Efficacy of Autologous Skeletal Myoblast Cell Sheet Transplantation for Liver Regeneration in Liver Failure.

BACKGROUND: No effective therapies have yet been established for liver regeneration in liver failure. Autologous skeletal myoblast cell sheet transplantation has been proven to improve cardiac function in patients with heart failure, and one of the mechanisms has been reported to be a paracrine effect by various growth factors associated with liver regeneration. Therefore, the present study focused on the effect of myoblast cells on liver regeneration in vitro and in vivo. METHODS: We assessed the effect of myoblast cells on the cells comprising the liver in vitro in association with liver regeneration. In addition, we examined in vivo effect of skeletal myoblast cell sheet transplantation in C57/BL/6 mouse models of liver failure, such as liver fibrosis induced by thioacetamide and hepatectomy. RESULTS: In vitro, the myoblast cells exhibited a capacity to promote the proliferation of hepatic epithelial cells and the angiogenesis of liver sinusoidal endothelial cells, and suppress the activation of hepatic stellate cells. In vivo, sheet transplantation significantly suppressed liver fibrosis in the induced liver fibrosis model and accelerated liver regeneration in the hepatectomy model. CONCLUSIONS: Autologous skeletal myoblast cell sheet transplantation significantly improved the liver failure in the in vitro and in vivo models. Sheet transplantation is expected to have the potential to be a clinically therapeutic option for liver regeneration in liver failure.

Change Impact of Body Composition During Neoadjuvant Chemoradiotherapy in Patients with Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma Undergoing Pancreatectomy.

BACKGROUND: The change impact of body composition during neoadjuvant therapy on clinical outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. The aim of this study was to investigate the association between changes in body composition during neoadjuvant chemoradiotherapy (NACRT) and postoperative outcomes in patients with PDAC undergoing pancreatectomy, using three-dimensional images. METHODS: We reviewed 66 consecutive patients with resectable/borderline resectable PDAC receiving gemcitabine and S-1 with radiotherapy between April 2010 and June 2016. Body compositions were evaluated pre- and post-NACRT. All patients were hospitalized and supplied with regulated diet during NACRT treatment. RESULTS: Psoas major muscle volume index (PMI), abdominal fat volume index, and visceral fat volume index decreased significantly after NACRT (P < 0.0001, P < 0.0001, P < 0.0001, respectively). The post-NACRT CA19-9 level decreased significantly in the small-PMI-decrease group compared with the large-PMI-decrease group (P = 0.046). Recurrence-free survival (RFS) and overall survival (OS) of the large-PMI-decrease group were significantly poorer than those of the small-PMI-decrease group (P = 0.002, P = 0.006, respectively). On the other hand, there were no significant differences in RFS and OS between groups with high and low PMI, at the point of either pre-NACRT (P = 0.117, P = 0.123, respectively) or post-NACRT (P = 0.065, P = 0.064, respectively). Multivariate analysis identified a large percentage decrease in PMI as an independent risk factor for recurrence and death (P = 0.003, P = 0.002, respectively). CONCLUSIONS: Loss of skeletal muscle mass during NACRT was an independent risk factor for survival in patients with PDAC.

Three-dimensional Vascularized ß-cell Spheroid Tissue Derived From Human Induced Pluripotent Stem Cells for Subcutaneous Islet Transplantation in a Mouse Model of Type 1 Diabetes.

BACKGROUND: Islet transplantation is an effective replacement therapy for type 1 diabetes (T1D) patients. However, shortage of donor organ for allograft is obstacle for further development of the treatment. Subcutaneous transplantation with stem cell-derived ß-cells might overcome this, but poor vascularity in the site is burden for success in the transplantation. We investigated the effect of subcutaneous transplantation of vascularized ß-cell spheroid tissue constructed 3-dimensionally using a layer-by-layer (LbL) cell-coating technique in a T1D model mouse. METHODS: We used MIN6 cells to determine optimal conditions for the coculture of ß-cell spheroids, normal human dermal fibroblasts, and human umbilical vein endothelial cells, and then, under those conditions, we constructed vascularized spheroid tissue using human induced pluripotent stem cell-derived ß-cells (hiPS ß cells). The function of insulin secretion of the vascularized hiPS ß-cell spheroid tissue was evaluated in vitro. Furthermore, the function was investigated in T1D model NOD/SCID mice subcutaneously transplanted with the tissue. RESULTS: In vitro, the vascularized hiPS ß-cell spheroid tissue exhibited enhanced insulin secretion. The vascularized hiPS ß-cell spheroid tissue also significantly decreased blood glucose levels in diabetic immunodeficient mice when transplanted subcutaneously. Furthermore, host mouse vessels were observed in the explanted vascularized hiPS ß-cell spheroid tissue. CONCLUSIONS: Vascularized hiPS ß-cell spheroid tissue decreased blood glucose levels in the diabetic mice. This therapeutic effect was suggested due to host angiogenesis in the graft. This method could lead to a promising regenerative treatment for T1D patients.

Correction to: Laparoscopic repair of an incarcerated diaphragmatic hernia after right hepatectomy for hepatic injury: a case report.

In the original publication of this article [1], the author found Fig. 1c has a redundant arrow.

Laparoscopic repair of an incarcerated diaphragmatic hernia after right hepatectomy for hepatic injury: a case report.

BACKGROUND: Diaphragmatic hernias (DH) are generally classified as either congenital or acquired. Acquired DH are generally of traumatic cause, being a rare complication after hepatectomy. Although repair of a DH can be performed via laparotomy, laparoscopy, or thoracoscopy, the use of laparoscopy is rare after hepatectomy owing to the formation of scar tissue. In this case, we describe our successful attempt at laparoscopic repair of a recurrent DH after hepatectomy. CASE PRESENTATION: A 30-year-old man underwent right hepatectomy for trauma and thoracotomy via the eighth intercostal space, with direct closure of the diaphragm by suturing. The patient subsequently developed a right DH, with strangulation ileus of the small intestine. He underwent laparotomy 3 months after the initial surgery. The defect was observed to be clearly separate from the previously sutured area of the diaphragm. Five years after treatment, the patient developed abdominal pain and vomiting due to incarceration of the transverse colon in the right intrathoracic space (detected via abdominal computed tomography and radiography). The patient was again diagnosed with DH and underwent laparoscopic repair of the hernia with direct closure. The patient was discharged 11 days after surgery without further complication. CONCLUSIONS: A laparoscopic approach was feasibly and safely used to repair a recurrent DH after hepatectomy. The surgical approach will need to be decided in a patient-specific manner.

[Two Resected Cases of Non-Isolated Splenic Metastasis of Colon Cancer].

We report 2 resected cases of patients with non-isolated splenic metastasis of colon cancer. Case 1: A 67-year-old man who underwent partial transverse colectomy and partial hepatectomy for transverse colon cancer and liver metastasis. Approximately 18 months after the operation, splenectomy and partial hepatectomy were performed for metastasis to the spleen and liver. After partial hepatectomy for another recurrence, no signs of new recurrence have been observed for 42 months after splenectomy. Case 2: A 53-year-old woman who presented with bloating. CT and MRI scans revealed masses of the ileocecum, both ovaries, and spleen. We performed right hemicolectomy, total hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, para-aortic lymphadenectomy, omentectomy, and splenectomy. Histological findings showed cecal cancer metastasizing to the bilateral ovaries and spleen. Metastatic splenic tumor is relatively rare(0.3-7.3%). Splenectomy was reported to be an effective treatment modality for isolated splenic metastasis, while that for non-isolated metastasis is uncertain. Surgical resection should be considered even in non-isolated splenic metastasis cases because of the evidence of long-term survival in case 1.

[Pathological Complete Response in a Case of Advanced Esophageal Cancer with Widespread Lymph Node Metastases Treated Using Preoperative Chemotherapy with Docetaxel, Cisplatin, and 5-FU(DCF therapy)].

The patient was a 66-year-old woman, who was diagnosed with cT3N3M0, cStage III esophageal cancer with widespread lymph node metastases in the mediastinum and abdomen. She was treated with 2 courses of chemotherapy with docetaxel/ cisplatin/5-FU(DCF therapy). CT and FDG PET-CT showed a significant reduction in both the primary tumor and the metastatic lymph nodes following treatment. We performed subtotal esophagectomy and gastric tube reconstruction with lymphadenectomy. The histopathological findings showed no residual viable tumor cells or foreign body-type giant cells with necrosis. The pathological effect of chemotherapy was defined as Grade 3(pCR). Our case suggested that DCF chemotherapy is potentially a very effective treatment for advanced esophageal cancer with widespread lymph node metastases.

[Surgical Resection for Advanced Gastric Cancer with Portal Vein Tumor Embolus - Two Cases].

Gastric cancer with portal tumor embolus is rare and there is no definite strategy for its surgical resection. We report 2 cases ofgastric cancer with portal vein tumor embolus treated using gastrectomy and thrombectomy. Case 1: The patient was a 56- year-old man. We performed total gastrectomy, distal pancreatectomy, splenectomy, and thrombectomy. The patient was treated with 4 courses ofS -1 plus CDDP chemotherapy followed by S-1 administration. Eight months after surgery, CT revealed metastasis in the left adrenal gland and he died 2 years after surgery. Case 2: The patient was a 57-year-old man. We performed total gastrectomy, distal pancreatectomy, splenectomy, partial resection of the transverse colon, and thrombectomy. The patient was treated using adjuvant S-1 chemotherapy followed by UFT administration for 3 years. The patient has been alive with no tumor recurrence for the past 10 years. If there is no other therapeutic option for portal vein embolus, gastrectomy with thrombectomy could increase the possibility oflong -term survival.