The impact of contour maps on estimating the risk of gastrointestinal stromal tumor recurrence: indications for adjuvant therapy: an analysis of the Kinki GIST registry.

INTRODUCTION: Contour maps enable risk classification of GIST recurrence in individual patients within 10 postoperative years. Although contour maps have been referred to in Japanese guidelines, their usefulness and role in determining indications for adjuvant therapy is still unclear in Japanese patients. The aims of this study are to investigate the validity of contour maps in Japanese patients with GIST and explore the new strategy for adjuvant therapy. MATERIALS AND METHODS: A total of 1426 Japanese GIST patients who were registered to the registry by the Kinki GIST Study Group between 2003 and 2012 were analyzed. Patients who had R0 surgery without perioperative therapy were included in this study. The accuracy of contour maps was validated. RESULTS: Overall, 994 patients have concluded this study. Using contour maps, we validated the patients. The 5-year recurrence-free survival rates of patients within the GIST classification groups of 0-10%, 10-20%, 20-40%, 40-60%, 60-80%, 80-90%, and 90-100% were 98.1%, 96.6%, 92.3%, 48.0%, 37.3%, 41.0% and 42.4%, respectively. We confirmed that this classification by contour maps was well reflected recurrence prediction. Further, in the high-risk group stratified by the modified National Institutes of Health consensus criteria (m-NIHC), the 10-year RFS rate was remarkably changed at a cutoff of 40% (0-40% group vs. 40-100% group: 88.7% vs. 50.3%, p < 0.001). CONCLUSION: Contour maps are effective in predicting individual recurrence rates. And it may be useful for the decision of individual strategy for high-risk patients combined with m-NIHC.

Laparoscopic and open minor liver resection for hepatocellular carcinoma with clinically significant portal hypertension: a multicenter study using inverse probability weighting approach.

BACKGROUND: Liver resection offers substantial advantages over open liver resection (OLR) for patients with hepatocellular carcinoma (HCC) in terms of reduced intraoperative blood loss and morbidity. However, there is limited evidence comparing the indications and perioperative outcomes with the open versus laparoscopic approach for resection. This study aimed to compare postoperative outcomes between patients undergoing laparoscopic liver resection (LLR) and OLR for HCC with clinically significant portal hypertension (CSPH). METHODS: A total of 316 HCC patients with CSPH (the presence of gastroesophageal varices or platelet count < 100,000/ml and spleen diameter > 12 cm) undergoing minor liver resection at eight centers were included in this study. To adjust for confounding factors between the LLR and OLR groups, an inverse probability weighting method analysis was performed. RESULTS: Overall, 193 patients underwent LLR and 123 underwent OLR. After weighting, LLR was associated with a lower volume of intraoperative blood loss and the incidence of postoperative complications (including pulmonary complications, incisional surgical site infection, and paralytic ileus) compared to the OLR group. The 3-, 5-, and 7-year postoperative recurrence-free survival rates were 39%, 26%, and 22% in the LLR group and 49%, 18%, and 18% in the OLR group, respectively (p = 0.18). And, the 3-, 5-, and 7-year postoperative overall survival rates were 71%, 56%, and 44% in the LLR group and 76%, 51%, 44% in the OLR group, respectively (p = 0.87). CONCLUSIONS: LLR for HCC patients with CSPH is clinically advantageous by lowering the volume of intraoperative blood loss and incidence of postoperative complications, thereby offering feasible long-term survival.

The prevalence and risk factors associated with zinc deficiency after pancreatic surgery.

PURPOSE: To clarify the prevalence, risk factors, and clinical implications associated with zinc deficiency in patients undergoing pancreatic surgery. METHODS: The serum zinc levels were measured in 329 patients post-pancreatic surgery between January and April 2021. The postoperative serum zinc levels and clinicopathological variables were retrospectively analyzed. RESULTS: The median serum zinc level was 73 µg/dL (33-218). Zinc deficiency (zinc level < 60 µg/dL) was observed in 52 patients (16%). A total of 329 patients were classified into zinc-deficient (n = 52) and non-deficient (zinc ≥ 60 µg/dL, n = 277) groups. A univariate analysis revealed significant differences in sex, postoperative body mass index, serum albumin, total cholesterol, creatinine, aspartate aminotransferase (AST), HbA1c levels, diabetes, surgical procedures, and operative blood loss. According to a multivariate analysis, male sex [odds ratio (OR) 3.70; 95% confidence interval (CI) 1.67-8.20; p = 0.001], postoperative serum albumin levels < 3.9 g/dL (OR 6.39; 95% CI 3.30-12.37; p < 0.001), postoperative serum AST ≥ 51 U/L (OR, 4.6; 95% CI 0.07-0.29; p < 0.001), and total pancreatectomy (OR 3.68; 95% CI 1.37-9.85; p = 0.009) were found to be independent predictors of zinc deficiency after pancreatic surgery. CONCLUSIONS: Zinc deficiency frequently occurs in patients undergoing pancreatic surgery. Lower postoperative zinc levels could be linked to sex, the serum albumin and AST levels, and surgery type.

The Prognostic Value of Preoperative Serum Markers and Risk Classification in Patients with Hepatocellular Carcinoma.

BACKGROUND: Complex hepatocellular carcinoma (HCC) prognostic biomarkers have been reported in various studies. We aimed to establish biomarkers that could predict prognosis, and formulate a simple classification using non-invasive preoperative blood test data. METHODS: We retrospectively identified 305 patients for a discovery cohort who had undergone HCC-related hepatectomy at four Japanese university hospitals between January 1, 2011 and December 31, 2013. Preoperative blood test parameter optimal cut-off values were determined using receiver operating characteristic curve analysis. Cox uni- and multivariate analyses were used to determine independent prognostic factors. Risk classifications were established using classification and regression tree (CART) analysis. Validation was performed with 267 patients from three other hospitals. RESULTS: In multivariate analysis, α-fetoprotein (AFP, p < 0.001), protein induced by vitamin K absence or antagonist-II (PIVKA-II, p = 0.006), and C-reactive protein (CRP, p < 0.001) were independent prognostic factors for overall survival (OS). AFP (p = 0.007), total bilirubin (p = 0.001), and CRP (p = 0.003) were independent recurrent risk factors for recurrence-free survival (RFS). CART analysis results formed OS (CRP, AFP, and albumin) and RFS (PIVKA-II, CRP, and total bilirubin) decision trees, based on machine learning using preoperative serum markers, with three risk classifications. Five-year OS (low risk, 80.0%; moderate risk, 56.3%; high risk, 25.2%; p < 0.001) and RFS (low risk, 43.4%; moderate risk, 30.8%; high risk, 16.6%; p < 0.001) risks differed significantly. These classifications also stratified OS and RFS risk in the validation cohort. CONCLUSION: Three simple risk classifications using preoperative non-invasive prognostic factors could predict prognosis.

Gastrectomy reduces pancreatic secretory function via pancreatic atrophy.

PURPOSE: Although reports suggest that the pancreatic volume decreases after gastrectomy for gastric cancer, the relationship between the pancreatic volume and secretory function after gastrectomy remains unclear. In this study, we examined the relationship between the pancreatic volume and exocrine and endocrine functions after total gastrectomy. METHODS: The pancreatic volumes of 18 distal gastrectomy and 15 total gastrectomy patients were retrospectively measured using computed tomography volumetry up to 5 years postoperatively. Ten low anterior resection patients were selected as controls. In addition, the pancreatic volume and exocrine function evaluated by fecal elastase and the insulin secretory function evaluated by glucagon tolerance testing were prospectively examined before and one year after surgery in nine cases of total gastrectomy. RESULTS: After low anterior resection, the pancreatic volume did not change, but after distal and total gastrectomy, the pancreatic volume decreased continuously until the fifth year. After total gastrectomy, fecal elastase decreased significantly from 865.8 µg/g to 603.2 µg/g in the first year (p = 0.0316), and the insulin secretion capacity also decreased significantly from 3.83 ng/mL to 2.26 ng/mL (p = 0.0019). CONCLUSIONS: The pancreatic volume decreases continuously after gastrectomy for gastric cancer, and the pancreatic exocrine and endocrine functions decrease along with pancreatic atrophy after total gastrectomy.

Efficacy of Anterior Quadratus Lumborum Block and Pain After Total Hip Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: Anterior quadratus lumborum block (AQLB) is one of the compartment blocks and has recently attracted attention as a new method of analgesia for postoperative hip surgery analgesia. This study aimed to compare the analgesic efficacy of AQLB in patients undergoing primary total hip arthroplasty (THA). METHODS: There were 120 patients undergoing primary THA under general anesthesia randomly allocated to receive a femoral nerve block (FNB) or an AQLB. The primary outcome was total morphine consumption over the initial 24-hour postoperative period. Secondary outcomes included the pain score evaluation while at rest and during active and passive motion over the 2 days following surgery and the manual muscle testing of the quadriceps femoris. The numerical rating scale (NRS) score was used for evaluating the postoperative pain score. RESULTS: There were no significant differences between the 2 groups concerning morphine consumption within 24 hours after surgery (P = .72). The NRS score at rest and passive motion were similar at all-time points (P > .05). However, there was a statistically significant difference in pain reported during the active motion for the FNB group compared to the AQLB (P = .04). No significant differences were found between the 2 groups concerning muscle weakness incidence. CONCLUSION: Both AQLB and FNB demonstrated adequate efficacy for postoperative analgesia at rest in THA. However, based on our study, whether AQLB is inferior or noninferior to FNB as an analgesic method for THA was inconclusive.

Utility of contrast-enhanced harmonic endoscopic ultrasonography for T-staging of patients with extrahepatic bile duct cancer.

BACKGROUND: The value of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for T-staging in patients with extrahepatic bile duct cancer was evaluated. METHODS: This single-center, retrospective study included consecutive patients with extrahepatic bile duct cancer who underwent surgical resection after preoperative EUS, CH-EUS, and contrast-enhanced CT (CE-CT) examinations between June 2014 and August 2017. The capacity of these modalities for T-staging of extrahepatic bile duct cancer was evaluated by assessing invasion beyond the biliary wall into the surrounding tissue, gallbladder, liver, pancreas, duodenum, portal vein system (portal vein and/or superior mesenteric vein), inferior vena cava, and hepatic arteries (proper hepatic artery, right. and/or left. hepatic artery). Blind reading of EUS, CH-EUS, and CE-CT images was performed by two expert reviewers each. RESULTS: 38 patients were eligible for analysis, of which eight had perihilar bile duct cancer and 30 had distal bile duct cancer. Postoperative T-staging was T1 in 6, T2 in 16, and T3 in 16 cases. CH-EUS was superior to CE-CT for diagnosing invasion beyond the biliary wall into surrounding tissue (92.1% vs. 45.9%, P = 0.0002); the ability to detect invasion to other organs did not differ significantly between the two modalities. The accuracy of CH-EUS for T-staging of tumors was better than that of CE-CT (73.7% vs. 39.5%, P = 0.0059). CH-EUS tended to have a better accuracy than EUS for the diagnosis of invasion beyond the biliary wall into the surrounding tissue (92.1% vs. 78.9%, P = 0.074) and T-staging (73.7% vs. 60.5%, P = 0.074). CONCLUSION: CH-EUS is useful for T-staging of extra hepatic bile duct cancer, especially in terms of invasion beyond the biliary wall into the surrounding tissue.

Gamma-Glutamylcysteine Production Using Phytochelatin Synthase-Like Enzyme Derived from Nostoc sp. Covalently Immobilized on a Cellulose Carrier.

Gamma-glutamylcysteine (γ-EC) is an intermediate generated in the de novo synthesis of glutathione (GSH). Recent studies have revealed that the administration of γ-EC shows neuroprotective effects against oxidative stress in age-related disorders and chronic diseases like Alzhiemer's disease in model animals, which is not expected function in GSH. A phytochelatin synthase-like enzyme derived from Nostoc sp. (NsPCS) mediates γ-EC synthesis from GSH. To achieve low-cost and stable commercial level supply, the availability of immobilized NsPCS for γ-EC production was investigated in this study. Among the tested immobilization techniques, covalent binding to the cellulose carrier was most effective, and could convert GSH completely to γ-EC without decreasing the yield. The stable conversion of γ-EC from 100 mM GSH was achieved by both batch repeated and continuous reactions using the immobilized NsPCS on cellulose sheet and column shape monolith, respectively. The immobilization of NsPCS on those carriers is promising alternative technique for high-yielding and cost-effective production of γ-EC on its commercial applications.

Treatment strategy for resectable colorectal cancer liver metastases from the viewpoint of time to surgical failure.

PURPOSE: The efficacy of pre or postoperative chemotherapy for resectable colorectal cancer liver metastases (CRLM) is disputed. This study aimed to examine the risk factors for time to surgical failure (TSF) and analyze the efficacy of pre or postoperative chemotherapy prior to liver resection for CRLM. METHODS: The clinicopathological factors of 567 patients who underwent initial hepatectomy for CRLM at 7 university hospitals between April 2007 and March 2013 were retrospectively analyzed. The prognostic factors were identified and then stratified into two groups according to the number of preoperative prognostic factors: the high-score group (H-group, score 2-4) and the low-score group (L-group, score 0 or 1). RESULTS: Patients who experienced unresectable recurrence within 12 months after initial treatment had a significantly shorter prognosis than other patients (p < 0.001). Multivariate analysis identified age ≥ 70 (p = 0.001), pT4 (p = 0.015), pN1 (p < 0.001), carbohydrate antigen 19-9 ≥ 37 U/ml (p = 0.002), Clavien-Dindo grade ≥ IIIa (p = 0.013), and postoperative chemotherapy (p = 0.006) as independent prognostic factors. In the H-group, patients who received chemotherapy had a better prognosis than those who did not (p = 0.001). CONCLUSION: Postoperative chemotherapy is beneficial in colorectal cancer patients with more than two of the following factors: age ≥ 70, carbohydrate antigen 19-9-positivity, pT4, and lymph node metastasis.

Efficacy of the slow firing method using a reinforced triple-row stapler for preventing postoperative pancreatic fistula during laparoscopic distal pancreatectomy.

PURPOSE: Postoperative pancreatic fistula (POPF) remains the most clinically relevant complication of laparoscopic distal pancreatectomy (LDP). The present study evaluated the efficacy of the "slow firing method" using a reinforced triple-row stapler (Covidien, Tokyo, Japan) during LDP. METHODS: This retrospective single-center study included 73 consecutive patients who underwent LDP using the slow firing method. A black cartridge was used in all patients. The primary endpoint was the rate of clinically relevant POPF (CR-POPF) after LDP. Secondary endpoints included perioperative outcomes and factors associated with CR-POPF as well as the correlation between the transection time and thickness of the pancreas. RESULTS: Four patients (5.5%) developed CR-POPF (grade B). Overall morbidity rates, defined as grade ≥ II and ≥ III according to the Clavien-Dindo classification, were 21 and 11%, respectively. The median postoperative hospital stay was 10 days. Preoperative diabetes (13.6 vs. 0.2%, P = 0.044) and thickness of the pancreas ≥ 15 mm (13.8% vs. 0%, P = 0.006) were identified as independent risk factors for CR-POPF. The median transection time was 16 (8-29) min. CONCLUSION: The slow firing method using a reinforced triple-row stapler for pancreatic transection is simple, safe, and effective for preventing CR-POPF after LDP.

Superiority of CRP-albumin-lymphocyte index (CALLY index) as a non-invasive prognostic biomarker after hepatectomy for hepatocellular carcinoma.

BACKGROUND: We aimed to investigate whether a novel biomarker incorporating albumin, lymphocytes, and CRP can predict the prognosis for hepatocellular carcinoma (HCC) after hepatectomy. METHODS: Between January 2011 and December 2013, 384 patients who underwent hepatectomy in four university hospitals in Japan were investigated as a discovery cohort. The CRP-Albumin-Lymphocyte (CALLY index) was defined as (Albumin × Lymphocyte)/(CRP × 104). Patients with a CALLY index ≥5 (n = 200) were compared to those with an index <5 (n = 184). Next, validation was performed using 267 patients from three other university hospitals (external validation cohort). RESULTS: The number of TNM Stage III and IV patients was significantly higher in the CALLY <5 group than the ≥5 group (p = 0.003). There was a significant difference in the 5-year survival rate (CALLY ≥5: 71% vs. <5: 46%; p < 0.001). Multivariate analysis identified the CALLY index as an independent factor of overall survival. Similarly, there was a significant difference in the 5-year survival rate between the CALLY ≥5 (73%) and <5 (48%) groups (p < 0.001), and the CALLY index was identified as an independent prognostic factor in the external validation cohort. CONCLUSION: The CALLY index derived from CRP, albumin, and lymphocyte values is a promising predictive biomarker for postoperative prognosis of patients with HCC.

Preoperative Risk Assessment for Loss of Independence Following Hepatic Resection in Elderly Patients: A Prospective Multicenter Study.

OBJECTIVE: To establish a preoperative risk assessment method for loss of independence after hepatic resection. SUMMARY BACKGROUND DATA: Hepatic resection often results in loss of independence in preoperatively self-sufficient elderly people. Elderly patients should therefore be carefully selected for surgery. METHODS: In this prospective, multicenter study, 347 independently-living patients aged ≥65 years, scheduled for hepatic resection, were divided into study (n = 232) and validation (n = 115) cohorts. We investigated the risk factors for postoperative loss of independence in the study cohort and verified our findings with the validation cohort. Loss of independence was defined as transfer to a rehabilitation facility, discharge to residence with home-based healthcare, 30-day readmission for poor functionality, and 90-day mortality (except for cancer-related deaths). RESULTS: In the study cohort, univariate and multivariate analyses indicated that frailty, age ≥ 76 years, and open surgery were independent risk factors for postoperative loss of independence. Proportions of patients with postoperative loss of independence in the study and validation cohorts were respectively 3.0% and 0% among those with no applicable risk factors, 8.1% and 12.5% among those with 1 applicable risk factor, 25.5% and 25.0% among those with 2 applicable risk factors, and 56.3% and 50.0% among those with all 3 factors applicable (P < 0.001 for both cohorts). Areas under the receiver operating characteristic curves for the study and validation groups were 0.777 and 0.783, respectively. CONCLUSIONS: Preoperative risk assessments using these 3 factors may be effective in predicting and planning for postoperative loss of independence after hepatic resection in elderly patients.

Conversion to open laparotomy during laparoscopic distal pancreatectomy: lessons from a single-center experience in 70 consecutive patients.

PURPOSE: The purpose of this study was to determine the factors influencing conversion from laparoscopic distal pancreatectomy (LDP) to open surgery, and the effect of such conversion on the outcome. METHODS: This retrospective single-center study included 70 consecutive patients undergoing LDP. The primary endpoint was the rate of conversion to open surgery during LDP. The secondary endpoints were determining the reasons for conversion to open surgery, with detailed analyses of these cases and a comparison of the surgical outcome with and without conversion. RESULTS: Seven patients (10%) required conversion to open surgery during LDP. Pancreatic ductal adenocarcinoma (PDAC) was identified as a risk factor for conversion (p = 0.010). The reasons for conversion included technical difficulty (two bleeding, one severe adhesion) and pancreatic stump-related issues (two margin-positive, two stapling failures). Although the overall morbidity rate (29 vs. 11%, p = 0.48) and the rate of clinically relevant postoperative pancreatic fistula (14 vs. 5%, p = 0.82) were no different for the patients with or without open conversion, the postoperative hospital stay was significantly longer in the former (median 15 vs. 10 days, p = 0.03). CONCLUSIONS: Careful preoperative assessment is required when planning LDP for PDAC. Although conversion to open surgery does not result in failure of LDP, efforts to reduce the duration of postoperative hospital stay and the occurrence of complications are desirable to improve the outcome of LDP.

Laparoscopic versus open liver resection for hepatocellular carcinoma in elderly patients: a multi-centre propensity score-based analysis.

BACKGROUND: The frequency of liver resection in elderly patients has been increasing. However, data are limited regarding the safety of laparoscopic liver resection (LLR) compared with that of open liver resection (OLR) for hepatocellular carcinoma (HCC) in elderly patients. The present study aimed to compare short-term outcomes between LLR and OLR in elderly patients with HCC using propensity score matching. METHODS: The study included 630 patients (age, ≥ 75 years) who underwent liver resection for HCC at nine liver centres between April 2010 and December 2017. Patients were divided into LLR and OLR groups, and perioperative outcomes were compared between the groups. In addition, subgroup analysis was performed according to age (75-79 and ≥ 80 years). RESULTS: Of the 630 patients, 221 and 409 were included in the LLR and OLR groups, respectively. After propensity score matching, 155 patients were included in each group. Intraoperative blood loss and the transfusion, post-operative overall complication and major complication rates were lower in the matched LLR than the matched OLR group (P < 0.001, P = 0.004, P < 0.001 and P < 0.001, respectively). Moreover, post-operative pulmonary and cardiovascular complications were less frequent in the matched LLR group (P = 0.008 and P = 0.014, respectively). In subgroup analysis, among octogenarians, the post-operative major complication rate was lower and hospital stay was shorter in the matched LLR than the matched OLR group (P < 0.001 and P < 0.001, respectively). CONCLUSION: LLR for HCC is associated with good short-term outcomes in patients aged ≥ 75 years compared with OLR. LLR is safe and feasible in selected octogenarians with HCC.

[A Case of Emergency Pancreaticoduodenectomy for Tumor Bleeding in Duodenal Cancer with Multiple Liver Metastases].

A 62 year-old female presenting with shortness of breath and severe anemia(Hb level 4.4 g/dL)was diagnosed with tumor bleeding and duodenal cancer by gastrointestinal endoscopy.Computed tomography scan revealed multiple liver metastases.After admission, the Hb level dropped from 9.1 g/dL to 5.1 g/dL in one night, and emergency pancreaticoduodenectomy( PD)was performed to control the bleeding.The postoperative course was uneventful, and the patient was discharged on postoperative day(POD)16.Systemic chemotherapy was initiated 1 month after surgery, but the patient died from the disease 13 months after surgery.Emergency PD could be a treatment option in patients with uncontrolled tumor bleeding and fatal conditions.

Laparoscopic versus open distal pancreatectomy for benign and low-grade malignant lesions of the pancreas: a single-center comparative study.

PURPOSE: The purpose of the study was to compare the outcomes of laparoscopic distal pancreatectomy (LDP) and open distal pancreatectomy (ODP) for benign and low-grade malignant lesions to determine the safety and efficacy of LDP. METHODS: This retrospective comparative study included 67 consecutive patients who underwent LDP (n = 32) and ODP (n = 35) for benign or low-grade malignant lesions of the pancreas from January 2012 to March 2017. Thirty-five patients who were eligible for LDP in the ODP group were carefully selected. The clinical outcomes were compared in an intention-to-treat analysis. RESULTS: LDP was associated with significantly less operative blood loss (182 ± 232 vs. 505 ± 376 ml, P < 0.001) but a longer operation time (327 ± 89 vs. 173 ± 48 min, P < 0.001), than ODP. There were no significant differences between the 2 groups in the overall morbidity rates defined by Clavien-Dindo classification ≥ grade II (13% vs. 11%), clinically relevant postoperative pancreatic fistula rates (6% vs. 9%), and lengths of postoperative hospital stay (11 vs. 11 days). CONCLUSION: The study showed that LDP was safe and feasible. LDP should be considered as the first-line treatment for benign and low-grade malignant lesions in the left side of the pancreas.

Perioperative allogenic blood transfusion is a poor prognostic factor after hepatocellular carcinoma surgery: a multi-center analysis.

PURPOSE: The influence of allogenic blood transfusion on the postoperative outcomes of hepatocellular carcinoma (HCC) surgery remains controversial. This study aims to clarify the clinical impacts of perioperative allogenic blood transfusion on liver resection outcome in HCC patients. METHODS: We analyzed data collected over 5 years for 642 patients who underwent hepatectomy for HCC at one of the five university hospitals. We investigated the impact of allogenic blood transfusion on postoperative outcome after surgery in all patients and in 74 matched pairs, using a propensity score. RESULTS: Of the 642 patients, 198 (30.8%) received perioperative allogenic blood transfusion (AT group) and 444 (69.2%) did not (non-AT group). Overall survival was lower in the AT group than in the non-AT group in univariate (P < 0.001) and multivariate analyses (risk ratio 1.521, P = 0.011). After matching the different distributions using propensity scores, perioperative blood transfusion was found to be a poor prognostic factor for HCC patients. CONCLUSIONS: In this multi-center study, perioperative blood transfusion was an independent factor for poor prognosis after curative surgery for primary HCC in the patient group and in pairs matched by propensity scores.

Contrast-enhanced harmonic endoscopic ultrasonography for differential diagnosis of localized gallbladder lesions.

BACKGROUND AND AIM: Differential diagnosis of localized gallbladder lesions is challenging. The aim of the present study was to evaluate the utility of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for diagnosis of localized gallbladder lesions. METHODS: One hundred and twenty-five patients with localized gallbladder lesions were evaluated by CH-EUS between March 2007 and February 2014. This was a single-center retrospective study. Utilities of fundamental B-mode EUS (FB-EUS) and CH-EUS in the differentiation of gallbladder lesions and sludge plug were initially compared. Thereafter, these two examinations were compared with respect to their accuracy in the diagnosis of malignant lesions. Five reviewers blinded to the clinicopathological results evaluated microcirculation patterns in the vascular and perfusion images. RESULTS: In the differentiation between gallbladder lesions and sludge plug, FB-EUS had a sensitivity, specificity, and accuracy of 82%, 100%, and 95%, respectively, whereas CH-EUS had a sensitivity, specificity, and accuracy of 100%, 99%, and 99%, respectively. FB-EUS-based diagnosis of carcinomas based on tumor size and/or shape had a sensitivity, specificity, and accuracy of 61-87%, 71-88%, and 74-86%, respectively. Additional information regarding irregular vessel patterns in the vascular image and/or heterogeneous enhancement in the perfusion image on CH-EUS increased the sensitivity, specificity, and accuracy for the diagnosis of carcinomas to 90%, 98%, and 96%, respectively. There was a significant difference between FB-EUS and CH-EUS in terms of carcinoma diagnosis. CONCLUSION: CH-EUS was useful for the evaluation of localized gallbladder lesions.