Positive Staining Group Research Articles

Use of indocyanine green fluorescence navigation in laparoscopic anatomical hepatectomy

Objective: To examine the clinical value of fluorescence-guided indocyanine green (ICG) laparoscopic anatomical hepatectomy in the treatment of primary hepatocellular carcinoma. Methods: Data from patients diagnosed with hepatocellular carcinoma and who underwent laparoscopic hepatectomy with ICG fluorescence navigation in the Department of Liver Surgery and Liver Transplantation Center of West China Hospital between September 2020 and May 2022 were retrospectively collected. There were 53 males and 19 females, with an age of (55.5±12.9)years(range:42.6 to 68.4 years). Among them, 13 of the cases underwent laparoscopic anatomical liver resection(LALR) guided by tans-arterial ICG,43 of the cases received LAIR guided by portal vein negative ICG, and 16 of the cases received LALR positive by portal vein. Comparison among the three groups was performed by one-way ANOVA; and the rank sum test was used for comparison between groups. The counting data was expressed as percentage,and the χ2 test or Fisher's exact probability method was used for comparison between groups. Results: (1) Postoperative pathology: Resection R0 was achieved in all operations. The maximum tumor diameter of the patients in the arterial staining group, the reverse staining group, and the positive staining group(M (IQR)) was 2.5 (2.4) cm, 3.0 (2.5) cm and 3.0(2.4) cm,respectively. There were no statistically significant differences in the maximum tumor diameter between the three groups (P=0.364). The minimum tumor margin was 1.1 (1.1) cm, 1.0 (1.0) cm, 1.1 (1.6) cm in the the arterial staining group, reverse staining group and the positive staining group, respectively. There was no significant difference in the margin among the three groups (P=0.878). (2) Operation conditions: the operation time of the arterial staining group, the negative staining group, and the positive portal staining group was (348±93)minutes,(277±112)minutes,and (295±116)minutes,respectively. There were no significant differences in operation time among the three groups (P=0.134). The intraoperative blood loss of the three groups was 80(150)ml,200(350)ml,and 100(150)ml,respectively. There was no statistically significant difference in intraoperative bleeding volume between the three groups(P=0.743). All cases were not transfused during the operation and were not converted to laparotomy. ALT in the arterial staining group was higher than in the negative staining group in the first two days after the operation ((559±398)IU/L307(257) IU/L, q=235.5,P=0.004;(611±389)IU/L(331±242) IU/L, q=265.2, P=0.002). There was only one case of a grade III complication (Clavien-Dindo grading system) postoperative complication in the negative and positive staining group of the portal vein, respectively. Tumor markers in all patients decreased to the normal range after 2 months of operation. Conclusion: Laparoscopic anatomical hepatectomy guided by ICG fluorescence through arterial staining and portal vein staining is safe and feasible for primary hepatocellular carcinoma treatment.

Lingering SARS-CoV-2 in Gastric and Gallbladder Tissues of Patients with Previous COVID-19 Infection Undergoing Bariatric Surgery

BackgroundLingering severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in gut tissue might be a source of infection during bariatric surgery. This study aimed to confirm the presence of SARS-CoV-2 nucleocapsid in gastric and gallbladder tissues removed during bariatric surgery in individuals previously infected with coronavirus disease 2019 (COVID-19) who had negative polymerase chain reaction results prior to the surgery.MethodsGastric and gallbladder specimens from 80 patients who underwent bariatric surgery between November 2021 and May 2022 and had a history of COVID-19 infection with gastrointestinal symptoms were examined for the presence of lingering SARS-CoV-2 nucleocapsid proteins using immunohistochemistry.ResultsGastric specimens from 26 (32.5%) patients and 4 (100%) cholecystectomy specimens showed positive cytoplasmic staining for the anti-SARS-CoV-2 nucleocapsid protein in surface mucosal epithelial cells. The mean age was 37.8 ± 10.3 years. The average body mass index was 44.2 ± 7.0 kg/m2; most of the patients were females (71.3%). The positive staining group was significantly younger than the negative staining group (p = 0.007). The full-dose vaccination rate was 58.8%, with a median of 91 days after the last vaccine dose. A positive serological anti-spike IgG response was observed in 99% of the patients. The median time between initial COVID-19 infection and surgery was 274 and 380 days in the positive and negative staining groups, respectively (p = 0.371).ConclusionGastric and gallbladder tissues can retain SARS-CoV-2 particles for a long time after COVID-19 infection, handling stomach specimens from patients during an operation must be done with care, as we usually do, but now with the knowledge that in 1/3 of patients they can be present. Performing LSG on post-COVID patients did not seem to increase perioperative morbidity.Graphical

Experimental and clinical rsearch of adiponectin receptor expression is associated with good prognosis in gastric cancer

Objective Background:Adiponectin is inversely related to body mass index( BMI),positively correlates with insulin sensitivity,and has antiatherogenic effects.In recent years,adiponectin has been well studied in the field of oncology.Adiponectin has been shown to have antiproliferative effects on gastric cancer,and adiponectin expression is inversely correlated with clinical staging of the disease.However,no studies have reported the correlation between serum adiponectin and receptor expression with disease progression.Methods In this study,we evaluated expression levels of 2 adiponectin receptorsAdipo R1 and Adipo R2-and attempted to correlate their expression with prognosis in gastric cancer patients.Adipo R1 and Adipo R2 expression in gastric cancer cell lines ( MKN45,TMK-1,NUGC3,and NUGC4) was evaluated by Western blotting analysis,and the antiproliferative potential of adiponectin was examinedin vitro.Serum adiponectin levels were evaluated in 100 gastric cancer patients,and the expression of Adipo R1 and Adipo R2 was assessed by immunohistochemical staining.Results MKN45 and NUGC3 expressed higher levels of Adipo R1 compared to NUGC4,even though there was no significance in Adipo R2 expression.The antiproliferative effect of adiponectin was confirmed in MKN45 and NUCC3 at 10 mg/L.No significant associations were observed between serum adiponectin levels and clinicopathological characteristics,but lymphatic metastasis and peritoneal dissemination were significantly higher in the negative Adipo R1 immunostaining group ( 24/32,P ＜ 0.05 and 9/32,P ＜ 0.05,respectively) compared to the positive Adipo R1 group (lymphatic metastasis,33/68; peritoneal dissemination,8/68).On the other hand,Adipo R2 expression was only associated with histopathological type (P ＜0.01 ).In survival analysis,the Adipo R1 positive staining group had significantly longer survival rates than the negative staining group (P ＜ 0.05 ).However,multivariate analysis indicated that Adipo R1 was not an independent prognostic factor on patient' s survival on gastric cancer.Conclusion In gastric cancer,adiponectin has the possibility to be involved in cell growth suppression via Adipo R1. Key words: Adiponectin; Adiponectin receptor 1 ; Adiponectin receptor 2 ; Gastric cancer; Survival rate

Adiponectin receptor-1 expression is associated with good prognosis in gastric cancer

BackgroundAdiponectin is inversely related to BMI, positively correlates with insulin sensitivity, and has anti-atherogenic effects. In recent years, adiponectin has been well studied in the field of oncology. Adiponectin has been shown to have antiproliferative effects on gastric cancer, and adiponectin expression is inversely correlated with clinical staging of the disease. However, no studies have reported the correlation between serum adiponectin and receptor expression with disease progression.MethodsIn this study, we evaluated expression levels of 2 adiponectin receptors--AdipoR1 and AdipoR2--and attempted to correlate their expression with prognosis in gastric cancer patients. AdipoR1 and AdipoR2 expression in gastric cancer cell lines (MKN45, TMK-1, NUGC3, and NUGC4) was evaluated by western blotting analysis, and the antiproliferative potential of adiponectin was examined in vitro. Serum adiponectin levels were evaluated in 100 gastric cancer patients, and the expression of AdipoR1 and AdipoR2 was assessed by immunohistochemical staining.ResultsMKN45 and NUGC3 expressed higher levels of AdipoR1 compared to NUGC4, even though there was no significance in AdipoR2 expression. The antiproliferative effect of adiponectin was confirmed in MKN45 and NUGC3 at 10 μg/ml. No significant associations were observed between serum adiponectin levels and clinicopathological characteristics, but lymphatic metastasis and peritoneal dissemination were significantly higher in the negative AdipoR1 immunostaining group (24/32, p = 0.013 and 9/32, p = 0.042, respectively) compared to the positive AdipoR1 group (lymphatic metastasis, 33/68; peritoneal dissemination, 8/68). On the other hand, AdipoR2 expression was only associated with histopathological type (p = 0.001). In survival analysis, the AdipoR1 positive staining group had significantly longer survival rates than the negative staining group (p = 0.01). However, multivariate analysis indicated that AdipoR1 was not an independent prognostic factor on patient's survival on gastric cancer.ConclusionsIn gastric cancer, adiponectin has the possibility to be involved in cell growth suppression via AdipoR1. The presence of AdipoR1 could be a novel anticancer therapeutic target in gastric cancer.

Prognostic Value of Epithelial Growth Factor Receptor, Vascular Endothelial Growth Factor, E-Cadherin, and p120 Catenin in Resected Non-Small Cell Lung Carcinoma

Introduction Several markers have been investigated to predict the prognosis of lung cancer. In the present study, the prognostic values of epithelial growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), E-cadherin, and p120 catenin expression were investigated by immunohistochemistry in patients with a surgically resected non-small cell lung carcinoma (NSCLC). Patients and method EGFR, VEGF, E-cadherin, and p120 catenin expression were prospectively determined in resected specimens from patients with NSCLC who had undergone surgery between 2003 and 2007. Patients’ and disease-related general characteristics and survival rate were recorded. Results One hundred seventeen patients with a mean age of 61.3 years were included in the study. After a mean follow-up of 27.5 months, the median survival was determined to be 44.0 months and the 5-year survival was 46.2%. The 5-year survival in negative and positive staining groups were as follows; 32% and 66.7% for EGFR ( P=.02), 37.8%, and 50.7% for VEGF ( P=.5), 41% and 66% for E-cadherin ( P=.19), and 46% and 50% for p120 catenin ( P=.27). The differentiation, N status, stage, and EGFR staining were variables significantly affecting survival ( P=.001, .006, .03, and .02, respectively). In multivariate Cox analysis, the EGFR staining level and N status were variables those significantly affecting survival ( P=.021 and P=.010). Conclusions While negative staining of EGFR was related with poor survival, staining of VEGF, E-cadherin, and p120 catenin were not related with survival in patients with resected NSCLC.

PlexinA1 expression in gastric carcinoma and its relationship with tumor angiogenesis and proliferation

To explore the expression of PlexinA1 in gastric carcinoma and its relationship with tumor angiogenesis and proliferation. PlexinA1 mRNA and protein expressions of Semaphorin6D were measured using semi-quantity reverse transcription PCR and Western blotting in 20 cases of gastric carcinoma and corresponding normal gastric mucosa. PlexinA1, Ki-67 expression and microvessel density (MVD) were detected by immunohistochemistry in 50 cases of gastric carcinoma and 20 cases of normal gastric mucosa. The mRNA and protein expressions of PlexinA1 in gastric carcinoma were significantly higher than that in normal gastric mucosa (0.71 +/- 0.37 vs 0.60 +/- 0.25, P = 0.0299 < 0.05, and 0.47 +/- 0.16 vs 0.21 +/- 0.08, P = 0.0000 < 0.01), and MVD within tumor tissues increased significantly with PlexinA1 mRNA expression (r =0.8736, P < 0.01) and PlexinA1 protein expression (r = 0.7286, P < 0.01), and MVD of the PlexinA1 positive staining group (25.25 +/- 3.93) was significantly higher than that of the negative group (19.56 +/- 1.75), (P < 0.01). Proliferation index of tumor cells within tumor tissues were positively correlated with PlexinA1 mRNA expression (r = 0.5420, P = 0.014 < 0.01) and PlexinA1 protein expression (r = 0.5024, P = 0.024 < 0.05). The proliferation index of the PlexinA1 positive staining group (567.69 +/- 125.61) was significantly higher than that of the negative group (369.58 +/- 116.88), (P < 0.01). PlexinA1 may play an important role in the occurrence and development of gastric carcinoma, and be related to tumor angiogenesis and proliferation.

Prognostic significance of reduced expression of beta-N-acetylgalactosaminylated N-linked oligosaccharides in human breast cancer.

Our previous studies showed that expression of the GalNAcbeta1-->4GlcNAc group on N-linked oligosaccharides is associated with functional differentiation of the bovine mammary gland. In the present study, the occurrence of the GalNAcbeta1-->4GlcNAc group was established in human milk proteins and membrane glycoproteins from a human breast cancer cell line, MRK-nu-1, by structural analysis of oligosaccharides released by hydrazinolysis. Whether the expression level of the disaccharide group is affected upon malignant transformation was examined in human breast cancer specimens using Wistaria floribunda agglutinin (WFA) which interacts with oligosaccharides with N-acetylgalactosamine at their termini. Lectin blot analysis of membrane glycoprotein samples from human breast cancer specimens showed that the number of protein bands reacting with WFA, as well as their intensities, are lower in samples from primary carcinoma lesions compared with samples from surrounding normal tissues. No lectin binding was observed when the blots were treated with jack bean beta-N-acetylhexosaminidase or N-glycanase, indicating that WFA-reactive oligosaccharides are N-linked. A histochemical study of tissue specimens from 92 patients with breast cancer revealed that the reduced WFA staining levels in primary carcinoma lesions correlate with advancing clinical stages and prognostic status (i.e., 58% of patients in a group showing reduced/negative staining died of disease recurrence, whereas more than 90% of those in the positive staining group survived for 5 years after surgery). These results indicate that reduced expression of beta-N-acetylgalactosaminylated N-linked oligosaccharides on primary carcinoma lesions predicts a poor prognosis for patients with breast cancer.

Immunohistochemical Analysis for the Expression of p27, CDK4, and Uteroglobin in Resected Non-small Cell Lung Cancer

Background : It has been reported that the expression of protein which influences on the cell cycle is significantly involved in the development, progress, treatment response, and survival of cancer, and also that the degree of expression of p27 and CDK4 is related to the prognosis. Recent research has revealed that uteroglobin, tumor suppressor gene, is related to cell cycle. This study is focused on the relations between expression of proteins related to cell cycle and clinical index of and survival of NSCLC. Methods : We examined immunohistochemically specimens of 110 surgically resected NSCLCs for expression of p27, CDK, Uteroglobin. Tissue array slide were obtained from 110 surgically resected NSCLCs. Immunohistochemical staining was performed by immuno-peroxidase technique using avidin-biotinylated horseradish peroxidase complex. Results : In 110 patients with resected NSCLCs, the ratio of male to female was 87:13, the median age was yrs. The positive staining of p27 was detected in 75% of the cases. A non-statistically significant trend toward increased p27 expression was observed in smoker and squamous cell cancer. The positive staining of CDK4 was detected in 89%, which was the highest expression of protein among 3 types. The survival ratio of CDK4 negative staining group was higher than that of positive staining group, which was significant diffrernce(P

TGF-βRI Expression and its Clinical Significance in the Elderly Gastric Carcinoma

Objective To study the relations between TGF\|βRIexpression and carcinogenesis of gastric mucosa, biological behavior or prognosis in gastric carcinoma.Methods The expression of TGF\|βRI was examined immunohistochemically in benign gastric mucoas, resected gastric carcinoma, using anti\|polyclonal antibody. Results Benign gastric mucosa tested, 95% showed positive staining of TGF\|βRI and 31.15% did in 61 old gastric cancer patients. Expression of TGF\|βRI is inversely correlated with tumor invasion and the progression of PTNM stage( P 0.01). Survival rate for positive staining group of TGF\|βRI was better than negative group ( P 0.01). Conclusion The expression of TGF\|βRI examined in benign gastric mucosa and old human gastric carcinoma may be a useful tool for biological behavior and prognosis of old human gastric carcinoma.

Role of Adhesion Molecule Expression and Soluble Fractions in Hepatic Resection

Background: Little has so far been documented about the relationship between liver injury and adhesion molecules. The aim of this study is to clarify the role of adhesion molecules in hepatic resection by studying both the expression of such adhesion molecules and the measurement of their soluble fractions in the blood.Study Design: To study adhesion molecule expression in the liver, liver biopsies were obtained before and after hepatectomy in 14 patients. Using frozen sections, immunochemical staining for intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was then performed. To study the soluble fractions of adhesion molecules in the hepatic venous blood, the serum soluble fractions of ICAM-1 and VCAM-1 from another 17 patients were measured using an enzyme-linked immunosorbent assay. The plasma levels of polymorphonuclear leukocyte (PMN) elastase were also measured using an enzyme immunoassay. Both the preoperative and postoperative values of the serum soluble fractions of ICAM-1, VCAM-1, and PMN elastase were then compared. The correlation between their values and the perioperative variables was also investigated.Results: Either ICAM-1 or VCAM-1 was stained on the sinusoidal endothelial cells and Kupffer cells or circulating PMNs in the sinusoid. The positive rate of either ICAM-1 or VCAM-1 staining in livers with more than 40 minutes of total ischemic time (80%) was significantly higher than that in livers with less than 40 minutes of total ischemic time (0%; p < 0.05). The incidence of postoperative complications in the ICAM-1 positive staining group tended to be higher than that in the ICAM-1 negative group.Both soluble fractions of ICAM-1 and VCAM-1 in patients with cirrhotic liver disease were also significantly higher than those in patients with a normal liver. The soluble VCAM-1 level in patients with a chronic active hepatitic liver tended to be higher than that in those with a nonactive hepatitic liver. The preoperative level of soluble ICAM-1 correlated with that of VCAM-1, PMN elastase, albumin, aspartate aminotransferease (AST), and the indocyanine green dye retention test at 15 minutes (ICG R15), while the preoperative level of VCAM-1 correlated with albumin, the hepaplastin test, AST, and ICG R15. Both the serum soluble ICAM-1 and VCAM-1 levels after hepatectomy were significantly lower than those before hepatectomy. By contrast, the posthepatectomy level of PMN elastase was significantly higher than its prehepatectomy level. The difference between the postoperative and preoperative values of soluble ICAM-1 correlated with the postoperative AST level, postoperative alanine aminotransferase level, and total ischemic time.Conclusions: Adhesion molecules were expressed in the liver after hepatic resection, and such expression correlated with a total ischemic time during hepatectomy. In addition, judging from the soluble forms of such molecules, these adhesion molecules play an important role in hepatic resection.

HSP70 and ER expression in cervical intraepithelial neoplasia and cervical cancer

Heat shock protein (HSP) is thought to play important roles in the cell cycle and various process of carcinogenesis. This study was performed to evaluate the expression of heat shock protein (HSP70) and estrogen receptor (ER) and Ki-67 and to assess relationship between them in cervical squamous cell neoplasia. The materials were 50 cervical squamous cell lesions, consisted of 30 cervical intraepithelial neoplasia (CIN) (6 moderate dysplasia, 11 severe dysplasia, 13 carcinoma in situ), and 20 invasive squamous cell carcinoma (ISCC) cases. These specimens were immunohistochemically stained for HSP70, ER and Ki-67. The score of HSP70 was significantly higher in ISCC than CIN. Expression rate of the ER was not significantly higher in CIN than in ISCC. Ki-67 labelling index was significantly higher in the ISCC and high HSP70 positive staining group. These results suggested that HSP70 may play an important role in tumor cell proliferation and is related with ISCC than CIN, but ER may be not related with tumor cell proliferation and differentiation. HSP70 may be a useful prognostic factor in cervical dysplasia and cancer.

Overexpression of c-ErbB-2 protein in gastric cancer by immunohistochemical stain.

An immunohistochemical stain to the c-ErbB-2 protein was performed in 225 paraffin-embedded tissue blocks from patients with locally advanced gastric cancer who underwent curative resection. The overexpression of the c-ErbB-2 protein was observed in 27.4% of the patients. The c-ErbB-2 positivity showed a statistically significant correlation with nodal status and stage. The patients with an overexpression of the c-ErbB-2 protein had a tendency to a shorter survival than those without, but it was not statistically significant (p = 0.08). The 5-year survival rate after surgery was 54% in the negative staining group to the c-ErbB-2 protein and 49% in the positive staining group. This suggests that the c-ErbB-2 protein has a possible role in lymph node metastasis. Therefore overexpression of the c-ErbB-2 protein is a useful indicator of disease progression in gastric carcinoma patients who received curative surgery.

Expression of nucleoside diphosphate kinase/nm23 gene product in human pancreatic cancer: an association with lymph node metastasis and tumor invasion

The expression of nucleoside diphosphate (NDP) kinase/nm23 has been reported to be inversely related to metastasizing potential of experimental cells and human breast cancer. In the present study, levels of NDP kinase/nm23 gene product in curatively resected human pancreatic adenocarcinomas were examined immunohistochemically using anti-NDP kinase antibody. Immunoreactivity for NDP kinase varied between tumors. Of 31 pancreatic tumors examined, 17 (55%; positive staining group) showed strong immunoreactivity for the NDP kinase, while 14 (45%; negative staining group) showed low or no immunoreactivity. Positive staining was associated with higher incidence of lymph node metastasis (13/17; 77%) and perineural invasion (13/17; 77%) than negative staining (5/14, 36%, P < 0.03; 4/14, 29%, P < 0.01, respectively). Positive staining was also associated with shorter overall survival and relapse-free survival than negative staining (P < 0.01, P < 0.01, respectively). No significant difference in age, sex, size, location of tumor, serum carcinoembryonic antigen (CEA) level, or histological type was found between the two groups. These results showed that, in contrast to the reports on breast cancer, NDP kinase/nm23 expression in human pancreatic cancer is positively associated with lymph node metastasis or perineural invasion and with poor prognosis. These, together with other previous reports, suggest that NDP kinase may play an important role in cancer progression or aggressiveness by altering its expression in a tissue-specific manner.