加藤 宏之

症例は、77歳男性。皮膚の黄染を自覚し近医を受診した。造影CTにて遠位胆管の壁肥厚を指摘され、遠位胆管癌疑いにて紹介となった。また、肝十二指腸間膜内に多発リンパ節転移と右肝動脈浸潤が疑われた。PET-CTにて大動脈周囲リンパ節転移も認め、切除不能遠位胆管癌と判断した。全身化学療法としてgemcitabine(GEM)+S-1併用療法(GS療法、GEM:800mg/m2、day 8、22TS1:80mg/body/day、day 1〜21、1サイクル28日)を3サイクル継続しながら肝十二指腸間膜内リンパ節転移と右肝動脈浸潤に対しては放射線療法(50.4Gy)を行った。腫瘍サイズは縮小し、CA19-9は3,307U/mLから11.3U/mLまで低下、肝十二指腸間膜内リンパ節転移も明らかなものは消失し、局所コントロールは良好であった。大動脈周囲リンパ節転移には変化がなかったが、腫瘍マーカーも持続低値であったため局所制御を目的として初回治療から4ヵ月目に亜全胃温存膵頭十二指腸切除術(SSPPD)+大動脈周囲リンパ節郭清を行った。16a2リンパ節には術中迅速検査にて転移を認めたが、右肝動脈浸潤はなく、剥離可能であった。術後7ヵ月にわたりGS療法を継続しており、画像上16b1 lateroリンパ節に直径15mmの孤立性のリンパ節再発を認めたが、局所放射線療法を施行し、局所制御良好である。大動脈周囲リンパ節転移を有する遠位胆管癌でも、切除も含めた集学的治療により予後改善が見込める可能性が示唆された。(著者抄録)

膵頭十二指腸切除(PD)術後の患者において、非アルコール性脂肪性肝疾患(NAFLD)が発生することが知られており、その頻度は20〜40%と非常に多く、なかには非アルコール性脂肪性肝炎(NASH)を経て肝不全へ進行する症例もある。NAFLDは術後の膵外分泌機能不全や栄養障害を背景に発症すると考えられており、その危険因子として、若年、女性、膵癌、膵の性状、膵切除量、術後早期の感染、術後下痢、摂食障害などがあげられる。NAFLDの治療では高力価・高用量の膵酵素補充療法に加え、栄養療法が重要な役割をはたす。NAFLDの予防においても、術後早期からの膵酵素療法の効果が期待されるが、その文献報告は少ない。(著者抄録)

Objectives Tenascin-C (TN-C) is an extracellular matrix protein that is up-regulated in pancreatic ductal adenocarcinoma (PDAC) stroma and associated with tumor invasion. We examined intratumor stromal expression of TN-C in resected specimens and the histologic effect of chemoradiotherapy (CRT) as prognostic indicators in initially locally advanced unresectable (UR-LA) PDAC. Methods Among 110 UR-LA PDAC patients enrolled in the CRT protocol from February 2005 to December 2015, 46 who underwent curative-intent resection were classified as high (tumor destruction &gt 50%) and low (≤50%) responders according to the Evans grading system. Tenascin-C expression was immunohistologically evaluated in all patients except one with complete response. Results The 12 high responders achieved a significantly higher R0 rate than did the 34 low responders (83.3 vs 47.1%), but disease-specific survival (DSS) time was not significantly different (median survival time, 29.8 vs 21.0 months). Tenascin-C expression was inversely correlated with histologic effect of CRT. The 22 patients with negative TN-C had significantly longer DSS time than did the 23 with positive TN-C (29.3 vs 17.1 months). In multivariate analysis, only TN-C expression was a significant prognostic factor for DSS. Conclusions Intratumor stromal expression of TN-C is a strong prognostic indicator in UR-LA PDAC patients with resection after CRT.

Background: The aim of this study was to validate a new definition of borderline resectable pancreatic ductal adenocarcinoma (PDAC) provided by the 2017 international consensus on the basis of three dimensions of anatomical (A), biological (B), and conditional (C) factors, using the data of the patients who had been registered for our institutional protocol of chemoradiotherapy followed by surgery (CRTS) for localized patients with PDAC. Methods: Among 307 consecutive patients pathologically diagnosed with localized PDAC who were enrolled in our CRTS protocol from February 2005 to December 2016, we selected 285 patients who could be re-evaluated after CRT. These 285 patients were classified according to international consensus A definitions as follows: R (resectable; n = 62), BR-PV (borderline resectable, superior mesenteric vein (SMV)/portal vein (PV) involvement alone; n = 27), BR-A (borderline resectable, arterial involvement; n = 50), LA (locally advanced; n = 146). Disease-specific survival (DSS) was analyzed according to A, B (serum CA 19-9 levels and lymph node metastasis diagnosed by computed tomography findings before CRT), and C factors (performance status (PS)) factors. Results: The rates of resection and R0 resection were similar between R (83.9 and 98.0%) and BR-PV (85.2 and 95.5%), but much lower in BR-A (70.0 and 84.8%) and LA (46.6 and 62.5%). DSS evaluated by median survival time (months) showed a similar trend to surgical outcomes: 33.7 in R, 27.3 in BR-PV, 18.9 in BR-A and 19.3 in LA, respectively. DSS in R patients with CA 19-9 levels > 500 U/mL was significantly poorer than in patients with CA 19-9 levels ≤ 500 U/mL, but there were no differences in DSS among BR-PV, BR-A, and LA patients according to CA 19-9 levels. Regarding lymph node metastasis, there was no significant difference in DSS according to each resectability group. DSS in R patients with PS ≥ 2 was significantly worse than in patients with PS 0-1. Conclusions: The international consensus on the definition of BR-PDAC based on three dimensions of A, B, and C is useful and practicable because prognosis of PDAC patients is influenced by anatomical factors as well as biological and conditional factors, which in turn may help to decide treatment strategy.

Portal vein thrombosis (PVT) is a serious complication after hepatobiliary-pancreatic surgery. Portal vein thrombosis often develops in patients with liver cirrhosis (LC) postoperatively, although they have low platelet counts. Platelet activation is one of the causes of thrombosis formation, and soluble form of glycoprotein VI (sGPVI) has received attention as a platelet activation marker. We had prospectively enrolled the 81 consecutive patients who underwent splenectomy (Sx) and/or hepatectomy: these patients were divided as Sx (n = 38) and hepatectomy (Hx, n = 46) groups. The 3 patients who underwent both procedures were added to both groups. Each group was subdivided into patients with non-LC and LC: non-LC-Sx (n = 22) and LC-Sx (n = 16), non-LC-Hx (n = 40) and LC-Hx (n = 6). The presence of PVT was diagnosed by using enhanced computed tomography (CT) scan. Platelet counts were significantly lower in LC-Sx than in non-LC-Sx, and incidence of PVT was significantly higher in LC-Sx than in non-LC-Sx (68.8% vs 31.8%, P = .024). Soluble form of glycoprotein VI /platelet ratios on preoperative day and postoperative day 1 were significantly higher in LC-Sx than in non-LC-Sx. Incidence of PVT was significantly higher in LC-Hx than in non-LC-Hx (50.0% vs 7.5%, P < .01). Soluble form of glycoprotein VI /platelet ratios were significantly higher in LC-Hx before and after Hx, compared to non-LC-Hx. Patients with LC stay in hypercoagulable state together with platelet activation before and after surgery. Under this circumstance, alteration of portal venous blood flow after Sx or Hx is likely to cause PVT in patients with LC.

BACKGROUND: Functional and structural damages in sinusoidal endothelial cells (SECs) have a crucial role during hepatic ischemia-reperfusion injury (IRI). In regulating endothelial function, sphingosine-1-phosphate receptor 1 (S1PR1), which is a G protein-coupled receptor, has an important role. The present study aimed to clarify whether SEW2871, a selective S1PR1 agonist, can attenuate hepatic damage caused by hepatic IRI, focusing on SEC functions. METHODS: In vivo, using a 60-min partial-warm IRI model, mice were treated with SEW2871 or without it (with vehicle). In vitro, isolated SECs pretreated with SEW2871 or without it (with vehicle) were incubated with hydrogen peroxide. RESULTS: Compared with the IRI + vehicle group, SEW2871 administration significantly improved serum transaminase levels and liver damage, attenuated infiltration of Ly-6G and mouse macrophage antigen-1-positive cells, suppressed the expression of vascular cell adhesion molecule-1 and proinflammatory cytokines in the liver, and enhanced the expressions of endothelial nitric oxide synthase (eNOS) and vascular endothelial (VE) cadherin in the liver (eNOS/β-actin [median]: 0.24 versus 0.53, P = 0.008; VE-cadherin/β-actin [median]: 0.21 versus 0.94, P = 0.008). In vitro, compared with the vehicle group, pretreatment of SECs with SEW2871 significantly increased the expressions of eNOS and VE-cadherin (eNOS/β-actin [median]: 0.22 versus 0.29, P = 0.008; VE-cadherin/β-actin [median]: 0.38 versus 0.67, P = 0.008). As results of investigation of prosurvival signals, SEW2871 significantly increased Akt phosphorylation in SECs and decreased lactate dehydrogenase levels in supernatants of SECs. CONCLUSIONS: These results indicate that S1PR1 agonist induces attenuation of hepatic IRI, which might be provided by preventing SEC damage. S1PR1 may be a therapeutic target for the prevention of early sinusoidal injury after hepatic IRI.

In accordance with previous reports, the incidence of biliary candidiasis (BC) after pancreaticoduodenectomy (PD) was reported to be 0 to 5%, and the clinical significance of BC still has been elusive. In this study, we prospectively evaluated the precise incidence of BC after PD using the CHROMagar Candida plate in an attempt to elucidate whether BC has a significant impact on the clinical outcomes after PD. Patients and Method. From November 2014 to March 2016, the consecutive 51 patients who underwent PD were enrolled for this study. The bile juice was prospectively collected through the biliary stent tube on postoperative days (POD) 3, 7, and 14 and directly incubated onto the CHROMagar Candida plate for the cultivation of various Candida species. In the presence or absence of BC, we compared the incidence of SSIs. Results. The incidence of postoperative BC was 15% on POD 3, 24% on POD 7, and 39% on POD 14, respectively. Taken together, 22 patients out of 51 (43.1%) developed BC after PD. Moreover, the incidence of SSIs was significantly higher in patients with BC than in those without it (71% versus 7%, p=0.005). BC was selected as the only significant risk factor of SSIs after PD among the various risk factors. Even though a cause of BC is unknown, high level of alkaline phosphatase (cut-off line >300 IU/L) was selected as the only preoperative risk factor of the development of BC. Conclusion. We elucidated new evidence in which BC could be the independent cause of SSIs after PD and should not be recognized as just contamination artifacts. Preoperative assessment for identifying carriers of Candida species might be essential for reducing the incidence of SSIs after PD.