Pulmonary arterial hypertension in a patient with hereditary hemorrhagic telangiectasia and family gene analysis: A case report.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant genetic disease. Very few patients suffering from HHT present with associated pulmonary arterial hypertension (PAH), which may result in a poor prognosis. Here, we report a case of HHT with PAH. The patient's clinical manifestations and treatment as well as genetic analysis of family members are reviewed, in order to raise awareness of this multimorbidity. CASE SUMMARY: A 45-year-old Chinese woman was admitted to the hospital to address a complaint of intermittent shortness of breath, which had lasted over the past 2 years. She also had a 30-year history of recurrent epistaxis and 5-year history of anemia. She reported that the shortness of breath had aggravated gradually over the 2 years. Physical examination discovered anemia and detected gallop rhythm in the precordium. Chest computerized tomography and cardiac ultrasound demonstrated PAH and hepatic arteriovenous malformation. The formal clinical diagnosis was HHT combined with PAH. The patient was treated with ambrisentan and her condition improved for a time. She died half a year after the diagnosis. Genetic testing revealed the patient and some family members to carry an activin A receptor-like type 1 mutation (c. 1232G>A, p. Arg411Gln); the family was thus identified as an HHT family. CONCLUSION: We report a novel gene mutation (c. 1232G>A, p. Arg411Gln) in a Chinese HHT patient with PAH.

Correction to: Magnetic resonance imaging of the Lisfranc ligament.

AbstractIn the original publication of this article [1], the spelling of the first author's name A. Ablimit was incorrect.

Magnetic resonance imaging of the Lisfranc ligament.

BACKGROUND: The Lisfranc joint has complex structures, and articular surfaces overlap on conventional X-ray radiographs. Hence, there is no available auxiliary examination for diagnosing related injuries. At present, few studies on the imaging of Lisfranc ligaments have been reported, and related imaging data are rare. Therefore, no imaging reference can be used for related diagnosis and repair operations. This study aims to observe and describe the morphology and structure of Lisfranc ligaments using magnetic resonance imaging (MRI), in order to provide imaging reference for the diagnosis and repair of Lisfranc joint injuries. METHODS: MRI scanning was performed on 60 sides of normal feet of 30 healthy adult volunteers. In the MRI scanning on the Lisfranc joint, sagittal scanning was focused on the area between the lateral margin and medial margin of the Lisfranc joint, while oblique coronal scanning was focused on the area parallel to the Lisfranc joint clearance. After acquisition of MRI images, data were burned into a CD, and the morphology and structure of the Lisfranc ligament on the MRI image were observed and described. Hence, the imaging parameters of the Lisfranc ligament were acquired, providing an imaging reference for the diagnosis and repair of Lisfranc joint injuries. RESULTS: By observing the obtained images of the Lisfranc ligament through appropriate MRI scanning, it was found that the Lisfranc ligament originates at the site 12.63 ± 1.20 mm from the lateral side of the base of the medial cuneiform bone, with a length of 8.02 ± 1.5 mm, a width of 2.53 ± 0.61 mm, a height of 6.96 ± 1.01 mm, forms an included angle of 46.79 ± 3.47° with the long axis of the first metatarsal bone, and finally ends at the base of the second phalanx. Detailed imaging parameters of the Lisfranc joint and ligament were obtained from the present imaging experiment, providing an imaging reference for the diagnosis and repair of Lisfranc joint injuries. CONCLUSIONS: On the MRI images, the sagittal section can clearly display the corresponding situation of the Lisfranc joint bone and longitudinal arch of the foot, tolerably display the Lisfranc joint dorsal ligaments and metatarsal ligaments, and poorly display the Lisfranc ligament. The oblique coronal section can clearly display the transverse arch of the foot and clearly display the cross-section of the Lisfranc ligament. The oblique crosssection can clearly display the horizontal arch of the Lisfranc joint and more clearly display its surrounding ligaments and tendons, especially the entire Lisfranc ligament and its attachment points. This is an important section for the diagnosis of Lisfranc ligament injuries. This study provides a certain imaging reference for the MRI scanning, diagnosis, and repair of Lisfranc joint injuries. Further research with large sample size is still needed to confirm the conclusions.

Stromal Expression of Vimentin Predicts the Clinical Outcome of Stage II Colorectal Cancer for High-Risk Patients.

BACKGROUND Increased expression of vimentin in tissue samples from patients with colorectal cancer (CRC) has been previously demonstrated, but its prognostic significance remains controversial, and the clinical significance for patients with stage II CRC is still unknown. The aim of this study was to evaluate the expression of vimentin in CRC and its potential prognostic significance. MATERIAL AND METHODS We analyzed vimentin expression in 203 CRC tissue samples from patients with stage II cancer using immunohistochemistry, and correlated the findings with clinicopathological patient features. CRC-specific survival (CSS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. Univariate and multivariate analysis was performed using the Cox proportional hazards method for survival. RESULTS Vimentin expression was significantly correlated only with tumor (T) stage (p=0.024). Kaplan-Meier survival analysis indicated that vimentin expression could stratify the CSS and DFS of patients with stage II CRC at high risk (p=0.029, p=0.042, respectively), but not those of low-risk stage II patients (p=0.208, p=0.361, respectively). Univariate and multivariate analysis further revealed that stromal vimentin expression is an independent prognostic factor for CSS and DFS of high-risk stage II patients (p=0.043, p=0.022, respectively). Moreover, high-risk stage II patients with low stromal vimentin expression benefitted more from standard adjuvant chemotherapy than those with high stromal vimentin expression (CSS: p=0.012 vs. p=0.407; DFS: p=0.017 vs. p=0.420). CONCLUSIONS Our study suggests that stromal vimentin expression is a promising indicator for survival prediction and adjuvant chemotherapy response in patients with stage II CRC with high-risk factors for recurrence.

Anorectal functional outcome following laparoscopic low anterior resection for rectal cancer.

Low anterior resection (LAR) with total mesorectal excision has been considered a standard treatment for patients with rectal cancer. However, the functional outcome and life quality of laparoscopic LAR (LLAR) in Chinese patients remain unclear. A cohort of 51 Chinese patients (22 men and 29 women) who had undergone LLAR was included in this study. Anorectal manometry combined with the Wexner scores questionnaire were applied to assess functional outcome preoperatively (1 week) and postoperatively (at 3, 6 and 9 months). The validated Chinese versions of the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires were also used to assess the patients' quality of life at the indicated time points. The results demonstrated that the manometric parameters exhibited a temporary decrease at 3 months postoperatively, but a gradual increase at 6 and 9 months, while the Wexner scores exhibited an opposite trend. Furthermore, patients with high anastomoses had significantly higher manometric parameters, a lower frequency of incontinence and lower Wexner scores compared with those with low anastomoses at 9 months (all P<0.05). For the entire cohort, quality of life at 3 months postoperatively was worse compared with the preoperative level, but returned to normal by 9 months. Patients with high anastomoses exhibited significantly better role, emotional and social function, had a better body image and sexual function, fewer problems with defecation and lower frequency of diarrhea, as well as fewer chemotherapy-related side effects at 6 months postoperatively when compared with the low anastomosis group (all P<0.05). In conclusion, LLAR is generally acceptable for Chinese patients with rectal cancer, particularly for those with middle or high rectal cancer, in terms of functional outcome and quality of life.

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.

[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.

[Applicability of anatomical vascular occlusion in hepatectomy for grand hepatocarcinoma].

OBJECTIVE: To retrospectively explore the clinical efficacies and applicability of anatomical vascular occlusion (AVO) in hepatectomy for grand primary hepatocarcinoma at different locations. METHODS: A total of 212 grand primary hepatocarcinoma cases undergoing hepatectomy were divided into 2 groups by vascular occlusion in the process of resection: AVO group (n = 97) and Pringle group (Pringle maneuver, n = 115). According to whether or not tumor was adjacent to main vessels, the cases were divided into 2 types: centrally (n = 98) and peripherally (n = 114) located lesions. And the perioperative outcomes were compared between 2 groups totally and by types respectively. RESULTS: No significance existed between the AVO and Pringle groups in the demographic characteristics and tumor background (P > 0.05). For total cases, there were no significant differences between 2 groups regarding the intraoperative blood loss volume ((632 ± 437) ml vs (546 ± 549) ml, P = 0.217) and the blood transfusion requirement (44.3% vs 33.0%, P = 0.092). The AVO group showed significantly better postoperative liver functions in terms of serum levels of total bilirubin and aminotransferase (P > 0.05). But no significant difference was found between 2 groups in the postoperative complication rate (18.6% vs 22.6%, P = 0.469) and hospital stay duration ((10.5 ± 4.8) vs (11.8 ± 5.6) days, P = 0.087). In centrally located lesions: the AVO group showed a significantly smaller intraoperative blood loss volume ((722 ± 492) ml vs (1032 ± 618) ml, P = 0.007) and blood transfusion requirement (45.6% vs 68.3%, P = 0.026). Also the AVO group showed significantly better postoperative liver functions in terms of serum levels of total bilirubin and aminotransferase (P < 0.01). As a consequence, the AVO group had a significantly lower postoperative complication rate (19.3% vs 39.0%, P = 0.031) and a shorter hospital stay duration ((10.7 ± 5.0) days vs (13.0 ± 6.2) days, P = 0.042). In peripheral located lesions: there were significantly larger intraoperative blood loss volume (504 ± 307 vs 278 ± 237 ml, P = 0.000) and blood transfusion requirement (42.5% vs 13.5%, P = 0.001) in the AVO group. The postoperative liver functions (total bilirubin and aminotransferase levels, P > 0.05), postoperative complication rate (17.5% vs 13.5%, P = 0.808) and hospital stay duration ((10.3 ± 4.6) days vs (11.1 ± 5.1) days, P = 0.429) showed no significant differences between 2 groups. CONCLUSION: The technique of AVO is unsuitable for all types of grand hepatocarcinoma. Whether or not the tumor is adjacent to main vessels is an important consideration of choosing the vascular control technique. Considering the risk of vascular damage in the process of hepatectomy, the AVO technique is indicated for the resection of central lesions but not for peripheral lesions.

[Application of selective and timely regional hepatic vascular occlusion for resection of large centrally located liver tumors: report of 133 cases].

OBJECTIVE: To improve the resection rate and increase operation safety for large centrally located liver tumors. METHODS: Clinical data from 133 patients with large centrally located liver tumors confirmed by surgery were analyzed retrospectively. Selective and timely regional hepatic vascular occlusion was used during the operation procedure. RESULTS: The resection rate was 100%. Perioperative death occurred in one patient. During operations, Forty-four patients underwent regional hepatic inflow occlusion ranging from 12 to 33 minutes. Twenty-three patients underwent left and right inflow occlusion, respectively, ranging from 8 to 50 minutes. One patient had right half-hepatic vascular exclusion for 40 minutes. The blood loss of 132 patients was (665 ± 424) ml (one patient experienced diffuse blood oozing and died in the next day). Among them, the blood loss of patients with liver cirrhosis was (723 ± 479) ml. On the contrary, those without liver cirrhosis was (458 ± 223) ml (P < 0.01). Liver function in 92.4% (122/132) patients recovered to Child-Pugh A within one week. No liver failure occurred. After operation, 3 patients presented ascites. Among them, two patients had liver cirrhosis and hepatocellular jaundice, one patient was accepted for transcatheter arterial chemoembolization preoperatively. Four patients had biliary fistula, one patient had gastroparesis, one patient had thrombus in the superior mesenteric vein and portal vein, and five patients had right pleural effusion. The 1-, 3- and 5-year survival rates of 112 patients were 89.1%, 57.7% and 36.9%, respectively. CONCLUSIONS: Selective and timely regional hepatic vascular occlusion is useful for the resection of large centrally located liver tumors. This kind of procedure can effectively control the blood loss during the operation and shorten the ischemic reperfusion time, beneficial for protecting the liver cell function. This procedure is a safe hepatic flow occlusion method.

[Progressive increase of serum circulating immune complexes and its significance in patients during the progression from chronic hepatitis B to hepatocellular carcinoma].

OBJECTIVE: To investigate the significance of increasing circulating immune complex (CIC) in patients during the progression from chronic hepatitis B to hepatocellular carcinoma (HCC). METHODS: Serum levels of CIC from 20 hospitalized patients diagnosed by pathology with primary HCC, and 13 with hepatic hemangioma, and from 45 subjects with chronic HBV infection who finally developed into HCC (45 cases), and age- and gender-matched 45 subjects who kept the chronic HBV infection after consecutively followed up for 10 - 13 years by June of 2009 were quantified by ELISA. The serum levels of anti liver-kidney microsomal (anti LKM-1) antibodies were also measured by ELISA, and that of HBV-DNA were quantified by Taqman probe-based real time PCR in the followed up chronic HBV infection subjects. In the 45 chronic HBV subjects who finally developed into HCC and the 45 controls, serum samples were collected and determined at 3 time points: the baseline when the subjects were recruited, the middle point during the follow-up, and the end of follow-up. RESULTS: The serum level of CIC was significantly higher in the 20 HCC patients than that in the 13 hemangioma cases (P < 0.001). When HCC was diagnosed, the CIC concentration was significantly higher than that in the baselines (P < 0.001) in the 45 chronic HBV subjects who finally developed into HCC after the consecutively follow-up for 5 - 13 years. Of them, 36 patients (80.0%) showed progressively increased CIC during the follow-up (P < 0.001). In the controls, the CIC levels were kept relatively stable during the follow-up. Among them, 17 patients (37.8%) showed CIC slightly increased (P = 0.046). Kaplan-Meier survival analysis indicated that elevated serum CIC during the follow-up increased cumulative HCC incidence (HR = 2.77, 95%CI 1.47 - 5.22). In addition, the serum levels of anti-LKM-1 and HBV-DNA were also significantly higher in the patients who finally progressed into HCC than that in the controls and maintained at a high level during the follow-up tested at all the 3 time points. Further analysis indicated that the serum level of CIC was correlated with that of serum HBV-DNA only when HCC was diagnosed (r = 0.344, P = 0.026). CONCLUSION: Progressive increase of serum CIC level may be one of risk factors reflecting HCC development from chronic HBV infection.

[Analysis of surgical treatment of 30 cases of small hepatocellular carcinoma in special position].

OBJECTIVE: To investigate the resection technique for small hepatocellular carcinoma (SHCC) in special sites and discuss their outcome. METHODS: Clinicopathological data of 30 patients with SHCC in special sites undergone liver resection were reviewed. There were 29 cases of hepatocellular carcinoma and 1 case of cholangiocarcinoma, confirmed by pathology. The tumor was close to the first porta hepatis in 8 cases, colse to the second porta hepatis in 15 cases, and close to the third porta hepatis in 7 cases. Twenty-five patients had one lesion, 4 patients had two and the other had three. The tumor diameter was (2.7 ± 1.2) cm. RESULTS: No perioperative death occurred. The operation time was (279 ± 101) min, the mean intraoperative blood loss was 566 ml, and the postoperative hospitalization was (10.5 ± 2.7) days. The 1- and 3-year survival rates were 100% and 83.3%, respectively, and the 1- and 3-year disease free survival rates were 85.0% and 41.3%, respectively. CONCLUSION: Although the surgery for SHCC in special sites is quite difficult and risky, surgical treatment is still safe with good perioperative management and is an effective treatment of SHCC in special sites.

[A survival analysis of patients with early-stage hepatocellular carcinoma fulfilling Milan criteria and undergoing hepatectomy].

OBJECTIVE: To summarize the experience of hepatectomy in patients with hepatocellular carcinoma fulfilling the Milan criteria and analyze the clinicopathological factors for patient survival and tumor recurrence. METHODS: The clinicopathological data of 104 patients with early-stage hepatocellular carcinoma fulfilling the Milan criteria and underwent hepatectomy at Peking Union Medical College Hospital between April 2003 and June 2009 were retrospectively analyzed. RESULTS: The median follow-up was 24 months. There were 54 recurrent cases. The 1-, 3- and 5-year cumulative disease-free survival rate were 63.0%, 32.6% and 22.4% respectively. Neither univariate analysis nor multivariate analysis indicated any factor significantly correlated with recurrence (P>0.05). The cumulative overall survival rate at 1, 3 and 5 years were 88.8%, 68.1% and 68.1% respectively. Univariate analysis revealed that blood transfusion (P=0.000), involvement of hepatic capsule (P=0.000) and postoperative transarterial chemotherapy (P=0.049) were significantly correlated with survival. And multivariate analysis indicated that blood transfusion (P=0.001) and involvement of hepatic capsule (P=0.000) were independent prognostic factors for survival. CONCLUSION: For the patients with early-stage hepatocellular carcinoma and compensated liver function fulfilling the Milan criteria, hepatectomy serves as the preferred treatment strategy.

Transcriptional profile of the Shigella flexneri response to an alkaloid: berberine.

Berberine, a natural isoquinoline alkaloid found in many medicinal herbs, has been shown to be active against a variety of microbial infections. To examine the potential effects of berberine on Shigella flexneri, a whole-genome DNA microarray was constructed and a transcriptome analysis of the cellular responses of S. flexneri when exposed to berberine chloride (BC) was performed. Our data revealed that BC upregulated a group of genes involved in DNA replication, repair and division. Intriguingly, the expression of many genes related to cell envelope biogenesis was increased. In addition, many genes involved in cell secretion, nucleotide metabolism, translation, fatty acid metabolism and the virulence system were also induced by the drug. However, more genes from the functional classes of carbohydrate metabolism, energy production and conversion as well as amino acid metabolism were significantly repressed than were induced. These results provide a comprehensive view of the changes in gene expression when S. flexneri was exposed to BC, and shed light on its complicated effects on this pathogen.

[Preparation of chicken egg yolk antibody against Candida albicans and effect of temperature on its titer].

OBJECTIVE: To prepare chicken egg yolk antibody (IgY) against Candida albicans and to study its biological properties in the interest of its further application. METHODS: Ten 25 weeks old laying hens were immunized with Candida albicans. IgY was isolated from the yolks of eggs by the water dilution (WD) method. Its yield, purity, and molecular weight were measured by Bradford method and Tris-tricine gel electrophoresis, respectively. The antigenicity of IgY was determined with Western blot method. The specific combination of IgY and Candida albicans was assayed with immunohistochemistry method. The activity of IgY was evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: The yield and purity of IgY were 7.9 g/L and 91.5%, respectively. It had the same molecular weight and antigenicity in comparison with IgY of chicken serum and normal chicken IgY. It could specifically combine with Candida albicans. Its titer was 1:12,000. CONCLUSION: The production and purity of IgY were high. Its titer was good and did not decrease under a body temperature condition after 48 h. The IgY antibody had a combination capacity of specificity for Candida albicans in vitro.

[Cloning and sequencing of the GTP cyclohydrolase I function region of azole target enzyme gene in artificially induced resistant Candida albicans].

OBJECTIVE: To study the relationship between gene mutation of GTP cyclohydrolase I function region in lanosterine 14 alpha-demethylase (14-DM) DNA sequence and drug resistance of Candida albicans. METHODS: One standard strain and 2 isolate strains of Candida albicans were induced artificially by fluconazole plus albendazole. The gene fragments of the 3 strains and another 2 clinical isolates which were resistant to fluconazol were detected by PCR, and then cloned onto pMD-18T vectors to sequence and analyze the change of gene sequence after the induction. RESULTS: The sequences underwent substantial gene mutations after induction. Some of the mutations resulted in alteration of amino acids. The sequence change and subsequent alteration of amino acids in the tested strains coincided with those in the clinical isolates. CONCLUSION: Gene mutation and alteration of amino acid of 14-DM GTP domain are related to azole-resistance in Candida albicans.