佐久間 康成

BACKGROUND: The genesis of the "complex type" classification of pancreaticobiliary maljunction (PBM) is unclear, and the pancreaticobiliary anatomy is also varied according to each case. We encountered a patient with PBM and incomplete pancreatic divisum (PD). We herein discussed about the embryological etiology of pancreaticobiliary system predicted from PBM with incomplete PD. CASE PRESENTATION: A 67-year-old man was found to have a dilatation of the common bile duct (CBD) during a medical examination at 62 years of age. The dilatation of the CBD subsequently progressed, and he was admitted to our hospital for surgical treatment. Magnetic resonance cholangiopancreatography revealed a dilatation from the common hepatic duct to the middle bile duct with PBM. Endoscopic retrograde cholangiopancreatography from the papilla of Vater revealed the pancreatic main duct via the pancreatic branch duct, and PBM with dilatation of the CBD and incomplete PD were revealed. We performed an extrahepatic bile duct resection and hepaticojejunostomy because of high risk of malignant transformation. Taping and transection of the bile duct without dilatation on the pancreatic side were performed, and thereafter, two orifices of the common channel and ventral pancreatic duct were ligated. The level of amylase in the bile was 7217 IU/L, and a histological examination of the CBD showed an inflammatory change of CBD, not a malignant transformation. CONCLUSION: It is somewhat easy to identify the pancreatobiliary anatomy when the cause of embryology of both PBM and PD is thought to be an abnormal embryology of the ventral pancreas.

Survivin plays a key role in regulating the cell cycle and apoptosis, and is highly expressed in the majority of malignant tumors. However, little is known about the roles of survivin in KRAS-mutant lung adenocarcinomas. In the present study, we examined 28 KRAS-mutant lung adenocarcinoma tissues and two KRAS-mutant lung adenocarcinoma cell lines, H358 and H441, in order to elucidate the potential of survivin as a therapeutic target. We found that 19 (68%) of the 28 KRAS-mutant lung adenocarcinomas were differentiated tumors expressing thyroid transcription factor‑1 (TTF‑1) and E-cadherin. Patients with tumors immunohistochemically positive for survivin (n=18) had poorer outcomes than those with survivin-negative tumors (n=10). In the H358 and H441 cells, which expressed TTF‑1 and E-cadherin, survivin knockdown alone induced senescence, not apoptosis. However, in monolayer culture, the H358 cells and H441 cells in which survivin was silenced, underwent significant apoptosis following combined treatment with ABT-263, a Bcl‑2 inhibitor, and trametinib, a MEK inhibitor. Importantly, the triple combination of survivin knockdown with ABT-263 and trametinib treatment, clearly induced cell death in a three-dimensional cell culture model and in an in vivo tumor xenograft model. We also observed that the growth of the H358 and H441 cells was slightly, yet significantly suppressed in vitro when TTF‑1 was silenced. These findings collectively suggest that the triple combination of survivin knockdown with ABT-263 and trametinib treatment, may be a potential strategy for the treatment of KRAS-mutant lung adenocarcinoma. Furthermore, our findings indicate that the well‑differentiated type of KRAS-mutant lung tumors depends, at least in part, on TTF‑1 for growth.

Despite recent advances in chemotherapy, outcomes of patients with peritoneal metastases (PM) from gastric cancer are still very poor and standard treatment has not been established. Although oral S-1 appears to be effective for patients with PM, the effects of systemic chemotherapy are limited. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) yield fewer benefits in patients with PM from gastric cancer than in patients with PM from other malignancies. In comparison, repeated intraperitoneal chemotherapy (RIPEC) with taxanes using an implantable peritoneal access port has a pharmacokinetic advantage for the control of peritoneal lesions and in combination with systemic chemotherapy can result in surprisingly long-term survival in patients with PM from gastric cancer. Herein, we review the results of recent clinical studies specifically targeting PM from gastric cancer and discuss future prospects for an intraperitoneal approach to the ideal treatment of patients with gastric cancer with peritoneal involvement.

症例は44歳,女性.主訴は心窩部不快感.CTで膵尾部に径約70mmの嚢胞性病変,それと連続し胃壁内に小嚢胞の集簇を認めた.経過観察中に突然の腹痛で当院へ救急搬送され,CTで胃側の嚢胞が長径95mmと増大しており入院した.超音波内視鏡検査で胃側の嚢胞は胃壁筋層内に存在し,膵尾部の嚢胞との交通を認めた.穿刺内容液は血性で,内容液中のamylase(AMY),CEAが高値であった.膵粘液性嚢胞腫瘍(MCN)が胃壁内へ穿破したことによる胃壁筋層内出血と診断し,待機的に手術を行った.手術は膵体尾部脾合併切除を行い,胃側の嚢胞は胃壁の筋層を温存し嚢胞壁のみ合併切除した.膵嚢胞内容液のAMY,CEAは高値で胃壁側の嚢胞液と類似していた.病理組織診断ではMCNの診断であった.MCNが膵管と交通を持ち,胃壁筋層内へ穿破し出血を生じたと考えられる1例を経験したため,文献的考察も含めて報告する.(著者抄録)

BACKGROUND: Type 1 and Type 2 diabetes mellitus (T1DM and T2DM) are caused by beta(β)-cell loss and functional impairment. Identification of mechanisms of β-cell death and therapeutic interventions to enhance β-cell survival are essential for prevention and treatment of diabetes. Oxidative stress is a common feature of both T1DM and T2DM; elevated biomarkers of oxidative stress are detected in blood, urine and tissues including pancreas of patients with DM. Islet transplantation is a promising treatment for diabetes. However, exposure to stress (chemical and mechanical) and ischemia-reperfusion during isolation and transplantation causes islet loss by generation of reactive oxygen species (ROS). Human intracellular antioxidant enzymes and related molecules are essential defenses against ROS. Antioxidant enzyme levels including superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) have been shown to be low in islet cells. However, little is known about the expression and function of antioxidant enzymes within islet cell subsets. We evaluated the expression of the key antioxidant enzymes in β- and alpha(α)-cell and accessed effects of oxidative stress, islet isolation and transplantation on β/α-cell ratio and viability in human islets. METHODS: Human pancreata from T1DM, T2DM and non-diabetic deceased donors were obtained and analyzed by confocal microscopy. Isolated islets were (I) transplanted in the renal sub-capsular space of streptozotocin-induced diabetic nude mice (in vivo bioassay), or (II) exposed to oxidative (H2O2) and nitrosative (NO donor) stress for 24 hrs in vitro. The ratio, % viability and death of β- and α-cells, and DNA damage (8OHdG) were measured. RESULTS AND CONCLUSIONS: Catalase and GPX expression was much lower in β- than α-cells. The β/α-cell ratio fells significantly following islet isolation and transplantation. Exposure to oxidative stress caused a significantly lower survival and viability, with higher DNA damage in β- than α-cells. These findings identified the weakness of β-cell antioxidant capacity as a main cause of vulnerability to oxidative stress. Potential strategies to enhance β-cell antioxidant capacity might be effective in prevention/treatment of diabetes.

We report a unique case of a 74-old man, who presented with double cancers, showing metastasis of pancreatic cancer to colon cancer. Histopathological examination after surgery revealed that the patient had ascending colon cancer, which metastasized to the liver (pT4N0M1), as well as pancreatic cancer (pT2N1M1) that metastasized to the most invasive portion of the colon cancer, namely the serosal to subserosal layers. Although the mechanisms for this scenario have yet to be elucidated, we speculate that the metastatic pancreatic carcinoma overtook the stromal microenvironment of the colon cancer. Namely, the cancer microenvironment enriched by cancer-associated fibroblasts, which supported the colon cancer, might be suitable for the invasion and engraftment by pancreatic carcinoma. The similarity of histological appearance might make it difficult to distinguish metastatic pancreatic carcinoma within colon cancer. Furthermore, the metastasis of pancreatic carcinoma in colon carcinoma might be more common, despite it not having been previously reported.

Studies on aortoiliac reconstruction for severe atherosclerosis with renal transplantation are limited. Here, we report a rare experience of the simultaneous reconstruction of the external iliac artery caused by severe atherosclerosis with polytetrafluoroethylene vascular graft and renal transplantation in a 55-year-old female; she was unable to undergo standard renal artery anastomosis to the right external iliac artery because of severe atherosclerosis, which would result in complete occlusion. Next, we directly anastomosed the donor renal artery to the polytetrafluoroethylene graft. After transplantation, delayed graft function occurred; therefore, the patient had to undergo hemodialysis. On day 7 after transplantation, her creatine level started to decrease. She was discharged from the hospital on the 14th day after transplantation. After 1 month, her serum creatinine level reduced to 1.12 mg/dL. After 3 years of transplantation, her serum creatinine level was 1.2 mg/dL. The simultaneous implantation of the polytetrafluoroethylene graft and renal transplantation was feasible as well as safe, with no infectious complications and stable renal function noted on long time follow-up. Although our case was rare, it emphasizes the need for transplant surgeons to gain surgical skills for vascular surgery using vascular grafts.

Recently, lateral interbody fusion (LIF) has become more prevalent, and evaluation of lumbar nerves has taken on new importance. We report on the assessment of anatomical relationships between lumbar nerves and vertebral bodies using diffusion tensor imaging (DTI). Fifty patients with degenerative lumbar disease and ten healthy subjects underwent DTI. In patients with lumbar degenerative disease, we studied nerve courses with patients in the supine positions and with hips flexed. In healthy subjects, we evaluated nerve courses in three different positions: supine with hips flexed (the standard position for MRI); supine with hips extended; and the right lateral decubitus position with hips flexed. In conjunction with tractography from L3 to L5 using T2-weighted sagittal imaging, the vertebral body anteroposterior span was divided into four equally wide zones, with six total zones defined, including an anterior and a posterior zone (zone A, zones 1-4, zone P). We used this to characterize nerve courses at disc levels L3/4, L4/5, and L5/S1. In patients with degenerative lumbar disease, in the supine position with hips flexed, all lumbar nerve roots were located posterior to the vertebral body centers in L3/4 and L4/5. In healthy individuals, the L3/4 nerve courses were displaced forward in hips extended compared with the standard position, whereas in the lateral decubitus position, the L4/5 and L5/S nerve courses were displaced posteriorly compared with the standard position. The L3/4 and L4/5 nerve roots are located posterior to the vertebral body center. These were found to be offset to the rear when the hip is flexed or the lateral decubitus position is assumed. The present study is the first to elucidate changes in the course of the lumbar nerves as this varies by position. The lateral decubitus position or the position supine with hips flexed may be useful for avoiding nerve damage in a direct lateral transpsoas approach. Preoperative DTI seems to be useful in evaluating the lumbar nerve course as it relates anatomically to the vertebral body.