Cancer therapy with major histocompatibility complex-deficient and interferon ß-producing myeloid cells derived from allogeneic embryonic stem cells.

We previously established a method to generate myeloid cells with a proliferative capability from pluripotent stem cells and designated them iPS-ML. Human iPS-ML cells share features with physiological macrophages including the capability to infiltrate into cancer tissues. We observed therapeutic effects of human iPS-ML cells expressing interferon ß (iPS-ML/interferon (IFN)-ß) in xenograft cancer models. However, assessment of host immune system-mediated therapeutic and adverse effects of this therapy is impossible by xenograft models. We currently evaluated the therapeutic effects of a mouse equivalent of human iPS-ML/IFN, a mouse embryonic stem (ES) cell-derived myeloid cell line producing IFN (ES-ML/IFN). The ES-MLs producing IFN-ß (ß-ML) and IFN-γ (γ-ML) and originating from E14 ES cells derived from the 129 mouse strain (H-2b ) were generated, and the MHC (H-2Kb , Db , and I-Ab ) genes of the ES-ML/IFN were disrupted using the clustered regularly interspaced short palindromic repeats (CRISPR)/CAS9 method. We used the ES-ML/IFN to treat allogeneic BALB/c mice (H-2d ) transplanted with Colon26 cancer cells. Treatment with ß-ML but not with γ-ML cells repressed the growth of colon cancer in the peritoneal cavity and liver. The transferred ES-ML/IFN infiltrated into cancer tissues and enhanced infiltration of T cells into cancer tissues. ES-ML/IFN therapy increased the number of immune cells in the lymphoid organs. Sensitization of both cancer antigen-specific CD8+ T cells and natural killer (NK) cells were enhanced by the therapy, and CD8+ T cells were essential for the therapeutic effect, implying that donor MHC-deficient ß-ML exhibited a therapeutic effect through the activation of host immune cells derived from allogeneic recipient mice. The results suggested the usefulness of HLA-deficient human iPS-ML/IFN-ß cells for therapy of HLA-mismatched allogeneic cancer patients.

[A case of carcinoma arising in a diverticulum of the transverse colon].

A 64 year-old woman presented with advanced, transverse colon cancer arising in the diverticulum. Tumor invasion extended beyond the serosa to the anal side of the colon. Anemia and fatigue progressed after 6 months of iron administration. The hemoglobin value was 5.3 g/dL and carcinoembryonic antigen (CEA) level was elevated to 44.2 ng/mL. A palpable and tender fist-sized mass was found in the right upper abdomen. Computed tomography (CT) revealed a low-density mass in the transverse colon invading beyond the serosa to the anal side of the colon. Right hemi-colectomy with lymph node dissection was performed. The resected specimen contained multiple diverticula including the one from which the tumor arose. Histological examination revealed a well-differentiated, tubular adenocarcinoma (UICC TNM T4bN0M0) arising in a transverse colon diverticulum. There has been no recurrence for 2 years. Colon cancer arising in a diverticulum may expand to the extra-serosa and easily invade to the adjacent organ. In such cases, malignancy should be considered.

[A case of juvenile colon cancer with peritoneal dissemination treated effectively by use of resection and chemotherapy].

A 37 -year-old man experienced abdominal pain and vomiting. Computed tomography showed massive ascites and obstruction of the colon by a tumor at the left colic flexure. The tumor was classified as advanced Borrmann type 3 on the basis of a colonoscopy. Palliative resection of the colon and colostomy on the oral side were performed. Operative findings showed massive peritoneal dissemination of the tumor. We administered palliative chemotherapy consisting of capecitabine/oxaliplatin (XELOX) and bevacizumab. After 4 courses of chemotherapy, the primary and disseminated tumors and ascites had disappeared, and tumor marker expression levels were within normal range. Palliative resection and subsequent chemotherapy was effective for this young patient with very advanced colon cancer that had disseminated and caused obstruction.

[A case of small intestinal gastrointestinal stromal tumor (GIST) with peritoneal dissemination, treated effectively with molecular target drug after operation].

A 54-year-old man, presenting with sudden onset of abdominal pain, was admitted to our hospital. Blood examination revealed high white blood cell counts and elevated C-reactive protein (CRP) levels. Ultrasonography and computed tomography detected a 12 cm mass in the lower abdomen, some ascites, and multiple small nodules spread through the abdomen. The preoperative diagnosis of the tumor was either a gastrointestinal stromal tumor (GIST) or a possible lymphoma. The 12 cm tumor and greater omentum with multiple nodules were resected. Upon pathological examination, the tumor was diagnosed as a GIST, and appeared KIT positive by immunostaining. After the operation, imatinib was administered; however, psoriasis vulgaris developed within 5 months. As the next line of therapy, sunitinib treatment was initiated; however, since peripheral nerve disorder developed, sunitinib dose was halved and maintained. Two years after the operation, the patient is still alive. Small intestinal GISTs, which make up only 20-30% of all GISTs, are considered to be more malignant than others. We report a rare case of GIST with peritoneal metastases originating from the small intestine, which was treated effectively with molecular target drugs.

[Large bowel malignant obstruction treated with SEMS placement as a bridge to surgery procedure].

We treated 5 cases of preoperative decompression using the self-expandable metallic stent (SEMS) against obstructive left side colon cancer since October 2013. The obstruction site was the descending colon in one patient, sigmoid colon in 2, rectal-sigmoid colon in 1, and rectum in 1. Colonic stent placements were successful in all cases. Oral intake started an average of 3.7 days after SEMS placement. All patients underwent radical surgery an average of 17.2 days after SEMS placement. Two patients waited for surgery while out of the hospital. All patients underwent colonoscopy. One patient had advanced colon cancer. Our findings show that SEMS placement can treat obstructive left-sided colon cancer.

Intussusception as a Presentation of Anisakis Infestation in the Global Era of Raw Fish Consumption: A Case Report and Literature Review.

Anisakiosis, also known as Anisakis larvae infestation, is an increasing parasitic infestation due to the worldwide spread of raw fish and shellfish consumption habits. We present a rare presentation of intestinal intussusception as a preoperative diagnosis and noticed it postoperatively due to Anisakis larvae. A 43-year-old man presented to the emergency department with abdominal pain around the umbilicus and vomiting for several hours. On physical examination at presentation, he had tenderness in the lower abdomen. His radiological studies showed a right-sided pseudo-kidney sign and ileo-colonic intussusception on ultrasound echography. His computed tomography images added findings of submucosal edema and wall thickening in the terminal ileum, swollen regional lymph nodes, and ascites. An urgent laparotomy was performed for ileo-colonic intussusception of an unknown cause. During the laparotomy, the ileocecal intussusception was manually reduced after dissecting the adhesion due to the previous appendectomy, and a partial ileotomy was undertaken using the Endo-GIA automatic anastomosis device. At the resected ileal wall surface, the presence of Anisakis larvae was noticed, and anisakidosis was diagnosed. The dietary history taken post-operatively revealed that he had eaten salmon, bonito, and squid sashimi four days prior to his emergency department visit. His postoperative course was uneventful, and he was discharged from the hospital on the fifth day postoperatively. Anisakiosis must be in the differential diagnosis of intussusception, and eating history seems like a cue to diagnose, and it might be meaningful to clinicians.

Gastric Small Cell Neuroendocrine Carcinoma With Loss of Epithelial Markers Expression.

Background/Aim: Given that gastric small cell neuroendocrine carcinoma (SCNEC) is notably more aggressive than conventional adenocarcinoma, and a platinum-based regimen aligned with the treatment for pulmonary SCNEC is advocated when chemotherapy is needed, ensuring an accurate pathological diagnosis is paramount. Case Report: A 63-year-old man, examined for melena, underwent gastroscopy which revealed a total circumferential Borrmann type 3 lesion extending from the pylorus to the antrum of the stomach. He underwent a distal gastrectomy with D2 lymphadenectomy. The microscopic examination revealed SCNEC with a minor adenocarcinoma component. Immunohistochemically, the SCNEC was diffusely positive for synaptophysin, CD56, and INSM1, very focally positive for chromogranin A, and negative for leukocyte common antigen, CD3, and CD20. A significant observation in this case was the complete negativity for epithelial markers including keratin (CK7, CK8, CK20, CAM5.2, and AE1/AE3) and epithelial membrane antigen. Conclusion: Diffuse positivity for neuroendocrine markers, negativity for other lineage markers, and a transition from the adenocarcinoma component, if present, serve as significant diagnostic clues for gastric SCNEC with loss of epithelial markers expression. SCNEC should not be excluded solely based on the negative result for epithelial markers.

Development of a novel controllable, multidirectional, reusable metallic port with a wide working space.

BACKGROUND: Endoscopic surgery is currently a standard procedure in many countries. Furthermore, conventional four-port laparoscopic cholecystectomy is developing into a single-port procedure. However, in many developing countries, disposable medical products are expensive and adequate medical waste disposable facilities are absent. Advanced medical treatments such as laparoscopic or single-port surgeries are not readily available in many areas of developing countries, and there are often no other sterilization methods besides autoclaving. Moreover, existing reusable metallic ports are impractical and are thus not widely used. MATERIAL AND METHODS: We developed a novel controllable, multidirectional single-port device that can be autoclaved, and with a wide working space, which was employed in five patients. RESULTS: In all patients, laparoscopic cholecystectomy was accomplished without complications. CONCLUSION: Our device facilitates single-port surgery in areas of the world with limited sterilization methods and offers a novel alternative to conventional tools for creating a smaller incision, decrease postoperative pain, and improve cosmesis. This novel device can also lower the cost of medical treatment and offers a promising tool for major surgeries requiring a wide working space.

[A case of advanced gastric cancer with esophageal severe dysplasia resected after neoadjuvant S-1+cisplatin therapy].

A 72-year-old man was admitted to our hospital complaining of upper abdominal pain and back pain. Advanced gastric cancer was found at the fundus of the stomach, and severe dysplasia was found at the lower esophagus. We proceeded with neoadjuvant chemotherapy (S-1+CDDP) because the lymph nodes in the lesser curvature of the stomach were metastasized and invasion of the pancreas and some vessels was suspected by computed tomography. The tumor size was reduced remarkably, the esophageal dysplasia disappeared after preoperative chemotherapy, and we were able to perform total gastrectomy.

[A case of no recurrence over 10 years in advanced rectal cancer with bleeding treated by urgent arterial embolization followed by synchronous liver resection and extended lymph node dissection].

A 68-year-old woman was brought by ambulance due to abrupt anal bleeding. Elastic hard and solid mass was found in rectal examination. The pathological diagnosis of the tumor revealed adenocarcinoma. The metastatic 40 × 40 mm liver tumor was also found at CT scan. Acute bleeding with hemoglobin level of 6 .0 g/dL necessitated an urgent arterial embolization of bilateral internal iliac artery and superior rectal artery. After recovery from the systemic condition, radical operation was performed, comprising abdomino-perineal resection of the rectum with extended lymph node dissection involving paraaortic area followed by synchronous liver resection. Arterial infusion of 5-FU (11.0 g in total) via proper hepatic artery was added postoperatively. She was followed for over 12 years, and no recurrence was observed.

Therapy of primary and metastatic liver cancer by human iPS cell-derived myeloid cells producing interferon-ß.

BACKGROUND: iPS-ML are myeloid lineage cells with a proliferative capacity derived from induced pluripotent stem (iPS) cells. This study aimed to examine therapeutic effect of iPS-ML producing interferon-ß (iPS-ML/IFN-ß) towards primary and metastatic liver cancer and investigate the mechanism of that effect. METHODS: We established a xenograft model of liver metastasis by injecting the spleen of SCID mice with MKN-45 human gastric cancer cells and also a primary liver cancer model by injecting SK-HEP-1 human hepatocellular carcinoma cells into the liver. After cancer lesions were established, iPS-ML/IFN-ß was administered by intraperitoneal injection, and therapeutic effect was evaluated. RESULTS: The i.p. injection of iPS-ML/IFN-ß resulted in a significant retardation of cancer progression and prolonged mouse survival. The infiltration of i.p. administered iPS-ML into tumor lesions located below the liver capsule was observed, suggesting tumor-directed migration and penetration of the liver capsule by iPS-ML. The IFN-ß concentration in the liver was maintained at levels sufficient to exert an anti-cancer effect for at least 3 days post-injection, accounting for the potent therapeutic effect obtained by injection two to three times per week. CONCLUSIONS: This study demonstrates the therapeutic potential of the iPS-ML/IFN-ß in patients with liver cancer.