Surgical strategy for incidental intrahepatic cholangiocarcinoma in terms of lymph node dissection.

BACKGROUND: Although many guidelines recommend performing lymph node dissection (LND) during surgery for intrahepatic cholangiocarcinoma (ICC), there is no evidence for patients with incidentally detected ICC who did not undergo LND. This study aimed to identify the role of LND in patients with incidental ICC. METHODS: The data from 284 patients who had undergone radical surgery for ICC from 2000 to 2020 were retrospectively reviewed. The enrolled patients were divided into 3 groups according to their T stage (T1 vs T2 vs T3 + 4). Moreover, the patients of each T group were divided into 3 groups according to their nodal status (N0 vs N1 vs Nx) and their survival outcomes were compared. RESULTS: Survival outcomes of Nx group were statistically similar to that of N0 group in T1 stage (Nx vs N0: disease-free survival [DFS] [months], 129.0 [75.6-182.4] vs 125.0 [65.7-184.3], P = .948; overall survival [OS] [months], 175.0 [153.9-196.1] vs 173.0 [109.0-237.0], P = .443). In contrast, survival outcomes of Nx group in the other T stage (T2 and T3 + 4) were poorer than that of N0 group and were better than that of N1 group. In addition, in the Nx subgroup analysis according to T stage, T1 group showed significantly better survival outcomes than the other groups (T1 vs T2 vs T3 + 4: DFS [months], 129.0 [75.9-182.1] vs 16.0 [9.8-22.2] vs 13.0 [0.3-25.7], P < .001; OS [months], 175.0 [153.9-196.1] vs 53.0 [30.8-75.2] vs 37.0 [17.6-56.4], P < .001). CONCLUSION: Patients with ICC incidentally diagnosed as having T2 or above T stage may consider additional LND.

Associations among the workplace violence, burnout, depressive symptoms, suicidality, and turnover intention in training physicians: a network analysis of nationwide survey.

Depression and anxiety are the most common mental disorders among physicians, who have a greater risk of suicide than those in other professional occupations. Relationships among a demanding workload, workplace violence, burnout, and intention to turnover have also been reported. The current study examined the principal components and propagating patterns of mental health and working environment interactions in training physicians. A total of 1981 training physicians completed online self-report questionnaires during September-October (midpoint of the training year) 2020. Regularized partial correlations in a mixed graphical model (MGM) and joint probability distributions (directed acyclic graph; DAG) were estimated for four subtypes of workplace violence (verbal abuse/physical violence perpetrated by clients/hospital staff), three burnout subdomains (Maslach Burnout Inventory), thoughts about quitting, and nine depressive symptoms, including suicidality, comprising the DSM-5 diagnostic criteria for major depressive disorder (assessed using the Patient Health Questionnaire-9). Thoughts of death/self-harm showed directional dependencies on the joint probability distributions of psychomotor agitation/retardation, concentration difficulty, self-reproach, and sadness in the DAG. In the MGM, a partial correlation with psychomotor agitation/retardation (r = 0.196) accounted for 56.5% of the variance in thoughts of death/self-harm. Partial correlations with concentration difficulties (r = 0.294), self-reproach (r = 0.257), changes in appetite (r = 0.184), and worker-on-worker physical violence (r = 0.240) in the MGM accounted for 54.4% of the variance in psychomotor agitation/retardation. Thoughts about quitting were partially correlated with and dependent upon the joint probability distributions of emotional exhaustion (r = 0.222), fatigue (r = 0.142), anhedonia (r = 0.178), and sadness (r = 0.237). In contrast, worker-on-worker (r = 0.417) and client-on-physician (r = 0.167) verbal abuse had regularized partial correlations with directional dependencies on thoughts about quitting. Organization-level interventions aiming to reduce the worker-on-worker violence and individual-level approaches of clinical screening program and psychiatric counseling clinic are required. Follow-up studies to verify the effectiveness of these interventions for training physicians are needed.

The novel use and feasibility of hemostatic oxidized regenerated cellulose agent (SurgiGuard®): multicenter retrospective study.

Background: SurgiGuard® is an absorbent hemostatic agent based on oxidized regenerated cellulose. The efficacy, effects and safety of SurgiGuard® are equivalent to existing hemostatic agents in animal experiments. This study was designed to confirm that the use of SurgiGuard® alone is effective, safe and feasible compared to combination with other hemostatic methods. Methods: We retrospectively reviewed clinical data from 12 surgery departments in seven tertiary centers in South Korea nationwide. All surgeries were performed between January and December 2018. Results: A total of 807 patients were enrolled; 447 patients (55.4%) had comorbidities. The rate of major surgery (operative time ≥4 hours) was 44% (n=355 patients). Regarding the type of SurgiGuard® used in surgery, more than 70% of minor surgeries used non-woven types. In major surgery, more than five SurgiGuards® were used in 7.3% (26 patients), and the proportion of co-usage (with four other hemostatic products) was 19.7% (70 patients). The effectiveness score was higher when SurgiGuard® was used alone in both major (5.3±0.5 vs. 5.1±0.6, P=0.048) and minor surgery (5.4±0.6 vs. 5.2±0.4, P<0.001). Seven patients had immediate re-bleeding, and all of them used SurgiGuard® and other products together. Nine patients reported adverse effects, such as abscess, bleeding, or leg swelling, but we found no direct correlation with SurgiGuard®. Conclusions: SurgiGuard® exhibited greater effectiveness when used alone. No direct adverse effects associated with SurgiGuard® use were reported, and SurgiGuard® had stable feasibility. Prospective comparative studies are needed in the future.

Gorlin-Goltz Syndrome: A Case Report and Literature Review with PTCH1 Gene Sequencing.

Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is an autosomal dominant disease characterized by multisystemic developmental defects caused by pathogenic variants such as patched-1 ( PTCH1 ) gene variants and/or SUFU gene variants. The presence of either two main criteria or one major and two minor criteria are required for the diagnosis of Gorlin-Goltz syndrome. Recently, a major criterion for molecular confirmation has also been proposed. In this article, we report the case of an 80-year-old male who was admitted at our department for multiple brown-to-black papules and plaques on the entire body. He was diagnosed with Gorlin-Goltz syndrome with clinical, radiologic, and pathologic findings. While the diagnosis was made based on the clinical findings in general, confirmation of the genetic variants makes an ideal diagnosis and suggests a new treatment method for target therapy. We requested a genetic test of PTCH1 to ideally identify the molecular confirmation in the hedgehog signaling pathway. However, no pathogenic variants were found in the coding region of PTCH1, and no molecular confirmation was achieved.

Preoperative Fistula Risk Prediction Using Computed Tomography Image Before Pancreatoduodenectomy.

BACKGROUND: Although many formulas for predicting postoperative pancreatic fistula (POPF) have been introduced, POPF is generally predicted during pancreatic surgery due to pancreatic texture. This study was designed to verify the correlation between Hounsfield units (HU) and pancreatic texture and to suggest a fistula risk score (FRS) that can be used before surgery. METHODS: Data from 545 patients who underwent pancreatoduodenectomy for malignant disease between January 2008 and December 2019 were retrospectively reviewed. The HU level of the pancreas was measured, and odds ratio (OR) of the HU for POPF was analyzed. Additionally, the assessed HU was compared with the pancreatic texture (soft vs. hard) and calculated cutoff level. Finally, the preoperatively chosen pancreatic texture according to HU level was applied to the FRS formula (preoperative-FRS: p-FRS), and the results were compared with a previously reported FRS formula (updated alternative-FRS: ua-FRS). RESULTS: The Hounsfield unit levels were correlated with clinically relevant POPF (CR-POPF) (odds ratio [OR]: 1.04 (1.01-1.07), p = 0.015). In the receiver operating characteristic curve, the HU showed significant prediction potential for pancreatic texture (area under the curve [AUC]: 0.744, p < 0.001). The p-FRS also showed acceptable results in predicting CR-POPF (AUC = 0.702, p < 0.001). There was no statistically significant difference in the DeLong's test compared with the ua-FRS (p = 0.314). In the Hosmer-Lemeshow test, observed probabilities were correlated with predicted probabilities (p = 0.596). CONCLUSIONS: The HU level on preoperative computed tomography (CT) is a predictive factor for POPF and could represent for pancreatic texture.

Effect of local treatment in patients with oligo-recurrence after surgery of distal bile duct cancer: A bi-institutional study.

BACKGROUND: Distal extrahepatic bile duct (EHBD) cancer is highly recurrent. More than 50% of patients suffer from disease relapse after curative resection. Some patients present with oligo-recurrence which could be a single loco-regional mass or lesions limited to a single solid organ. The aim of this study was to examine the effect of local control (surgical resection or radiofrequency ablation) on survival outcomes in patients with oligo-recurrent distal EHBD cancer. METHODS: Data of 1219 patients who underwent surgery for distal EHBD cancer from 2000 to 2018 were retrospectively reviewed. Clinicopathological characteristics and survival outcomes of patients with recurrence were investigated. Post-recurrence survival (PRS) was analyzed according to modalities of re-treatment (local treatment or systemic therapy alone). RESULTS: Among 654 patients with recurrence, 90 patients who had oligo-recurrence showed better recurrence-free and overall survival than patients with non-oligo-recurrent disease. Lymph node ratio and perineural invasion at initial pathology, timing of recurrence, and platelet-to-lymphocyte ratio at recurrence were independent risk factors for PRS in the oligo-recurrent group. Patients with local treatment for oligo-recurrence had better 3- and 5-year PRS than those with systemic treatment alone (38.3% vs. 14.1%, p = 0.04; 28.3% vs. 7.1%, p = 0.04, respectively). Recurrence within 24 months after initial surgery was the only significant factor for PRS in the local treatment group. CONCLUSION: In patients with oligo-recurrence after resection of distal EHBD cancer, post-recurrence local treatment could improve survival outcomes, particularly for those with recurrence more than 2 years after initial resection.

Validation of quantitative prognostic prediction using ADV score for resection of hepatocellular carcinoma: A Korea-Japan collaborative study with 9200 patients.

BACKGROUND: A score derived from the concentrations of α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) and tumor volume (TV), called ADV score, has been shown to be prognostic of hepatocellular carcinoma (HCC) recurrence following hepatic resection (HR) or liver transplantation. METHODS: This multicenter, multinational validation study included 9200 patients who underwent HR from 2010 to 2017 at 10 Korean and 73 Japanese centers, and were followed up until 2020. RESULTS: AFP, DCP, and TV showed weak correlations (ρ ≤ .463, r ≤ .189, p < .001). Disease-free survival (DFS), overall survival (OS), and post-recurrence survival rates were dependent on 1.0 log and 2.0 log intervals of ADV scores (p < .001). Receiver operating characteristic (ROC) curve analysis showed that ADV score cutoffs of 5.0 log for DFS and OS yielded the areas under the curve ≥ .577, with both being significantly prognostic of tumor recurrence and patient mortality at 3 years. ADV score cutoffs of ADV 4.0 log and 8.0 log, derived through K-adaptive partitioning method, showed higher prognostic contrasts in DFS and OS. ROC curve analysis showed that an ADV score cutoff of 4.2 log was suggestive of microvascular invasion, with both microvascular invasion and an ADV score cutoff of 4.2 log showing similar DFS rates. CONCLUSIONS: This international validation study demonstrated that ADV score is an integrated surrogate biomarker for post-resection prognosis of HCC. Prognostic prediction using ADV score can provide reliable information that can assist in planning treatment of patients with different stages of HCC and guide individualized post-resection follow-up based on the relative risk of HCC recurrence.

Left-sided Hepatectomy Leads to Less Postoperative Liver Failure and Comparable Overall Survival to Right-sided Hepatectomy in Type II or IV Perihilar Cholangiocarcinoma.

INTRODUCTION: Right-side hepatectomy (RH) is used in oncological resection for perihilar cholangiocarcinoma (PHC); however, the decision between performing left-side hepatectomy (LH) or RH is still controversial. We compared surgical and oncologic outcomes of LH and RH in PHC type II or IV where either hepatectomy was expected to have a negative margin. METHODS: From 2001 to 2020, 99 patients underwent major liver resection for type II or IV PHC. Patients with unilateral vascular invasion, unilateral tumor growth, and atrophy of unilateral liver were excluded. Preoperative characteristics, perioperative, and long-term outcomes were compared between the remaining RH and LH patients. RESULTS: After excluding 47 cases with side predominance, the RH group (n = 29) and LH group (n = 23) were compared. Clinical characteristics and disease severity did not differ between the groups. Portal vein embolization (RH: 48.3% vs. LH: 0.0%, p < 0.001) and days from diagnosis to operation (RH: 31.0 ± 16.2 vs. LH: 18.8 ± 13.4, p = 0.006) were significantly higher in the RH group. The RH group had statistically higher rate of postoperative hepatic failure (RH: 55.2% vs. LH: 21.7%, p = 0.015) and a higher mortality rate that was not significant (RH: 13.8% vs. LH: 0%, p = 0.120). The R0 resection rate (RH: 72.4% vs. LH: 78.3%, p = 0.629), median disease-free (p = 0.620), and overall (p = 0.487) survival did not differ between groups. R1 resection and lymph node metastasis were significant risk factors for disease-free survival in multivariate analysis. CONCLUSIONS: In type II or type IV PHC where either LH or RH was feasible, LH provided a shorter period of preoperative preparation, lower postoperative hepatic failure rate, similar R0 rate, and comparable long-term outcomes. LH should be considered a reasonable option in type II or IV PHC.

Risk factors for prolonged hospitalization and delayed treatment completion after laparoscopic appendectomy in patients with uncomplicated acute appendicitis.

PURPOSE: We sought to identify the risk factors for prolonged hospitalization and delayed treatment completion after laparoscopic appendectomy in patients with uncomplicated acute appendicitis. METHODS: The study retrospectively analyzed 497 patients who underwent laparoscopic appendectomies for uncomplicated appendicitis between January 2018 and December 2020. The patients were divided into an early discharge group (≤2 days) and a late discharge group (>2 days) based on the length of hospital stay (LOS). The patients were also divided into uneventful and complicated groups according to the need for additional treatment after standard follow-up. RESULTS: Thirty-seven patients (7.4%) were included in the late discharge group. The mean LOS of the late discharge groups was 3.9 days. There were significant differences according to age, preoperative C-reactive protein (CRP), and operative time between the 2 groups. Only operative time was significantly associated with prolonged LOS in multivariate analysis. Thirty-five patients (7.0%) were included in the complicated group. The mean duration of treatment in the uneventful and complicated groups was 7.4 and 25.3 days, respectively. Significant differences existed between the uneventful and complicated groups in preoperative body temperature, preoperative CRP levels, maximal appendix diameter, and the presence of appendicoliths. In multivariate analysis, preoperative CRP levels and maximal appendix diameter were independent predictors of delayed treatment completion. CONCLUSION: Shorter operative time is desirable to ensure minimal hospital stay in patients with uncomplicated appendicitis. Further efforts are needed to ensure that patients with uncomplicated appendicitis do not experience delayed treatment completion after laparoscopic appendectomies.

The prognostic value of the number of metastatic lymph nodes on the long-term survival of intrahepatic cholangiocarcinoma using the SEER database.

Background: In the 8th edition of the American Joint Committee on Cancer, the nodal staging of intrahepatic cholangiocarcinoma (ICC) is classified as N0 and N1 in accordance with lymph node (LN) metastases. Recently, several studies have reported that the number of metastatic LNs is associated with prognosis in patients with ICC. However, the majority of these studies were published in Eastern countries, and there are few available data for Western countries. This study aimed to investigate the association between metastatic LN number and prognosis in ICC patients using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Data from 658 ICC patients in the SEER database who underwent hepatectomy with LN dissection from 2000 to 2018 were retrospectively reviewed. Hazard ratios (HRs) according to increasing numbers of metastatic LN were calculated. The patients were then divided into three groups according to their metastatic LN numbers (N0: no metastatic LNs; N+ <4: 1-3 metastatic LNs; N+ ≥4: ≥4 metastatic LNs), and cause-specific survival (CSS) was compared. Results: Metastatic LN number was a prognostic factor of oncologic survival [CSS: HR =1.300; 95% confidence interval (CI): 1.225-1.379; P<0.001]. In survival analysis, an increasing number of metastatic LNs was significantly correlated with poorer oncologic outcomes [CSS: N0 vs. N+ <4 vs. N+ ≥4: 40.856 (95% CI: 38.806-42.919) vs. 22.000 (95% CI: 18.283-25.717) vs. 15.000 (95% CI: 11.520-18.480) months, P<0.001]. In post hoc analysis, a significant difference was found between adjacent groups (N0 vs. N+ <4, P<0.001; N+ <4 vs. N+ ≥4, P=0.004). Conclusions: Patients with ICC in the SEER database were reaffirmed to have worse prognosis with an increasing number of metastatic LNs.

Effectiveness of Acupuncture, Mind and Body Practices, and Natural Products for Insomnia: an overview of systematic reviews.

Objectives: This overview summarizes the evidence for the effectiveness and safety of complementary therapies for insomnia through systematic reviews (SRs) and meta-analyses (MAs). Methods: A comprehensive literature search on SRs and MAs for complementary therapies for insomnia was conducted using six databases. Results: This overview included 30 SRs/MAs. The Pittsburgh Sleep Quality Index (PSQI) analysis of insomnia included 383 randomized controlled trials and 31,748 participants. Twenty-four SRs/MAs (80%) out of 30 SRs/MAs reported a positive result, and six SRs/MAs reported a partially positive result. The most frequently used form of acupuncture reported a positive effect in 89.5% (17/19) of SRs/MAs and a superior effect to western medicine, sham/placebo, and no treatment. The lack of protocol registration and the excluded studies list resulted in generally poor methodological and reporting quality in SRs/MAs with AMSTAR 2. Conclusion: This overview confirmed that complementary therapies positively affected the PSQI scores in patients with insomnia. However, better-designed primary studies are needed to strengthen the relevant evidence in the future. A more stringent assessment of multiple systematic reviews 2 must be followed when performing SR and MA.

Extracellular Citrate Treatment Induces HIF1α Degradation and Inhibits the Growth of Low-Glycolytic Hepatocellular Carcinoma under Hypoxia.

HCC is well known for low glycolysis in the tumors, whereas hypoxia induces glycolytic phenotype and tumor progression. This study was conducted to evaluate the expression of SLCs in human HCCs and investigated whether extracellular nutrient administration related to SLCs in low-glycolytic HCC can prevent hypoxic tumor progression. SLCs expression was screened according to the level of glycolysis in HCCs. Then, whether extracellular nutrient treatment can affect hypoxic tumor progression, as well as the mechanisms, were evaluated in an in vitro cell line and an in vivo animal model. Low-glycolytic HCCs showed high SLC13A5/NaCT and SLC16A1/MCT1 but low SLC2A1/GLUT1 and HIF1α/HIF1α expression. Especially, high SLC13A5 expression was significantly associated with good overall survival in the Cancer Genome Atlas (TCGA) database. In HepG2 cells with the highest NaCT expression, extracellular citrate treatment upon hypoxia induced HIF1α degradation, which led to reduced glycolysis and cellular proliferation. Finally, in HepG2-animal models, the citrate-treated group showed smaller tumor with less hypoxic areas than the vehicle-treated group. In patients with HCC, SLC13A5/NaCT is an important SLC, which is associated with low glycolysis and good prognosis. Extracellular citrate treatment induced the failure of metabolic adaptation to hypoxia and tumor growth inhibition, which can be a potential therapeutic strategy in HCCs.

Anti-Cancer Effects of YAP Inhibitor (CA3) in Combination with Sorafenib against Hepatocellular Carcinoma (HCC) in Patient-Derived Multicellular Tumor Spheroid Models (MCTS).

PURPOSE: To assess the expression levels of YAP and TAZ in patient-derived HCC tissue and identify the effects of YAP/TAZ inhibition depending on the baseline YAP/TAZ expression when combined with sorafenib using a patient-derived multicellular tumor spheroid (MCTS) model. METHODS: Primary HCC cell lines were established from patient-derived tissue. Six patient-derived HCC cell lines were selected according to YAP/TAZ expression on Western blot: high, medium, low. Then, MCTS was generated by mixing patient-derived HCC cells and stroma cells (LX2, WI38, and HUVECs) and YAP/TAZ expression was assessed using Western blot. Cell viability of MCTS upon 48 h of drug treatment (sorafenib, sorafenib with CA3 0.1 µM, and CA3 (novel YAP1 inhibitor)) was analyzed. RESULTS: Out of six patient-derived HCC cell lines, cell lines with high YAP/TAZ expression at the MCTS level responded more sensitively to the combination therapy (Sorafenib + CA3 0.1 µM) despite the potent cytotoxic effect of CA3 exhibited in all of the patient-derived HCCs. CONCLUSION: Targeting YAP/TAZ inhibition using the novel YAP1 inhibitor CA3 could be a promising therapeutic strategy to enhance sensitivity to sorafenib especially in HCCs with high YAP/TAZ expression in MCTS.

Impact of Exogenous Treatment with Histidine on Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Sorafenib, a multi-kinase inhibitor, is the first-line therapy for advanced HCC. However, long-term exposure to sorafenib often results in reduced sensitivity and the development of resistance. Although various amino acids have been shown to contribute to cancer initiation and progression, little is known about the effects of histidine, a dietary essential amino acid that is partially taken up via histidine/large neutral amino acid transporter (LAT1), on cancer cells. In this study, we evaluated the effects of histidine on HCC cells and sensitivity to sorafenib. Remarkably, we found that exogenous histidine treatment induced a reduction in the expression of tumor markers related to glycolysis (GLUT1 and HK2), inflammation (STAT3), angiogenesis (VEGFB and VEGFC), and stem cells (CD133). In addition, LAT1 expression was downregulated in HCC tumor regions with high expression of GLUT1, CD133, and pSTAT3, which are known to induce sorafenib resistance. Finally, we demonstrated that combined treatment with sorafenib and histidine could be a novel therapeutic strategy to enhance the sensitivity to sorafenib, thereby improving long-term survival in HCC.

Laparoscopic Minor Liver Resections for Hepatocellular Carcinoma in the Posterosuperior Segments Using the Rubber Band Technique.

BACKGROUND: Although laparoscopic minor liver resections (LLR) of posterosuperior (PS) segments are technically challenging, several expert centers are increasingly performing this procedure. In the present study, we introduced novel techniques, including the rubber band traction method and positional changes, and compared surgical outcomes of LLR for hepatocellular carcinoma (HCC) located in PS segments with open minor liver resection (OLR). METHODS: From January 2008 to August 2019, 113 patients underwent laparoscopic (n = 55) or open (n = 58) minor liver resections for single small HCCs (<5 cm) located in PS segments. Propensity score matching in a 1:1 ratio was conducted to minimize preoperative selection bias, and surgical outcomes were compared between the two groups. RESULTS: There was no intraoperative mortality or reoperation in either group. One conversion to open surgery was necessary due to severe post-operative adhesions. The matched LLR group compared to OLR had significantly shorter operative time (215.16 vs. 251.41 min, P = 0.025), lesser blood loss (218.11 vs. 358.92 mL, P = 0.046), lower complication rate (8.1% vs. 29.7%, P = 0.018), and shorter hospital stay (7.03 vs. 11.78 days, P = 0.001). Intraoperative transfusion, R0 resection, resection margin, 5-year disease-free survival and 5-year overall survival were comparable. CONCLUSION: Our standardized LLR provided improved short-term outcomes and similar long-term outcomes, when compared with OLR. With advanced techniques and accumulated surgical experience, LLR can be the first option for HCC in PS segments at expert centers.

Prognostic impact of the metastatic lymph node number in intrahepatic cholangiocarcinoma.

BACKGROUND: Lymph node metastasis in intrahepatic cholangiocarcinoma is a poor prognostic factor after radical surgery. However, unlike other biliary tract malignancies, the nodal stage of intrahepatic cholangiocarcinoma only reflects the presence of metastatic lymph nodes, not the number of metastatic lymph nodes. This study aimed to identify the prognostic impact of the metastatic lymph node number in intrahepatic cholangiocarcinoma. METHODS: The data from 87 patients with intrahepatic cholangiocarcinoma who had undergone hepatectomy with 5 or more harvested lymph nodes and covering stations 12 and 8 based on the previous criteria from January 2006 to December 2019 were retrospectively reviewed. The hazard ratio according to the increasing metastatic lymph node number was calculated with other known prognostic factors for intrahepatic cholangiocarcinoma. The patients were then divided into 3 groups according to the metastatic lymph node number (N0 [n = 45]: no metastatic lymph nodes; N+ <4 [n = 32]: 1 to 3 metastatic lymph nodes; N+ ≥4 [n = 10]: ≥4 metastatic lymph nodes). Disease-free survival and overall survival were also analyzed. RESULTS: The metastatic lymph node number was a prognostic factor of oncologic survival (disease-free survival: hazard ratio = 1.18 [1.05-1.32], P = .005; overall survival: hazard ratio = 1.21 [1.06-1.37], P = .004). Survival analysis revealed significantly poorer outcomes with an increasing metastatic lymph node number (disease-free survival: N0 vs N+ <4 vs N+ ≥4: 36.0 [0.0-76.0] vs 8.0 [0.0-16.9] vs 2.0 [0.0-5.1] months, P < .001; overall survival: N0 vs N+ <4 vs N+ ≥4: 69.0 [24.5-113.5] vs 28.0 [18.9-37.1] vs 11.0 [6.4-15.6] months, P < .001). In post hoc analysis, a significant difference was found between adjacent groups (disease-free survival and overall survival: N+ <4 vs N+ ≥4, P = .001). CONCLUSION: With proper lymph node dissection, the number of metastatic lymph nodes is a prognostic factor of intrahepatic cholangiocarcinoma.