肝血行遮断下での肝静脈血の役割についてブタを用いて実験的に検討した. すなわち, 流入血行遮断時に肝静脈から肝組織に酸素が供給され, それが利用されているか否かを明らかにするため, 60分間の肝流入血行遮断中, 肝静脈を介した肝組織の持続的酸素化を図り, それにより血行遮断後の肝障害が軽減されるか否かを検討した. その結果, PGE1を併用した肝静脈血酸素化により肝組織酸素飽和度が高く維持され, 肝組織の酸素化が可能であった. また, PGE1を併用した肝静脈血酸素化群において, 血流再開120分後の血清GOT値, ICGk値が流入血行遮断のみの対照群と比較し有意に良好であり, 光顕・電顕で観察した組織学的障害も軽度であった. したがって, 流入血行遮断時には, 肝静脈血中の酸素が逆行性に肝組織に供給され利用されることが示唆された.

Venous blood

10.5833/jjgs.32.805

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Randomized clinical trial comparing standard diet with perioperative oral immunonutrition in total gastrectomy for gastric cancer

British journal of surgery (2017)

Satoshi Ida Naoki Hiki H Cho Kentaro Sakamaki Seiji Ito

Abstract Background Total gastrectomy for gastric cancer is associated with excessive weight loss and decreased calorie intake. Nutritional support using eicosapentaenoic acid modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the perioperative period is unclear. Methods This was a randomized phase III clinical trial of addition of eicosapentaenoic acid-rich nutrition to a standard diet in patients having total gastrectomy for gastric cancer. Patients were randomized to either a standard diet or standard diet with oral supplementation of an eicosapentaenoic acid (ProSure®), comprising 600 kcal with 2·2 g eicosapentaenoic acid, for 7 days before and 21 days after surgery. The primary endpoint was percentage bodyweight loss at 1 and 3 months after surgery. Results Of 127 eligible patients, 126 were randomized; 124 patients (61 standard diet, 63 supplemented diet) were analysed for safety and 123 (60 standard diet, 63 supplemented diet) for efficacy. Across both groups, all but three patients underwent total gastrectomy with Roux-en-Y reconstruction. Background factors were well balanced between the groups. Median compliance with the supplement in the immunonutrition group was 100 per cent before and 54 per cent after surgery. The surgical morbidity rate was 13 per cent in patients who received a standard diet and 14 per cent among those with a supplemented diet. Median bodyweight loss at 1 month after gastrectomy was 8·7 per cent without dietary supplementation and 8·5 per cent with eicosapentaenoic acid enrichment (P = 0·818, adjusted P = 1·000). Similarly, there was no difference between groups in percentage bodyweight loss at 3 months (P = 0·529, adjusted P = 1·000). Conclusion Immunonutrition based on an eicosapentaenoic acid-enriched oral diet did not reduce bodyweight loss after total gastrectomy for gastric cancer compared with a standard diet. Registration number: UMIN000006380 (http://www.umin.ac.jp/)

Clinical endpoint

10.1002/bjs.10417

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Citations (94)

A resected case of acinar cell carcinoma of the pancreas with liver metastasis following chemotherapy using modified FOLFIRINOX

Surgical Case Reports (2023)

Shuhei Yamada H. Motegi Yoshiki Kurihara Tomonori Shimbo Isao Kikuchi

Abstract Background Acinar cell carcinoma of the pancreas is a rare exocrine malignancy representing less than 1% of all pancreatic neoplasms. It has been reported that it responds to treatment differently from pancreatic ductal adenocarcinoma and the treatment algorithm for acinar cell carcinoma usually depends on the stage of the respective tumor and the patient’s current status. Case presentation A 60-year-old man presented with upper abdominal pain and anorexia. Abdominal ultrasonography showed a large-sized hepatic mass and he was referred to our hospital. Contrast-enhanced computed tomography demonstrated a 110-mm low-density area occupying the right hemi-liver and an enhanced mass of 70 × 56 mm in the tail of the pancreas, which seemed to directly infiltrate into the spleen. The case was diagnosed as acinar cell carcinoma with a simultaneous liver metastasis identified by liver biopsy. Upfront resection of pancreatic cancer with distant metastasis might not be considered as an optimal choice, and in this case chemotherapy was administered prior to curative resection. Chemotherapy using the modified FOLFIRINOX regimen was undertaken, resulting in a partial remission; the liver tumor reduced in size from 110 to 47 mm and the pancreatic tumor from 70 to 40 mm. The patient then safely underwent curative hepatic resection with distal pancreato-splenectomy. Histological examinations revealed small-sized atypical cells with large nuclei that had formed acinar patterns, and immunostaining with trypsin was positive in tumor cells, which was in accordance with acinar cell carcinoma. More than 3 years later, the patient is doing well without any recurrence. Conclusion Aggressive and curative surgery in combination with chemotherapy such as FOLFIRINOX could be a treatment option to achieve long-term survival in cases of acinar cell carcinoma with liver metastases.

FOLFIRINOX

Pancreatic tumor

10.1186/s40792-023-01729-1

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Molecular modeling study of the thymidine phosphorylase inhibitor by SBDD and classical QSAR analysis

Chem-Bio Informatics Journal (2017)

Yukio Tada Hideki Kazuno Tsutomu Sato Norihiko Suzuki Tomohiro Emura

Trifluorothymidine (TFT) has antitumor activity, but it is easily metabolized to inert trifluorothymine by thymidine phosphorylase (TP). Accordingly, TFT alone cannot show satisfactory clinical antitumor effects. Human TP (HTP) is the main enzyme of pyrimidine nucleoside phosphorylase in human. Therefore, it has been necessary to develop a HTP inhibitor to maintain antitumor activity of TFT. Here we reveal the drug design process of HTP inhibitor based on SBDD and classical QSAR analysis. Thymine was selected as a seed compound and then 5-chlorouracil (3) was selected as a lead compound. The introduction of the imino moiety to C6 position of the lead compound (3) enhanced the inhibitory activity of TP. As a result, 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride (TPI) was chosen as the candidate for the clinical trials. And TAS-102 (the combination of TFT and TPI in a 1:0.5 molar ratio) has been approved as Trifluridine/Tipiracil (Lonsurf) for the treatment of metastatic colorectal cancer in Japan, United States and EU.

Thymidine phosphorylase

Uracil

Thymine

Lead compound

10.1273/cbij.17.19

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Citations (1)

[Cholangiocarcinoma with bile duct adenoma and hamartoma-like lesion in the bile duct].

The Japanese journal of gastro-enterology (2010)

Sho Takahashi Kohichi Takada Yutaka Kawano Koji Miyanishi Hirotoshi Ishiwatari

A 76-year-old man presented with fever of unknown origin. Diagnostic imaging showed a liver tumor measuring 3cm in maximum dimension. The tumor was subsequently resected, and histopathology showed a moderately differentiated adenocarcinoma. This showed a number of bile ductules with variable amounts of stroma, well circumscribed but not encapsulated, so the lesion was diagnosed as a cholangiocarcinoma. Within the tumor there was also a cholangiolocarcinoma-like lesion. In addition, cystically dilated ductules resembling bile duct hamartoma and bile duct adenoma adjacent to the tumor were found, but with no area of transition among them. In the Glisson's capsule around the tumor, there was also a bile duct hamartoma.

Histopathology

Hamartoma

Source

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Citations (2)

Successful Treatment by Fibrin Glue Sealant for Pneumothorax with Chronic GVHD Resistant to Autologous Blood Patch Pleurodesis

Internal Medicine (2012)

Satoshi Iyama Tsutomu Sato Kazuyuki Murase Shohei Kikuchi Yusuke Kamihara

Pneumothorax associated with chronic graft-versus-host disease (cGVHD) after stem cell transplantation is a rare complication. Autologous blood has been used successfully for pleurodesis, which was less toxic than chemical agents. However, when pneumothorax is resistant to pleurodesis, no other procedure is more effective and conservative. Here, we describe a case of myelodysplastic syndromes complicated with cGVHD-related pneumothorax. His pneumothorax has been resistant to pleurodesis using autologous blood and was treated successfully with fibrin glue sealant. In our limited experience, we believe the best success could be achieved when this method is used to treat persistent pneumothorax with cGVHD.

Pleurodesis

Autologous blood

Fibrin Tissue Adhesive

10.2169/internalmedicine.51.7355

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Citations (5)

Novel approach toward minimally invasive surgery for mid‐transverse colon cancer: ‘moving the left colon’ technique

Colorectal Disease (2023)

Kenta Iguchi Nobuhiro Sugano Atsuhiko Sugiyama Kentaro Saito Yosuke Atsumi

Abstract Aim During surgery for mid‐transverse colon cancer (MTC), surgeons often face the dilemma of whether to mobilize the hepatic or splenic flexure. There is no established optimal minimally invasive surgical procedure for MTC. Methods We present our novel minimally invasive surgical technique, called the ‘moving the left colon’ technique for MTC, along with a video demonstration. The procedure involves four main steps: (i) mobilization of the splenic flexure using a medial‐to‐lateral approach, (ii) dissection of lymph nodes around the middle colic artery from the left side of the superior mesenteric artery approach, (iii) separation of the pancreas and transverse mesocolon and (iv) ‘moving the left colon’ and performing an intracorporeal anastomosis. By mobilizing the splenic flexure, anatomical landmarks are revealed, which enables safer dissection. Combining this technique with intracorporeal anastomosis allows for a safe and easy anastomosis. Results Between April 2021 and January 2023, a single‐skilled colorectal surgeon performed laparoscopic transverse colectomies using our new approach on three consecutive patients with MTC. The patients had a median age of 75 years (range 46–89 years). The median operative time was 194 min (range 193–228 min) and blood loss was 8 mL (range 0–20 mL). None of the patients experienced any perioperative complications and the median postoperative hospital stay was 6 days. Conclusion We introduced a novel approach for laparoscopic surgery for MTC. This technique can be performed safely and may help standardize minimally invasive surgery for MTC.

Transverse colon

Invasive surgery

10.1111/codi.16653

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A Case of Resected Colon Metastasis of Renal Cell Carcinoma

Nihon Gekakei Rengo Gakkaishi (Journal of Japanese College of Surgeons) (2013)

Yasuko Onakatomi Tsutomu Sato Yasushi Rino Daisuke Inagaki Nobuhiro Sugano

1998年７月左腎癌の診断で，左腎摘出術（淡明細胞腎癌，pT1bN0M0）施行．2006年２月右肺転移（２病変）出現．胸腔鏡下肺部分切除施行．2006年６月両肺に多発転移が出現し，インターフェロン療法開始．2006年10月に膵腫瘍が出現．腫瘍増大傾向のため転移と考え，2008年５月ソラフェニブを導入．2008年１月CTにてS状結腸の腫瘍指摘．下部消化管内視鏡で直腸S状部に粘膜下腫瘍．狭窄，出血なく経過観察．2010年２月脳転移出現，γ－ナイフ施行．2010年３月血便．下部消化管内視鏡にて粘膜下腫瘍の増大．他の転移巣は病勢のコントロールが出来ているため，出血コントロール目的で，2010年５月腹腔鏡補助下直腸高位前方切除術施行．病理組織学結果は，淡明細胞癌であり，直腸S状部転移と診断．術後39病日からソラフェニブ内服を再開し，術後１年経過した現在も再燃なく外来通院中．

Colon carcinoma

10.4030/jjcs.38.164

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A Case of Liver Metastasis from Leiomyosarcoma of the Small Intestine Treated by Hepatectomy

Nihon Gekakei Rengo Gakkaishi (Journal of Japanese College of Surgeons) (1998)

Ryuichi Yanagida Tsutomu Sato Yoshihiro Asanuma Tomoki Furuya Makio MIK

小腸平滑筋肉腫切除後の再発部位としては, 肝転移が最も多い。今回われわれは回腸平滑筋肉腫切除から2年8ヵ月後に肝転移をきたした症例を経験し, これに対し肝切除を行った。これまでに報告されている小腸平滑筋肉腫肝転移切除13例の予後を調査し, 肝切除の意義について検討した。その結果, (1) 肝切除を行った症例はすべて1年以上生存していた。 (2) 肝切除後の無再発例は認められなかった。 (3) 肝転移巣が単発のものは多発例に比較し長期生存していた。 (4) 長期生存例は肝切除後の再発巣に対して再切除を行った症例であった。以上から, 小腸平滑筋肉腫肝転移に対して肝切除を行う意義はあるが, 切除後の再発は高頻度である。しかし, 肝切除後の再発巣に対し再切除を行うことで, 患者の延命を図ることが可能と考えられた。

10.4030/jjcs1979.23.2_282

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Citations (1)