[Advances in the relationship between lung cancer and microbiota].

Interaction exists in lung cancer and microbiota. Lung microecological homeostasis can improve the immune tolerance, enhance immune suppression, and inhibit inflammatory responses, to reduce the lung cancer; while lung cancer can lead to pulmonary microecological imbalance, change the lung environment, and promote tumor cell proliferation. Therefore, modulating microbial flora and microecological immunotherapy may be a potential and preventive treatment for lung cancer, to restore tumor immunosuppression and improve patient survival. However, the individual differences in the lung microecology, because of different genetics, ethnic characteristics, and dietary habits, increasing the difficulty of precise diagnosis and treatment, which is also the current bottleneck in the application of microecological immunotherapy. Otherwise, the effectiveness of regulatory measures such as probiotics, prebiotics or antimicrobials is questionable. The research on microbial flora is still in its infancy, and further exploration is needed to form a standardized, effective, and precise treatment plan. So, standardized, effective, and precise microbial flora treatment strategies need to be further explored.

Magnetic navigation in ultrasound-guided interventional radiology procedures.

AIM: To evaluate the usefulness of magnetic navigation in ultrasound (US)-guided interventional procedures. MATERIALS AND METHODS: Thirty-seven patients who were scheduled for US-guided interventional procedures (20 liver cancer ablation procedures and 17 other procedures) were included. Magnetic navigation with three-dimensional (3D) computed tomography (CT), magnetic resonance imaging (MRI), 3D US, and position-marking magnetic navigation were used for guidance. The influence on clinical outcome was also evaluated. RESULTS: Magnetic navigation facilitated applicator placement in 15 of 20 ablation procedures for liver cancer in which multiple ablations were performed; enhanced guidance in two small liver cancers invisible on conventional US but visible at CT or MRI; and depicted the residual viable tumour after transcatheter arterial chemoembolization for liver cancer in one procedure. In four of 17 other interventional procedures, position-marking magnetic navigation increased the visualization of the needle tip. Magnetic navigation was beneficial in 11 (55%) of 20 ablation procedures; increased confidence but did not change management in five (25%); added some information but did not change management in two (10%); and made no change in two (10%). In the other 17 interventional procedures, the corresponding numbers were 1 (5.9%), 2 (11.7%), 7 (41.2%), and 7 (41.2%), respectively (p=0.002). CONCLUSION: Magnetic navigation in US-guided interventional procedure provides solutions in some difficult cases in which conventional US guidance is not suitable. It is especially useful in complicated interventional procedures such as ablation for liver cancer.

Imaging features of intrahepatic biliary cystadenoma and cystadenocarcinoma on B-mode and contrast-enhanced ultrasound.

PURPOSE: To investigate the imaging features of intrahepatic biliary cystadenoma and cystadenocarcinoma on B-mode and contrast-enhanced ultrasound. MATERIALS AND METHODS: The B-mode and contrast-enhanced ultrasound features of 6 intrahepatic biliary cystadenomas and 7 intrahepatic biliary cystadenocarcinomas were retrospectively analyzed, and the differences between cystadenomas and cystadenocarcinomas were compared. RESULTS: There were no significant differences between cystadenomas and cystadenocarcinomas in terms of patient gender, age, lesion location, size, and shape (all p > 0.05). On conventional ultrasound, biliary cystadenomas were more likely to be multilocular (6/6 for cystadenoma vs. 2/7 for cystadenocarcinoma) and cystadenocarcinomas more likely presented the features of a mural or septal nodule and a nodule diameter > 1.0 cm (0/6 for cystadenoma vs. 5/7 for cystadenocarcinoma). On contrast-enhanced ultrasound, hyper-enhancement (n = 4) or iso-enhancement (n = 2) was present in the cystic wall, septations or mural nodules of the cystadenomas during the arterial phase and the enhancement washed out to hypo-enhancement (n = 6) during the late phase. Cystadenocarcinomas also showed hyper-enhancement (n = 4) or iso-enhancement (n = 3) in the cystic wall, septations or mural nodules during the arterial phase and iso-enhancement (n = 1) or hypo-enhancement (n = 6) during the late phase. CONCLUSION: Intrahepatic biliary cystadenomas are more typically multilocular cystic lesions. A mural or septal nodule and a nodule diameter greater than 1.0 cm on conventional ultrasound are suggestive of cystadenocarcinomas. Contrast-enhanced ultrasound is helpful for depicting the vascularity of the lesions but there was no significant difference between cystadenomas and cystadenocarcinomas.

Unscheduled DNA synthesis after treatment with 20-methylcholanthrene and N-nitrosodimethylamine in primary culture of human gallbladder epithelial cells.

Unscheduled DNA synthesis (UDS) induced by treatment with 20-methylcholanthrene (MCA) and N-nitrosodimethylamine (DMN) was measured in cultured human gallbladder epithelial cells. MCA induced UDS very efficiently, while DMN was far less effective than MCA. Addition of rat S9 mixture did not affect the amount of UDS by the chemicals. Differences between the present results in human cells and our previous findings in bovine cells could be due to species and tissue specificity.

Significance of portal hemodynamic investigation in prediction of hepatic functional reserve in patients with hepatocellular carcinoma undergoing operative treatment.

BACKGROUND/AIMS: To evaluate clinical significance of portal hemodynamic investigation in prediction of hepatic functional reserve in patients with hepatocellular carcinoma undergoing operative treatment. METHODOLOGY: By using the color Doppler velocity profile technique, preoperative portal hemodynamic status was assessed in 29 patients with hepatocellular carcinoma treated surgically, including 15 segmentectomies, 6 hemihepatectomies and 8 transarterial chemoembolizations. Forty-six normal volunteers were taken as control. Comparison of preoperative portal hemodynamics between patients recovering from operation smoothly (tolerant subgroup) and those with major complications or death (intolerant subgroup) was done, and discriminant analysis was employed to identify the cut-off value for significant parameters that maximally separate the tolerant subgroup from the intolerant subgroup. RESULTS: In the portal trunk, CSVmax (maximum cross-sectional mean velocity) was significantly lower in the hepatocellular carcinoma group compared with the normal group (P < 0.01); flow volume was not obviously different between the two groups; congestion index was markedly higher in the hepatocellular carcinoma group than that of the normal group (P < 0.05). In the splenic vein, CSVmax and congestion index was not obviously different between the hepatocellular carcinoma and the normal groups; flow volume was significantly higher in the hepatocellular carcinoma group than that of the normal group (P < 0.05). In the hepatocellular carcinomas, twenty-three patients recovered smoothly from the operation and the remaining 6 had severe complications or death. Tolerant subgroup had a significantly higher preoperative CSVmax and flow volume and lower congestion index of the portal trunk compared with the intolerant subgroup (all P < 0.01). Discriminant analysis revealed that portal trunk CSVmax > 13.50 cm/s and flow volume > 12.13 mL/min/kg could predict tolerance for surgery, with an accuracy of 82.7% and 89.7%, respectively. CONCLUSIONS: The results suggest that preoperative portal hemodynamic status in hepatocellular carcinomas had a close correlation with hepatic functional reserve, and CSVmax and flow volume of portal trunk might become valuable predictive parameters.

Intraoperative liver ultrasound: the Chinese experience.

This article introduces the experience in intraoperative liver ultrasound in China. Intraoperative liver ultrasound was mainly used in patients treated for hepatocellular carcinoma (HCC) and hepatolithiasis, with purposes for further diagnosis and decision making and guidance of surgical procedures. With respect to detection of liver tumors, intraoperative ultrasound (IOUS) was significantly more sensitive, especially in small foci, as compared with preoperative ultrasound and computed tomography scanning, as well as intraoperative inspection and palpation. It was also more precise in localizing lesions than preoperative imaging investigations. Intraoperative echoangiography via hepatic arterial injection of carbon dioxide was shown not only to help assess position of catheter and vascularity of tumors but also to improve sensitivity in detecting small tumor foci in patients undergoing hepatic arterial chemoembolization. Intraoperative ultrasound was also used to guide hepatectomies. It ensured to obtain curative resection of the tumors and maximum preservation of functioning hepatic parenchyma simultaneously. For hepatolithiasis, IOUS offered accurate localization of stones, lithotomy (with its guidance), reduction of the rate of residual stones, and follow-up of the outcome of lithotomy.

[Oral glucose tolerance test and glucagon loading test as useful parameters for evaluating liver functional reserve].

Oral glucose tolerance test (OGTT) and glucagon loading test (GLT) were performed preoperatively in 46 patients with hepatocellular carcinoma and underlying liver cirrhosis. After operation 17 cases fared with good recovery (group A), 17 with hepatic functional damages (group B) and 12 with liver failure (group C). The glucose tolerance patterns could be classified into three types: (1) blood glucose level returned to 7.3 mmol/L or less 120 minutes after glucose loading, in 82.4% of the patients in group A, (2) with return of glucose level but greater than 7.3 mmol/L, in 60% of the cases in group B and 20% in group C, (3) linear pattern with increasing of glucose level in 100% of the patients in group B or C. For GLT, the plasma cyclic AMP concentration reached a peak level at 10 minute and the peak level/basal level (P/B ratio) was found to be a reliable index, that 70.6% of the patients in group A had a P/B ratio greater than 20, 64.7% in group B with the ratio between 10-20, and 83.3% in group C with that less than 10. For evaluating liver functional reserve, predictability test indicated the sensitivity and efficiency were greater significantly for OGTT and GLT than Pugh's grading (P < 0.05).

[Portal vein embolization via a fine needle guided by angio-echography: experimental and clinical study].

This paper introduced a technique of portal vein embolization by injection of ethanol via fine needle under guidance of angio-echography. First introportal ethanol injection were done in 28 dogs to evaluate its embolic efficacy and safety. The result showed if a dose of injected ethanol was chosen properly, expected embolization could be obtained with slight toxicity to hepatic parenchyma and function. For clinical application, selective portal vein puncture was percutaneous transhepatic under echo guidance. Ultrasound angiography by injecting carbon dioxide (CO2) into portal vein was introduced initially. After confirmed that the injected branch was that supplied the tumor and there was no retrograde overflow of portal blood, ethanol was injected at a dose no more than 10ml. Eighteen patients with hepatocellular carcinoma and underlying liver cirrhosis underwent the procedure preoperatively. Of 14 cases who received hepatectomies, portal vein embolization developed in 12. Since the procedure was guided by angio-echography it could be used for indicated cases with satisfactory embolic effect and not harmful to liver. The procedure had advantages of simple manipulation and made selective embolization easier compared to interventional transcatheter portal vein embolization.

[Two-stage multivariant analyses for prediction of hepatic function reserve].

Eleven liver function tests were used for preoperative estimations of the hepatic function reserve in 103 patients with primary hepatocellular carcinoma (HCC) and underlying liver cirrhosis. Postoperatively, the patients' liver function could be classified as good recovering (Grade A, n = 38), functional damage (Grade B, n = 37) and liver failure (Grade C, n = 28). Single factor analyses showed 6 of those tests were significant indicators, including the ratio of blood glucose level at 120 minutes and 60 minutes by oral glucose tolerance test, total bilirubin, the ratio of albumin and globulin, prealbumin, prothrombin time and indocyanine green retention at 15 minutes. The correlations between 11 preoperative parameters (xi) and postoperative course scored (Y) were analysed by Fisher's discriminant test. The multiple regression equation Y1 was obtained by comparing from groups of Grade A with B and formula Y2 from groups of Grade B with C. The predictive accuracy of both equations were 88.0%, 83.1%, respectively. To select adequate surgical procedures with the best therapeutic effect and minimal liver damage for the patients with HCC, we proposed a method of "two-stage predications" combining use of Y1 and Y2 for evaluation of liver function reserve.

[Cultured biliary tract epithelial cells/alkaline and neutral elution as a model for the detection of carcinogens to the biliary tract epithelium].

Alkaline and neutral elution techniques were applied to detect chemical carcinogens in biliary tract cancer using biliary tract epithelial cells in culture. Since biliary tract epithelial cells actively grow in culture, DNA breaks induced by carcinogens in the [14C] thymidine-prelabeled DNA could be detected as radioactivities in the eluted fractions. Our study demonstrated that aflatoxin B1, 20-methylcholanthrene and dimethylnitrosamine induced DNA single-strand breaks in the biliary tract epithelial cells by the use of this system. Cultured biliary tract epithelial cells/alkaline and neutral elution offers a sensitive and organ-specific model for the detection of chemical carcinogens to the biliary tract epithelium.

[Isolation and culture of bile duct epithelial cells as an useful tool for screening of biliary tract carcinogens].

A method of isolation and culture of extrahepatic bile duct epithelial cells from Holstein cows has been established for detection of carcinogens in relation to bile duct cancer. Cells were isolated by digestion with Dispase followed by scraping of the mucosa. The integrity, the epithelial character and the purity of cells isolated were confirmed by electron microscopy. By the use of this culture induction of unscheduled DNA synthesis by chemicals which are capable of developing bile duct cancers in experimental animals, were assessed autoradiographically with or without addition of S-9 mixture. MNNG and ENNG induced UDS, which was not influenced by S-9 mixture. MCA elicited UDS only if S-9 mixture was added. Regardless of the presence of S-9 mixture, DMN failed to induce UDS but AFB1 induced UDS dose-dependently. The contact routes of the carcinogens with bile duct cells were established and this culture system way be an useful tool for the detection of biliary tract carcinogens.

Percutaneous ultrasound-guided thermal ablation for intrahepatic cholangiocarcinoma.

OBJECTIVE: The objective of this study was to evaluate the treatment efficacy and overall survival (OS) of percutaneous ultrasound-guided thermal ablation by means of microwave ablation or radiofrequency ablation for intrahepatic cholangiocarcinoma (ICC). METHODS: 18 patients with 25 ICC nodules underwent ultrasound-guided thermal ablation with curative intention. 8 patients were primary cases and 10 were recurrent cases after curative resection. The local treatment response, complications and survivals were analysed. RESULTS: Complete ablation was achieved in 23 (92.0%, 23/25) nodules (diameter, 0.7-4.3 cm; mean, 2.5 ± 0.9 cm) and incomplete ablation was found in 2 (8.0%, 2/25) larger tumours (6.4 and 6.9 cm in diameter). No death associated with the treatment was found. The major complication rate was 5.5% (1/18). The follow-up periods ranged from 1.3 to 86.2 months (mean, 20.5 ± 26.3 months; median, 8.7 months). OS rates for all patients at 6, 12, 36 and 60 months were 66.7%, 36.3%, 30.3% and 30.3%, respectively. By univariate analysis, the patient source (primary or recurrent case) was found to be a significant prognostic factor for OS rates (p=0.001). The patient source (p=0.001) and the number of nodules (p=0.038) were found to be significant prognostic factors for recurrence-free survival. OS rates for the primary ICC at 6, 12, 36 and 60 months were 87.5%, 75.0%, 62.5% and 62.5%, respectively. CONCLUSION: Percutaneous ultrasound-guided thermal ablation is a safe and effective therapeutic technique for ICC. Acceptable survival can be achieved in primary ICCs, whereas the prognosis of recurrent ICCs is relatively poor.

Discrimination between neoplastic and non-neoplastic lesions in cirrhotic liver using contrast-enhanced ultrasound.

OBJECTIVES: To assess the value of contrast-enhanced ultrasound (CEUS) in differentiating hepatocellular carcinoma (HCC) from non-neoplastic lesion in cirrhotic liver in comparison with baseline ultrasound. METHODS: A total of 147 nodules (diameter ≤5.0 cm) in 133 cirrhotic patients (mean age±standard deviation: 52±13 years, range 20-82 years; gender: 111 males and 22 females) were examined with CEUS. There were 116 HCCs, 26 macroregenerative nodules and 5 high-grade dysplastic nodules. CEUS was performed with a real-time contrast-specific mode and a sulphur hexafluoride-filled microbubble contrast agent. RESULTS: Hypervascularity was observed in 94.8% (110/116) HCCs, 3.8% (1/26) macroregenerative nodules and 60.0% (3/5) high-grade dysplastic nodules during arterial phase on CEUS. Detection rates of typical vascular pattern (i.e. hypervascularity during arterial phase and subsequent washout) in HCCs with a diameter of ≤2.0 cm, 2.1-3.0 cm and 3.1-5.0 cm were 69.2% (27/39), 97.1% (33/34) and 100.0% (43/43), respectively. CEUS significantly improved the sensitivity [88.8% (103/116) vs 37.1% (43/116), p<0.001], negative predictive value [70.5% (31/44) vs 31.5% (29/92), p<0.001], and accuracy [91.2% (134/147) vs 49.0% (72/147), p<0.001] in differentiating HCCs from non-neoplastic lesions when compared with baseline ultrasound. However, the sensitivity and accuracy of CEUS for HCCs ≤2.0 cm in diameter were significantly lower than those for HCCs of 2.1-3.0 cm and 3.1-5.0 cm in diameter. CONCLUSIONS: CEUS improves diagnostic performance in differentiating HCCs from non-neoplastic nodules in cirrhotic patients compared with baseline ultrasound. Diagnosis of HCCs ≤2.0 cm diameter by CEUS is still a clinical concern, and thus needs further investigation.

Imaging features of hepatic angiomyolipomas on real-time contrast-enhanced ultrasound.

The aim of this study was to evaluate the imaging features of hepatic angiomyolipoma (AML) on contrast-enhanced ultrasound (CEUS). The imaging features of 12 pathologically proven hepatic AML lesions in 10 patients who had undergone baseline ultrasound (BUS) and CEUS examinations were evaluated retrospectively. The enhancement extent, pattern and dynamic change, along with the enhancement process, on CEUS were analysed. The diagnostic results of BUS and CEUS before pathological examination were also recorded. The results showed that 75% (9/12) of the AML lesions exhibited mixed echogenicity on BUS and most showed remarkable hyperechogenicity in combination with a hypoechoic or anechoic portion. Arterial flow signals were detected in 75% (9/12) of the lesions on colour Doppler imaging. On CEUS, 66.7% (n = 8) of the 12 lesions exhibited hyperenhancement in the arterial phase, slight hyperenhancement (n = 2) or isoenhancement (n = 6) in the portal phase, and slight hyperenhancement (n = 1) or isoenhancement (n = 7) in the late phase. Three (25%) lesions exhibited hyperenhancement in the arterial phase and hypoenhancement in both portal and late phases. One (8.3%) lesion exhibited hypoenhancement throughout the CEUS process. Before pathological examination with BUS, only 3 (25%) lesions were correctly diagnosed as hepatic AML. Conversely, on CEUS, correct diagnoses were made for 66.8% (8/12) of hepatic AMLs. Therefore, arterial hyperenhancement and subsequent sustained enhancement on CEUS were found in the majority of hepatic AMLs. The combination of BUS and CEUS leads to the correct diagnosis in the majority of hepatic AMLs, and is higher than the success rate achieved by BUS alone.

Enhancement patterns of intrahepatic cholangiocarcinoma: comparison between contrast-enhanced ultrasound and contrast-enhanced CT.

The aim of this study was to compare the enhancement pattern of intrahepatic cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) with that on contrast-enhanced computed tomography (CECT). 40 pathologically proven ICC lesions in 40 patients were evaluated retrospectively with both CEUS and CECT. The enhancement level and pattern in the dynamic phases on both CEUS and CECT were analysed. The diagnostic results of CEUS and CECT before pathological examination were also recorded. During arterial phases, the number of lesions that appeared as (i) peripheral irregular rim-like hyperenhancement, (ii) diffuse heterogeneous hyperenhancement, (iii) diffuse homogeneous hyperenhancement and (iv) diffuse heterogeneous hypoenhancement were 19 (47.5%), 9 (22.5%), 5 (12.5%) and 7 (17.5%), respectively, on CEUS, and 22 (55.0%), 3 (7.5%), 2 (5.0%) and 13 (32.5%), respectively, on CECT (p = 0.125). In the portal phase, the number of lesions showing hyperenhancement and hypoenhancement were 1 (2.5%) and 39 (97.5%), respectively, on CEUS, and 15 (37.5%) and 25 (62.5%) on CECT (p = 0.0001). CEUS made a correct diagnosis in 32 (80.0%) lesions before pathological examination; CECT made a correct diagnosis in 27 (67.5%) lesions (p = 0.18). In conclusion, the enhancement patterns of ICC on CEUS were consistent with those on CECT in the arterial phase, whereas in the portal phase ICC faded out more obviously on CEUS than on CECT. CEUS had the same accuracy as CECT in diagnosing ICCs, and so can be used as a new modality for the characterization of ICC.

Correlation between enhancement pattern of hepatocellular carcinoma on real-time contrast-enhanced ultrasound and tumour cellular differentiation on histopathology.

The objective of this study was to evaluate the correlation between the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS) and tumour cellular differentiation on histopathology. 189 HCC lesions in 189 patients were retrospectively evaluated with CEUS and histopathological examination. CEUS was performed with SonoVue and contrast pulse sequencing. Histopathological diagnoses were made according to the Edmonson grading system. Significant differences were shown between the time that the HCC became hypoenhancing or remained echogenic in late phase and tumour cellular differentiation (p = 0.006; p = 0.036), but not with the time of commencement of hyperenhancing or commencement of isoenhancing in arterial phase and portal phase (p = 0.164, p = 0.113; p = 0.186, p = 0.070). The timing of HCC becoming hypoenhancing on CEUS is correlated with tumour cellular differentiation; well differentiated tumours wash out more slowly than poorly differentiated ones.

Percutaneous thermal ablation for recurrent hepatocellular carcinoma after hepatectomy.

BACKGROUND: Tumour ablation using a thermal energy source has shown promising results, and is particularly suitable for recurrent hepatocellular carcinoma (HCC). The present study evaluated long-term outcomes after percutaneous thermal ablation for recurrent HCC following liver resection. METHODS: Radiofrequency ablation or microwave ablation was used to treat a total of 124 tumour nodules (0.9-7.0 cm in diameter) in 72 patients with recurrent HCC. RESULTS: Complete ablation of 119 (96.0 per cent) of 124 tumour nodules was achieved. There was no treatment-related death and the major complication rate was 4 per cent. During a mean(s.d.) follow-up of 27.9(17.8) months, local recurrence developed in 16 (13.6 per cent) of 118 successfully treated tumour nodules. Distant recurrence developed in 60 (85 per cent) of 71 patients, of whom 26 had repeat metachronous distant recurrence. With repeated ablation for both local and distant recurrence, the 1-, 3- and 5-year overall survival rates after initial ablation were 75, 43 and 18 per cent respectively. Patients with a serum alpha-fetoprotein level greater than 200 ng/ml before treatment had significantly poorer survival than those with a lower level (P = 0.034) and multivariate analysis identified preablation AFP level as an independent prognostic factor (P = 0.054). CONCLUSION: With their advantages of preservation of non-tumorous liver tissue and easy repetition, percutaneous thermal ablative therapies were particularly suitable for recurrent HCC and improved long-term survival.

Prognostic factors for long-term outcome after percutaneous thermal ablation for hepatocellular carcinoma: a survival analysis of 137 consecutive patients.

AIM: To identify prognostic factors for long-term outcome for patients with hepatocellular carcinoma (HCC) after percutaneous microwave or radiofrequency ablation. MATERIALS AND METHODS: In total, 137 consecutive patients with HCC underwent microwave or radiofrequency ablation with curative intent; 16 possible prognostic factors were evaluated for their association with overall survival (OS) and disease-free survival (DFS) using univariate and multivariate analysis. RESULTS: The median OS and DFS were 27.0 months and 8.2 months, respectively. OS rates for all patients at 1, 2, 3, 4 and 5 years were 73.9%, 52.1%, 42.8%, 26.2% and 20.1%, respectively. DFS rates at 1, 2, 3 and 4 years were 38.1%, 21.9%, 18.8%, and 14.1%, respectively. Pretreatment serum alpha-fetoprotein (AFP) >200 ng/ml, pretreatment serum albumin 14 s were identified to be significant predictors for DFS by univariate analysis, and the former was the only independent predictor for DFS by multivariate analysis. CONCLUSION: Prognosis for patients with HCC after thermal ablation with curative intent was determined by treatment response to ablation, pretreatment serum AFP, and liver function reserve. Tumour response to treatment was the most predictive factor for long-term survival and was related to tumour size, thus careful selection of patients for ablation therapy is recommended.