佐田 尚宏

Peritoneal dissemination is a major metastatic pathway for gastrointestinal and ovarian malignancies. The miR-29b family is downregulated in peritoneal fluids in patients with peritoneal metastases (PM). We examined the effect of miR-29b on mesothelial cells (MC) which play critical a role in the development of PM through mesothelial-mesenchymal transition (MMT). Human peritoneal mesothelial cells (HPMCs) were isolated from surgically resected omental tissue and MMT induced by stimulation with 10 ng/ml TGF-β1. MiR-29b mimics and negative control miR were transfected by lipofection using RNAiMAX and the effects on the MMT evaluated in vitro. HPMC produced substantial amounts of miR-29b which was markedly inhibited by TGF-β1. TGF-β1 stimulation of HPMC induced morphological changes with decreased expression of E-cadherin and calretinin, and increased expression of vimentin and fibronectin. TGF-β1 also enhanced proliferation and migration of HPMC as well as adhesion of tumor cells in a fibronectin dependent manner. However, all events were strongly abrogated by simultaneous transfection of miR-29b. MiR-29b inhibits TGF-β1 induced MMT and replacement of miR-29b in the peritoneal cavity might be effective to prevent development of PM partly through the effects on MC.

There is little information about the outcomes of pediatric patients with hepatolithiasis after living donor liver transplantation (LDLT). We retrospectively reviewed hepatolithiasis after pediatric LDLT. Between May 2001 and December 2020, 310 pediatric patients underwent LDLT with hepaticojejunostomy. Treatment for 57 patients (18%) with post-transplant biliary strictures included interventions through double-balloon enteroscopy (DBE) in 100 times, percutaneous transhepatic biliary drainage (PTBD) in 43, surgical re-anastomosis in 4, and repeat liver transplantation in 3. The median age and interval at treatment were 12.3 years old and 2.4 years after LDLT, respectively. At the time of treatments, 23 patients (7%) had developed hepatolithiasis of whom 12 (52%) were diagnosed by computed tomography before treatment. Treatment for hepatolithiasis included intervention through DBE performed 34 times and PTBD 6, including lithotripsy by catheter 23 times, removal of plastic stent in 8, natural exclusion after balloon dilatation in 7, and impossibility of removal in 2. The incidence of recurrent hepatolithiasis was 30%. The 15-years graft survival rates in patients with and without hepatolithiasis were 91% and 89%, respectively (p = 0.860). Although hepatolithiasis after pediatric LDLT can be treated using interventions through DBE or PTBD and its long-term prognosis is good, the recurrence rate is somewhat high.

Background: The peritoneal cavity contains many site-specific immune cells which constitute a unique immune microenvironment. However, it is unclear how the local immune signature is altered in patients with peritoneal metastases (PM). Methods: Peritoneal lavage fluid or ascites were obtained from 122 patients with various stages of gastric cancer (GC). Cells recovered from peritoneal fluids were immunostained with mAbs for lymphocyte-, macrophage- and tumor cell-specific antigens and the frequencies of leukocyte subsets and antigen expression levels were evaluated with multi-color flowcytometry. Results: The proportions of CD8(+) T cells, CD3(+)CD56(+) NKT-like cells, and CD3(-)CD56(+) NK cells to CD45(+) leukocytes were significantly reduced in patients with PM compared to those without PM. In patients with PM, the rates of CD8 (+) T cells and NKT-like cells correlated inversely with the tumor leukocyte ratio (TLR), the relative frequency of CD326(+) tumor cells to CD45(+) leukocytes. In contrast, the proportion of CD19(+) B cells was significantly increased in patients with PM, and their proportion correlated positively with the TLR and peritoneal carcinomatosis index (PCI) score. In patients with PM, CD14(+) macrophages tended to be increased with enhanced expression of CD14, CD16 and a M2-macrophage marker, CD163. In particular, macrophages in patients with high TLR contained many granules with high side scatter and CD14 expression in their flow profile compared to those without PM. Conclusion: PM are accompanied by a drastic change in phenotypes of lymphocyte and macrophage in the peritoneal cavity, which might be involved in the development and progression of intraperitoneal tumor growth.

Background: Previous systematic reviews have not clarified the effect of postoperative coffee consumption on the incidence of postoperative ileus (POI) and the length of hospital stay (LOS). We aimed to assess its effect on these postoperative outcomes. Methods: Studies evaluating postoperative coffee consumption were searched using electronic databases until September 2021 to perform random-effect meta-analysis. The quality of evidence was assessed using the Cochrane risk-of-bias tool. Caffeinated and decaffeinated coffee were also compared. Results: Thirteen trials (1246 patients) and nine ongoing trials were included. Of the 13 trials, 6 were on colorectal surgery, 5 on caesarean section, and 2 on gynecological surgery. Coffee reduced the time to first defecation (mean difference (MD) −10.1 min; 95% confidence interval (CI) = −14.5 to −5.6), POI (risk ratio 0.42; 95% CI = 0.26 to 0.69); and LOS (MD −1.5; 95% CI = −2.7 to −0.3). This trend was similar in colorectal and gynecological surgeries. Coffee had no adverse effects. There was no difference in POI or LOS between caffeinated and decaffeinated coffee (p > 0.05). The certainty of evidence was low to moderate. Conclusion: This review showed that postoperative coffee consumption, regardless of caffeine content, likely reduces POI and LOS after colorectal and gynecological surgery.

膵全摘では周術期血糖・栄養管理が重要である.12年間の膵全摘32例の周術期血糖・栄養状態を検討した.一期的・二期的膵全摘は各々16例で計48病変の約80%を膵管内乳頭粘液性腫瘍と浸潤性膵管癌が占めた.5年生存率は60.2%,一期的・二期的膵全摘で差はなかった.HbA1cは術前6.7%,術後1年は7.7%と上昇,prognostic nutritional index(PNI)は術前47.8,術後1年は43.0と低下した.予後因子を単変量解析すると術後1年neutrophil-lymphocyte ratio,術前platelet-lymphocyte ratio,術後1年PNIが抽出され,多変量解析では術後1年PNIが有意な因子であった.術後1年PNI 40.5未満は予後不良で,高力価パンクレアチン製剤投与群は予後良好であった.膵全摘後は正しい病態把握のもとに内外分泌治療を行うことが重要である.(著者抄録)

症例は57歳男性.検診で膵体部の嚢胞性病変が指摘され,当院を紹介された.造影CTでは膵体部に17mm大の中心部に嚢胞成分を伴う充実性腫瘤が認められた.3年後の造影CTでは,嚢胞成分を伴いながら23mm大に腫瘍径が増大し,MRIでは中心部の嚢胞成分はT1WI,T2WIともに高信号を示し,辺縁は拡散低下を伴う充実成分として観察された.超音波内視鏡検査でも同様に,中心に嚢胞成分を伴う充実性腫瘤として観察された.膵体尾部切除が施行され,病理学的にmixed acinar-neuroendocrine carcinoma(MAcNEC)と診断された.腫瘍中央の嚢胞成分は壊死によるものが疑われ,その周囲にsynaptophysin陽性の領域が,更にその周囲にBCL10,trypsin陽性の領域が分かれて確認された.本症例はMAcNECの発生様式を考察する上で示唆に富む症例であり,文献的考察を加え報告する.(著者抄録)

症例は57歳男性.検診で膵体部の嚢胞性病変が指摘され,当院を紹介された.造影CTでは膵体部に17mm大の中心部に嚢胞成分を伴う充実性腫瘤が認められた.3年後の造影CTでは,嚢胞成分を伴いながら23mm大に腫瘍径が増大し,MRIでは中心部の嚢胞成分はT1WI,T2WIともに高信号を示し,辺縁は拡散低下を伴う充実成分として観察された.超音波内視鏡検査でも同様に,中心に嚢胞成分を伴う充実性腫瘤として観察された.膵体尾部切除が施行され,病理学的にmixed acinar-neuroendocrine carcinoma(MAcNEC)と診断された.腫瘍中央の嚢胞成分は壊死によるものが疑われ,その周囲にsynaptophysin陽性の領域が,更にその周囲にBCL10,trypsin陽性の領域が分かれて確認された.本症例はMAcNECの発生様式を考察する上で示唆に富む症例であり,文献的考察を加え報告する.(著者抄録)

<title>Abstract</title>Polyamines are important to the survival and activation of organs and tissues via a homeostatic cell-metabolic process, and the polyamine content in cytoplasm decreases with aging. Decreases in cellular polyamine have been known to augment mutagenesis and cell death. Thus, supplementary polyamine in food is important to the prevention of aging. Here we show the anti-aging effects of oral intake of polyamine using luciferase-transgenic rats. Healthy rats, 10–12 weeks old, were given foods containing 0.01% and 0.1% (w/w) of polyamine, as compared a control food without polyamine, for 4 weeks. Using a bioimaging system, the photon intensities seen in the whole bodies and livers of rats consuming 0.1% of polyamine in food were stronger than those in rats consuming 0.01% and 0% of polyamine. However, there were no differences between groups in other characteristics, such as liver damage and body weight. In conclusion, we found that polyamine intake can activate cells throughout the whole body, providing an anti-aging effect.

BACKGROUND/AIMS: Recent studies have demonstrated that the populations of several microbes are significantly increased in fecal samples from patients with colorectal cancer (CRC), suggesting their involvement in the development of CRC. The aim of this study was to identify microbes which are increased in distal CRCs and to identify the specific location of microbes increased in mucosal tissue around the tumor. METHODS: Tissue specimens were collected from surgical resections of 28 distal CRCs. Five samples were collected from each specimen (location A: tumor, B: adjacent normal mucosa, C: normal mucosa 1 cm proximal to the tumor, D: normal mucosa 3 cm proximally, and E: normal mucosa 6 cm proximally). The microbiota in the sample were analyzed using 16S rRNA gene amplicon sequencing and the relative abundance (RA) of microbiota compared among the 5 locations. RESULTS: At the genus level, the RA of Fusobacterium and Streptococcus at location A was the highest among the 5 locations, significantly different from that in location E. The dominant species of each genus was Fusobacterium nucleatum and Streptococcus anginosus. The RAs of these species gradually decreased from locations B to E with a statistically significant difference in F. nucleatum. The genus Peptostreptococcus also showed a similar trend, and the RA of Peptostreptococcus stomatis in location A was significantly associated with depth of tumor invasion and tumor size. CONCLUSION: Although the clinical relevance is not clear yet, these results suggest that F. nucleatum, S. anginosus, and P. stomatis can spread to the adjacent normal tissues and may change the surrounding microenvironment to support the progression of CRC.

症例は72歳男性.膀胱癌術後の経過観察目的に施行した造影CTにて胆嚢底部の壁肥厚が指摘され当科を受診した.造影CTやMRIでは胆嚢底部に造影効果を示す隆起性病変と連続する壁肥厚が認められた.EUSでは,広基性の隆起性病変における外側高エコー層の不整が認められた.ERCP時の胆汁細胞診から腺癌を認め,拡大胆嚢摘出術が施行された.肉眼所見では大小不同の顆粒状粘膜を伴う壁肥厚性病変と,隆起性病変の一部と考えられる脱落した組織片が確認された.病理所見では肥厚した胆嚢壁と一致して管状腺癌と神経内分泌癌の所見が認められ,混合型神経内分泌癌と診断した.また脱落した組織には腺癌と肉腫が混在していた.胆嚢における腺癌,神経内分泌癌,肉腫が混ずる腫瘍は稀と考えられた.神経内分泌癌と癌肉腫の進展様式のまとめから,混合する腫瘍成分の影響により隆起性病変と壁肥厚性病変が混在する特異的な形態を呈した可能性が示唆された.(著者抄録)

大腸癌の血行性転移には、肝転移、肺転移、その他(脳、骨、副腎など)がある。肝転移と肺転移は、治癒切除により予後改善効果が報告されており、多発転移であっても他臓器に転移を認めない場合は、治癒切除可能かどうかを注意深く見極めることが重要である。また近年の化学療法の進歩により、初診時には切除不能な肝転移であっても、化学療法後の縮小により切除可能となる場合がある。切除後の予後ははじめから切除可能な肝転移のそれとほぼ同等とされ、このconversion therapyは多発肝転移を有する進行大腸癌に対する治療戦略のひとつとして確立されている。肺転移についても、一定の条件を満たす症例では切除により予後の改善が報告されており、近年の胸腔鏡手術の技術や器機の進歩により、両葉や多発病変の切除も可能となっている。ただし肺転移切除の治療成績については大規模研究の報告が少なく、ほとんどが後ろ向き研究であることから、今後の研究結果の集積が待たれる。(著者抄録)

BACKGROUND There is no consensus about the long-term prognosis of pediatric patients with a variety of rare liver diseases but with inherited metabolic diseases (IMDs). We retrospectively reviewed the developmental outcomes of patients with IMDs undergoing living donor liver transplantation (LDLT). MATERIAL AND METHODS Between May 2001 and December 2020, of 314 pediatric patients who underwent LDLT, 44 (14%) had IMDs. The median age at LDLT was 3.0 years old (range 0-15.0 years). Associations between the post-transplant complications and graft survival rate in patients with IMDs and biliary atresia (BA) were calculated. We evaluated the safety of LDLT from heterozygous carrier donors, the prognosis of patients with IMDs who have metabolic defects expressed in other organs, and developmental outcomes of patients with IMDs. RESULTS The 10-year graft survival rates in patients with IMDs and BA were 87% and 94%, respectively (P=0.041), and the causes of graft failure included pneumocystis pneumonia, acute lung failure, hemophagocytic syndrome, hepatic vein thrombosis, portal vein thrombosis, and sepsis. The rate of post-transplant cytomegalovirus viremia in patients with IMDs was higher than that of patients with BA (P=0.039). Of 39 patients with IMDs, 15 patients (38%) had severe motor and intellectual disabilities in 4 patients, intellectual developmental disorders including epilepsy in 2, and attention-deficit hyperactivity disorder in 2. Of 28 patients with IMDs, 13 (46%) needed special education. CONCLUSIONS The long-term outcomes of LDLT in patients with IMDs are good. However, further long-term social and educational follow-up regarding intellectual developmental disorders is needed.

大腸癌の血行性転移には、肝転移、肺転移、その他(脳、骨、副腎など)がある。肝転移と肺転移は、治癒切除により予後改善効果が報告されており、多発転移であっても他臓器に転移を認めない場合は、治癒切除可能かどうかを注意深く見極めることが重要である。また近年の化学療法の進歩により、初診時には切除不能な肝転移であっても、化学療法後の縮小により切除可能となる場合がある。切除後の予後ははじめから切除可能な肝転移のそれとほぼ同等とされ、このconversion therapyは多発肝転移を有する進行大腸癌に対する治療戦略のひとつとして確立されている。肺転移についても、一定の条件を満たす症例では切除により予後の改善が報告されており、近年の胸腔鏡手術の技術や器機の進歩により、両葉や多発病変の切除も可能となっている。ただし肺転移切除の治療成績については大規模研究の報告が少なく、ほとんどが後ろ向き研究であることから、今後の研究結果の集積が待たれる。(著者抄録)

PURPOSE: The aim of this study was to evaluate both the intestinal mucosa staple line integrity and anastomotic leak pressure after healing in a porcine survival model. METHODS: We used two suture models using two different size staples (incomplete mucosal closure model: group G [staple height 0.75 mm], complete mucosal closure model: group B [staple height 1.5 mm]) in the porcine ileum. Five staple lines were created in each group made in the ileum for each model, and the staple sites harvested on days 0, 2, and 7. The leak pressure at the staple site was measured at each time point. RESULTS: On day 0, the leak pressure for group G (79.5 mmHg) was significantly lower than that for group B (182.3 mmHg) (p < 0.01). On days 2 and 7, there was no significant difference between groups G and B (171 mmHg and 175.5 mmHg on day 2, 175.5 mmHg and 175.5 mmHg on day 7, p > 0.05). The histological findings in both groups showed similar healing at postoperative days 2 and 7. CONCLUSION: The integrity of the mucosal staple lines was associated with the postoperative leak pressure on day 0. However, there was no association with the leak pressure at two days or more postoperatively in a porcine model.

Introduction Although new techniques and devices have been introduced, the incidence of postoperative pancreatic fistula (POPF) after distal pancreatectomy remains high. To reduce the risk of POPF, we developed an innovative ligation band and conducted this pilot study to assess the possibility of reducing the incidence of POPF and pancreatic necrosis after distal pancreatectomy. Methods Distal pancreatectomy was performed in three pigs. In two animals, ligation of the pancreas was performed while maintaining arterial blood flow to the stump, and in one animal, the arterial blood flow was occluded. After ligation, the pancreas was sharply divided. Animals were sacrificed seven days later, and the remnant pancreas was assessed histologically. POPF was defined as amylase in ascites > 3x the preoperative serum amylase level. The following equation was used to quantify the extent of necrotic tissue: necrotic tissue residual rate = necrotic tissue area/ cross-sectional area. Results All animals survived, and no POPF developed. For two animals in which arterial blood flow to the stump was maintained, necrotic tissue residual rates at the ligation line were 24% and 31%. At the pancreatic stump, necrotic tissue residual rates were 37% and 50%. In the animal in which arterial blood flow to the stump was occluded, the necrotic tissue residual rate at the ligation line was 83% and that at the pancreatic stump was 78%, both higher than that in animals in which arterial blood flow was maintained. In all animals, there was no injury to pancreatic tissue at the ligation line. Conclusion The pancreas ligation band can potentially prevent POPF after distal pancreatectomy by atraumatic ligation, and the band ligates the pancreatic stump while maintaining arterial blood flow and limiting pancreatic necrosis.

Introduction and importance: Metastases to common iliac lymph nodes from cancer of the rectosigmoid are extremely rare. We report a patient with a right common iliac lymph node metastasis after rectosigmoid cancer resection. Case presentation: The patient is a 57-year-old woman diagnosed with rectosigmoid cancer (Stage IIIc) who underwent laparoscopic resection followed by 8 courses of adjuvant chemotherapy with capecitabine. Sixteen months after resection, an intra-abdominal mass and a left lung nodule were found on computed tomography scans, which were suspected to be recurrences. Exploratory laparoscopy showed that the abdominal lesion was an enlarged common iliac lymph node, which was completely excised. No other intraabdominal recurrences were found. Subsequently, a left upper lobe lung metastasis was resected thoracoscopically. However, multiple lung metastases developed four months after the lung resection, and systemic therapy was begun. Clinical discussion: A lower incidence of lateral lymph node metastases from cancer in the rectosigmoid has been reported. Direct lymphatic pathways from the sigmoid colon or rectosigmoid to lateral lymph nodes have been suspected, which may be associated with the poor prognosis in this patient. Conclusion: A metachronous metastasis to a common iliac lymph node from primary rectosigmoid cancer is reported. Common iliac lymph node metastases from rectosigmoid cancer might have more malignant potential, and should be treated in the same manner as peri-aortic lymph node metastases.

目的:大腸憩室出血治療の現状を調査し,外科治療必要症例の頻度や臨床的特徴を検討した.対象と方法:2010年1月から2020年4月までに当院で経験した大腸憩室出血194例を対象とし後方視的に検討した.結果:手術は7例(4%)に行われていた.手術理由は内視鏡止血困難5例,内視鏡+IVR治療困難2例,循環動態不安定3例であった(重複あり).全例とも上行結腸で,経過中にショック状態となり輸血を受けていた.手術は開腹の結腸右半切除が行われていた.左右結腸の多発例で,抗凝固薬を内服していた1例は術後3年間に3度血便を認めたが保存的に治癒した.結語:当院における憩室出血治療は概ねガイドラインに沿って行われていた.手術例では,ショック状態で輸血例であったが,周術期治療成績は良好であった.切除範囲については術後のQOLを考慮に入れた総合的な判断が必要と考えられた.(著者抄録)

Adenocarcinoma in a Meckel's diverticulum is rare and difficult to diagnose preoperatively. We report the first case of a metachronous Krukenberg tumor from adenocarcinoma in a Meckel's diverticulum. A 45-year-old woman was admitted for recurrent abdominal pain. Computed tomography scan showed a lesion with contrast enhancement, and a Meckel's diverticulum-associated tumor was suspected. Double-ballon enteroscopy revealed intestinal stenosis and biopsy showed adenocarcinoma. Operative findings showed a Meckel's diverticulum with tumor. Histopathological evaluation revealed well-differentiated adenocarcinoma, interrupted by ectopic gastric mucosa, diagnosed as adenocarcinoma in a Meckel's diverticulum. Two years postoperatively, a multi-cystic mass with contrast enhancement was observed in the pelvis on imaging evaluation and oophorectomy performed. Histological examination of the resected ovary showed proliferation of atypical glandular ducts, consistent with metastatic adenocarcinoma. This case demonstrates that adenocarcinoma in a Meckel's diverticulum may result in distant metastases and requires appropriate follow-up.

症例は48歳の男性で,約1ヵ月前に左手外傷に対して鼠径部より採皮,植皮術を施行され,退院後より腹部違和感を自覚していた.腹部症状が増悪し意識障害も出現したため前医を受診し,造影CTで広範な門脈血栓症を認め,入院となった.翌日,下部消化管出血を認め,当院転院となった.転院時造影CTで上腸間膜静脈血栓症と診断された.小腸壊死は明らかでなく,抗凝固療法を開始し,約40日の経過で血栓はほぼ消失した.経口摂取開始後に嘔吐が出現したため,小腸造影および小腸3D-CTを撮影したところ上部空腸の器質的狭窄を認めた.転院後第59病日に小腸部分切除術を施行した.病理学的には血栓形成を伴う虚血性腸炎の診断であった.術後20日目に退院し,現在も再発は認めていない.本症例では,3D-CTが遅発性小腸狭窄の範囲の推定と切除範囲の決定に有用であった.(著者抄録)