Characterization of parotid gland tumors using diffusion-relaxation correlation spectrum imaging: a preliminary study.

AIM: To assess the performance of diffusion-relaxation correlation spectrum imaging (DR-CSI) in the characterization of parotid gland tumors. MATERIALS AND METHODS: Twenty-five pleomorphic adenomas (PA) patients, 9 Warthin's tumors (WT) patients and 7 malignant tumors (MT) patients were prospectively recruited. DR-CSI (7 b-values combined with 5 TEs, totally 35 diffusion-weighted images) was scanned for pre-treatment assessment. Diffusion (D)-T2 signal spectrum summating all voxels were built for each patient, characterized by D-axis with range 0∼5 × 10-3 mm2/s, and T2-axis with range 0∼300ms. With boundaries of 0.5 and 2.5 × 10-3 mm2/s for D, all spectra were divided into three compartments labeled A (low D), B (mediate D) and C (high D). Volume fractions acquired from each compartment (VA, VB, VC) were compared among PA, WT and MT. Diagnostic performance was assessed using receiver operating characteristic analysis and area under the curve (AUC). RESULTS: Each subtype of parotid tumors had their specific D-T2 spectrum. PA showed significantly lower VA (8.85 ± 4.77% vs 20.68 ± 10.85%), higher VB (63.40 ± 8.18% vs 43.05 ± 7.16%), and lower VC (27.75 ± 8.51% vs 36.27 ± 11.09) than WT (all p<0.05). VB showed optimal diagnostic performance (AUC 0.969, sensitivity 92.00%, specificity 100.00%). MT showed significantly higher VA (21.23 ± 12.36%), lower VB (37.09 ± 6.43%), and higher VC (41.68 ± 13.72%) than PA (all p<0.05). Similarly, VB showed optimal diagnostic performance (AUC 0.994, sensitivity 96.00%, specificity 100.00%). No significant difference of VA, VB and VC was found between WT and MT. CONCLUSIONS: DR-CSI might be a promising and non-invasive way for characterizing parotid gland tumors.

[Clinical analysis of 7 cases of pregnancy with non-Hodgkin lymphoma].

Objective: To investigate the clinicopathological features, diagnosis, treatment and outcomes of pregnancy with non-Hodgkin lymphoma (NHL). Methods: The clinicopathological data of 7 patients of pregnancy with NHL admitted to Nanjing Drum Tower Hospital from January 2010 to May 2022 were reviewed. General information, diagnosis, treatment and maternal and child outcomes were retrospectively analyzed. Results: (1) The median age of the 7 patients was 28 years old (range: 26-33 years); 3 cases complained of abdominal pain (2 cases of huge pelvic or abdominal mass with multiple metastases), 2 cases of cough (1 case with superior vena cava syndrome), 1 case of facial swelling and pain, and 1 case of poor appetite. The median time from the onset of symptoms to initial visit was 30 days (range: 15-188 days). (2) Only 3 cases were diagnosed during pregnancy through biopsy, and the biopsy sites including right nasal vestibular mass, left supraclavicular lymph node and lung respectively. One case was suspected to be splenic marginal zone lymphoma through bone marrow puncture during pregnancy, and confirmed by pathological results observed in splenectomy specimens after termination of pregnancy. Three cases were diagnosed as NHL by pathological results of focus biopsy or partial tumor resection during cesarean section. Pathological types: 5 cases of diffuse large B cell lymphoma, one splenic marginal zone lymphoma and one nasal cavity natural killer (NK)/T cell lymphoma. Stages: 1 case of stage Ⅱ, 6 cases of stage Ⅳ. Pathological examination of placentas was performed for 4 patients after delivery, included one case with tumor metastasis to the placenta. (3) Among the 7 patients, 1 case was induced in the second trimester; 5 cases were terminated by cesarean section in the third trimester, all of which were premature; one case of full-term was delivered with forceps. All 6 neonates survived healthy. Treatments: 5 cases received chemotherapy after termination of pregnancy (included 1 case received autologous hematopoietic stem cell retransfusion therapy after chemotherapy), and 1 case received chemotherapy combined nasopharyngeal radiotherapy, and six cases survived without recurrence (follow-up until October 2022). The other case was a patient with hepatitis B virus infection and congenital heart disease who died of multiple organ failure 18 days after cesarean section. Conclusions: It is difficult to diagnose, necessary to pay attention to the complaints of pregnant women, and to actively carry out related examinations during pregnancy. When the lesion involves multiple organs, the possibility of lymphoma should be considered. Pregnancy with NHL is sensitive to chemotherapy. Even for advanced patients, good outcome could still be obtained after standardized treatment.

[Safety analysis of cesarean myomectomy in twin pregnancies with intramural myomas].

Objective: To estimate the safety of myomectomy in twin pregnant women with intramural myomas during cesarean section. Methods: The clinical data of 145 cases of twin pregnancies with intramural myomas who were delivered by cesarean section in Beijing Obstetrics and Gynecology Hospital, Capital Medical University from June 2013 to December 2021 were collected. Maternal demographics, fibroids' characteristics, maternal and fetal outcomes were compared between groups of cesarean section with myomectomy (myomectomy group, 49 cases) and cesarean section only (non-myomectomy group, 96 cases). Results: Compared with non-myomectomy group, myomectomy group had significantly prolonged operative time [50.0 minutes (37.5-57.5 minutes) vs 40.0 minutes (35.0-50.0 minutes), respectively; P=0.007] and significantly longer postoperative hospital stay [4.0 days (3.0-4.0 days) vs 3.0 days (3.0-4.0 days), respectively; P=0.047). Other maternal and fetal outcomes such as estimated blood loss, hemoglobin difference, postpartum hemorrhage, blood transfusion, B-Lynch structure, uterine artery ligation, postoperative fever and neonatal Apgar score showed no significant differences (all P>0.05). For intramural myomas <5 cm, there were no significant differences in maternal and fetal outcomes between myomectomy group and non-myomectomy group (all P>0.05). For intramural myomas ≥5 cm, operative time [55.0 minutes (40.0-60.0 minutes) vs 42.5 minutes (40.0-50.0 minutes), respectively; P=0.019] was significantly prolonged, postoperative hospital stay [4.0 days (4.0-5.0 days) vs 4.0 days (3.0-4.0 days), respectively; P=0.048] was significantly longer in myomectomy group than non-myomectomy group, but there were no significant differences in other maternal and fetal outcomes (all P>0.05). Conclusion: For twin pregnancies with intramural myomas, it is safe and feasible to remove intramural myomas during cesarean section by experienced obstetricians.

[Risk factors and characteristics of gut microbiota and metabolites in inflammatory bowel diseases patients with urolithiasis].

Objective: To identify the related factors and characteristics of gut microbiota and metabolites in inflammatory bowel disease (IBD) patients with urolithiasis. Methods: A total of 68 IBD patients with urolithiasis and 136 gender-and age-matched IBD patients without urolithiasis in the Department of Gastroenterology, Peking Union Medical College Hospital from January 2014 to December 2019 were recruited. The diagnosis of urolithiasis was confirmed by plain films, ultrasonography, abdominal computed tomography or intravenous urography. The clinical data of patients were collected, and the association between the clinical characteristics and urolithiasis was further analyzed. The fecal samples were collected from 10 patients with urolithiasis and 18 patients without urolithiasis, and the gut microbiota and metabolites composition were analyzed. Results: There were 49 male and 19 female IBD patients with urolithiasis, with a mean age of (36.0±12.4) years, and 98 male and 38 female patients without urolithiasis, with a mean age of (36.1±12.5) years. Univariate analysis revealed that the rate of ileostomy and the resection of small intestine in Crohn's disease (CD) patients with urolithiasis (n=34) was significantly higher than CD patients without urolithiasis (n=68) (26.5% vs 7.4%, P=0.019). And the erythrocyte sedimentation rate was also higher [26.5 (12.0, 40.8) vs 13.0 (7.2, 32.5) mm/1 h, P=0.022] in CD patients with urolithiasis. There were no significant differences in clinical characteristics and biochemical parameters between the ulcerative colitis (UC) patients with urolithiasis (n=34) and without urolithiasis (n=68) (all P>0.05). The multivariate logistic regression analysis indicated that ileostomy and the resection of small intestine were the independent related factors for urolithiasis in CD patients (OR=4.619, 95%CI: 1.178-18.111, P=0.028). There was no significant difference in α and ß diversity between the two groups (all P>0.05). At the phylum level, there was no significant difference in the abundance of microbiota (all P>0.05). At the genus level, the abundance of Enterococcus (P=0.049), Eubacterium_eligens (P=0.036) was significantly decreased. At the species level, the abundance of Bacteroides_coprocola was increased in urolithiasis group (P=0.035), while the abundance of Blautia_caecimuris was significantly decreased (P=0.042). No significant difference was found in fecal metabolites between the two groups (all P>0.05). According to LDA effect size (Lefse) analysis, taxa including Sphingomonadales, Fenollaria, Bacteroides_coprocola contributed greatly to the difference between the two groups. Conclusions: Ileostomy and the resection of small intestine are related factors for urolithiasis in patients with CD. Gut microbiota may be involved in the occurrence of urolithiasis in patients with IBD.

MicroRNA-1269a promotes the occurrence and progression of osteosarcoma by inhibiting TGF-ß1 expression.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MicroRNA-1269a promotes the occurrence and progression of osteosarcoma by inhibiting TGF-ß1 expression, by S.-N. Yu, Y.-Y. Miao, B.T. Zhang, Y.-M. Dai, L. Liu, Z.-L. Gao, G.-F. Liu, published in Eur Rev Med Pharmacol Sci 2019; 23 (3): 972-981-DOI: 10.26355/eurrev_201902_16984-PMID: 30779063" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16984.

[Intrauterine balloon tamponade combined with temporary abdominal aortic balloon occlusion in the management of women with placenta accreta spectrum:a randomized controlled trial].

Objective: To access the effectiveness and safety of the intrauterine balloon tamponade verse gauze packing combined with temporary abdominal aortic balloon occlusion in the management of placenta accreta spectrum (PAS). Methods: This was an open-label, randomized controlled trial conducted in Nanjing Drum Tower Hospital. The patients suspected with PAS for uterine preservation surgery under the multidisciplinary team care were recruited between Aug 2015 and Jan 2018. When bleeding could not be achieved after fetus delivered, and a temporary abdominal aortic balloon occlusion and the compression sutures as needed, the women were randomly allocated 1∶1 into balloon tamponade (n=81) or gauze packing (n=80) group. The primary outcome was successful bleeding arrests by avoiding second line surgeries. The secondary outcomes included the volume of blood loss during and after cesarean section, the rate of PPH, incidence and amount of blood transfusion, hysterectomy, postpartum pain, ICU admission, need for re-laparotomy, and the length of hospital stay, readmission, and interventional radiology complications. Results: All the women [100% (81/81)] in the balloon group were obtained hemostasis without further intervention, significantly higher than 88% (70/80) in the gauze group (P=0.001). Before uterine tamponade, blood loss were 820 ml (620-1 230) ml and 850 ml (605-1 442) ml, while placenta bed were sutured in 96%（78/81, 77/80） respectively (P>0.05).The proportion of blood loss≥1 000 ml was higher in the gauze group than that in the balloon group (P=0.006). Maternal adverse events involving total blood loss, puerperal morbidity and postpartum pain occurred more frequently in the gauze group (P<0.05). The following outcome showed no statistically significant difference between the two groups: the vascular occlusion time, the dose of radiation, and interventional radiology complication (P>0.05). The median volume infused into the lower and upper balloons is 70 ml (50-100 ml) and 180 ml (100-240 ml). Conclusions: Incrauterine balloon tamponade is as effective as gauze packing in hemostasis following the placenta delivery in PAS. Compared with gauze packing, the uterine balloon tamponade is more effective.

Circular RNA circ-ABCB10 promotes non-small cell lung cancer proliferation and inhibits cell apoptosis through repressing KISS1.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Circular RNA circ-ABCB10 promotes non-small cell lung cancer proliferation and inhibits cell apoptosis through repressing KISS1, by J.-P. Zheng, Y.-M. Dai, Z. Chen, Q. Chen, Y. Zheng, X. Lin, T.-J. Cui, published in Eur Rev Med Pharmacol Sci 2020; 24 (5): 2518-2524-DOI: 10.26355/eurrev_202003_20519-PMID: 32196602" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20519.

Circular RNA circ-ABCB10 promotes non-small cell lung cancer proliferation and inhibits cell apoptosis through repressing KISS1.

OBJECTIVE: Recent researches have proved that circular RNAs (circRNAs) act as an important role in many diseases. Our study aims to uncover the role of circ-ABCB10 in the progression of non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to detect circ-ABCB10 expression in NSCLC patients. Then, we conducted Cell Counting Kit-8 (CCK-8) assay, colony formation assay, Ethynyl deoxyuridine (EdU) incorporation assay, cell cycle assay, and cell apoptosis assay in treated NSCLC cells. Besides, further experiments including RT-qPCR and Western blot assay were performed to explore the potential mechanism in vitro. RESULTS: Circ-ABCB10 expression level was significantly higher in NSCLC samples comparing to that in adjacent tissues. Moreover, functional assays showed that the cell growth ability of NSCLC cells was inhibited after circ-ABCB10 was knocked down. In addition, the cell apoptosis of NSCLC cells was promoted after circ-ABCB10 was knocked down. Also the expression of KISS1 was upregulated by the knockdown of circ-ABCB10. Furthermore, it was found that KISS1 expression was negatively correlated to the circ-ABCB10 expression in NSCLC tissues. CONCLUSIONS: Results above indicated that circ-ABCB10 promoted cell proliferation and inhibited cell apoptosis of NSCLC by suppressing KISS1, which suggested that circ-ABCB10 may be a potential therapeutic target in NSCLC.

Which of the fibrous layer is more important in the genesis of traumatic temporomanibular joint ankylosis: The mandibular condyle or the glenoid fossa?

INTRODUCTION: The aim of this experimental study was to investigate, under the premise of discectomy, whether damage to either the fibrous layer of the condyle or that of the glenoid fossa, could induce temporomanibular joint (TMJ) ankylosis. And if not, which of the fibrous layer was more important in the genesis of TMJ ankylosis. MATERIALS AND METHODS: Bilateral TMJ surgery was performed in 6 growing Xiao-wei Han sheep. Disk and condylar fibrous layer removal (DCFLR) was performed on the left TMJ, and disk and glenoid fibrous layer removal (DGFLR) was performed on the right TMJ. All animals were sacrificed at 3 months postoperatively. The TMJ complexes were examined by histological evaluation. RESULTS: Partial fibrous ankylosis was achieved on the DCFLR side in the 6 sheep at 3 months after surgery. On the DGFLR side, pathologic characteristics of TMJ osteoarthritis could be seen; however, no evidence of ankylosis was observed. The scores of TMJ ankylosis for the DGFLR side were significantly lower than those for the DCFLR side (P<0.05). CONCLUSION: This study demonstrated that removal of the condylar fibrous layer, not the glenoid fibrous layer, combined with discectomy could lead to traumatic TMJ ankylosis.

LncRNA HOXA-AS2 regulates microRNA-216a-5p to promote malignant progression of non-small cell lung cancer.

OBJECTIVE: Previous studies have shown that long non-coding RNA (lncRNA) HOXA-AS2 is a cancer-promoting gene. However, the role of HOXA-AS2 in non-small cell lung cancer (NSCLC) has not been reported. This study aims to investigate the expression characteristics of HOXA-AS2 in NSCLC and whether HOXA-AS2 can promote the malignant progression of NSCLC by regulating microRNA-216a-5p. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine the HOXA-AS2 level in 40 pairs of NSCLC tumor tissue samples and adjacent ones. Then, the relationship between HOXA-AS2 expression and clinical indicators and prognosis of NSCLC was analyzed. Meanwhile, qRT-PCR further verified the expression level of HOXA-AS2 in NSCLC cell lines. Also, HOXA-AS2 knockdown and overexpression models were constructed using lentivirus in NSCLC cell lines, and the effects of HOXA-AS2 on the biological function of NSCLC cells were analyzed using the Cell Counting Kit-8 (CCK-8), transwell migration, and cell wound healing assays. Finally, Western blotting assay and cell recovery experiment were used to explore the regulatory mechanism of HOXA-AS2 and microRNA-216a-5p in NSCLC. RESULTS: In this experiment, qRT-PCR results revealed that HOXA-AS2 level in NSCLC tumor tissue specimens was remarkably higher than that in adjacent tissues. Compared with those with low expression of HOXA-AS2, the patients with high expression had a higher incidence of distant metastases and a lower overall survival rate. The proliferative and metastasis abilities of the cells in the HOXA-AS2 overexpression group were remarkably increased when compared with the control group, while the opposite results were observed in HOXA-AS2 silence group. Subsequently, qRT-PCR verified that microRNA-216a-5p level was remarkably decreased in NSCLC tissues and negatively correlated with HOXA-AS2 expression. In addition, the result of the cell recovery experiment and Western blotting revealed that there might be a mutual regulation between HOXA-AS2 and microRNA-216a-5p, the two of which could jointly regulate the malignant progression of NSCLC. CONCLUSIONS: The results indicate that lncRNA HOXA-AS2 is upregulated in NSCLC and is remarkably associated with distant metastasis and poor prognosis of NSCLC patients. In addition, lncRNA HOXA-AS2 is found to be able to promote the malignant progression of NSCLC via regulating microRNA-216a-5p.

MicroRNA-1269a promotes the occurrence and progression of osteosarcoma by inhibit-ing TGF-ß1 expression.

OBJECTIVE: MicroRNAs are endogenous, non-coding small RNAs that are capable of regulating biological and pathological processes. Previous studies have shown that microRNA-1269a serves as an oncogene. However, the role of microRNA-1269a in the pathogenesis of osteosarcoma (OS) has not been reported. The aim of this work was to investigate the expression characteristics of microRNA-1269a in OS and to further study its regulatory effects on the malignant progression of OS. PATIENTS AND METHODS: The expression of microRNA-1269a in 61 pairs of OS tissues and para-cancerous tissues was detected by quantitative Real Time-polymerase Chain Reaction (qRT-PCR). Chi-square test was used to analyze the relationship between microRNA-1269a expression and the characteristics of OS patients, including age, sex, clinical stage and distant metastasis. Subsequently, microRNA-1269a expression in OS cell lines was detected as well. After knockdown of microRNA-1269a by constructing relevant small interference RNA, biological performances of MG63 and U2OS cells were accessed by cell counting kit-8 (CCK-8), colony formation and transwell assay. Meanwhile, the protein expressions of key genes in the EMT/Smad pathway were detected by Western blot. Finally, si-TGF-ß1 (transforming growth factor-ß1) was transfected into OS cells, and cell migration and invasion were detected by transwell assay. RESULTS: MicroRNA-1269a was highly expressed in OS tissues compared with para-cancerous tissues. High expression of microRNA-1269a was positively correlated with young OS patients and high rate of distant metastasis, whereas was not correlated with age, sex and Enneking stage. Kaplan-Meier survival curves showed that high expression of microRNA-1269a was significantly associated with poor prognosis of OS. The knockdown of microRNA-1269a in MG63 and U2OS cells significantly inhibited cell proliferation, migration and invasion. Meanwhile, microRNA-1269a knockdown in OS cells markedly downregulated the expressions of TGF-ß1, p-Smad2, p-Smad3, N-cad, Vimentin and MMP9. Furthermore, TGF-ß1 knockdown remarkably decreased migratory and invasive abilities of OS cells. CONCLUSIONS: MicroRNA-1269a is highly expressed in OS, which is remarkably correlated with tumor stage, distant metastasis and poor prognosis of OS. In addition, microRNA-1269a promotes the malignant progression of OS by regulating TGF-ß1 expression.

Diagnostic performance of anti-citrullinated protein/peptide antibodies in juvenile idiopathic arthritis.

The prevalence rates of anti-citrullinated protein/peptide antibodies (ACPAs) were investigated in a cohort of juvenile idiopathic arthritis (JIA) patients, and their diagnostic performances were compared. ACPAs, including anti-cyclic citrullinated peptide IgG (anti-CCP), anti-CCP IgG/IgA (anti-CCP3.1), citrullinated recombinant rat filaggrin antibodies (CPA), anti-mutated citrullinated vimentin (anti-MCV), and antibodies to citrullinated human IgG-derived peptides (RA/CP), were measured in the sera from 81 JIA patients. Serum samples from 55 children with other joint diseases or viral infections and 49 healthy donors were tested as controls. Of the 81 JIA patients, 7 (8.6%), 8 (9.9%), 17 (21.0%), 23 (28.4%), and 18 (22.2%) were found to be positive for anti-CCP, anti-CCP3.1, CPA, anti-MCV, and RA/CP, respectively, with specificities of 98.1, 95.1, 93.3, 84.6, and 86.5%. Analysis by subtype revealed that 7/7 (100%) of RF-positive polyarticular JIA patients tested positive at high serum levels for anti-MCV or RA/CP, and 5/7 (71.4%) were positive for anti-CCP, anti- CCP3.1, or CPA (P < 0.001, compared with controls). Eighteen of 81 JIA patients demonstrated joint erosions on radiographs and erosive arthritis occurred more often in ACPAs positive patients (P < 0.01). Our findings indicate that although ACPAs are not satisfactory screening biomarkers for JIA due to low sensitivity, ACPA measurement can aid in diagnosing RF-positive polyarticular JIA and identifying JIA patients with severe bone involvement. The diagnostic performance of each ACPA in JIA is different, and the careful selection of assays is necessary.

A pilot study of conformal radiotherapy combined with erlotinib-based multimodality therapy in newly diagnosed metastatic non-small-cell lung cancer.

OBJECTIVE: Lung cancer is the leading cause of cancer-related death in the world, particularly in major cities in China. We aimed to determine the benefit of survival and toxicity of Conformal Radiotherapy (CRT) combined with erlotinib-based multimodality therapy in newly diagnosed metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Newly diagnosed metastatic NSCLC patients were treated with CRT and erlotinib, with or without chemotherapy matched protocol. The patients received CRT with a dose of 30-66 Gy. Erlotinib was used at least one 28-day cycle. The primary end point was overall survival (OS). RESULTS: Thirty-two patients were analyzed. The median OS was 517 days. Patients with only one metastasis showed longer survival than patients with multi-metastases (986 vs. 380 days, n = 8 vs. 24, p = .009). Patients with multiple metastases in brain conferred worse survival for patients without and with sole brain metastasis (321 vs. 700 days, n=11 vs 21, p = .006). There was no significant difference in median survival whether erlotinib was used as a first-, second- or third-line therapy (380 vs. 700 vs. 310 days, n = 10 vs. 15 vs 7, respectively. p = .179). Patients with TTCRT > 90 days had longer OS than patients with TTCRT ≤ 90 days (749 vs. 322 days, n = 11 vs. 21, p = .012). Patients tolerated treatment with limited Grade 1/2 toxicity. CONCLUSIONS: In this study, patients with newly diagnosed metastatic NSCLC had survival benefits when erlotinib was used combined with CRT. Further prospective trials are needed to derive maximal benefit from the drug treatment.

A unique magnetic resonance imaging feature of glioblastoma multiforme: the 'pseudopalisade' sign.

This study was designed to investigate the unique magnetic resonance imaging (MRI) appearance of histopathologically-proven glioblastoma multiforme (GBM) with pseudopalisade necrosis and to assess its value for grading gliomas and providing a differential diagnosis. The study included 169 patients with intracranial masses who underwent surgery and had a proven histopathological diagnosis: 50 with GBM, 77 with gliomas (46 grade II and 31 grade III) and 42 with other intracranial masses (20 metastases, 14 lymphomas and eight abscesses). All patients underwent preoperative brain MRI including post-contrast T(1)-weighted imaging. The presence of the 'pseudopalisade' sign on post-contrast T(1)-weighted images was compared among the different types of brain mass. The frequency of the 'pseudopalisade' sign in GBMs (94.00%) was significantly higher than that seen in grade II and III gliomas (11.69%) and other intracranial masses (7.14%). The 'pseudopalisade' sign on post-contrast T(1)-weighted images was useful for grading gliomas and for differentiating GBM from other brain masses.

Tumor heterogeneity in small hepatocellular carcinoma: analysis of tumor cell proliferation, expression and mutation of p53 AND beta-catenin.

Most hepatocellular carcinomas (HCCs) first occur as well-differentiated HCCs, from which poorly differentiated HCC cells develop because of dedifferentiation. In this study, we try to clarify the changes of dedifferentiation and cell proliferative activity and their relationship in small HCCs (less than 3.0 cm in diameter) and try to learn the mechanism of these changes by analysing the expressions and genetic changes of proliferation-related genes p53 and beta-catenin. Of 41 surgically resected small HCCs, 11 were identified to have tumor heterogeneity. DNA from the 11 small HCCs, consisting of 29 intratumoral lesions and 11 noncancerous liver tissues adjacent to HCCs, was extracted from paraffin embedded tissue sections. Exons 5-8 of p53 gene and exon 3 of beta-catenin gene were amplified by polymerase chain reaction and analyzed by direct sequence. The serial sections were also immunostained by anti-Ki-67, p53 and beta-catenin antibody. Immunohistochemistry showed that the p53 overexpression was significantly related to the proliferative activities as evaluated by Ki-67 immunostaining and to the histological differentiation. The expression of beta-catenin was found to be heterogeneously distributed not only in various histological grades of the same tumor but also in areas of the same histological grade. p53 and beta-catenin gene mutations were detected in 1 tumor respectively, both of which were second primary HCCs and also recurred later. The p53 mutation showed the same mutation pattern in heterogeneous subpopulations. beta-catenin mutation was detected only in the less differentiated lesion but not in the well-differentiated lesion of tumor. In conclusion, our findings suggest that there was histological heterogeneity in small but established HCC, which was accompanied by increased proliferative activity and p53 overexpression. The overexpression of beta-catenin may be related to the proliferative activity and dedifferentiation of HCC.

Clinicopathological risk factors and prognostic evaluation in hepatocellular carcinoma recurrence after surgery.

AIM: To analyze the clinicopathological risk factors in hepatocellular carcinoma recurrence after surgery. METHODS: We used significance testing (χ(2) and Student's t-test) of single and multiple factors, and Wilcoxon Cox tropic examination; a retrospective clinicopathological analysis was performed on 156 cases of hepatocellular carcinoma after hepatectomy. RESULTS: Of the 156 cases, 68.4%, 57.3%, 46.7%, 31.5%, and 28.6% had one, two, three, four, and five postoperative tumor-free years, respectively; the total recurrence rate was 53.2% (83/156). In the 83 recurrent cases, 65 were intrahepatic subclinical, with a resection rate of 78.3% (65/83). The relevant factors involved in recurrence were: male gender, tumor number and size, capsule infiltration, and portal vein involvement. These factors were an obvious influence on the prognosis of the patients with postoperative hepatocellular carcinoma (P < 0.05). In the recurrent liver carcinomas, 63.1% of tumor nodes (41/65) were at the ipsilateral segment of the primary tumor nodes. CONCLUSION: Male gender, tumor number and size, capsule infiltration, and portal vein involvement are factors for postoperative hepatocellular carcinoma recurrence. Recurrence is mainly unicentral. The right front liver lobe is the segment with a high rate of recurrence.

[Interstitial collagen distribution and its mRNA expression in human primary liver cancer].

The localization of type I collagen and type III procollagen in 29 cases of hepatocellular carcinoma (HCC) and 2 cases of cholangiocarcinoma as well as their surrounding tissues were studied with ABC method. The results showed that the distribution of these two types of collagen was similar in PLC as well as in its surrounding tissues. The distribution of interstitial collagen in HCC might be classified into two patterns by the authors' namely, the vasiform and non-vascular distributions. The carcinoma with vasiform distribution pattern tends to grow infiltratively with much higher rate of portal venous embolism and intrahepatic metastasis development than that of the non-vascular pattern (P < 0.05). Employing the in situ hybridization technique for type I collagen mRNA, the transcription of collagen mRNA occurred not only in the interstitial cells but also in some of the liver carcinoma cells and giant tumor cells. No positive signals of type I collagen mRNA were noticed in the non-tumorous surrounding tissues.

[AFP gene expression and antigenic protein localization in the cells of hepatocellular carcinoma and its surrounding tissues].

Using a double immunoenzymatic technique (PAP) and AFPcDNA-RNA in situ hybridization technique, we detected and analyzed the AFP gene expression and antigenic protein localization in hepatocellular carcinoma (HCC) and its surrounding tissues. The results demonstrated that AFP was truly synthesized again by some host liver cells around the cancer nodules. We considered that the cells which showed AFPmRNA positive hybridized signs might be a kind of preneoplastic cells. Their appearance might be related to injury caused by HBV infection and the inactivities of the inhibited gene on the AFP control mechanism. The substances secreted by the involved cancer cells, might be another causative factor for the excessive expression of the AFP in the liver cells near the cancer.