三木 厚

Little is known concerning the prognostic significance of the degree of lymphatic vessel invasion in pancreatic head cancer. To address this gap in knowledge, we retrospectively examined 60 patients with locally advanced, surgically resectable pancreatic head cancer who underwent pancreaticoduodenectomy and lymph node (LN) dissection.All cases were histopathologically diagnosed as ductal adenocarcinoma, stage II (25 pT3N0 cases, 35 pT3N1 cases). The following variables were investigated: age; sex; neoadjuvant therapy; adjuvant therapy; tumor size; tumor grade; invasion into the serosa, retropancreatic tissue, duodenum, bile duct, portal venous system and perineural area; cut margins; LN metastasis; and the number of invaded lymphatic vessels (LVI-score).Univariate analysis demonstrated that LN metastasis and an LVI-score ≥5 were significantly associated with poor disease-free survival. Multivariate Cox regression analysis confirmed that LN metastasis and an LVI-score ≥7 were significantly associated with poor disease-free survival. Additionally, LVI-scores ≥9 and ≥10 were comparable to or surpassed the significance of LN metastasis based on the hazard ratio. Univariate analysis demonstrated that tumor size >30 mm, duodenal invasion, LN metastasis and an LVI-score ≥2 were significantly associated with poor overall survival. Multivariate Cox regression analysis confirmed that LN metastasis and LVI-scores ≥9 and ≥10 were significantly associated with poor overall survival, and an LVI-score ≥10 was comparable to or surpassed the significance of LN metastasis based on the hazard ratio.Our study strongly suggests that a high degree of lymphatic vessel invasion is associated with a poor prognosis in patients with locally advanced, surgically resectable pancreatic head cancer.

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.

症例1は30歳男性で、発熱と左腹部痛で来院した。CTで感染性Walled-off necrosis(WON)と診断し、保存的治療を行ったが、症状ならびに炎症所見の改善を認めず、インターベンション治療目的に当院転院となった。造影CT所見から壊死物質を主成分とした感染性WONと診断し、小切開Videoscope補助下に後腹膜経路でネクロセクトミーを行った。1回のネクロセクトミーで炎症所見とCT所見は速やかに改善し、追加の処置は不要となった。左後腹膜のドレーンは留置したまま入院40日目に退院した。症例2は34歳男性で、急性膵炎の診断で保存的治療が開始され、退院約2週間後に間歇的腹痛と発熱で来院し、炎症反応高値、CTで感染性WONと診断され再入院した。造影CT所見から膵体尾部の壊死物質を主成分とする左側感染性WONと診断し、腹腔経路で小切開Videoscope補助下にネクロセクトミーを行った。その後、右側WON増大による閉塞性黄疸が出現し、開腹ネクロセクトミーと胆道ドレナージが必要となった。症状出現から7ヵ月後、ERCPで左右肝管にERBD tubeを留置し退院した。

Pathological complete response (pCR) is considered to be a useful prognostic marker for neoadjuvant chemotherapy to improve the survival rate of patients with operable breast cancer. In the present study, we identified differentially expressed microRNAs (miRNAs) between pCR and non-pCR groups of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who received neoadjuvant chemotherapy with trastuzumab. Expression profiles were examined by miRNA microarrays using total RNA extracted from formalin-fixed, paraffin-embedded tissues from pretreatment biopsy specimens. Significant differences were observed in miRNAs associated with pCR between the luminal B-like (HER2-positive) and HER2-positive (nonluminal) subtypes, which were further classified according to their estrogen receptor (ER) status. Prediction models constructed with differentially expressed miRNAs performed well. In conclusion, the combination of miRNA profiles and ER status may improve the accuracy of pCR prediction in patients with HER2-positive breast cancer and enable the development of personalized treatment regimens.

近年、内視鏡的治療の進歩により、慢性膵炎およびその合併症(膵石症、膵仮性嚢胞、internal pancreatic fistula(IPF:膵性胸腹水)、胆道狭窄)に対して、膵管ステント留置、経胃的ドレナージなどの難易度の高い内視鏡手技が開発され、その低侵襲性から多くの病態では第一選択の治療となっている。しかし、すべての例で内視鏡的治療が実施できる訳ではなく、奏効率、長期成績では外科的治療に劣る部分もあり、どのようなタイミングで外科的治療を行うかを常に念頭に置いて治療計画を検討することが重要である。治療コンプライアンスの悪い症例などでは外科的治療を第一選択とすることも選択肢として、施設の熟達度を考慮し、十分なインフォームドコンセントを行ったうえで治療法を決定する必要がある。(著者抄録)

BACKGROUND: Long-term term survival in patients with pancreatic neuroendocrine tumors has been reported, even in patients with metastatic disease. Metastases to the spleen are extremely rare, but have been reported from a number of primary malignancies, such as breast cancer, lung cancer, melanoma and ovarian cancer. This is the first report of a splenic metastasis from a primary pancreatic neuroendocrine tumor. CASE PRESENTATION: The patient presented as a 53 years old white male with anemia and fatigue. Physical examination revealed a left upper quadrant fullness and computed tomography showed a 24 cm left upper quadrant mass with multiple liver metastases, splenomegaly and a 1 cm mass in the spleen. Resection of the primary pancreatic tumor (T4N0M1) was accompanied by gastrectomy, splenectomy and resection of adherent bowel. The spleen contained a metastatic lesion 1.0 cm in diameter, consistent with a primary neuroendocrine tumor of the pancreas. This operation was followed 8 months later, by delayed resection of liver metastases. The patient receives monthly administration of somatostatin long-acting analogue and has undergone several ablations of liver lesions with percutaneous radiofrequency ablation as well as a second liver resection. The patient is alive seven years after initial presentation, with no evidence of disease on imaging studies. CONCLUSIONS: This is the first report of a splenic metastasis from a primary pancreatic neuroendocrine tumor. The patient initially presented with synchronous multiple liver metastases and a single splenic metastasis. After resection of the primary tumor and spleen, the patient has undergone aggressive cytoreductive surgery/ablation of liver lesions and somatostatin therapy with resulting long-term survival.

慢性膵炎の疼痛治療として、まず内科的治療が行われる。外科的治療は内科的治療無効例に対して適応が検討される。膵管拡張例には膵管ドレナージ術が適応になり、術式としては主にPartington手術とFrey手術が行われる。膵切除術は、膵管拡張がなく病変が頭部もしくは体尾部に限局した症例が適応になるが、術後の膵内分泌機能低下が必発であり、それを上回る利点があると判断された症例に実施すべきである。膵全摘術、腹腔神経叢ブロック、(胸腔鏡下)内臓神経切除術は限られた症例のみが適応となる。慢性膵炎の疼痛治療は、症例により所見、疼痛の状態はさまざまで、慢性膵炎が良性疾患であることも考慮して、治療方針を決定する必要がある。外科的治療の実施にあたっても、断酒・禁煙を中心とする生活指導は重要で、治療コンプライアンスの高い症例に対してのみ治療を行うことが推奨される。(著者抄録)