The clinical significance of lymph node dissection (LND) in patients with peripheral type intrahepatic cholangiocarcinoma (ICC) remains unclear. Although LND is usually performed for perihilar type ICC, there is no consensus on whether routine LND should be performed for peripheral type ICC. This study aimed to investigate the prognostic significance of LND in patients who underwent hepatectomy for peripheral type ICC. This study included consecutive patients who underwent macroscopically curative initial hepatectomy for ICC at our hospital from 2000 to 2018. Among them, peripheral type ICCs with the macroscopic appearance of mass-forming (MF) or MF + periductal infiltrating (PI) types were analyzed. Propensity score analyses (1:1 matching and inverse probability treatment weighting) were adopted to adjust confounding variables. Overall survival (OS) and disease-free survival (DFS) were compared between the LND and no LND (NLND) groups. During the study period, 201 patients underwent hepatectomy for ICC. The number of peripheral ICC patients with MF type or MF + PI type was 142. The LND group comprised 94 patients and the NLND group comprised 48 patients. The N1 group showed significantly poorer OS and DFS than the N0 and NLND groups (P < 0.001). After propensity score adjustment, there were no significant differences in OS and DFS between the LND and NLND groups. The prognostic impact of lymph node metastasis was significant; however, the therapeutic effect of LND was not demonstrated in peripheral type ICC. The indication of LND should be carefully considered on an individual patient basis.

Laparoscopic liver resection (LLR) has expanded to include major liver resection and systematic resection as the techniques have advanced. Regardless of the oncological significance of anatomical resection, dissection of the intersegmental plane is useful in liver resection because it makes liver dissection easier and does not leave an ischemic area. In laparoscopic surgery, the hepatic vein can be exposed with less bleeding than in open surgery because bleeding can be controlled by pneumoperitoneum pressure. Therefore, the hepatic vein is a useful indicator to guide the dissected surface and to determine the depth. However, the basic technique of exposing the hepatic vein during LLR is required. The hepatic vein root can be approached using either a cranial or dorsal approach, with the dorsal approach providing the favorable view characteristic of laparoscopy. Selecting the dissection layer with the Laennec's capsule of the hepatic vein roots in mind is also a useful technique to ensure more reliable dissection of the hepatic vein. We summarize previous reports on techniques for facilitating LLR using the hepatic vein as a guide and outline the role of each hepatic vein type. Although there are many reports of procedures using the hepatic vein as a guide, the terminology of the approach awaits standardization in the future.

Prep-02/JSAP-05 trialで術前補助化学療法(NAC)としてのゲムシタビン+S-1療法(GS療法)による有用性が示されて以降,切除可能膵癌(R膵癌)の周術期治療は大きく変化しつつある.これまでR膵癌は手術先行が基本であったが,Prep-02/JSAP-05 trial以降は全国的に術前GS療法が広がりつつある.またそれに伴い組織学的診断の必要性が高まり,超音波内視鏡下穿刺吸引法(EUS-FNA)の必要性が増している.当院におけるR膵癌に対するEUS-FNAは正診率98.9%,偶発症割合2.0%(2/100例)であり,有用で安全と考えられる.また手術成績に関しては,Prep-02/JSAP-05 trialと同様にNACの導入後も高い治癒切除率を認めている.一方で成績に関しては導入初期のものであり,今後は,多数例・長期フォローアップでの慎重な追跡が必要である.

Genomic analyses have recently discovered the malignant subtype of human intrahepatic cholangiocarcinoma (ICC) characterized by frequent mutations of chromatin remodeling gene ARID1A; however, the biological and molecular functions still remain obscure. We here examined the clinical and biological significances of ARID1A deficiency in human ICC. Immunohistochemical analysis demonstrated that the loss of ARID1A was an independent prognostic factor for overall survival of ICC patients (P = 0.023). We established ARID1A-knockout (KO) cells by using the CRISPR/Cas9 system from two human cholangiocarcinoma cell lines. ARID1A-KO cells exhibited significantly enhanced migration, invasion, and sphere formation activity. Microarray analysis revealed that ALDH1A1, a stemness gene, was the most significantly elevated genes in ARID1A-KO cells. In addition, ALDH enzymatic activity as a hallmark of cancer stem cells was markedly high in the KO cells. ARID1A and histone deacetylase 1 were directly recruited to the ALDH1A1 promoter region in cholangiocarcinoma cells with undetectable ALDH1A1 expression by chromatin immunoprecipitation assay. The histone H3K27 acetylation level at the ALDH1A1 promoter region was increased in cells when ARID1A was disrupted (P < 0.01). Clinically, inverse correlation between ARID1A and ALDH1A1 expression was also identified in primary ICC (P = 0.018), and ARID1A-negative and ALDH1A1-positve ICCs showed worse prognosis than only ARID1A-negative cases (P = 0.002). In conclusion, ARID1A may function as a tumor suppressor in ICC through transcriptional downregulation of ALDH1A1 expression with decreasing histone H3K27 acetylation. Our studies provide the basis for the development of new epigenetic approaches to ARID1A-negative ICC. Immunohistochemical loss of ARID1A is an independent prognostic factor in intrahepatic cholangiocarcinoma patients. ARID1A recruits HDAC1 to the promoter region of ALDH1A1, a stemness gene, and epigenetically suppresses ALDH1A1 expression with decreasing histone H3K27 acetylation in cholangiocarcinoma cells.

Pancreatic fistula after distal pancreatectomy (DP) remains an unsolved problem, and postoperative CT imaging often demonstrates fluid collection (FC) around the pancreatic remnant. This study sought to clarify the clinical implications of FC. This study enrolled 146 patients who underwent DP. FC was defined as a cyst-like lesion ≥ 10 mm in diameter on CT imaging at postoperative day (POD) 7. FC size, irregularity of FC margin, and air bubbles in FC were investigated. In addition, clinical data were retrospectively collected, and useful predictive factors for postoperative pancreatic fistula (POPF) were analyzed. Clinically relevant POPF was observed in 26 patients (17.8%), and FC was detected in 136 patients (94.4%). Multivariate analysis identified FC size and drain amylase levels on POD3 as significant risk factors for POPF. Cutoff values were determined by ROC analyses, and the levels of the FC size and drain amylase on POD3 were determined as 41 mm and 1026 IU/L, respectively. The sensitivity and specificity of FC diameters > 41 mm were 76.9% and 75.0%, respectively, while those of drain amylase levels > 1026 IU on POD3 were 73.1% and 75.8%, respectively. While treating some FCs after DP was necessary for the management of POPF, others did not require any intervention since most of them spontaneously disappeared. FC size and drain amylase levels on POD3 were found to be significantly associated with POPF and could potentially help to determine appropriate treatment.