Integrative transcriptomic and genomic analyses unveil the IFI16 variants and expression as MASLD progression markers.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a broad and continuous spectrum of liver diseases ranging from fatty liver to steatohepatitis. The intricate interactions of genetic, epigenetic, and environmental factors in the development and progression of MASLD remain elusive. Here, we aimed to achieve an integrative understanding of the genomic and transcriptomic alterations throughout the progression of MASLD. APPROACH AND RESULTS: RNA-Seq profiling (n = 146) and whole-exome sequencing (n = 132) of MASLD liver tissue samples identified 3 transcriptomic subtypes (G1-G3) of MASLD, which were characterized by stepwise pathological and molecular progression of the disease. Macrophage-driven inflammatory activities were identified as a key feature for differentiating these subtypes. This subtype-discriminating macrophage interplay was significantly associated with both the expression and genetic variation of the dsDNA sensor IFI16 (rs6940, A>T, T779S), establishing it as a fundamental molecular factor in MASLD progression. The in vitro dsDNA-IFI16 binding experiments and structural modeling revealed that the IFI16 variant exhibited increased stability and stronger dsDNA binding affinity compared to the wild-type. Further downstream investigation suggested that the IFI16 variant exacerbated DNA sensing-mediated inflammatory signals through mitochondrial dysfunction-related signaling of the IFI16-PYCARD-CASP1 pathway. CONCLUSIONS: This study unveils a comprehensive understanding of MASLD progression through transcriptomic classification, highlighting the crucial roles of IFI16 variants. Targeting the IFI16-PYCARD-CASP1 pathway may pave the way for the development of novel diagnostics and therapeutics for MASLD.

Epididymal lymphoma: report of two cases and imaging findings.

Epididymal lymphoma is a very rare tumor that is difficult to differentiate radiologically from other paratesticular tumors. Most cases of epididymal lymphoma are secondary involvement of the epididymis in patients with testicular lymphoma. However, isolated epididymal lymphoma is very rare. We herein report two cases of isolated epididymal lymphoma with different imaging findings. Patient 1 was a 52-year-old man who presented with a painless scrotal mass. Patient 2 was a 65-year-old man who presented with painless scrotal swelling. Ultrasound (US) demonstrated different imaging findings: US in patient 1 showed a well-defined round mass in the tail of the epididymis with hypervascularity confined to the epididymis, while US in patient 2 showed diffuse infiltrative enlargement with hypervascularity confined to the epididymis. Orchiectomy performed in both patients revealed diffuse large B-cell lymphoma confined to the epididymis.

Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression.

BACKGROUND/AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. METHODS: Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. RESULTS: After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. CONCLUSION: We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

Variability of Transrectal Shear Wave Elastography in a Phantom Model.

Purpose: This study aimed to assess the variability of transrectal shear wave elastography (SWE) using a designed phantom. Materials and Methods: In a phantom, the SWE values were examined by two radiologists using agarose and emulsion silicone of different sizes (1, 2, and 3 cm) and shapes (round, cubic) at three depths (1, 2, and 3 cm), two region of interest (ROI) and locations (central, peripheral) using two ultrasound machines (A, B from different vendors). Variability was evaluated using the coefficient of variation (CV). Results: The CVs decreased with increasing phantom size. Significant changes in SWE values included; agarose phantom at 3 cm depth (p < 0.001; machine A), 1 cm depth (p = 0.01; machine B), emulsion silicone at 2 cm depth (p = 0.047, p = 0.020; both machines). The CVs increased with increasing depth. Significant changes in SWE values included; 1 cm agarose (p = 0.037, p = 0.021; both machines) and 2 cm agarose phantom (p = 0.047; machine A). Significant differences in SWE values were observed between the shapes for emulsion silicone phantom (p = 0.032; machines A) and between ROI locations on machine B (p ≤ 0.001). The SWE values differed significantly between the two machines (p < 0.05). The intra-/inter-operator agreements were excellent (intraclass correlation coefficient > 0.9). Conclusion: The phantom size, depth, and different machines affected the variability of transrectal SWE.

Recurrent hepatic alveolar echinococcosis: report of the first case in Korea with unproven infection route.

Human alveolar echinococcosis (AE), a hepatic disorder that resembles liver cancer, is a highly aggressive and lethal zoonotic infection caused by the larval stage of the fox tapeworm, Echinococcus multilocularis. E. multilocularis is widely distributed in the northern hemisphere; the disease-endemic area stretches from north America through Europe to central and east Asia, including northern parts of Japan, but it has not been reported in Korea. Herein, we represent a first case of AE in Korea. A 41-year-old woman was found to have a large liver mass on routine medical examination. The excised mass showed multinodular, necrotic, and spongiform appearance with small irregular pseudocystic spaces. Microscopically, the mass was composed of chronic granulomatous inflammation with extensive coagulation necrosis and parasite-like structure, which was revealed as parasitic vesicles and laminated layer delineated by periodic acid-Schiff (PAS) stain. Clinical and histologic features were consistent with AE. After 8 years, a new liver mass and multiple metastatic pulmonary nodules were found and the recurred mass showed similar histologic features to the initial mass. She had never visited endemic areas of AE, and thus the exact infection route is unclear.

Rational strain selection and engineering creates a broad-spectrum, systemically effective oncolytic poxvirus, JX-963.

Replication-selective oncolytic viruses (virotherapeutics) are being developed as novel cancer therapies with unique mechanisms of action, but limitations in i.v. delivery to tumors and systemic efficacy have highlighted the need for improved agents for this therapeutic class to realize its potential. Here we describe the rational, stepwise design and evaluation of a systemically effective virotherapeutic (JX-963). We first identified a highly potent poxvirus strain that also trafficked efficiently to human tumors after i.v. administration. This strain was then engineered to target cancer cells with activation of the transcription factor E2F and the EGFR pathway by deletion of the thymidine kinase and vaccinia growth factor genes. For induction of tumor-specific cytotoxic T lymphocytes, we further engineered the virus to express human GM-CSF. JX-963 was more potent than the previously used virotherapeutic Onyx-015 adenovirus and as potent as wild-type vaccinia in all cancer cell lines tested. Significant cancer selectivity of JX-963 was demonstrated in vitro in human tumor cell lines, in vivo in tumor-bearing rabbits, and in primary human surgical samples ex vivo. Intravenous administration led to systemic efficacy against both primary carcinomas and widespread organ-based metastases in immunocompetent mice and rabbits. JX-963 therefore holds promise as a rationally designed, targeted virotherapeutic for the systemic treatment of cancer in humans and warrants clinical testing.

Risk factors for recurrent symptomatic pigmented biliary stones after percutaneous transhepatic biliary extraction.

PURPOSE: To evaluate risk factors for the recurrence of biliary stones after a percutaneous transhepatic biliary stone extraction. MATERIALS AND METHODS: The procedures were performed on 339 patients between July 2004 and December 2008 (54 months). Medical records and images were retrospectively reviewed for 135 patients (mean age, 66.4 years; 83 men and 52 women) who had undergone follow-up for a mean of 13.2 months (range, 3-37 months). To evaluate risk factors for the recurrence of biliary stones, variables were evaluated with univariate and multivariate analyses. Variables included sex, age, stone location, number of stones, stone size, presence of a peripapillary diverticulum, application of antegrade sphincteroplasty, presence of a biliary stricture, largest biliary diameter before the procedure, and gallbladder status. RESULTS: Thirty-three of the 135 patients (24%) had recurrent symptomatic biliary stones and underwent an additional extraction. The mean time to recurrence was 17.2 months +/- 8.7. Univariate analysis of risk factors for recurrence of biliary stones demonstrated that location, number of stones, stone size, application of antegrade sphincteroplasty, presence of a biliary stricture, and biliary diameter were significant factors (P < .05). With use of multivariate analysis, the number of stones (> or =6; relative risk, 64.8; 95% confidence interval: 5.8, 717.6) and stone size (> or =14 mm; relative risk, 3.8; 95% confidence interval: 1.138, 13.231) were determined to be significant risk factors. CONCLUSIONS: The independent risk factors for recurrence of symptomatic biliary stones after percutaneous transhepatic biliary stone extraction were a stone size of at least 14 mm and the presence of at least six stones.

A novel method to determine hepatic segments using Sonazoid, an ultrasound contrast agent.

The conventional radiologic method for liver segmentation is based on the position of the hepatic and portal veins. However, during surgery, liver segments are resected based on the distribution of hepatic portal blood flow. This discrepancy can lead to a number of problems, such as miscommunication among clinicians, missing the location of the segment with the hepatic mass, and the risk of extended hepatic resection. We suggest a novel method to determine hepatic segments based on portal blood flow, as in the surgical approach, but by using high and low mechanical indexes in contrast-enhanced ultrasonography with Sonazoid. This approach is helpful for preoperatively determining hepatic segments and reducing the risk of missing the location of a hepatic tumor or extended hepatic resection.

[A case of autoimmune pancreatitis combined with extensive involvement of biliary tract].

Autoimmune pancreatitis is a distinct disease characterized by the presence of autoantibodies and hypergammaglobulinemia, inflammation of the pancreatic parenchyma, and irregular stricture of the pancreatic duct. The involvement of distal common bile duct is frequently observed, but intrahepatic bile duct involvement is very rare, which seem to have similar feature to primary sclerosing cholangitis. We report a case of the patient with autoimmune pancreatitis combined with extensive involvement of extrahepatic and intrahepatic bile duct, which had a favorable response to steroid therapy.

Benign submucosal lesions of the stomach and duodenum: imaging characteristics with endoscopic and pathologic correlation.

Benign submucosal lesions of the stomach and duodenum are occasionally encountered during endoscopy. But endoscopy has its limitations in the diagnosis and differentiation of these lesions, because submucosal lesions are often difficult to visualize at endoscopy due to minimal change of the overlying mucosa. Furthermore, endoscopic biopsy may not always yield adequate tissue for diagnosis due to the submucosal location of the lesions. For this reason, the role of radiologic imaging is important in the diagnosis of submucosal lesions of the stomach and duodenum. Recent advances in computed tomography (CT) and sonographic technology are helpful in narrowing the differential diagnosis of gastroduodenal submucosal lesions. In contrast to endoscopy and barium studies, CT or ultrasonography (US) provides information about both the gastric wall and the extragastric extent of the disease. Arterial phase contrast enhanced CT enables us to discriminate a mass of submucosal from that of a mucosal origin in the differential diagnosis of gastric or duodenal lesions. Although endoscopic sonography has been considered the better modality in the diagnosis of gastroduodenal submucosal lesions, transabdominal sonography can still be an alternative method to endoscopic sonography in assessing of the origin and character of the submucosal lesions. Some gastroduodenal submucosal lesions have similar radiologic findings that make differentiation difficult. But despite overlaps in radiologic findings, some lesions have characteristic radiologic features that may suggest a specific diagnosis. Knowledge of the differential diagnosis of benign submucosal lesions in the stomach and duodenum may promote correct diagnosis and appropriate treatment.

Radiofrequency ablation treatment for renal cell carcinoma: early clinical experience.

OBJECTIVE: To evaluate the early clinical experience associated with radiofrequency (RF) ablation in patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: The RF ablation treatment was performed on 17 tumors from 16 patients (mean age, 60.5 years; range, 43-73 years) with RCC. The treatment indications were localized, solid renal mass, comorbidities, high operation risk, and refusal to perform surgery. All tumors were treated by a percutaneous CT (n = 10), followed by an US-guided (n = 2), laparoscopy-assisted US (n = 2), and an open (n = 2) RF ablation. Furthermore, patients underwent a follow-up CT at one day, one week, one month, three and six months, and then every six months from the onset of treatment. We evaluated the technical success, technical effectiveness, ablation zone, benign periablation enhancement, irregular peripheral enhancement, and complications. RESULTS: All 17 exophytic tumors (mean size, 2.2 cm; range, 1.1-5.0 cm) were completely ablated. Technical success and effectiveness was achieved in all cases and the mean follow-up period was 23.8 months (range, 17-33 months). A local recurrence was not detected in any of the cases; however, five patients developed complications as a result of treatment, including hematuria (n = 2), mild thermal injury of the psoas muscle (n = 1), mild hydronephrosis (n = 1), and fistula formation (n = 1). CONCLUSION: The RF ablation is an alternative treatment for exophytic RCCs and represents a promising treatment for some patients with small RCCs.

Gallstone, cholecystectomy and risk of gastric cancer.

BACKGROUNDS/AIMS: The aim of this retrospective study is to compare stomach cancer incidence, characteristics between gallstones, cholecystectomy and control groups. It also aims to investigate key variables' potential effects on overall survival. METHODS: A total of 99 patients, diagnosed with stomach cancers between April 1994 and December 2015, were identified. We excluded stomach cancer patients, accrued during the first year of follow-up in both the gallstones and cholecystectomy groups, assuming that they missed cancers. The main analyses addressing the objective were a chi-square analysis and a survival analysis. RESULTS: The incidence of stomach cancers was increased in both the gallstone and cholecystectomy groups, compared with the control group (p=0.003). Multivariate regression analysis showed that the overall survival in gallstones, cholecystectomy group patients as compared with those in the control group decreased (HR=6.66, 95 CI: 1.94-22.80, p=0.003). Also, T-stage was found to statistically affect the rate of overall survival (HR=9.85, 95% CI: 3.09-31.39, p=.000). The stomach cancer showed the worse survival at the posterior, greater curvature location than anterior, lesser curvature of the stomach. (HR=0.30, 95% CI: 0.11-0.80, p=0.017). CONCLUSIONS: We provided an awareness of the possible increased risks of stomach cancer in gallstone and cholecystectomy group patients, which might be induced by duodenogastric bile reflux. Also, the survival rate was poor (p<0.000). Therefore, close follow-up strategies for early detection are recommended for such patients.

Sigmoidorectal intussusception of adenoma of sigmoid colon treated by laparoscopic anterior resection after sponge-on-the-stick-assisted manual reduction.

We present herein a case report of sigmoidorectal intussusception as an unusual case of sigmoid adenomatous polyp. The patient was a 56-year-old man who suffered from rectal bleeding for one day. He initially visited his general practitioner and was diagnosed as having an intraluminal mass of 15 cm from the anal verge. Several hours after admission to our coloproctology clinic, he suddenly presented with lower abdominal cramping pain with rectal bleeding during his bowel preparation using polyethylene glycol electrolyte solution. An emergency colonoscopy revealed that the invaginated colon with polypoid mass was protruded to the lower rectum. Gastrograffin enema showed that the invaginated bowel segment was 3 cm from the anal verge. CT scan showed the typical finding of intussusception. We performed laparoscopic anterior resection and anastomosis after the sponge-on-the-stick-assisted manual reduction. The permanent pathologic finding showed villotubular adenoma of the sigmoid colon.

[A case of splenic pseudocyst difficult to differentiate from splenic lymphangioma].

Splenic pseudocyst is a rare complication of abdominal trauma. Although it is rare, splenic pseudocyst is well-documented in the literature. According to the current classification, approximately 30% of all splenic cysts or pseudocysts result from direct abdominal trauma. In addition, chronic pancreatitis leads to change of nearby organs with possible acute and chronic complications including splenic lesions. This unusual complication can occur in both emergent and non-emergent conditions. The useful diagnostic procedures to assess intrasplenic pseudocyst are sonogram, CT scan, splenic scan, and occasionally angiography. However, definite diagnosis of pseudocyst is possible only after splenectomy when the absence of epithelial lining is confirmed histologically. Splenic pseudocyst requires surgical resection. We experienced a 31-year-old man who confirmed of warmness in the left side of back with left upper quadrant abdominal pain for several months. First impression was splenic lymphangioma based on CT scan and sonogram finding. Splenectomy was performed. Microscopic examination revealed splenic pseudocyst with fibrous capsule without epithelial lining.

Intraoperative radiofrequency ablation for hepatocellular carcinoma in 112 patients with cirrhosis: a surgeon's view.

PURPOSE: This retrospective study was an investigation of overall survival (OS), disease-free survival (DFS) and prognostic factors affecting OS and DFS in cirrhotic patients who received intraoperative radiofrequency ablation (IORFA). METHODS: Between April 2009 and November 2013, 112 patients (94 men, 84%; 18 women, 16%) underwent IORFA for 185 cases of hepatocellular carcinomas (HCC). Repeat IORFA was done in 9 patients during the same period (total of 121 treatments). RESULTS: All patients were followed-up for at least 12 months (mean follow-up, 32 months). Surgical resection combined with IORFA was performed in 20 patients. The technical effectiveness at 1 week was 91.78% (111 of 121). Readmission was 9.1% (11 of 121) and the most common cause was ventral hernia. Procedure-related mortality was 2.7% (3 of 112) and continued fatal biliary leakage was 1.8% (2 of 112). Local recurrence developed in 10 patients (8.9%). Most recurrence was intrahepatic. Cumulative survival was assessed in 33 patients who received IORFA as primary treatment (naive patients) and 79 non-naive patients. The cumulative DFS and OS rate at l and 3 years was 54% and 24%, and 87% and 66%, respectively. Moderate ascites (P = 0.001), tumor located segment I (P = 0.001), portal vein thrombosis (P = 0.001) had poor survival were significant factors by multivariate analysis. CONCLUSION: IORFA alone or in combination with surgical resection extends the spectrum of liver surgery. A fundamental understanding of RFA, additional comorbidities, and postablation complication are necessary to maximize the safety and efficacy of IORFA for treating HCC with cirrhosis.

[A case of giant gastric villous tumor with carcinomatous change].

Villous tumors of the stomach are somewhat rare with approximately 100 cases only reported in the literatures and have tendency to undergo malignant transformation as high as 72%. They are frequently multiple and associated with other gastrointestinal neoplasm. Thirty percent of them are associated with an independent gastric carcinoma. Gastric villous tumor has certain radiologic characteristics that may permit a preoperative diagnosis and also some distinctive clinicopathologic features which make early diagnosis and proper treatment possible. We experienced a 64-year-old man who complained of prolonged general weakness, weight loss for several months and left upper quadrant pain for four days. Esophagogastroduodenoscopy and barium study of upper gastrointestinal tract demonstrated typical, irregular, frond-like surfaced villous tumor occupying nearly whole gastric lumen and located eccentrically along the lesser curvature side. Endoscopic biopsy of the tumor revealed a gastric villous tumor with carcinomatous change.

[A case of primary small cell carcinoma of the liver].

Primary small cell carcinoma of the liver is an extremely rare tumor. Extrapulmonary small cell carcinoma shares many features of pulmonary small cell carcinoma, including the histological appearance, the aggressive clinical behavior and the frequent short-lasting response to either chemotherapy or radiotherapy. We experienced a 56-year-old man with small cell carcinoma that arose in the liver. Abdominal CT scan showed an 8 cm size, low density mass in the segment 4 of the liver and also multiple lymphadenopathies. Chest X-ray showed no abnormal finding, but the chest CT showed a right lower paratracheal lymphadenopathy. The pathological findings showed nests of small round cells with fine granular chromatin, inconspicuous nucleoli and scanty cytoplasm. Distinct and strong immunoreactions were seen for CD56 and c-kit, and sparse immunoreaction was seen for synaptophysin. Thyroid transcription factor-1 showed no immunoreaction. The tumor did not decrease in size despite chemotherapy. We report this case along with a review of the relevant literatures.

Usefulness of acoustic radiation force impulse elastography in the differential diagnosis of benign and malignant solid pancreatic lesions.

PURPOSE: The aim of this study was to evaluate the tissue stiffness of solid pancreatic lesions by using acoustic radiation force impulse (ARFI) elastography to differentiate benign from malignant pancreatic lesions. METHODS: ARFI elastography was performed in 26 patients who had 27 focal solid pancreatic lesions, including 8 benign lesions (mass-forming pancreatitis, 5; autoimmune pancreatitis, 3) and 19 malignant lesions (pancreatic adenocarcinoma, 16; metastasis from colorectal cancer, 2; malignant neuroendocrine tumor, 1). On the elastographic images of virtual touch tissue imaging (VTI), the echogenicity of the mass was categorized on a 5-grade scale. On the elastographic image of virtual touch tissue quantification (VTQ), the shear wave velocities (SWVs) of the lesion and surrounding parenchyma were measured. RESULTS: On the VTI images, the mean echogenicity score of the malignant lesions (3.7±1.0) was higher than that of the benign lesions (3.1±0.4; P=0.023). On the VTQ images, there were no statistical differences in the mean SWV between the benign (2.4±1.1 m/sec) and malignant (3.3±1.0 m/sec) lesions (P=0.101). However, the mean SWV difference values between the lesion and background parenchyma of the malignant lesions (1.5±0.8 m/sec) were higher than those of the benign lesions (0.4±0.3 m/sec; P=0.011). CONCLUSION: ARFI elastography can determine the relative stiffness between a lesion and the background pancreatic parenchyma using VTI and VTQ, which is helpful in the differentiation between benign and malignant solid pancreatic lesions.

Focal thickening at the fundus of the gallbladder: computed tomography differentiation of fundal type adenomyomatosis and localized chronic cholecystitis.

BACKGROUND/AIMS: The objective of our study was to identify useful computed tomography (CT) findings for differentiating fundal type adenomyomatosis from localized chronic cholecystitis involving the fundus of the gallbladder. METHODS: We retrospectively identified cases of 41 patients with pathologically proven adenomyomatosis (n=21) or chronic cholecystitis (n=20) who had fundal thickening of the gallbladder on preoperative abdominal CT. Analysis of the CT findings included evaluation of the thickness, contour, border, intralesional cystic area, adjacent gallbladder wall thickening, presence of inner layer enhancement, enhancement grade, enhancement pattern, and presence of stones. Statistical analyses were performed using the Mann-Whitney U test and Fisher exact test. RESULTS: Oval contour, inner layer enhancement and intralesional cystic area were more frequently noted in adenomyomatosis than in chronic cholecystitis (p<0.05 for each finding). Flat contour and adjacent gallbladder wall thickening were more frequently observed in chronic cholecystitis than in adenomyomatosis. No differences between adenomyomatosis and chronic cholecystitis in terms of the thickness, enhancement grade, enhancement pattern and presence of stones were apparent. CONCLUSIONS: CT may help to differentiate fundal type adenomyomatosis from localized chronic cholecystitis involving the fundus of the gallbladder.

Prognostic factors for gallbladder cancer in the laparoscopy era.

PURPOSE: Hepatobiliary surgery has changed dramatically in recent decades with the advent of laparoscopic techniques. The aim of this retrospective study was to compare survival rates according to stages, adjusting for important prognostic factors. METHODS: A retrospective study of a 17-year period from January 1994 to April 2011 was carried out. The cases studied were divided into two time period cohorts, those treated in the first 9-years (n = 109) and those treated in the last 7-years (n = 109). RESULTS: An operation with curative intent was performed on 218 patients. The 5-year survival rates according to the depth of invasion were 86% (T1), 56% (T2), 45% (T3), and 5% (T4). The number of cases of incidental gallbladder cancer found during 3,919 laparoscopic cholecystectomies was 96 (2.4%). Incidental gallbladder cancer revealed a better survival rate (P = 0.003). Iatrogenic bile spillage was found in 20 perforations of the gallbladder during laparoscopic cholecystectomies, 16 preoperative percutaneous transhepatic gallbladder drainages and 16 percutaneous transhepatic biliary drainages; only percutaneous transhepatic biliary drainage patients showed a significantly lower survival rate than patients without iatrogenic bile spillage (P < 0.034). Chemoradiation appeared to improve overall survival (P < 0.001). Multivariate analysis also revealed that time period, type of surgery, surgical margin, lymphovascular invasion, lymph node involvement, and chemoradiation therapy had significant effects. CONCLUSION: This study found that the prognosis of gallbladder cancer is still determined by the stage at presentation due to the aggressive biology of this tumor. Early diagnosis, radical resection and appropriate adjuvant therapy can increase overall survival.