high) subpopulation of HSC-58 was more sensitive to an aminopeptidase N inhibitor bestatin. In terms of antibody-drug therapy, anti-CD13-immunotoxin was highly cytotoxic towards HSC-58 cells and was more cytotoxic than anti-EpCAM-immunotoxin. CONCLUSION: These data suggest that CD13 is a suitable cell surface candidate for targeted antibody-drug therapy of scirrhous gastric cancer.

Laparoscopic resection of schwannoma of the ascending colon.

Schwannomas of the colon are rare and difficult to diagnose preoperatively. We report a case of schwannoma of the ascending colon that was resected laparoscopically. A 64-year-old woman was referred to our hospital by her local clinic for further evaluation and management of a submucosal tumor of the ascending colon. A definitive preoperative diagnosis could not be reached despite examinations. Gastrointestinal stromal tumor, leiomyoma and lymphoma were the differential diagnoses. We performed a laparoscopic right hemicolectomy with D2 lymph node dissection. Histological findings with hematoxylin-eosin staining revealed spindle-like tumor cells, and immunohistochemical analysis showed that the tumor was positive for S-100 but negative for c-kit, CD34, smooth muscle actin and desmin, with a Ki-67 index of <5%. Thus, the diagnosis in this case was benign schwannoma of the ascending colon.

Report of a case: Retroperitoneal mucinous cystadenocarcinoma with rapid progression.

INTRODUCTION: Retroperitoneal mucinous cystic neoplasms are uncommon, and little is known about the etiology of the disease. Malignant forms of these are extremely rare. Here, we report a case of primary retroperitoneal mucinous cystadenocarcinoma (PRMC), which demonstrated unexpectedly aggressive progression despite finding only a limited area of adenocarcinoma. PRESENTATION OF CASE: A 62-year-old woman with a complaint of abdominal discomfort was admitted to the hospital. Abdominal CT and MRI showed multiple large retroperitoneal cysts dislocating the right kidney nearly to the center of the abdomen. Transabdominal resection of the cysts was performed. Those cysts contained 1100ml of mucinous fluids in total. Cytological examination of those fluids revealed no malignant cells. The cyst wall was lined with mucinous epithelial cells, and contained some ovarian-type stroma. Also, there was a focal area of adenocarcinoma in the cyst wall, and the lesion was diagnosed as primary retroperitoneal mucinous cystadenocarcinoma. Eight months later, the patient developed lumbar bone metastasis. Chemotherapy with S-1, an oral fluoropyrimidine, and docetaxel had been begun immediately; however, the disease had rapidly spread in the retroperitoneum. Eventually, the patient died of the disease 15 months after surgery. DISCUSSION: Retroperitoneal mucinous cystic neoplasms are considered to be metaplasia of embryonal coelomic epithelium. Complete excision without rupture is essential. However, variance of biological aggressiveness might exist in PRMCs. CONCLUSION: Retroperitoneal mucinous cystadenocarcinoma is a rare tumor, and it is urgently necessary to elucidate the etiology of an effective therapy for the disease.

A case of small bowel obstruction caused by bezoars diagnosed with double balloon enteroscopy.

Primary small bowel bezoars are rare and cause acute abdomen due to small bowel obstruction (SBO). A 69-year-old Japanese man presented with epigastric pain associated with fullness. Physical examination of the abdomen showed no marked signs of peritoneal irritation. An erect X-ray film of the abdomen showed small bowel obstruction. Computed tomography (CT) showed a dilated small bowel loop proximal to the site of the obstruction. Retrograde double balloon enteroscopy (DBE) was performed and showed yellow, hard bezoars blocking the distal ileum. At surgery, a bezoar was found impacted in the distal ileum, and enterotomy with extraction was performed. After 9 days, the patient was discharged from our hospital in satisfactory condition. DBE also appears to be a safe and useful diagnostic tool in patients with SBO, and the findings of DBE influence the strategy of therapy in patients in whom the cause of SBO could not be determined by conventional radiography.