加藤 宏之

BACKGROUND: Several inflammation-based scores are used to assess the surgical outcomes of hepatocellular carcinoma (HCC). The aim of the present study was to elucidate the prognostic value of the prognostic nutritional index (PNI) in HCC patients who underwent hepatectomy with special attention to preoperative liver functional reserve. METHODS: Preoperative demographic and tumor-related factors were analyzed in 189 patients with HCC undergoing initial hepatectomy from August 2005 to May 2016 to identify significant prognostic factors. RESULTS: Multivariate analysis for overall survival (OS) revealed that female sex (p = 0.005), tumor size (p < 0.001) and PNI (p = 0.001) were independent prognostic factors. Compared to the High PNI group (PNI ≥ 37, n = 172), the Low PNI group (PNI < 37, n = 17) had impaired liver function and significantly poorer OS (13% vs. 67% in 5-year OS, p = 0.001) and recurrence-free survival (RFS) (8 vs. 25 months in median PFS time, p = 0.002). In the subgroup of patients with a preserved liver function of LHL15 ≥ 0.9, PNI was also independent prognostic factor, and OS (21% vs. 70% in 5-year OS, p = 0.008) and RFS (8 vs. 28 months in median PFS time, p = 0.018) were significantly poorer in the Low PNI group than the High PNI group. CONCLUSIONS: PNI was an independent prognostic factor for HCC patients who underwent hepatectomy. Patients with PNI lower than 37 were at high risk for early recurrence and poor patient survival, especially in the patients with preserved liver function of LHL ≥ 0.9.

限局性肝内胆管拡張例では良悪性の鑑別がしばしば困難である。今回、肝内胆管拡張を呈した良性胆管狭窄に対し、腹腔鏡下左肝切除術を行った2例を経験した。症例1、73歳女性。早期食道癌ESD後のCTでB2、B4に限局性の肝内胆管拡張を認めた。ERCPでは狭窄のためB2の拡張胆管は描出されず、胆汁細胞診は陰性であった。肝内胆管癌を疑って腹腔鏡下左肝切除術を行った。術後病理では、B2胆管狭窄部に炎症細胞浸潤を認めた。症例2、76歳女性。発熱、心窩部痛を契機にCTでB3の限局性肝内胆管拡張を指摘された。ERCPでB3の高度の狭窄を認めたが、胆汁細胞診は陰性であった。胆管狭窄による急性胆管炎、肝内胆管癌の疑いで腹腔鏡下左肝切除術を行った。術後病理では、B3の胆管狭窄部、拡張部ともに炎症細胞浸潤を認めた。限局性肝内胆管拡張の術前診断は困難で、胆管炎の原因ともなり、悪性を否定できない場合肝切除を検討するべきと考えられた。(著者抄録)

BACKGROUND: Arterial pseudoaneurysm is a rare but potentially fatal complication after pancreaticoduodenectomy (PD). This study aimed to evaluate the incidence and predictors associated with pseudoaneurysm formation and patient death caused by its rupture. PATIENTS AND METHOD: We retrospectively reviewed the data of 453 patients who underwent PD from April 2007 to February 2019. Uni- and multivariate analysis and receiver operating characteristic (ROC) curve analysis were performed to identify risk factors and optimal cutoff values. RESULTS: Among the 453 patients, 22 (4.9%) developed pseudoaneurysm after PD. Median duration from surgery to detection of pseudoaneurysm was 17.0 (1-51) days. The locations of pseudoaneurysms were hepatic artery in 8, splenic artery in 3, gastroduodenal artery in 4, gastric artery in 2 and others in 5 patients, and 72.7% (16/22) of patients presented with hemorrhage. All pseudoaneurysms were treated using angioembolization. Lower age (<65.5 years, p = 0.004), prolonged operation time (Cutoff ˃610 min, p = 0.026) and postoperative pancreatic fistula (POPF) (p = 0.013) were the independent risk factors for development of pseudoaneurysm. 6 (27.3%) patients died due to rupture of pseudoaneurysm and prolonged operation time (Cutoff ˃657 min, p = 0.043) was a significant risk factor for death related to pseudoaneurysm. CONCLUSION: Prolonged operating time was identified as a risk factor for both pseudoaneurysm formation and patient death following pseudoaneurysm bleeding. Interventional radiology treatment offered a central role in the treatment of pseudoaneurysms after PD. Therefore, it is important to have a high index of suspicion in high risk patients of the possibility of pseudoaneurysm formation and bleeding.

We present the case of a 66-year-old female diagnosed with gallbladder cancer that was initially discovered with contrast enhanced computed tomography. The primary gall bladder tumor displayed heterogeneous enhancement. The patient underwent cholecystectomy with full-thickness excision of the gallbladder cancer. After 3 rounds of adjuvant chemotherapy with the oral fluoropyrimidine derivative, S-1(administered for 4 weeks at 120 mg/day and then stopped for 2 weeks), a metastasis measuring 15 mm in diameter emerged within hepatic segment 5. The chemotherapy regimen was altered to include 6 months of combination therapy with gemcitabine(1,000 mg/m2)and cisplatin(25 mg/m2)given once every week for 2 weeks and then stopped for 1 week. The hepatic metastasis decreased in size to 8 mm in diameter, and a partial liver resection was performed. After hepatectomy, the patient remains alive and without disease recurrence.

BACKGROUND: We experienced a rare case of intraductal papillary mucinous neoplasm arising from Santorini's duct (SD) forming a tumor protruding into the duodenum . CASE PRESENTATION: A 71-year-old woman was incidentally diagnosed with a 3 cm type Isp polypoid tumor in the second portion of the duodenum at another hospital. Enhanced CT and endoscopic ultrasound revealed that the origin of this protruding tumor was arising from SD and that the tumor mimicked a pedunculated duodenal tumor. Our preoperative diagnosis was a malignant pancreatic tumor arising from SD with invasion into the duodenum. She underwent a subtotal stomach-preserving pancreaticoduodenectomy, and the resected specimen showed a 25 mm tumor protruding into the duodenum with a villous surface. The pathological findings revealed that the tumor was intraductal papillary mucinous adenoma (IPMA) arising from SD. CONCLUSIONS: To the best of our knowledge, this is the first case of IPMA protruding into the duodenal lumen from SD, although most of the tumors arising from SD have been reported to be malignant.

症例は73歳女性。検診で肝機能異常を認めたため、近医を受診した。造影CTで、ドーム直下(S4/8)に動脈相で強く濃染され平衡相まで遷延する3cm大の腫瘍を認めた。血管造影では、CT-HAで腫瘍周囲が染まるも腫瘍濃染は認めず、CT-APで欠損像を認めた。EOB-MRIの肝細胞相では、陰影欠損を呈した。胆管細胞癌または肝細胞癌が考えられ腫瘍生検が試みられたが、腫瘍組織は採取できなかった。そのときの肝組織で、門脈域の限界板を超えるリンパ球主体の炎症細胞浸潤を認め、血清抗核抗体陽性(320倍)、IgG2,034mg/dLとあわせて自己免疫性肝炎(自己免疫性肝炎診療ガイドライン診断基準:典型例、簡易型国際診断基準:7点)と診断された。手術目的に当科紹介となり、肝機能不良(ICGR15 27%、LHL15 0.899)のため肝部分切除を行った。術中、肝臓は豆板状の完成された肝硬変であった。病理診断は低分化型肝内胆管癌で背景肝は肝硬変(f4)であった。(著者抄録)

OBJECTIVE: The aim of the study was to identify the prognostic factors before neoadjuvant chemoradiotherapy (NCRT) in the patients with localized PDAC. Furthermore, to identify the post-surgical survival predictors of patients with LAPC. SUMMARY OF BACKGROUND DATA: Surgical resection may occupy an important position in multimodal therapy for patients with LAPC; however, its indication and who obtains the true benefits, is still uncovered. MATERIALS AND METHOD: From 2005 to 2017, 319 patients with localized PDAC who underwent NCRT were reviewed. Only 159 patients were diagnosed with LAPC, of these 72 patients underwent surgical resection. We examined the pre-NCRT prognostic factors in the entire cohort and conducted further subgroup analysis for evaluating the post-surgical prognostic factors in LAPC patients under the pretext of favorable local tumor control. RESULTS: In the entire cohort, pre-NCRT CEA value was recognized as the most significant prognostic indicator by multivariate analysis. In the 72 LAPC patients who underwent surgical resection, only high CEA level was identified as an independent dismal prognostic factor before surgery. At the cut-off value: 7.2 ng/mL, survival of the 15 patients whose CEA value >7.2 ng/mL was significantly unfavorable compared to those of 57 patients with <7.2 ng/mL: Median disease-specific survival time: 8.0 versus 24.0 months (P < 0.00001). Moreover, the median recurrence-free survival time of the high CEA group was only 5.4 months and there was no 1-year recurrence-free survivor. CONCLUSIONS: CEA before NCRT is a crucial prognostic indicator for localized PDAC. Moreover, LAPC with a high CEA level, especially more than 7.2 ng/mL, should still be recognized as a systemic disease, and we should be careful to decide the indication of surgery even if tumor local control seems to be durable.

BACKGROUND: Our aim is to elucidate the true preoperative risk factors for postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD), making it possible to select POPF high-risk patients preoperatively regardless of intraoperative pancreatic consistency judged by the surgeon's hand. METHODS: Among the 298 patients who underwent PD with pancreaticojejunostomy from 2007 to 2016, 262 patients had preoperative CT configurations that could be precisely evaluated. Risk factor analyses were conducted using various perioperative factors, including preoperative CT findings, such as CT values of the pancreas, pancreas-visceral fat CT value ratio and pancreatic outer contour. Pancreatic outer contour was further divided into smooth- (smooth interlobular) and serrated-type contours (feathery, irregular interlobular) by preoperative CT. RESULTS: In terms of the incidence of POPF, among the 262 patients, POPF grade B/C was found in 27 (10.3%): grade B in 23 (8.8%) and grade C in 4 (1.5%). According to multivariate analysis, a high pancreas-visceral fat CT value ratio (p = 0.002), serrated-type contour (p = 0.02) and no history of chemoradiotherapy (p = 0.019) were identified as independent risk factors for POPF grade B/C. Even in patients with soft pancreas, the incidence of POPF grade B/C was 0% (0/57) in patients with a pancreas-visceral fat CT value ratio of less than - 0.4 and smooth-type contour, whereas the incidence was markedly high (45.0%, 9/20) in patients with a pancreas-visceral fat CT value ratio of - 0.4 or greater and serrated-type contour, indicating that patients with soft pancreas should be categorized into POPF high-risk and low-risk groups according to preoperative CT scan results. CONCLUSIONS: The pancreas-visceral fat CT value ratio and serrated-type pancreas are useful markers to preoperatively identify true POPF high-risk groups in patients undergoing PD, regardless of the pancreatic texture judged intraoperatively.

(背景)膵全摘(Total pancreatectomy:TP)術後にはインスリン以外にもグルカゴンなどの全ての内分泌機能が消失するため重症低血糖を起こすことも少なくない。一方、膵頭側亜全摘(Proximal subtotal pancreatectomy:PSTP)を施行することにより尾側膵を少量温存することができるが、その意義や有用性は明らかではない。(方法)2008年8月から2018年12月までに施行されたTP15例(膵管内乳頭状腫瘍8例、膵癌7例)とPSTP15例(膵癌14例、膵管内乳頭状腫瘍1例)を対象とし術後30日以内の低血糖回数、インスリン必要量を2群間で比較した。さらにTP15例を対象として術後低血糖の術前危険因子について解析した。(結果)PSTPの残膵量の中央値はCT Volumetryで計算すると3.8mlしか残っていなかったが、術後30日以内の低血糖回数(0 vs.5.0、p=0.0003)とインスリン必要量(0 vs.15.5unit、p=0.002)はPSTPで有意に少なかった。またTP群における術後低血糖発作(5回以上/30日)の術前危険因子として低CHE値(p=0.021)、低リンパ球数(p=0.011)、低PNI(prognostic nutrition index)(p=0.006)が挙げられた。(結語)術前低栄養状態の患者への膵全摘の適応には慎重になるべきであり、代替術式としてPSTPの有用性が示唆された。(著者抄録)

当科で施行した血管合併切除再建(VR)を伴う肝門部領域胆管癌の手術成績と予後、血管関連合併症の治療法における血管ステントの有用性について検討した。肝門部領域胆管癌89例(男性55例、女性34例、中央値70歳)を対象とした。術後経過については、Clavien-Dindo III以上の合併症はnon-VR群24例(50.0%)、VR群14例(34.1%)で、ともに高率であったが有意差を認めなかった。また、血管関連合併症については、non-VR群2例(4.2%)、VR群2例(4.9%)に認めた。90日以内死亡はnon-VR群2例(4.2%)、VR群1例(2.4%)で有意差を認めず、血管吻合に関する合併症による在院死はなかった。疾患特異的5年生存率はnon-VR群が45.3%、VR群が29.4%と統計学的有意差はなかったが、non-VR群で良好な傾向が認められた。また、同時期に遠隔転移症例を除く局所進行肝門部領域胆管癌症例で非切除となった24例の6.2%と比較すると、切除例はそれぞれ有意差をもって予後の改善が認められた。肝門部胆管癌に対して積極的に血管合併切除再建を行う意義は大きいと考えられた。

BACKGROUND: The prognosis of patients with perihilar cholangiocarcinoma have been unsatisfactory. We established new anatomical resectability classification for patients with localized perihilar cholangiocarcinoma and performed neoadjuvant chemotherapy followed by curative-intent surgery based on its resectability classification and lymph node status to improve prognosis. This study aimed to clarify the long-term outcomes and validation of our strategy. METHODS: Between September 2010 and August 2018, 72 consecutive patients with perihilar cholangiocarcinoma were classified into three groups: Resectable (R = 29), Borderline resectable (BR = 23), and Locally advanced (LA = 20), based on the two factors of tumor vascular and biliary extension. R with clinically lymph node metastasis, BR, and LA patients received neoadjuvant chemotherapy using gemcitabine plus S-1. RESULTS: Forty-seven patients (65.3%) received neoadjuvant chemotherapy: R in 8, BR in 21, and 18 in LA, respectively. Fifty-nine patients (68.1%) underwent curative-intent surgery: R in 26, BR in 17, and LA in 6. Five-year disease-specific survival was 31.5% (median survival time: 33.0 months): 50.3% (not reached) in R, 30.0% (31.4 months) in BR, and 16.5% (22.5 months) in LA, which were relatively stratified. Among 49 patients with resection, disease-specific survival was 43.8% (57.0 months): 57.6% (not reached) in R, 41.0% (52.4 months) in BR, and 0% (49.4 months) in LA, which were significantly good prognosis compared to 23 patients without resection (17.2 months). Multivariate analysis identified preoperative high carcinoembryonic antigen levels (more than 8.5 ng/ml) and pT4 as independent poor prognostic factor of patients with resection. CONCLUSION: Neoadjuvant chemotherapy based on resectability classification and lymph node status was feasible, and was considered efficacious in selected patients.

BACKGROUND: Portal annular pancreas (PAP) is a rare pancreatic anomaly in which the uncinate process wraps annularly around the portal vein and fuses to the body of the pancreas. PAP is highly relevant to the development of postoperative pancreatic fistula (POPF) in pancreatic surgery. Here, we describe our experience and surgical technique of laparoscopic spleen-preserving distal pancreatectomy using Warshaw's procedure for patients with the PAP. CASE PRESENTATION: A 49-year-old woman with PAP was referred to our hospital for a suspicious mucinous cystic neoplasms 1.5 cm in diameter in the pancreatic tail. Laparoscopic spleen-preserving distal pancreatectomy using Warshaw's procedure was performed. Mobilization of the pancreatic tail was first performed, and then, the splenic artery was cut. After dividing the pancreatic tail from the splenic hilum, the ventral pancreatic parenchyma was divided using a stapler. After cutting the splenic vein, complete mobilization of the pancreatic body and tail enabled easy division of the PAP. Finally, the PAP was also divided using the stapler. Although grade B POPF occurred, she was discharged on the 9th postoperative day. CONCLUSIONS: Surgeons should understand the anatomical characteristics of PAP and be aware of the possibility of POPF.

BACKGROUND: Tumor budding (TB) is used as an indicator of poor prognosis in various cancers. However, studies on TB in perihilar cholangiocarcinoma are still limited. We examined the significance of TB in resected perihilar cholangiocarcinoma with or without neoadjuvant therapy. METHODS: Seventy-eight patients who underwent surgical resection at our institution for perihilar cholangiocarcinoma from 2004 to 2017, (36 with neoadjuvant therapy), were enrolled in this study. TB was defined as an isolated cancer cell or clusters (< 5 cells) at the invasive front and the number of TB was counted using a 20 times objective lens. Patients were classified into two groups according to TB counts: low TB (TB < 5) and high TB (TB ≥5). RESULTS: In this 78 patient cohort, high TB was significantly associated with advanced tumor status (pT4: 50.0% vs 22.2%, p = 0.007, pN1/2: 70.8% vs 39.6%, p = 0.011, M1: 20.8% vs 1.9%) and higher histological grade (G3: 25.0% vs 5.7%, p = 0.014). Disease specific survival (DSS) in high TB was significantly inferior compared to that in low TB group (3-y DSS 14.5% vs 67.7%, p < 0.001). Interestingly, DSS in high TB showed similar to survival in unresected patients. In addition, high TB was also associated with advanced tumor status and poor prognosis in patients with neoadjuvant therapy. Multivariate analysis identified high TB as an independent poor prognostic factors for DSS (HR: 5.206, p = 0.001). CONCLUSION: This study demonstrated that high TB was strongly associated with advanced tumor status and poor prognosis in resected perihilar cholangiocarcinoma patients. High TB can be a novel poor prognostic factor in resected perihilar cholangiocarcinoma regardless of neoadjuvant therapy.

BACKGROUND: Coagulation disturbances in several liver diseases lead to thrombin generation, which triggers intracellular injury via activation of protease-activated receptor-1 (PAR-1). Little is known about the thrombin/PAR-1 pathway in hepatic ischemia-reperfusion injury (IRI). The present study aimed to clarify whether a newly selective PAR-1 antagonist, vorapaxar, can attenuate liver damage caused by hepatic IRI, with a focus on apoptosis and the survival-signaling pathway. METHODS: A 60-min hepatic partial-warm IRI model was used to evaluate PAR-1 expression in vivo. Subsequently, IRI mice were treated with or without vorapaxar (with vehicle). In addition, hepatic sinusoidal endothelial cells (SECs) pretreated with or without vorapaxar (with vehicle) were incubated during hypoxia-reoxygenation in vitro. RESULTS: In naïve livers, PAR-1 was confirmed by immunohistochemistry and immunofluorescence analysis to be located on hepatic SECs, and IRI strongly enhanced PAR-1 expression. In IRI mice models, vorapaxar treatment significantly decreased serum transaminase levels, improved liver histological damage, reduced the number of apoptotic cells as evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling staining (median: 135 versus 25, P = 0.004), and induced extracellular signal-regulated kinase 1/2 (ERK 1/2) cell survival signaling (phospho-ERK/total ERK 1/2: 0.96 versus 5.34, P = 0.004). Pretreatment of SECs with vorapaxar significantly attenuated apoptosis and induced phosphorylation of ERK 1/2 in vitro (phospho-ERK/total ERK 1/2: 0.66 versus 3.04, P = 0.009). These changes were abolished by the addition of PD98059, the ERK 1/2 pathway inhibitor, before treatment with vorapaxar. CONCLUSIONS: The results of the present study revealed that hepatic IRI induces significant enhancement of PAR-1 expression on SECs, which may be associated with suppression of survival signaling pathways such as ERK 1/2, resulting in severe apoptosis-induced hepatic damage. Thus, the selective PAR-1 antagonist attenuates hepatic IRI through an antiapoptotic effect by the activation of survival-signaling pathways.