Targeted bile acid profiles reveal the liver injury amelioration of Da-Chai-Hu decoction against ANIT- and BDL-induced cholestasis.

Multiple types of liver diseases, particularly cholestatic liver diseases (CSLDs) and biliary diseases, can disturb bile acid (BA) secretion; however, BA accumulation is currently seen as an important incentive of various types of liver diseases' progression. Da-Chai-Hu decoction (DCHD) has long been used for treating cholestatic liver diseases; however, the exact mechanisms remain unclear. Currently, our study indicates that the liver damage and cholestasis status of the α-naphthylisothiocyanate (ANIT)-induced intrahepatic cholestasis and bile duct ligation (BDL)-induced extrahepatic cholestasis, following DCHD treatment, were improved; the changes of BA metabolism post-DCHD treatment were investigated by targeted metabolomics profiling by UPLC-MS/MS. DCHD treatment severely downregulated serum biochemical levels and relieved inflammation and the corresponding pathological changes including necrosis, inflammatory infiltration, ductular proliferation, and periductal fibrosis in liver tissue. The experimental results suggested that DCHD treatment altered the size, composition, and distribution of the BAs pool, led the BAs pool of the serum and liver to sharply shrink, especially TCA and TMCA, and enhanced BA secretion into the gallbladder and the excretion of BAs by the urinary and fecal pathway; the levels of BAs synthesized by the alternative pathway were increased in the liver, and the conjugation of BAs and the pathway of BA synthesis were actually affected. In conclusion, DCHD ameliorated ANIT- and BDL-induced cholestatic liver injury by reversing the disorder of BAs profile.

Quality evaluation of rhubarb based on qualitative analysis of the HPLC fingerprint and UFLC-Q-TOF-MS/MS combined with quantitative analysis of eight anthraquinone glycosides by QAMS.

Rhubarb is one of the most ancient and important herbal medicines, but its current quality evaluation (QE) methods have some limitations. In this study, a new method was developed for the comprehensive QE of rhubarb. First, fingerprints of 28 batches of three species of rhubarb samples were determined by HPLC, the reference fingerprint was established and the common peaks were assigned. Second, the components of common peaks in the fingerprints were identified by ultrafast liquid chromatography quadrupole time-of-flight mass spectrometry. Finally, a method for the simultaneous determination of the contents of eight anthraquinone glycosides in rhubarb using quantitative analysis of multiple components by a single marker (QAMS) was established, and the contents of these eight components in 28 batches of rhubarb determined by QAMS and the external standard method were compared. The results showed that there were 31 common peaks in the rhubarb fingerprint. The components of these 31 common peaks were identified, and 20 of them were unambiguously confirmed by reference substances, including eight anthraquinone glycosides. The contents of eight anthraquinone glycosides in the 28 batches of rhubarb determined by QAMS and the external standard method were not significantly different. In conclusion, the method established in this study can be used for the comprehensive QE of rhubarb and can also provide a reference for the QE of other herbal medicines.

[Study on the prognosis of the T1a non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: The new edition of the TNM staging for lung and pleural tumours has been finished, which put weight on the extent of primary tumor as one of the important prognosises. But little study has performed on the primary tumor extent < or = 2 cm. The aim of this study is to explore the prognosis of patients with tumor extent < or = 2 cm in stage I of non-small cell lung cancer, which helps us to choose the best treatment for these patients. METHODS: Retrospective study on the clinical response and survival time of whom underwent complete surgical resection and diagnosed as T1a of stage I NSCLC from 1998 to 2004 was analyzed. Data was analyzed by SPSS 17.0 software. RESULTS: Overall survival rate was 80.8%. By the study, age (P = 0.241), gender (P = 0.175), history of smoking (P = 0.845), pathologic type ( P =0.265), and systematic mediastinal lymphadenectomy (SML )(P = 0.918) or not, postoperative adjuvant chemotherapy or not ( P = 0.616) and visceral pleural invasion (P = 0.827) were not the prognosises of these patients. Only the tumor differentiation such as poorly differentiated was the important prognosis ( P = 0.01). CONCLUSION: In the tumor extent < or = 2 cm of stage I non-small cell lung cancer, the visceral pleural invasion maybe not influence the patients survival. The tumor differentiation is one of the important prognostic factors.

[Effects of MVP regimen on operation and cancer tisswes of Lung Cancer patients.].

BACKGROUND: Preoperative chemotherapy increases the difficulty and risk of patients' operation. The aim of this study is to analyze the change of thoracic tissue, study the influence of chemotherapy to operation, discuss the special aspects of surgical management and observe the pathological change of focus after chemotherapy. METHODS: 100 patients were chosen and randomly divided into two groups(operation first group, 50 cases; chemotherapy first group, 50 cases) . Some patient's pathological sections were observed to investigate focus morphological influence of preoperative chemotherapy and the clinical response rate were compared with pathological response rate. RESULTS: It was showed that preoperative chemotherapy conduced different degree thoracic tissue fibrosis. Data statistics demonstrated that there were no significance difference of the operation time, blood loss during operation and drainage volume in first day after operation between two groups. The preoperative chemotherapy increased the difficulty of operation because of tissue fibrosis and scarification, but the risk could be avoided by skillful operation. In first operation group, there were various pathological changes in tumor tissue and the pathological response rate was not completely accordance with the clinical response rate. The focus pathological response rate of two cycles chemotherapy was more higher than that of one cycle chemotherapy. CONCLUSIONS: IDO Chemotherapy increases the risks of operation. Surgeons carefulness and better skills during operation are the key points to avoid the hazards of surgery. Two preoperative chemotherapy cycles are more suitable for the patients.

[Effects of pulmonary veins ligation style for the patients' stress and cardiac on lung cancer.].

BACKGROUND: It is needed to explore the effects of operation on stress statue, myocardial damage and arrhythmia to lung cancer. This study would compare the effects of two ligation styles of pulmonary vein on lung cancer patients' stress and cardiac postoperative. METHODS: 54 cases were divided into two groups randomly: the pulmonary vein trunk-ligation group (trunk group, 27 cases) and the pulmonary vein branch-ligation group (branch group, 27 cases). The blood concentrations of hydrocortisone (HC), blood glucose (BG) and cardial troponin-I (cTnI) were determined at different time point. The surgical data, the quantum of pain and ECG also recorded. RESULTS: (1) There were no significance difference of the operation time, blood loss during operation and drainage volume in first day after operation between two groups. (2) There're no differences of the quantum of pain between two groups. (3) The HC of the two groups' ascend obviously on the end of operation and descend during postoperative. (4) The BG of the two groups' rise on the 1st day obviously, maintain high level on the 2nd day, descend on the 3rd day but still higher than that of preoperation. (5) The BG and HC show a direct positive correlation postoperative. (6) The cTnIs of the trunk group ascend immediately after operation, but there's no statistically significance between two groups. (7) The arrhythmia incidence is higher in the trunk group, but the arrhythmia incidences classified by the date after operation of the two groups' show no distinction. CONCLUSIONS: (1) The effects of two pulmonary vein ligation styles on postoperative stress show no significance differences. (2) The style of pulmonary vein trunk-ligation has a more obvious tendency to do harm to heart than that of branch-ligation. (3) The style of pulmonary vein branch-ligation may reduce the arrhythmia incidence after operation.

[The prognostic value of detection of serum VEGF-C level and lymphangiogenesis in mediastinal lymph nodes in the patients with lung cancer.].

BACKGROUND: There is still lack of special prognostic factor on lung cancer, this study will explore the prognostic value of serum VEGF-C level and lymphangiogenesis of primary cancer and mediastinal lymph nodes in the patients with lung cancer. METHODS: Thirty patients with NSCLC would accept operation (new group) and 30 cases followed up three years postoperative (history group) were chosen respectively. The serum VEGF-C level of new group was tested. The VEGF-C and LYVE-1 expression in the mediastinal lymph nodes were put in practice between two groups. The relationship was analyzed for the serum VEGF-C level, VEGF-C and LYVE-1 expression of primary cancer and mediastinal lymph nodes, mediastinal lymph nodes metastasis and the 3-year survival rate of the patients. RESULTS: (1)In new group, the serum VEGF-C level of N2 patients was significantly higher than that of non-N2 patients. (2)In new group, the serum VEGF-C level was closely correlated with VEGF-C expression of primary cancer. (3)In two groups, the primary cancer and mediastinal metastasis lymph nodes had high VEGF-C expression. (4)VEGF-C expression of primary cancer and mediastinal lymph nodes was closely correlated with LYVE-1 expression between the two groups. (5)VEGF-C and LYVE-1 expression of N2 patients was significantly higher than that of non-N2 patients between two groups. (6)The patients' 3-year-survival rate was closely correlated with VEGF-C expression of primary cancer and mediastinal lymph nodes metastasis. CONCLUSIONS: Serum VEGF-C level has close correlation with VEGF-C expression of primary cancer, lymphangiogenesis of primary cancer/mediastinal lymph nodes, mediastinal lymph nodes metastasis status and patient's survival rate. Serum VEGF-C level is possible to be used as prognostic factor on lung cancer.

[Trachea-bronchoplasty in the surgical treatment of locally advanced non-small cell lung cancer].

BACKGROUND: Some of the locally advanced non-small cell lung cancer (NSCLC) need different trachea-bronchoplasty operative styles in order to make the widest possible to resect the tumor and remain normal pulmonary function. The aim of this study is to explore the surgical problem during trachea-bronchoplasty operation. METHODS: There were 2206 patients with NSCLC underwent surgical treatment from January 2003 to June 2005 in this hospital. Of the 2206 cases, 100 patients accepted the trachea-bronchoplasty, whose clinic data were analyzed. There were 42 cases of squamous cell carcinoma, 23 adenosquamous carcinoma, 11 adenocarcinoma, 5 mucoepidermoid carcinoma, 4 adeoid cystic carcinoma, 3 carcinoid and 12 undetermined. Thirty-four cases were in stage IB, 23 in stage IIB, 23 in stage IIIA and 20 in stage IIIB. There were 42 cases of right upper sleeve lobectomy, 1 right lower sleeve lobectomy, 24 left upper sleeve lobectomy, 4 left lower sleeve lobectomy, 8 sleeve bilobectomy, 17 carinal reconstruction, 4 sleeve lobectomy plus pulmonary artery angioplasty. RESULTS: Complete resection (R0) of the cancer was performed in 97 patients and uncomplete resection (margin positive, R1) was performed in 3 patients. Postoperative complication happened in 5 cases (the occurrence rate was 5%): Pneumonia in 2 cases, pleura cavity infection in 1 case, broncho-pleura fistula in 1 case, alveoli-pleura fistula in 1 case. One patient died of pulmonary infection, the operative mortality was 1%. The postoperative inpatient time was from 4 days to 27 days, with median of 11 days. CONCLUSIONS: Trachea-bronchoplasty is suitable for some patients of the locally advanced NSCLC and consistent to the tumor surgical treatment principle. A satisfactory cure effect can be obtained for undergoing such operative style. The key point of successful operation is the operating skill to manage trachea, bronchi and pulmonary vessels.

[Treatment of 40 patients with primary tracheal carcinoma].

OBJECTIVE: To study the efficacy of treatment in 40 patients with primary tracheal carcinoma. METHODS: From 1970 to 2001, 40 patients with primary tracheal carcinoma treated in our hospital were retrospectively reviewed. Twenty-eight were male and 12 were female with median age of 47 years. The median interval from onset of symptoms to diagnosis was 10 months (1 - 60 months). Fifteen patients had adenoid cystic carcinoma, 14 squamous cell carcinoma, 8 adenocarcinoma, 2 small-cell carcinoma and 1 mucoepidermoid carcinoma. Thirty-two patients received operation plus adjuvant radiotherapy, 6 received radiotherapy alone and 2 received operation alone. RESULTS: The median survival time for all patients was 40 months. The 1-, 5-, and 10-year survival rate was 86%, 59% and 29%, respectively. The 1-, 5-, and 10-year local control rate was 84%, 60% and 50%, respectively. Distant metastasis rate in 1, 5, and 10 years was 17%, 51% and 84%, respectively. CONCLUSION: Surgical resection plus adjuvant radiotherapy is a reasonable mode of treatment. Despite late local recurrence after initial treatment, its intrinsic feature, excellent long-term palliation can be achieved after treatment.

[Surgical treatment of apical chest tumor in 27 patients].

OBJECTIVE: To explore the "hemi-clamshell" approach to the resection of the apical chest tumors, and to evaluate its advantages of operative safety and completeness. METHODS: We conducted a retrospective review of the records of 27 patients undergoing resection of the primary apical chest tumors from January 1995 to January 2001. Tumor type included NSCLC, sarcoma, neurofibromatosis, esophageal carcinoma. Data collected included clinical presentation, tumor type and involvement, type of resection, complication, and survival. RESULTS: A clinical operation for gross-total resection of tumors and invaded structures was performed on six patients by means of a successful anterior approach. Among other 21 patients on whom a clinical operation was performed by posterior approach, only 13 patients obtained gross-total resection. There were significant difference between the two groups (P < 0.01). The mean duration for follow-up was 29 months, and the overall median survival was 21 months. Median survival in patients undergoing gross-total resection was 29 months, and this is significantly better than in incomplete resection group (P < 0.01). CONCLUSIONS: The anterior "hemi-clamshell" approach is a successful technique for the exposure and resection of these tumors and invaded structures. Release of symptoms and long-term survival is acceptable if complete resection can be performed.

[Ultrasound surveillance of cervical lymph node metastasis in thoracic esophageal carcinoma].

OBJECTIVE: To improve the accuracy of preoperative evaluation of cervical lymph node metastasis in thoracic esophageal squamous carcinoma. METHODS: Forty-two patients with thoracic esophageal squamous carcinoma underwent neck ultrasonography. Enlarged lymph nodes with their long axis greater than 10 mm and a short-to-long axis ratio greater than 0.5 were considered as metastatic. RESULTS: Preoperative neck ultrasonography revealed the enlarged lymph nodes in 16 patients, but only in 5 (31%) cases the nodes were palpable. Among them 9 were classified as metastatic (cM(1-LN)), including 4 patients with palpable nodes. In 5 cM(1-LN) patients surgical intervention was canceled and the remaining 37 patients underwent trans-thoracic esophagectomy. Cervical node metastasis (pM(1-LN)) was confirmed pathologically in 6 surgical patients, 4 with tumors invading the adventitia (pT3) and the other 2 into the surrounding structure (pT(4)) (pT(1), pT(2) vs. pT(3), pT(4), P = 0.020). All 6 pM(1-LN) patients had concomitant mediastinal node metastasis and 4 of them had upper abdominal node metastasis. Statistically significant relationship was detected between cervical and abdominal nodal status (r = 0.536, P = 0.007). In comparison with the results of pathological examination and treatment response, the accuracy and sensitivity were 81% and 95% (P = 0.043), 36% and 82% (P = 0.081), respectively, for palpation and ultrasonography. Five out of 39 (13%) patients had their therapy changed due to ultrasonographic findings. CONCLUSIONS: Neck ultrasonography for cervical lymphadenopathy is of high sensitivity and accuracy, which plays an important role in the preoperative evaluation and therapeutic decision-making.

[The study of peri-operative chemotherapy in stage I-IIIa NSCLC].

OBJECTIVE: A number of studies had evaluated the benefit of neoadjuvant chemotherapy combined surgery on stage IIIa-IIIb NSCLC, survival benefit was found in several papers. We attempt to evaluate the survival and prognosis of cisplatinum-based schedule as peri-operative CT for resectable stage I-IIIa NSCLC. METHODS: A prospective, randomized, multicenter study was conducted by Shanghai Lung Cancer Team (supported by Shanghai Branch of Discipline Foundation) since 1995-1997 for 211 cases of stage I-IIIa NSCLC with curative resection (99 stage I, 47 stage II, 65 stage III), age of or= 80, staged by 1997 AJC TNM Criteria. They were randomized to be 103 cases with 1 - 2 cycles of pre-operative CT and 108 cases with no pre-operative CT, 2 - 4 cycles of post-operative CT were used for stage II and stage IIIa NSCLC, it was totally 4 cycles of MVP or MOP CT schedule each case. Follow-up team had been trained, the follow-up rate should be >or= 95%, last follow-up date was March of 2002. Lobectomy was performed for most patients. Accumulated survival, log rank, MST, Cox uni-variance and multi-variance analyses were used as statistics for evaluation. RESULTS: The two arms were well balanced for baseline demographic and clinical characteristics (P > 0.05 for all). Stage I NSCLC had the best year-survival in whole patients. No statistical survival difference was found between the group with pre-op CT and with no pre-op CT, P = 0.074, 0.087 and 0.097, respectively, 5-year survival rates were of 31.98%:36.68%. In various stage, a statistical survival difference was only shown in stage IINSCLC, P = 0.042, 5-year survival rates and MST were worse in the group with pre-operation CT, 20%:65.2% and 24 months:48 months, respectively, but no difference was seen in stage I and stage IIIa NSCLC. Stage and post-operation CT were the only two meaningful parameters with statistical survival difference calculated by multi-variance analyses, P = 0.000 all, but no difference was found in others 4 parameters (age, sex, type and pre-operation CT). The response rate of pre-operation CT was of 50%. Though there was no statistical difference, the responders were with slightly better year-survival rates than MR + NR patients, 38.9% and 33.3%, respectively. In the cases with pathological "T" down stage and "T" unchanged after pre-operation CT had a better yr-survival rates than "T" up-stage, P = 0.03, 5-year survival rates were of 41.67%, 40.51% and 11.76%, respectively, thus, effective chemotherapy might be beneficial to survival. Besides, in the cases with >or= 3 cycles of post-operation CT have better survival rates than less cycles. CONCLUSION: A prospective, randomized, multicenter peri-operation CT study for stage I-IIIa NSCLC conducted in Shanghai, China., it showed there had no benefit in survival between with pre-operation CT arm and with no pre-operation CT arm. In stage II NSCLC, pre-operation CT cases had a worse year-survival than with no pre-operation CT, P = 0.042, but no difference was seen in stage I and stage IIIa NSCLC. The responder of CT and "T" down stage, "T" unchanged had better survival rates than those of not response and "T" up-stage. From multivariate analyses, stage and post-operation CT were the two meaningful parameters to year-survival, >or= 3 - 4 cycles of post-operation CT had a better statistical higher year-survival than less cycles. Nutrition, supportive treatment, immunity status and prevention of toxicity might be the next study worthy to conduct, for CT combined with OP.

Hematogenous dissemination of lung cancer cells during surgery: quantitative detection by flow cytometry and prognostic significance.

Shedding of neoplastic cells into the circulation is an essential event for the hematogenous metastasis of solid tumors. Recently, several studies reported that a high frequency of cancer cells could be detected in the bloodstream during surgery. The intraoperative detection of hematogenous dissemination of cancer cells was able to identify a subset of patients with malignant diseases at high risk for postoperative metastasis and to predict a poor prognosis. In order to evaluate the association between intraoperative dissemination of cancer cells and postsurgical survival of patients with non-small cell lung cancer (NSCLC), we developed a flow cytometric assay for specific detection of lung cancer cells in the blood. The monocyte-enriched population in the blood was separated by a modified Ficoll-Hypaque density centrifugation and then labeled with a combination of monoclonal antibodies specific for CD45, cytokeratin (CK) and two antigens expressed on lung cancer cells (2F7 and S5A). The assay could detect quantitatively lung cancer cells (defined as CD45(-1) CK(+) 2F7/S5A(+) cells), with the sensitivity limit of one cancer cell in 10(5) normal leukocytes. The specificity for lung cancer was 97%, which was calculated from the results of healthy subjects (20 cases) and patients affected with benign pulmonary diseases (26 cases) or esophageal cancer (14 cases). Blood samples of 31 NSCLC patients were collected from pulmonary vein during open thoracic surgery. Fifteen of them (48.4%) were found to have positive test results. The average cancer cell counts in these cases were 0.306 x 10(6)/l. Patients under 55 years of age had a significantly higher percentage of positive findings than those over 55 years of age (P < 0.05). The positive rate increased over the stages and lymph node status, but the differences were not statistically significant. Moreover, patients with squamous cell carcinoma at later stages (stages III and IV) had an increased frequency of positive test results than those at earlier stages (stages I and II, P < 0.05). In contrast, no such a difference was found in cases with adenocarcinoma. On the basis of 30-months follow-up date, the median survival time and 2-year survival rate for patients with positive and negative findings were 11 vs. 27 months, and 26.7 vs. 62.5%, respectively. There was a statistically significant difference between overall survival curves that favored the patients with negative test results (P = 0.023). Multivariate analysis indicated the stage of disease and the positive test results as two independent factors that affected survival time (P = 0.017 and 0.027). When a comparison was made within the patients at stages III and IV, the presence of cancer cells in blood was associated with a significantly shorter survival. These data indicate that the hematogenous dissemination of lung cancer cells during surgery would be one of the mechanisms of postoperative tumor metastasis. The detection of these cells may help to identify patients with poor prognosis.