Kiyoshi Ishigure

Human liver disease decreases methacrylyl-CoA hydratase and β-hydroxyisobutyryl-CoA hydrolase activities in valine catabolism☆

BACKGROUND Methacrylyl-coenzyme A (MC-CoA) hydratase and beta-hydroxyisobutyryl-coenzyme A (HIB-CoA) hydrolase are key enzymes regulating the toxic concentration of MC-CoA generated in valine catabolism. MATERIALS AND METHODS We studied the activities and mRNA expression levels of these enzymes in normal human livers and in human livers with chronic hepatitis, cirrhosis, or hepatocellular carcinoma. RESULTS The activities of both enzymes were significantly lower by 36% to 46% in livers with cirrhosis or hepatocellular carcinoma compared with normals, suggesting a decrease in the capability of detoxifying MC-CoA with these diseases. The mRNA levels for both enzymes measured by quantitative polymerase chain reaction were significantly increased in livers with cirrhosis, but were not altered in those with chronic hepatitis or hepatocellular carcinoma when compared with normal livers. CONCLUSION Our results suggest that low levels of these enzyme activities in livers with cirrhosis or hepatocellular carcinoma are the result of posttranscriptional regulation in the damaged liver.

Carcinomatous meningitis secondary to cholangiocarcinoma without other systemic metastasis

Carcinomatous meningitis is clinically less common than brain metastasis or spinal cord compression, but has dire consequences for both the quality of life and the overall survival of patients with various kinds of malignancies. It occurs in about 5% of all adult cancer patients, though autopsies may double this number. The primary tumors that frequently cause carcinomatous meningitis include lung cancer, breast cancer, leukemia, lymphoma, and melanoma. Carcinomatous meningitis secondary to primary tumors in the gastrointestinal tract is clinically infrequent. In this report, we describe a 73-year-old man with lower bile duct cancer, who developed carcinomatous meningitis following surgical resection of the primary cancer. To our knowledge, this is the third case of carcinomatous meningitis secondary to cholangiocarcinoma described in the literature so far.

Oral Food Intake Versus Fasting on Postoperative Pancreatic Fistula After Distal Pancreatectomy: A Multi-Institutional Randomized Controlled Trial.

AbstractThe usefulness of enteral nutrition via a nasointestinal tube for patients who develop postoperative pancreatic fistula (POPF) after miscellaneous pancreatectomy procedures has been reported. However, no clear evidence regarding whether oral intake is beneficial or harmful during management of POPF after distal pancreatectomy (DP) is currently available.To investigate the effects of oral food intake on the healing process of POPF after DP.Multi-institutional randomized controlled trial in Nagoya University Hospital and 4 affiliated hospitals.Patients who developed POPF were randomly assigned to the dietary intake (DI) group (n = 15) or the fasted group (no dietary intake [NDI] group) (n = 15). The primary endpoint was the length of drain placement.No significant differences were found in the length of drain placement between the DI and NDI groups (12 [6–58] and 12 [7–112] days, respectively; P = 0.786). POPF progressed to a clinically relevant status (grade B/C) in 5 patients in the DI group and 4 patients in the NDI group (P = 0.690). POPF-related intra-abdominal hemorrhage was found in 1 patient in the NDI group but in no patients in the DI group (P = 0.309). There were no significant differences in POPF-related intra-abdominal hemorrhage, the incidence of other complications, or the length of the postoperative hospital stay between the 2 groups.Food intake did not aggravate POPF and did not prolong drain placement or hospital stay after DP. There may be no need to avoid oral DI in patients with POPF.

Nutritional Recovery after Open and Laparoscopic Distal Gastrectomy for Early Gastric Cancer: A Prospective Multicenter Comparative Trial (CCOG1204)

Background: Little information from prospective clinical trials is available on the influences of surgical approaches on postoperative body compositions and nutritional status. We designed a prospective non-randomized trial to compare postoperative chronological changes in body composition and nutritional status between laparoscopic and open distal gastrectomy for stage I gastric cancer (GC). Methods: Body compositions and nutritional indicators in blood tests were measured at the baseline and at the 1st, 3rd, 6th, and 12th postoperative months (POM). The primary end point was the decrease relative to the baseline in the body muscle mass at POM 6. Results: Ninety-six patients for the laparoscopic group and 52 for the open group were eligible for data analysis. No significant differences were found in any baseline demographics, body compositions, and nutritional indicators between the groups. The changes of body muscle mass at POM 6 were similar in both groups. Overall, no significant differences between the groups were observed in any of the body composition and nutritional indicators during the first year after surgery. Conclusions: Postoperative body compositions and nutritional status were not affected by surgical approaches during the first 12 months after surgery in patients who underwent distal gastrectomy for stage I GC.

Randomized Phase II Trial of CapOX plus Bevacizumab and CapIRI plus Bevacizumab as First‐Line Treatment for Japanese Patients with Metastatic Colorectal Cancer (CCOG‐1201 Study)

PURPOSE The aim of this randomized, multicenter, noncomparative, phase II trial was to investigate the efficacy and safety of two potential first-line treatments, capecitabine and oxaliplatin (CapOX) plus bevacizumab (BEV) and capecitabine and irinotecan (CapIRI) plus bevacizumab, in Japanese patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS Patients with untreated mCRC were randomly assigned to receive either CapOX plus bevacizumab (CapOX/BEV arm: bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1 and oral capecitabine 2,000 mg/m2 on days 1-14, every 3 weeks) or CapIRI plus bevacizumab (CapIRI/BEV arm: bevacizumab 7.5 mg/kg and irinotecan 200 mg/m2 on day 1 and capecitabine 1,600 mg/m2 on days 1-14, every 3 weeks). The primary endpoint was overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. RESULTS A total of 107 patients were enrolled. The intent-to-treat population comprised 54 patients in the CapOX/BEV arm and 53 patients in the CapIRI/BEV arm. The median follow-up period was 35.5 months. ORR was 56% in the CapOX/BEV arm and 55% in the CapIRI/BEV arm. Median PFS and OS were 12.4 and 26.7 months in the CapOX/BEV arm and 11.5 and 28.7 months in the CapIRI/BEV arm, respectively. The frequencies of hematological and nonhematological adverse events above grade 3 were 13% and 30% in the CapOX/BEV arm and 25% and 23% in the CapIRI/BEV arm, respectively. CONCLUSION CapOX plus bevacizumab and CapIRI plus bevacizumab are equally effective and feasible as the first-line treatments in Japanese patients with mCRC. IMPLICATIONS FOR PRACTICE The CCOG-1201 study was designed to evaluate the efficacy and safety of capecitabine and oxaliplatin plus bevacizumab and capecitabine and irinotecan plus bevacizumab as a first-line treatment in Japanese patients with metastatic colorectal cancer. This article reports on the trial and efforts to define the role of these regimens, including the effect of KRAS status and UGT1A1 polymorphisms in metastatic colorectal cancer.

A Case of Acinar Cell Carcinoma of the Pancreas with Subcutaneous Fat Necrosis of Extremities

膵腺房細胞癌の発生頻度は膵外分泌腫瘍の約1%とまれな腫瘍で, 特に皮下結節脂肪壊死を伴った報告例は本邦で過去2例のみである. 症例は75歳の男性で, 主訴は食欲低下で, 左上腹部には10cm大の弾性硬な腫瘤を認め, 両下腿に皮下結節を認めた. 血液生化学検査ではリパーゼ, エラスターゼIで高値を認め, CEA, CA19-9は基準値範囲内であった. 腹部CTで左上腹部に充実成分と液体成分の混在する巨大な腫瘍を認めた. 膵原発の腫瘍を疑い, 膵尾部切除術を行った. 病理組織検査の結果, 膵腺房細胞癌と診断された. 術前高値を示したリパーゼ, エラスターゼIは正常値となり下腿の皮下結節も消失した. 術後, 4年経過した現在, 再発の兆候なく経過観察中である.

A CASE OF LARVA MIGRANS CAUSING ILEUS AFTER EATING RAW FIREFLY SQUIDS (WATASENIA SCINTILLANS)

症例は27歳,男性.生ホタルイカの摂食1日後に嘔吐,上腹部痛にて発症.摂食7日後に自制不能となり来院した.腹部単純X線検査,腹部CT検査にて腸閉塞の所見を認め,血液生化学検査では好酸球の増多を伴う炎症所見を認めた.腸閉塞をきたした急性腹症と診断し,緊急開腹手術を行った.開腹所見にて回盲部より約10cmと約80cm口側の部位に発赤,腫脹を伴う狭窄所見を認め,狭窄部小腸の部分切除を行った.切除標本上,腫脹部の粘膜面に肉眼的に虫体を確認しえた.病理所見では,小腸壁全層に及ぶ著明な好酸球浸潤を認め,好酸球性腸炎と診断された.術後ペア血清にて測定したアニサキス特異的IgE抗体価の上昇は認めず,ホタルイカの内臓に寄生する旋尾線虫幼虫移行症による腸閉塞と最終診断した.原因不明の腸閉塞を伴う急性腹症の診断と治療に際し,幼虫移行症による好酸球性腸炎の存在も念頭におく必要があると思われた.