[Electroacupuncture improves learning and memory impairment and enhances hippocampal synaptic plasticity through BDNF/TRKB/CREB signaling pathway in cerebral ischemia-reperfusion injury rats].

OBJECTIVE: To observe the effect of electroacupuncture on brain-derived neurotrophin factor (BDNF) / tyrosine kinase receptor B (TRKB) / cyclic adenosine monophosphate response element binding protein (CREB) pathway, synaptic plasticity marker protein and synaptic ultrastructure in the hippocampus of rats with learning and memory impairment induced by cerebral ischemia reperfusion (IR), so as to explore its mechanisms underlying improvement of cognitive impairment after stroke. METHODS: SD rats were randomly divided into blank, sham operation, model, and EA groups, with 12 rats in each group. The model of IR was established by occlusion of the middle cerebral artery. EA (2 Hz/10 Hz, 1-3 mA) was applied to "Shenting" (GV24) and "Baihui" (GV20) for 30 min, once daily for 14 days. The neurological function was evaluated according to the Zea Longa's score criteria. Morris water maze test was used to detect the learning and memory function of the rats. Nissl staining was used to observe the pathological morphology of the hippocampus. Transmission electron microscopy was used to observe the ultrastructure of the syna-pse in the hippocampus, the synaptic gap width and postsynaptic dense substance (PSD) thickness were measured. Immunofluorescence staining was used to observe the positive expression levels of BDNF, PSD-95 and synaptophysin (SYN) in hippocampal CA1 region. The protein expression levels of BDNF, TRKB, CREB, PSD-95, and SYN in hippocampal tissue were detected by Western blot. RESULTS: Compared with the sham operation group, the neurological function score and escape latency (EL) were significantly increased (P<0.01), the times of crossing the original platform were decreased (P<0.01), the number of neurons in the CA1 area of the hippocampus was reduced, with incomplete morphology, widened synaptic gaps and significantly decreased PSD thickness (P<0.01), the positive expressions of BDNF, PSD-95, SYN and the protein expression levels of BDNF, TRKB, CREB, PSD-95, SYN were significantly decreased (P<0.01) in the model group. Compared with the model group, the neurological function scores and EL on the 12th and 13th day were decreased (P<0.01, P<0.05), the times of crossing the original platform were increased (P<0.01), the morphology of hippocampal CA1 neurons improved, the synaptic gaps was decreased (P<0.01), the PSD thickness was significantly increased (P<0.01), the positive expressions of BDNF, PSD-95, SYN, and the protein expression levels of BDNF, TRKB, CREB, PSD-95, SYN were increased (P<0.05, P<0.01) in the EA group. CONCLUSION: EA can alleviate cognitive impairment in IR rats, which may be related to its function in up-regulating the proteins of BDNF/TRKB/CREB pathway, promoting the expressions of synaptic plasticity marker proteins PSD-95 and SYN, thus improving the synaptic plasticity.

The Clinical Observation and Mechanism of Acupuncture on Cancer-Related Fatigue of Breast Cancer Based on "Gut-Brain Axis": Study Protocol for a Randomized Controlled Trial.

Background. Cancer-related fatigue (CRF) is a painful, persistent feeling of physical and cognitive subjective fatigue related to cancer or cancer remedy. The occurrence of CRF may be related to the hypothalamic-pituitary-adrenaline (HPA) axis, inflammatory mediator theory, and gut microbiota. Moreover, acupuncture could play a vital part in the therapy of CRF. The study will evaluate whether acupuncture can improve fatigue symptoms of CRF patients after breast cancer chemotherapy by regulating the gut-brain axis. Methods/design. Seventy patients with CRF will be enrolled in this study, with 35 patients randomly assigned to each group. Blood and feces will be collected at the beginning and end of treatment. Piper fatigue scale, KPS score scale, and quality-of-life scale will be used to observe the changes of fatigue symptoms and life quality of CRF patients and to evaluate the effect of acupuncture on CRF. Then, the method of ELISA will be used to explore the regulatory effect of acupuncture on the HPA axis and inflammatory cytokines. Moreover, based on 16SrDNA, the changes of gut microbiota structure and flora of CRF patients will be observed. Ultimately, the correlation analysis of gut microbiota can be related to inflammatory cytokines, HPA axis, and clinical efficacy evaluation. Discussion. This study will identify the effect and the mechanism of acupuncture therapy in CRF. And it will offer an alternative treatment modality for the treatment of CRF after chemotherapy for breast cancer. Furthermore, it will also provide the clinical and theoretical bases for the extensive application of acupuncture therapy in tumor rehabilitation. Trial Status. Protocol version number and date: V2.0, 6 May 2021. The trial is registered with the Chinese Clinical Trial Registry on 20 June 2021 (trial identifier: ChiCTR2100047510).

[Effect of moxibustion on M2 and P2X3 receptors of bladder tissue in rats with neurogenic bladder of detrusor areflexia after lumbar-sacral spinal cord injury].

OBJECTIVE: To observe the effect of moxibustion at "Guanyuan" (CV 4) and "Shenque" (CV 8) on acetylcholine (Ach), adenosine triphosphate (ATP) and muscarinic-type choline receptor (M2) and purine receptor P2X3 in bladder tissue in the rats with neurogenic bladder (NB) of detrusor areflexia after lumbar-sacral spinal cord injury and explore the underlying mechanism of moxibustion for promoting detrusor contraction. METHODS: Sixty SD rats were randomly divided into a model preparation group (n=45) and a sham-operation group (n=15). In the model preparation group, the modified Hassan Shaker spinal cord transection method was used to prepare the model of NB. In the sham-operation group, the spinal cord transection was not exerted except laminectomy and spinal cord exposure. Among the rats with successfully modeled, 30 rats were selected and divided randomly into a model group and a moxibustion group, with 15 rats in each one. On the 15th day after the operation, moxibustion was applied at "Guanyuan" (CV 4) and "Shenque" (CV 8) in the moxibustion group, 10 min at each acupoint, once a day. The consecutive 7-day treatment was as one course and the intervention for 2 courses was required. Urodynamic test was adopted to evaluate bladder function in rats. Using HE staining, the morphological changes in bladder tissue were observed. The content of Ach and ATP in bladder tissue was measured with biochemical method, and the protein and mRNA expression levels of M2 and P2X3 receptors in bladder tissue were detected with Western blot and real-time fluorescence quantification PCR method. RESULTS: Compared with the sham-operation group, the maximum bladder capacity, leakage point pressure and bladder compliance were increased in the rats of the model group (P<0.05). Compared with the model group, the maximum bladder capacity, the leakage point pressure and bladder compliance were decreased in the rats of the moxibustion group (P<0.05). In the model group, the detrusor fibres were arranged irregularly, bladder epithelial tissues were not tightly connected and cell arrangement was disordered, combined with a large number of vacuolar cells. In the moxibustion group, compared with the model group, the detrusor fibres were arranged regularly, bladder epithelial cells were well distributed and vacuolar cells were reduced. Compared with the sham-operation group, the content of Ach and ATP in bladder tissue was decreased (P<0.05), the protein and mRNA expression levels of M2 and P2X3 receptors were reduced (P<0.05) in the model group. In the moxibustion group, the content of Ach and ATP in bladder tissue was increased (P<0.05) and the protein and mRNA expression levels of M2 and P2X3 receptors were increased (P<0.05) as compared with the model group. CONCLUSION: Moxibustion at "Guanyuan" (CV 4) and "Shenque" (CV 8) may effectively improve bladder function in the rats with NB of detrusor areflexia after lumbar-sacral spinal cord injury and its underlying mechanism is related to promoting the release of Ach and up-regulating the expression of M2 receptor, thereby enhancing the release of ATP and increasing the expression of P2X3 receptor. Eventually, detrusor contraction is improved.

Targeting-YAP/TAZ therapies for head and neck cancer, directly or indirectly?

YAP/TAZ are wild over-activated in head and neck squamous cell carcinoma (HNSCC) with high potential as a direct therapy target for HNSCC treatments. However, the efforts on the directly targeting-YAP/TAZ therapies over the past decade, have very limited impacts, mainly caused by: 1. There is still none effective and specific YAP/TAZ inhibitor with clinical potential; 2. YAP/TAZ might not be directly targeted, because of their multiple important biological functions, such as: regulation of cell proliferation and survival, stem cell maintain, regulation of organ development, organ size control, and tissue regeneration. Interestingly, the over-activation of YAP/TAZ in HNSCC mainly be regulated by upstream abnormal molecular or biological events, instead of genes alteration of YAP/TAZ. Therefore, exploring the alternative molecular events regulating YAP/TAZ activation and molecular mechanism in HNSCC might help to uncover novel indirect targets of YAP/TAZ therapies for HNSCC prevention and treatment.

Circulating serum exosomal miR-20b-5p and miR-3187-5p as efficient diagnostic biomarkers for early-stage non-small cell lung cancer.

IMPACT STATEMENT: The high mortality of non-small cell lung cancer (NSCLC) is mainly because the cancer has progressed to a more advanced stage before diagnosis. If NSCLC can be diagnosed at early stages, especially stage 0 or I, the overall survival rate will be largely improved by definitive treatment such as lobectomy. We herein validated two novel circulating serum ExmiRs as diagnostic biomarkers for early-stage NSCLC to fulfill the unmet medical need. Considering the number of specimens in this study, circulating serum exosomal miR-20b-5p and miR-3187-5p are putative NSCLC biomarkers, which need to be further investigated in a larger randomized controlled clinical trial.

[Effects of microRNA-218 on proliferation, apoptosis and invasion of human tongue cancer cell line SCC-4 and SCC-9].

PURPOSE: To study the effects of miR-218 on cell proliferation, apoptosis and invasion of human tongue cancer cell line SCC-4 and SCC-9 cells. METHODS: SCC-4 and SCC-9 cells were transfected with negative control, miR-218 mimics and inhibitor, then cell proliferation was detected by MTT assay, cell cycle and cell apoptosis were measured by flow cytometry, cell invasion ability was tested by Transwell assay. The data were analyzed using GraphPad 7.0 software package. RESULTS: Compared with control cells, there was no significant difference for cell proliferation, cell cycle, cell apoptosis and invasion ability in cells transfected with miR-218 inhibitor. However, decreased cell proliferation and invasion ability and increased apoptosis ratio were found in cells transfected with miR-218 mimics. CONCLUSIONS: The expression level of miR-218 in tongue cancer cell lines may be correlated with cell proliferation, apoptosis and invasion.

Catgut implantation at acupoints increases the expression of glutamate aspartate transporter and glial glutamate transporter-1 in the brain of rats with spasticity after stroke.

Catgut implantation at acupoints has been shown to alleviate spasticity after stroke in rats. However, the underlying mechanisms are poorly understood. In this study, we used the rat middle cerebral artery occlusion model of stroke. Three days after surgery, absorbable surgical catgut sutures were implanted at Dazhui (GV14), Jizhong (GV6), Houhui, Guanyuan (CV4) and Zhongwan (CV12). The Zea Longa score was used to assess neurological function. The Modified Ashworth Scale was used to evaluate muscle tension. The 2,3,5-triphenyl-tetrazolium chloride assay was used to measure infarct volume. Immunohistochemical staining was performed for glutamate aspartate transporter (GLAST) and glial glutamate transporter-1 (GLT-1) expression. Western blot assay was used to analyze the expression of GLAST and GLT-1. Reverse transcription and polymerase chain reaction were carried out to assess the expression of GLAST and GLT-1 mRNAs. After catgut implantation at the acupoints, neurological function was substantially improved, muscle tension was decreased, and infarct volume was reduced in rats with spasticity after stroke. Furthermore, the expression of GLAST and GLT-1 mRNAs was increased on the injured (left) side. Our findings demonstrate that catgut implantation at acupoints alleviates spasticity after stroke, likely by increasing the expression of GLAST and GLT-1.

Using the entrapment sequence method as a standard to evaluate key steps of proteomics data analysis process.

BACKGROUND: The mass spectrometry based technical pipeline has provided a high-throughput, high-sensitivity and high-resolution platform for post-genomic biology. Varied models and algorithms are implemented by different tools to improve proteomics data analysis. The target-decoy searching strategy has become the most popular strategy to control false identification in peptide and protein identifications. While this strategy can estimate the false discovery rate (FDR) within a dataset, it cannot directly evaluate the false positive matches in target identifications. RESULTS: As a supplement to target-decoy strategy, the entrapment sequence method was introduced to assess the key steps of mass spectrometry data analysis process, database search engines and quality control methods. Using the entrapment sequences as the standard, we evaluated five database search engines for both the origanal scores and reprocessed scores, as well as four quality control methods in term of quantity and quality aspects. Our results showed that the latest developed search engine MS-GF+ and percolator-embeded quality control method PepDistiller performed best in all tools respectively. Combined with efficient quality control methods, the search engines can improve the low sensitivity of their original scores. Moreover, based on the entrapment sequence method, we proved that filtering the identifications separately could increase the number of identified peptides while improving the confidence level. CONCLUSION: In this study, we have proved that the entrapment sequence method could be an useful strategy to assess the key steps of the mass spectrometry data analysis process. Its applications can be extended to all steps of the common workflow, such as the protein assembling methods and data integration methods.

Clinical efficacy of epicardial application of drug-releasing hydrogels to prevent postoperative atrial fibrillation.

OBJECTIVE: Postoperative atrial fibrillation is the most frequent complication arising after cardiac surgery, occurring in 40% of cases. The treatment of postoperative atrial fibrillation with epicardial amiodarone/corticosteroid hydrogel delivery can increase efficacy and reduce side effects. To further evaluate whether amiodarone hydrogel is superior to corticosteroid hydrogel or placebo, we performed a randomized prospective study in 150 patients with coronary artery bypass grafting to compare the effectiveness with different epicardial drug approaches in the postoperative period. METHODS: After institutional review board approval, 150 patients, from January 2012 to July 2014, who had undergone cardiac surgery were randomized to 3 equal groups. Group I received poly-based hydrogel with amiodarone, and group II received poly-based hydrogel with triamcinolone. Both hydrogels were sprayed diffusely over the biatrial epicardium. The control group underwent the procedure with only hydrogel spray. Continuous telemetry monitored for postoperative atrial fibrillation, and amiodarone or triamcinolone levels in the atria, plasma, and tissue were measured postoperatively. Daily electrocardiographic parameters were measured until postoperative day 14. RESULTS: The incidence of postoperative atrial fibrillation was significantly less in group I, with 4 of 50 patients (8%) incurring atrial fibrillation compared with 11 of 50 patients (22%) in group II and 13 of 50 patients (26%) in the control group (P < .01). The mean amiodarone and triamcinolone concentrations in the atria (12.06 ± 3.1/1.5 ± 0.7) were significantly greater than those in the extracardiac tissues (1.32 ± 0.9/0.2 ± 0.4; P < .01). The plasma amiodarone and triamcinolone levels remained below the detection limit (<8 µg/mL and <0.2 µg/mL) during the 14 days of follow-up. Bradycardia was observed less in the control group (93 ± 18) than in study group I (76 ± 29; P < .01). CONCLUSIONS: Epicardial application of amiodarone-releasing adhesive hydrogel is a less-invasive, well-tolerated, quick, and effective therapeutic option for preventing postoperative atrial fibrillation with minimal risk of extracardiac adverse side effects. However, there was no clinical evidence that epicardial corticosteroid prevented postoperative atrial fibrillation.

Structural maintenance of chromosomes 4 is a predictor of survival and a novel therapeutic target in colorectal cancer.

BACKGROUND: Structural maintenance of chromosomes 4 (SMC-4) is a chromosomal ATPase which plays an important role in regulate chromosome assembly and segregation. However, the role of SMC-4 in the incidence of malignancies, especially colorectal cancer is still poorly understood. MATERIALS AND METHODS: We here used quantitative PCR and Western blot analysis to examine SMC-4 mRNA and protein levels in primary colorectal cancer and paired normal colonic mucosa. SMC-4 clinicopathological significance was assessed by immunohistochemical staining in a tissue microarray (TMA) in which 118 cases of primary colorectal cancer were paired with noncancerous tissue. The biological function of SMC-4 knockdown was measured by CCK8 and plate colony formation assays. Fluorescence detection has been used to detect cell cycling and apoptosis. RESULTS: SMC-4 expression was significantly higher in colorectal cancer and associated with T stage, N stage, AJCC stage and differentiation. Knockdown of SMC-4 expression significantly suppressed the proliferation of cancer cells and degraded its malignant degree. CONCLUSIONS: Our clinical and experimental data suggest that SMC-4 may contribute to the progression of colorectal carcinogenesis. Our study provides a new therapeutic target for colorectal cancer treatment.

Effectiveness of biatrial epicardial application of amiodarone-releasing adhesive hydrogel to prevent postoperative atrial fibrillation.

OBJECTIVE: Postoperative atrial fibrillation (POAF) is the most frequent complication arising after cardiac surgery, occurring in 30% of cases. Amiodarone is the most effective drug for prophylaxis and treatment. However, because of significant extracardiac side effects, only high-risk patients are eligible for prophylactic amiodarone therapy. We performed a randomized prospective study of 100 patients undergoing cardiac surgery with epicardial application of amiodarone-releasing hydrogel to determine the effectiveness of preventing POAF. METHODS: After institutional review board approval, 100 patients, from January 2012 to July 2013, who had undergone cardiac surgery, were randomized to 2 equal groups. The study group received poly-based hydrogel with amiodarone sprayed diffusely over the epicardium. The control group underwent the procedure without the spray. Continuous telemetry monitored for POAF, and amiodarone levels in the atria, plasma, and tissue were measured postoperatively. Daily electrocardiographic parameters were measured until postoperative day 14. RESULTS: The incidence of POAF was significantly less in the study group, with 4 of 50 patients (8%) incurring atrial fibrillation compared with 13 of 50 patients (26%) in the control group (P < .01). The mean amiodarone concentrations in the atria (12.06 ± 3.1) were significantly greater than those in the extracardiac tissues (1.32 ± 0.9; P < .01). The plasma amiodarone levels remained below the detection limit (<8 µg/mL) during the 14 days of follow-up. Bradycardia was observed less in the study group (76 ± 29) than in the control group (93 ± 18; P < .01). CONCLUSIONS: Epicardial application of amiodarone-releasing adhesive hydrogel is a less invasive, well-tolerated, quick, and effective therapeutic option for preventing POAF at minimal risk of extracardiac adverse side effects.

Continuous biatrial pacing to prevent early recurrence of atrial fibrillation after the Maze procedure.

OBJECTIVE: It has been suggested that overdrive biatrial pacing may prevent the recurrence of atrial fibrillation after the Maze procedure. To further evaluate this hypothesis, we performed a randomized prospective study in 100 patients undergoing valve surgery concomitant with a full Maze procedure to determine the effectiveness of biatrial pacing in the postoperative period to reduce early recurrence of atrial fibrillation. METHOD: Between January 2002 and December 2008, 100 patients undergoing mitral valve ± tricuspid valve surgery concomitant with the Maze procedure were randomized into 2 equal groups: the study group using overdrive biatrial pacing and a control group without pacing. One pacing wire was attached to the crista terminalis area of the right atrium, and the other pacing wire was attached to the Bachmann's bundle area located in the roof of the left atrium. The atria were paced continuously in AAI mode at a rate of 80 pulses per minute or 10 pulses above the underlying rate for 5 days. The end points were the onset of recurrent atrial fibrillation or discharge. RESULTS: The incidence of recurrent postoperative atrial fibrillation was significantly less in the study group, with 6 of 50 patients (12%) incurring atrial fibrillation compared with 18 of 50 patients (36%) in the control group (P < .01). The length of hospital stay was significantly reduced in the study group (P < .01), and the mean costs of hospital stay were significantly lower in the control group (P < .05). CONCLUSIONS: Biatrial overdrive pacing is well tolerated and more effective in preventing the early recurrence of atrial fibrillation after the Maze procedure. This therapy also results in shortened hospital stays and decreased hospital costs. However, the impacts of the long-term results in the Maze procedure require further study.

Left atrial wall tension directly affects the restoration of sinus rhythm after Maze procedure.

OBJECTIVE: The surgical treatment of permanent atrial fibrillation (AF) continues to be a clinical challenge. Increased left atrial (LA) wall tension affected by LA wall thickness and volume has been associated with poor restoration of sinus rhythm after the Maze procedure. This study was designed to investigate the impact of conversion rates to sinus rhythm using LA wall tension reduction techniques in conjunction with aggressive postoperative pharmacological therapy in comparison to a modified Maze procedure alone. METHODS: From 1999 to 2008, 322 patients with permanent AF and biatrial enlargement, who required mitral valve ± tricuspid valve surgery were exactly randomized into two groups: The study group used biatrial reduction with reef-imbricate suture technique concomitant with the Maze procedure and aggressive postoperative pharmacological therapy; the control group was treated with the Maze procedure alone. LA dimension was measured by transesophageal echocardiogram (TEE) or transthoracic echocardiography (TTE); LA wall thickness was measured by TEE and manually during surgery. Pulmonary artery (PA) pressures were measured by PA catheter or TTE, BNP test and clinical follow-up at discharge, 3 months, 6 months and 1 year. There were 187 woman (58%) and 135 men (42%). Their mean age was 45 ± 9.5 years. RESULTS: Overall restoration of sinus rhythm was significantly improved in the group with aggressive reduction of LA wall tension during 1-year clinical follow-up (89.3% vs 67.2%, p < 0.001). Calculated LA wall tension was significantly reduced at discharge in the study group versus control group (4.012 ± 1.650 dyn cm(-1) vs 20 384 ± 3313 dyn cm(-1) (p < 0.001)) and at 1-year follow-up (1059 ± 1161 dyn cm(-1) vs 17 139 ± 3170 dyn cm(-1) (p < 0.001)), respectively. Significant differences in changes in LA dimension were detected at discharge and 1-year follow-up in the study group versus control group (43 ± 7 vs 61 ± 11, p < 0.001). LA wall (3.9 ± 1.3 vs 2.3 ± 0.9) thickness also significantly differed at the 1-year follow-up. CONCLUSION: An aggressive approach to reduce LA wall tension significantly improves restoration of sinus rhythm after the Maze procedure. LA wall tension directly affects sinus conversion. Further studies using pharmacologic intervention to reduce LA wall tension for maintenance of sinus rhythm need to be evaluated.

Biatrial reduction plasty with reef imbricate technique as an adjunct to maze procedure for permanent atrial fibrillation associated with giant left atria.

Success of the modified maze procedure after valvular operation with giant atria and permanent atrial fibrillation (AF) remains suboptimal. We report an aggressive approach for these patients utilizing biatrial reduction plasty with a reef imbricate suture technique concomitantly with valvular and maze procedure for AF. From January 1999 to December 2006, 122 consecutive Chinese patients with permanent AF and biatrial enlargement who required mitral valve+/-tricuspid valve (TV) surgery underwent aggressive left atrial reduction combined with radiofrequency bipolar full maze procedure. Left atrial dimensions were measured by TTE or TEE. There were 71 women (58.1%) and 51 men (41.9%) and their mean age was 45+/-9.5 years. Mean duration of AF was 48.4+/-21.4 months. All patients underwent left atrial reduction plasty with reef imbricate suture technique and full maze procedure. Their preoperative left atria measured 64+/-12 mm in the enlarged left atria (ELA) group and 86+/-17 mm in the giant left atria (GLA). Mitral valve replacement (MVR) combined with TV repair was performed in 102 patients (83%) while 21 patients underwent MVRs combined with aortic valve replacements (17%). Sixty-six (54%) patients required additional procedures and 61 (50%) of the patients also underwent left atrial appendage clot evacuation. Postoperative left atrial size was reduced to 49+/-8 mm (ELA) and 51+/-11 mm (GLA), respectively (P<0.05). Ninety-three of 122 (76%) patients were restored in normal sinus rhythm after one year clinical follow-up. Aggressive biatrial reduction plasty combined with full maze procedure is an effective treatment for patients with permanent AF undergoing concomitant valvular surgery. Further studies utilizing the reef imbricate suture technique for atrial reduction need to subsequently be evaluated.

[Clinical significance of sentinel lymph node detection by combining the dye-directed and radioguided methods in gastric cancer].

OBJECTIVE: To investigate the feasibility and accuracy of detection of sentinel lymph nodes (SLN) with combining the dye-directed and radioguided methods in gastric cancer and assess its potential role in determining the rational extent of lymphadenectomy in gastric cancer surgery. METHODS: Twenty-six patients of gastric cancer diagnosed as T(1)-T(3) were enrolled in this study. Endoscopic injection submucosally of (99m)Tc labeled sulfur colloid solution was performed around the primary tumor 2 - 4 h before operation. Immediately after laparotomy, patent blue violet was injected into subserosal layer adjacent to the tumor. SLNs were defined as blue stained nodes or(and) those containing 10 times more radioactivity than surrounding tissue with a gamma probe. Standard radical gastrectomy with lymphadenectomy (D(2) or D(3)) was performed in most of the patients, however, limited surgery was performed in early gastric cancer (EGC) when a rapid frozen examination indicated negative SLNs. All resected nodes were examined postoperatively by routine HE stain and those negative SLNs were examined with further cytokeratin immunohistochemistical staining. The diagnostic accuracy, sensitivity, negative predictive value and false-negative rate of regional lymph node status on the basis of SLN status were calculated respectively. RESULTS: SLNs were dectected in 25 of 26 patients with a successful detection rate of 96%. The number of SLNs ranged from 1 to 6, with a mean value of 3.2 per case. The SLNs of gastric cancer were only found in N(1) area in 50% of the cases, and only in N(2) or N(3) in 12%. The incidence of metastasis was significantly higher in SLNs than in non-SLNs (35% vs 7%). The diagnostic accuracy, sensitivity, negative predictive value and false-negative rate were 96%, 94%, 7/8 and 6% respectively. Complete analysis of SLN upstaged 2/7 of patients of gastric cancer. CONCLUSIONS: The SLN concept is validated in gastric cancer. Combined-agent SLN mapping is an accurate diagnostic procedure for detecting lymph node metastasis in patients with gastric cancer and may indicate rational extent of lymphadenectomy for gastric cancer.

[Sclerosing epithelioid fibrosarcoma: a clinicopathologic study of eight cases].

OBJECTIVE: To study the clinicopathologic features, immunophenotype and differential diagnosis of sclerosing epithelioid fibrosarcoma (SEF). METHODS: Eight cases of SEF were investigated by light microscopy and immunohistochemistry. RESULTS: There were five males and three females. Clinically, most patients presented as a slowly growing mass. Six tumors were located in the extremities or limb girdles, and two in the trunk. Grossly, most lesions were relatively well-circumscribed with a nodular or lobulated appearance. They ranged from 2.0 to 10.5 cm in size (mean 6 cm). On sectioning, they had a gray-whitish cut surface and were firm in consistency. Microscopically, the tumors were composed of uniformly round or polygonal epithelioid cells with clear to eosinophilic cytoplasm. The tumor cells were arranged predominantly in single strands or cords and embedded in a heavily hyalinized matrix. In some areas, nests, sheets, acini or alveolar structures were also noted. Nuclei atypia and brisk mitotic activity was not evident. The mitotic count measured less than 1 per 10 high power fields. However in two cases, focal areas exhibited increased cellularity, nuclei atypia and higher mitotic activity, resembling conventional fibrosarcoma. Immunohistochemically, the tumor cells showed diffuse and strong positivity for vimentin and focal or weak positivity for EMA. There was no expression for AE1/AE3, S-100 protein, HMB45, alpha-SMA, MSA, desmin, CD34, bcl-2, CD30 and LCA. Follow-up information in six patients revealed local recurrence in 3 cases and lung metastasis in 1 case. CONCLUSIONS: SEF is a rare variant of fibrosarcoma. Despite the relatively bland appearance and low mitotic activity, the tumor is capable of local recurrence and distant metastasis. Thus, it should be considered and treated as a low to intermediate grade sarcoma. SEF needs to be differentiated from a variety of benign or malignant tumors exhibiting epithelioid features and sclerotic stromal response.