堀江 久永

INTRODUCTION: We previously reported in ob/ob mice, one of animal models of human type 2 diabetes mellitus (DM2), that (i) acetylation of histone H3 lysine 9 (H3K9) at the promoter region of clock gene Dbp and DBP mRNA expression are reduced in epididymal adipose tissue, (ii) binding of DBP to the promoter region of peroxisome proliferator-activated receptor (Ppar)-γ and mRNA expression of PPAR-γ1sv were decreased in preadipocytes and (iii) adiponectin secretion was decreased, leading to the impaired insulin sensitivity. RESEARCH DESIGN AND METHODS: The present study was undertaken to evaluate whether such the changes in visceral adipose tissue were detected in patients with DM2. We obtained omental and mesenteric adipose tissue during surgery of lymph node dissection for gastric and colorectal cancers, and investigated these variables in adipose tissue (omental from gastric cancer; 13 non-DM, 12 DM2: mesenteric from colorectal cancer; 12 non-DM, 11 DM2). RESULTS: Acetylation of histone H3K9 at the promoter region of Dbp and DBP mRNA expression in omental, but not in mesenteric adipose tissue were significantly lower in DM2 than in patients without DM. PPAR-γ mRNA expression in omental adipose tissue was also lower in patients with DM2, but not in mesenteric adipose tissue. CONCLUSIONS: The changes in DBP-PPAR-γ axis observed in mice with diabetes were also detected in patients with DM2. Because adiponectin secretion is reported to be enhanced through the PPAR-γ-related mechanism, this study supports the hypothesis that omental adipose tissue is involved in the mechanism of DM2.

BACKGROUND: Goblet cell carcinoid (GCC) is a neuroendocrine tumor usually found in the appendix. GCCs exhibit characteristic findings with mixed endocrine-exocrine features such as staining positive for neuroendocrine markers and producing mucin. The primary GCC of the rectum is exceedingly rare. CASE PRESENTATION: A 77-year-old Japanese male presented with hematochezia. Anal tenderness and a hard mass in the anal canal were found on the digital rectal examination, and colonoscopy was performed. Colonoscopy showed an irregularly shaped mass in the anal canal. Biopsy showed mixed features including adenocarcinoma in situ, well-differentiated adenocarcinoma, and mucinous carcinoma with invasive proliferation. No metastatic lesions were found on the computed tomography scan. Pelvic magnetic resonance imaging scan showed extramural growth of a tumor on the ventral side of the rectum without invasion to the prostate. Laparoscopic abdominoperineal resection was performed. The final diagnosis was well-differentiated adenocarcinoma in the mucosa and goblet cell carcinoid from the submucosa to the adventitia of the rectum. The patient was discharged from the hospital on postoperative day 16. Six months after resection, a computed tomography scan revealed multiple metastatic lesions in the liver. Several chemotherapy regimens were given, and the patient has stable disease 27 months after surgery. CONCLUSION: We present a patient with rectal GCC with metachronous liver metastases. Since GCC grows intramurally and is biologically aggressive compared to typical carcinoid lesions, the disease is usually diagnosed at an advanced stage. The development of optimal adjuvant chemotherapy is needed for those patients.

＜文献概要＞▼下剤の適応は,大腸の蠕動運動能が低下している大腸通過遅延型便秘症である.▼非刺激性下剤を毎日内服して,排便回数を1回/2日〜2回/日,便性状をブリストル便性状スケールでタイプ3〜5になるように調節し,調節できるまでは刺激性下剤をレスキューとして頓用使用する.▼大腸通過遅延型便秘症の重症度はさまざまなので,非刺激性下剤の第一選択は,微調節が可能な酸化マグネシウム,モビコール,ラグノスNFゼリーのいずれかを使用する.▼非刺激性下剤は,保険局医療課長通知(保医発)に従って,薬価の低い酸化マグネシウムが第一選択である(小児ではモビコールも可).それが無効か使用できない場合にのみ,新規便秘症治療薬を使用する.

BACKGROUND: Anti-tumor effects of radiation therapy (RT) largely depend on host immune function. Adenosine with its strong immunosuppressive properties is an important immune checkpoint molecule. METHOD: We examined how intra-tumoral adenosine levels modify anti-tumor effects of RT in a murine model using an anti-CD73 antibody which blocks the rate-limiting enzyme to produce extracellular adenosine. We also evaluated CD73 expression in irradiated human rectal cancer tissue. RESULTS: LuM-1, a highly metastatic murine colon cancer, expresses CD73 with significantly enhanced expression after RT. Subcutaneous (sc) transfer of LuM-1 in Balb/c mice developed macroscopic sc tumors and microscopic pulmonary metastases within 2 weeks. Adenosine levels in the sc tumor were increased after RT. Selective RT (4Gyx3) suppressed the growth of the irradiated sc tumor, but did not affect the growth of lung metastases which were shielded from RT. Intraperitoneal administration of anti-CD73 antibody (200 μg × 6) alone did not produce antitumor effects. However, when combined with RT in the same protocol, anti-CD73 antibody further delayed the growth of sc tumors and suppressed the development of lung metastases presumably through abscopal effects. Splenocytes derived from RT+ CD73 antibody treated mice showed enhanced IFN-γ production and cytotoxicity against LuM-1 compared to controls. Immunohistochemical studies of irradiated human rectal cancer showed that high expression of CD73 in remnant tumor cells and/or stroma is significantly associated with worse outcome. CONCLUSION: These results suggest that adenosine plays an important role in the anti-tumor effects mediated by RT and that CD73/adenosine axis blockade may enhance the anti-tumor effect of RT, and improve the outcomes of patients with locally advanced rectal cancer.

77歳男。会陰部の膨隆と疼痛を主訴とした。下部進行直腸癌に対する術前化学療法+腹腔鏡下腹会陰式直腸切断術後1ヵ月に絞扼性イレウスを発症し、緊急開腹手術を行ったが、術後に会陰部の膨隆と歩行障害を伴うほどの疼痛が出現した。腹部CTでは骨盤底への腸管の脱出はみられなかったが、会陰部皮下まで腹水の貯留を認め、会陰ヘルニアと診断して会陰ヘルニア修復術を行った。手術操作、合併症対策、ヘルニアの確実な修復の観点から経腹・経会陰の同時アプローチを選択し、前立腺から肛門挙筋で構成された3×3cmのヘルニア門をメッシュで被覆、固定した。本症例は放射線治療後であること、初回手術時に骨盤底の修復が行われていなかったことが会陰ヘルニア発症の一因と考えられた。

症例は55歳女性。4年前にC型慢性肝炎と診断されたが治療を自己中断していた。心窩部痛を主訴に来院。CTで肝S8に径8cmの低濃度腫瘍、肝内胆管拡張を認め肝内胆管癌と診断。右3区域切除を予定したが、術中に肝門板左側まで腫瘍浸潤を認め背景にC型肝炎も併存していたため1期的切除は困難と判断。2期的拡大肝右葉切除の方針へ変更し右門脈結紮術を施行した。治療目的に肝動注化学療法を3回施行したが効果なく、経過中に腫瘍の右横隔膜浸潤を認めたため根治切除は不能と判断、肝動脈化学塞栓療法(TACE)へ変更した。TACE1回目直後から腫瘍マーカーは低下し治療効果を認めた。発症から1年9ヵ月間に計7回のTACEを施行し腫瘍はコントロールされていたが、発症から2年2ヵ月目に腫瘍が増大し4年2ヵ月目に死亡した。遠隔転移のない局所進行肝内胆管癌に対し門脈結紮後にTACEを併施し有効な治療効果を得た1例を経験したので報告する。(著者抄録)

A 45-year-old man who presented with fever, polyarthritis and deafness was referred to our hospital, and given a diagnosis of granulomatosis with polyangiitis. Twelve days after starting corticosteroid and cyclophosphamide therapy, he suddenly developed abdominal pain. Abdominal CT scan showed an edematous small intestine with free air and fluid collection in the pelvis. Emergency laparotomy was performed for diagnosis of gastrointestinal perforation, which revealed 5-10 mm erythematous lesions at 20 sites on the anti-mesenteric side of the small intestine. Three of these lesions were perforated. Local resection with anastomosis were performed at each site. The postoperative course was uneventful, and medical treatment was resumed 9 days after the operation. Fifty-three days postoperatively, he developed abdominal pain again. Abdominal CT scan showed a partially-dilated small intestine with a small amount of ascites, suggesting a strangulated obstruction. Emergency laparotomy was performed, which showed edema at one of the previous anastomotic sites with a small amount of purulent ascites. There was no evidence of strangulation or perforation of the intestine. An omental patch was placed over the anastomotic site, and a drain placed in the pelvis. The postoperative course was uneventful, and he restarted medical treatment. Histopathology of the resected specimen showed vasculitis at the sites of perforation, suggesting a relationship with granulomatosis with polyangiitis. We report a patient with granulomatosis with polyangiitis with multiple perforations of the small intestine. Special attention should be paid for re-perforation in the treatment of the disease. Furthermore, medical information should be shared with patients and their families as well as medical staff.

INTRODUCTION: Metastases to the thyroid gland in patients with colorectal cancer are uncommon. We report a patient with rectal cancer who developed a metastasis to the thyroid gland. PRESENTATION OF CASE: The patient was a 45-year-old female five years status post rectal cancer resection. A thyroid lesion was detected on PET-CT scan with synchronous lung metastases. After pulmonary resection, a partial thyroidectomy was performed and pathological examination with immunohistochemical staining confirmed that the lesion was a metastasis from previous rectal cancer. She is free from recurrence two years after thyroid surgery. DISCUSSION: Colorectal metastases to the thyroid gland are usually seen with widespread disease, often with lung and liver metastases. The overall outcomes of previously reported patients with thyroid metastases were extremely poor, with most patients dying within months of diagnosis. Careful attention should be given to other sites of metastatic disease including the thyroid gland during postoperative follow-up. PET scan may be helpful to establish the diagnosis. CONCLUSION: Treatment decisions must be individualized, and depend on the presence of systemic disease. Selected patients may benefit from resection of metastases, and PET scan may be useful to identify patients who will benefit from resection.

INTRODUCTION: Internal hernias are rare after laparoscopic colorectal resections. We report a patient with an internal hernia through a defect in the transverse mesocolon following laparoscopic resection. PRESENTATION OF CASE: A 52-year-old male underwent laparoscopic colectomy for transverse colon cancer and had an unremarkable postoperative course. Thirty days postoperatively, he presented to the emergency room with sudden onset abdominal pain and vomiting. Enhanced abdominal computed tomography scan showed strangulated small intestine in the left upper abdomen. An internal hernia through the mesenteric defect created during the recent colon resection was suspected, and emergency laparotomy was performed. One hundred thirty cm of small intestine was found herniated through a mesenteric defect. After repositioning the ischemic-appearing intestine, a 5 cm defect in the transverse mesocolon was found which had not been closed during the previous laparoscopic operation. No intestinal resection was needed, and the mesenteric defect closed with non-absorbable sutures. The post-operative course was unremarkable except for paralytic ileus, which resolved without further intervention. DISCUSSION: The incidence of internal hernia through a mesenteric defect after laparoscopic colorectal resection is quite low. Therefore, routine closure of the mesenteric defect after laparoscopic colorectal resection is not required. However, a left sided defect in the transverse mesocolon might be at higher risk of causing an internal hernia on anatomic grounds. CONCLUSION: We believe that mesenteric defects should be closed after laparoscopic resection of the left side of transverse colon, regardless of their size.

Aim: Peritoneal metastases (PM) frequently occur in patients with gastric cancer and result in a poor prognosis. Exosomes play pivotal roles in tumor metastasis through the transfer of microRNAs (miRNAs). We examined the exosomal miRNA profile in peritoneal fluids to identify novel biomarkers to reflect tumor burden in the peritoneum. Methods: Exosomes were isolated from peritoneal fluids of patients of gastric cancer with macroscopic (P1) or microscopic (P0CY1) peritoneal metastasis (PM) and comprehensive miRNA expression analysis was carried out. Expressions of candidate miRNAs were then validated in all 58 samples using TaqMan Advanced miRNA Assays. Results: In initial screening, we carried out comprehensive analysis of exosomal miRNA using peritoneal fluids from 11 and 14 patients with or without PM, respectively, and identified 11 dysregulated miRNAs in PM (+) samples. Validation analysis showed that four miRNAs (miR-21-5p, miR-92a-3p, miR-223-3p, and miR-342-3p) were significantly upregulated in 12 PM (+) samples, and their expression levels showed positive correlation with peritoneal cancer index. In contrast, miR-29 family were all downregulated in patients with PM (+) samples. Moreover, in 24 patients with pT4 tumor, miR-29 at gastrectomy tended to be lower in six patients with peritoneal recurrence with significant differences in miR-29b-3p (P = .012). Conclusion: Expression pattern of miRNAs in peritoneal exosomes well reflects the tumor burden in the peritoneal cavity and could be a useful biomarker in the treatment of PM.

症例は45歳の男性で,多発血管炎性肉芽腫症に対して当院アレルギー・リウマチ科で薬剤療法を開始した.開始後12日目に下腹部痛が出現し,腹部CTにて消化管穿孔と診断し緊急手術を施行した.小腸間膜対側に10mm以下の発赤を20ヶ所認め,うち2ヶ所の穿孔部を含む3ヶ所を部分切除した.術後経過は良好で,9日目に薬剤療法を再開した小腸穿孔部の病理組織学的検査所見では,血管壁への炎症細胞の浸潤を認め,多発血管炎性肉芽腫症に伴う消化管穿孔と診断した.術後53日目に絞扼性イレウスが疑われ緊急手術を施行したが,明らかな絞扼性イレウスや穿孔の所見は認めなかった.その後の経過は良好で,薬剤療法を再開,継続中である.今回の検討から多発血管炎性肉芽腫症に伴う消化管穿孔は重症化しやすく,潰瘍性病変が多発する傾向にあり,ときに再穿孔を来すことがわかった.これらを十分理解し,患者・家族へ説明し,治療にあたることが必要である.(著者抄録)