Prognostic Significance of Preoperative Serum Alpha- fetoprotein in Hepatocellular Carcinoma and Correlation with Clinicopathological Factors: a Single-center Experience from China.

OBJECTIVES: To investigate the prognosis significance of preoperative serum alpha-fetoprotein (AFP) and the correlation with clinicopathological factors of hepatocellular carcinoma (HCC) patients who underwent hepatectomy. MATERIALS AND METHODS: Clinicopathological data of retrospective analysis were collected for 251 HCC patients undergoing hepatectomy in this study. According to preoperative AFP level, patients were categorized into AFP-negative (0-20 ng/mL) and AFP-positive (>20 ng/mL) groups for Kaplan-Meier analysis and Cox proportional hazard regression modeling. RESULTS: The results demonstrated that increased AFP was associated with longer prothrombin time (PTs), liver capsule invasion, low grade differentiation, and late Barcelona Clinic Liver Center (BCLC) stage. Moreover, the female patients had a greater prevalence of increased preoperative AFP than male patients [284.8 (3.975-3167.5) vs (3.653-140.65); Z-2.895, p=0.004]. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 78.1, 57.5, and 40.6 % in the AFP-negative group and 61.8, 37.7, and 31.4 %, respectively, in the AFP-positive group (log-rank test 8.312, p=0.004). The 1-, 3-, and 5-year overall survival (OS) rates were 94.4, 83.8, and 62.3% in the AFP-negative group and 87.2, 60.0, and 36.7%, respectively, in the AFP-positive group. The difference was statistically significant (log-rank test, 16.884, p=0.000). Cox proportional-hazards model identified preoperative AFP to be an independent prognostic predictor of overall survival. CONCLUSIONS: Preoperative serum AFP is an independent predictor of prognosis among HCC patients following surgical resection. Female patients have a higher preoperative AFP than their male counterparts.

Hepatocellular adenoma with malignant transformation in male patients with non-cirrhotic livers.

INTRODUCTION: Hepatocellular adenomas (HCAs), with a risk of malignant transformation into hepatocellular carcinoma (HCC), classically develop in young women who are taking oral contraceptives. It is now clear that HCAs may also occur in men. However, it is rarely reported that HCAs with malignant transformation occur in male patients with non-cirrhotic livers. This study aimed to characterize the malignancy of HCAs occurring in male patients. METHODS: All patients with HCAs with malignant transformation who underwent hepatectomy at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 1, 1999 and December 31, 2011 were enrolled in the study. The clinical characteristics as well as radiologic and pathologic data were reviewed. RESULTS: HCAs with malignant transformation were observed in 5 male patients with non-cirrhotic livers, but not in female patients. The alpha-fetoprotein (AFP) levels were higher in patients with HCAs with malignant transformation than in patients with HCAs without malignant transformation. The diameters of the tumors with malignant transformation were larger than 5 cm in 3 cases and smaller than 5 cm in 2 cases. The 5 patients were all alive without recurrence by the end of the study period. The disease-free survival times of the 5 patients were 26, 48, 69, 69, and 92 months. CONCLUSION: Our results indicate that resection would be advised even if the presumptive diagnosis is adenoma smaller than 5 cm in diameter, especially in male patients.

Primary lymphoepithelioma-like hepatocellular carcinoma: report of a locally advanced case and review of literature.

Lymphoepithelioma-like hepatocellular carcinoma is rare, which has been recognized as a variant of hepatocellular carcinoma. Here we report a locally advanced case of lymphoepithelioma-like hepatocellular carcinoma. A 50-year-old man with chronic hepatitis B virus infection presented with a single mass in the liver and two enlarged lymph nodes in retroperitoneum suspected to be hepatocellular carcinoma with lymph node metastasis. After discussion by multidisciplinary team, the patient underwent hepatectomy of VIII segment and dissection of two enlarged lymph nodes. One month after the operation, pre-chemotherapy abdominal computed tomography (CT) showed retroperitoneal enlarged lymph nodes, considered as local recurrence. Therefore, 3 cycles of oxaliplatin and tegafur gimeracil oteracil potassium capsule and 3 cycles of paclitaxel and cisplatin were offered, and post-chemotherapy abdominal CT revealed disease remained stable. The patient has been alive for 6 months since performance of surgery. Our report suggests that even locally advanced lymphoepithelioma-like hepatocellular carcinoma may have a good prognosis and operation and postoperative chemotherapy may benefit the patient.

Three-dimensional morphometric analysis for hepatectomy of centrally located hepatocellular carcinoma: a pilot study.

AIM: To describe a three-dimensional model (3DM) to accurately reconstruct anatomic relationships of centrally located hepatocellular carcinomas (HCCs). METHODS: From March 2013 to July 2014, reconstructions and visual simulations of centrally located HCCs were performed in 39 patients using a 3D subject-based computed tomography (CT) model with custom-developed software. CT images were used for the 3D reconstruction of Couinaud's pedicles and hepatic veins, and the calculation of corresponding tumor territories and hepatic segments was performed using Yorktal DMIT software. The respective volume, surgical margin, and simulated virtual resection of tumors were also estimated by this model preoperatively. All patients were treated surgically and the results were retrospectively assessed. Clinical characteristics, imaging data, procedure variables, pathologic features, and postoperative data were recorded and compared to determine the reliability of the model. RESULTS: 3D reconstruction allowed stereoscopic identification of the spatial relationships between physiologic and pathologic structures, and offered quantifiable liver resection proposals based on individualized liver anatomy. The predicted values were consistent with the actual values for tumor mass volume (82.4 ± 109.1 mL vs 84.1 ± 108.9 mL, P = 0.910), surgical margin (10.1 ± 6.2 mm vs 9.1 ± 5.9 mm, P = 0.488), and maximum tumor diameter (4.61 ± 2.16 cm vs 4.53 ± 2.14 cm, P = 0.871). In addition, the number and extent of portal venous ramifications, as well as their relation to hepatic veins, were visualized. Preoperative planning based on simulated resection facilitated complete resection of large tumors located in the confluence of major vessels. And most of the predicted data were correlated with intraoperative findings. CONCLUSION: This 3DM provides quantitative morphometry of tumor masses and a stereo-relationship with adjacent structures, thus providing a promising technique for the management of centrally located HCCs.

Catalytic Isonitrile Insertions and Condensations Initiated by RNC-X Complexation.

Isonitriles are delicately poised chemical entities capable of being coaxed to react as nucleophiles or electrophiles. Directing this tunable reactivity with metal and non-metal catalysts provides rapid access to a large array of complex nitrogenous structures ideally functionalized for medicinal applications. Isonitrile insertion into transition metal complexes has featured in numerous synthetic and mechanistic studies, leading to rapid deployment of isonitriles in numerous catalytic processes, including multicomponent reactions (MCR). Covering the literature from 1990-2014, the present review collates reaction types to highlight reactivity trends and allow catalyst comparison.

Retrospective evaluation of discrepancies between radiological and pathological size of hepatocellular carcinoma masses.

BACKGROUND: The size of a hepatic neoplasm is critical for staging, prognosis and selection of appropriate treatment. Our study aimed to compare the radiological size of solid hepatocellular carcinoma (HCC) masses on magnetic resonance imaging (MRI) with the pathological size in a Chinese population, and to elucidate discrepancies. MATERIALS AND METHODS: A total of 178 consecutive patients diagnosed with HCC who underwent curative hepatic resection after enhanced MRI between July 2010 and October 2013 were retrospectively identified and analyzed. Pathological data of the whole removed tumors were assessed and differences between radiological and pathological tumor size were identified. All patients were restaged using a modified Tumor-Node-Metastasis (TNM) staging system postoperatively according to the maximum diameter alteration. The lesions were classified as hypo-staged, iso-staged or hyper-staged for qualitative assessment. In the quantitative analysis, the relative pre and postoperative tumor size contrast ratio (%Δsize) was also computed according to size intervals. In addition, the relationship between radiological and pathological tumor diameter variation and histologic grade was analyzed. RESULTS: Pathological examination showed 85 (47.8%) patients were overestimated, 82 (46.1%) patients underestimated, while accurate measurement by MRI was found in 11 (6.2%) patients. Among the total subjects, 14 (7.9%) patients were hypo-staged and 15 (8.4%) were hyper-staged post-operatively. Accuracy of MRI for calculation and characterized staging was related to the lesion size, ranging from 83.1% to 87.4% (<2cm to ≥5cm, p=0.328) and from 62.5% to 89.1% (cT1 to cT4, p=0.006), respectively. Overall, MRI misjudged pathological size by 6.0 mm (p=0.588 ), and the greatest difference was observed in tumors <2cm (3.6 mm, %Δsize=16.9%, p=0.028). No statistically significant difference was observed for moderately differentiated HCC (5.5mm, p=0.781). However, for well differentiated and poorly differentiated cases, radiographic tumor maximum diameter was significantly larger than the pathological maximum diameter by 3.15 mm and underestimated by 4.51 mm, respectively (p=0.034 and 0.020). CONCLUSIONS: A preoperative HCC tumor size measurement using MRI can provide relatively acceptable accuracy but may give rise to discrepancy in tumors in a certain size range or histologic grade. In pathological well differentiated subjects, the pathological tumor size was significantly overestimated, but underestimated in poorly differentiated HCC. The difference between radiological and pathological tumor size was greatest for tumors <2 cm. For some HCC patients, the size difference may have implications for the decision of resection, transplantation, ablation, or arterially directed therapy, and should be considered in staging or selecting the appropriate treatment tactics.

[Comparative study of three types of anatomical vascular occlusion method in hepatectomy for liver neoplasms].

OBJECTIVE: To assess the clinical efficacies of three types of anatomical hepatic inflow occlusion method in hepatectomy for liver neoplasms. METHODS: A non-randomized concurrent controlled trial was performed from January 2011 to October 2012, a total of 180 consecutive patients with liver neoplasms underwent hepatectomy similarly. They were divided into 3 groups according to the hepatic inflow occlusion methods during resection: HHV group (hemi-hepatic vascular inflow occlusion, n = 60), MPV group (main portal vein inflow occlusion, n = 60) and HPP group (hemi-portal vein preserved inflow occlusion, n = 60). The primary endpoints were intraoperative blood loss and transfusion requirement while the secondary outcomes were assessed with operating duration, postoperative morbidity, hospital stay, gastrointestinal function and postoperative liver injury. RESULTS: No significant differences existed among three groups in demographic and tumor characteristics and operation-related background (P > 0.05). No mortality happened in 30 days postoperatively in all patients. Intraoperative volume of blood loss had no significant differences among three groups (P = 0.272). Among the patients requiring transfusion, HPP group had the least transfusion requirement (HHV group: (5.00 ± 1.51) U, MPV group:(3.50 ± 1.41) U, HPP group: (2.50 ± 0.93) U, P = 0.004). MPV group showed a significant shorter operating duration (HHV group: (227 ± 59) min, MPV group:(198 ± 56) min, HPP group:(221 ± 79) min, P = 0.042). No significant differences were found among three groups in hospital stay (P = 0.673) or postoperative morbidity (P = 0.735), including hepatic insufficiency, infection and ascites. HHV group showed an earlier recovery of gastrointestinal function (HHV group: (60 ± 12) h, MPV group:(69 ± 9) h, HPP group:(64 ± 8) h, P = 0.000).MPV group had a significantly lower level of aminotransferase at Day 1 and 3 postoperation (d1 ALT: HHV group: (403 ± 271) U/L, MPV group:(304 ± 211) U/L, HPP group: (448 ± 396) U/L, P = 0.033; d1 AST: HHV group: (394 ± 271) U/L, MPV group:(278 ± 189) U/L, HPP group: (432 ± 405) U/L, P = 0.017; d3 ALT: HHV group: (309 ± 193) U/L, MPV group:(232 ± 161) U/L, HPP group:(325 ± 277) U/L, P = 0.048; d3 AST: HHV group:(136 ± 105) U/L, MPV group:(91 ± 73) U/L, HPP group:(120 ± 87) U/L, P = 0.024).But no significant differences were found among three groups regarding total bilirubin, albumin, prealbumin and prothrombin time activity (P < 0.05) during any postoperative stage. CONCLUSION: All three types of anatomical vascular occlusion method are both safe and efficacious in hepatectomy. But no single method has absolute advantage over the other two. HPP method has the best hemostatic effect, MPV offers better postoperative liver function and HHV promotes early recovery of gastrointestinal function.

Anti-AIDS agents 86. Synthesis and anti-HIV evaluation of 2',3'-seco-3'-nor DCP and DCK analogues.

In a continuing study of novel anti-HIV agents with drug-like structures and properties, 30 1'-O-, 1'-S-, 4'-O- and 4'-substituted-2',3'-seco-3'-nor DCP and DCK analogues (8-37) were designed and synthesized. All newly synthesized seco-compounds were screened against HIV-1(NL4-3) and a multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR) strain in the TZM-bl cell line, using seco-DCK (7) and 2-ethyl-DCP (4) as controls. Several compounds (14, 18, 19, 22-24, and 32) exhibited potent anti-HIV activity with EC(50) values ranging from 0.93 to 1.93 µM and therapeutic index (TI) values ranging from 20 to 39. 1'-O-Isopropoxy-2',3'-seco-3'-nor-DCP (12) showed the greatest potency among the newly synthesized compounds with EC(50) values of 0.47 and 0.88 µM, and TI of 96 and 51, respectively, against HIV-1(NL4-3) and RTMDR strains. The seco-compounds exhibited better chemical stability in acidic conditions compared with DCP and DCK compounds. Overall, the results suggested that seco-DCP analogues with simplified structures may be more favorable for development as novel anti-HIV candidates.