Effectiveness of no drainage after elective day-case laparoscopic cholecystectomy, even with intraoperative gallbladder perforation: a randomized controlled trial.

BACKGROUND: Laparoscopic cholecystectomy (LC) has been carried out as day-case surgery. Current guidelines do not mention the role of drainage after LC. In particular, data stay blank with no prospective study on drainage management when gallbladder perforation (GP) accidentally occurs intraoperatively. METHODS: A randomized controlled trial was conducted to compare clinical outcomes of drainage and no drainage after elective day-case LC. Intraoperative GP was recorded. The primary and secondary outcomes were major and minor complications, respectively. RESULTS: Two hundred patients were randomized. No major complications occurred in either group. In secondary outcomes, nausea/vomiting, pain, hospital stay, and cost were similar in the drainage group and no drainage group; postoperative fever, WBC, and CRP levels were significantly lower in the no drainage group. GP occurred in 32 patients. Male patients with higher BMI and CRP and abdominal pain within 1 month were more likely to occur GP. Subgroup analysis of GP, primary outcomes, and most secondary outcomes had no difference. Postoperative WBC and CRP were higher in the drainage group. Postoperative fever occurred in 63 patients. Univariate analysis of fever showed that blood loss, drainage, postoperative WBC, CRP, and hospital stay were significant. Multivariable logistic regression analysis demonstrated that drainage was an independent risk factor for fever after LC (OR 3.418, 95% CI 1.392-8.390; p = 0.007). CONCLUSIONS: No drainage after elective day-case LC is safe and associated with fewer complications, even in intraoperative GP. The trial proves that drainage is an independent risk factor for postoperative fever. The use of a drain after LC may lead to an unsuccessful day-case procedure by causing fever, elevated CRP, and extended hospital stay (NCT03909360).

Hem-o-lok clip migration to the common bile duct after laparoscopic common bile duct exploration: A case report.

BACKGROUND: Laparoscopic cholecystectomy (LC) and laparoscopic common bile duct exploration (LCBDE) has been widely used for management of gallbladder and common bile duct (CBD) stones. Post-operative clip migration is a rare complication of laparoscopic biliary surgery, which can serve as a nidus for stone formation and cause recurrent cholangitis. CASE SUMMARY: A 59-year-old female was admitted to hospital because of fever and acute right upper abdominal pain. She has a history of LC and had a LCBDE surgery 2 mo ago. Physical examination revealed tenderness in the upper quadrant of right abdomen. Computed tomography scan demonstrated a high-density shadow at the distal CBD, which was considered as migrated clips. The speculation was confirmed by endoscopic retrograde cholangiopancreatography examination, and two displaced Hem-o-lok clips were removed with a stone basket. No fever or abdominal pain presented after the operation. In addition to the case report, literature regarding surgical clip migration after laparoscopic biliary surgery was reviewed and discussed. CONCLUSION: Incidence of postoperative clip migration may be reduced by using clips properly and correctly; however, new methods should be explored to occlude cystic duct and vessels. If a patient with a past history of LC or LCBDE presents with features of sepsis and recurrent upper quadrant pain, clip migration must be considered as one of the differential diagnosis.

MiR-135b-5p is an oncogene in pancreatic cancer to regulate GPRC5A expression by targeting transcription factor KLF4.

KLF4 is implicated in tumor progression of pancreatic cancer, but the molecular regulatory mechanism of KLF4 needs to be further specified. We aimed to probe molecular regulatory mechanism of KLF4 in malignant progression of pancreatic cancer. qRT-PCR or western blot was completed to test levels of predicted genes. Dual-luciferase and chromatin immunoprecipitation (ChIP) assays were designed to validate binding between genes. Cell viability and oncogenicity detection were used for in vitro and vivo functional assessment. KLF4 was a downstream target of miR-135b-5p. KLF4 could regulate GPRC5A level. MiR-135b-5p was notably increased in cancer cells, and overexpressing KLF4 functioned a tumor repressive role, which could be restored by miR-135b-5p. Besides, cell malignant phenotypes could be inhibited through reducing miR-135b-5p level, but they were restored by GPRC5A. Our results stressed that KLF4, as a vital target of miR-135b-5p, could influence promoter region of GPRC5A, thus affecting the malignant progression of pancreatic cancer.

Treatment of microvascular invasion in hepatocellular carcinoma with drug-loaded nanocomposite platform under synergistic effect of magnetic field/near-infrared light.

Despite progress in clinical treatment, microvascular invasion (MVI) remains a major factor for frequent recurrence and metastasis of hepatocellular carcinoma (HCC) after liver resection and surgery. Thus, this study constructed a target nanoplatform (αCD97-USPIO-Au-DDP) with magnetic field/near-infrared (NIR) light response using ultrasmall superparamagnetic iron oxide-gold nanoporous spheres (USPIO-Au) as multifunctional nanocarrier. Anticancer drug cisplatin (DDP) was loaded, and specifically expressed CD97 protein in MVI was taken as the therapeutic target. The αCD97-USPIO-Au-DDP showed favorable photothermal and stable properties under the NIR light at 808 nm wavelength. As suggested by in vitro and in vivo research, this composite nanopreparation could effectively reduce damage to normal organs and showed good biocompatibility. Excellent magnetic targeting function of nanocarrier and modification of αCD97 strengthened accumulation of composite nanodrug in tumor to inhibit tumor growth. This system may have important ramifications for treatment of MVI in HCC.

Exome sequencing and analysis of 454,787 UK Biobank participants.

A major goal in human genetics is to use natural variation to understand the phenotypic consequences of altering each protein-coding gene in the genome. Here we used exome sequencing1 to explore protein-altering variants and their consequences in 454,787 participants in the UK Biobank study2. We identified 12 million coding variants, including around 1 million loss-of-function and around 1.8 million deleterious missense variants. When these were tested for association with 3,994 health-related traits, we found 564 genes with trait associations at P ≤ 2.18 × 10-11. Rare variant associations were enriched in loci from genome-wide association studies (GWAS), but most (91%) were independent of common variant signals. We discovered several risk-increasing associations with traits related to liver disease, eye disease and cancer, among others, as well as risk-lowering associations for hypertension (SLC9A3R2), diabetes (MAP3K15, FAM234A) and asthma (SLC27A3). Six genes were associated with brain imaging phenotypes, including two involved in neural development (GBE1, PLD1). Of the signals available and powered for replication in an independent cohort, 81% were confirmed; furthermore, association signals were generally consistent across individuals of European, Asian and African ancestry. We illustrate the ability of exome sequencing to identify gene-trait associations, elucidate gene function and pinpoint effector genes that underlie GWAS signals at scale.

Establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids.

BACKGROUND: Patient-derived organoids (PDO) have been proposed as a novel in vitro method of drug screening for different types of cancer. However, to date, extrahepatic biliary tract carcinoma (eBTC) PDOs have not yet been fully established. METHODS: We collected six samples of gallbladder carcinoma (GBC) and one sample of extrahepatic cholangiocarcinoma (eCCA) from seven patients to attempt to establish eBTC PDOs for drug screening. We successfully established five GBC and one eCCA PDOs. Histological staining was used to compare structural features between the original tissues and cancer PDOs. Whole exome sequencing (WES) was performed to analyze the genetic profiles of original tissues and cancer PDOs. Drug screening, including gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, infigratinib, and ivosidenib, was measured and verified by clinical effects in certain cases. RESULTS: Different PDOs exhibited diverse growth rates during in vitro culture. Hematoxylin and eosin staining demonstrated that the structures of most cancer PDOs retained the original structures of adenocarcinoma. Immunohistological and periodic acid-schiff staining revealed that marker expression in cancer PDOs was similar to that of the original specimens. Genetic profiles from the four original specimens, as well as paired cancer PDOs, were analyzed using whole exome sequencing. Three of the four PDOs exhibited a high degree of similarity when compared to the original specimens, except for GBC2 PDO, which only had a concordance of 74% in the proportion of single nucleotide polymorphisms in the coding sequence. In general, gemcitabine was found to be the most efficient drug for eBTC treatment, as it showed moderate or significant inhibitory impact on cancer growth. Results from drug screening were confirmed to a certain extent by three clinical cases. CONCLUSIONS: Our study successfully established a series of eBTC PDOs, which contributed to the field of eBTC PDOs. Additional enhancements should be explored to improve the growth rate of PDOs and to preserve their immune microenvironment.

Exome sequencing and characterization of 49,960 individuals in the UK Biobank.

The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world1. Here we describe the release of exome-sequence data for the first 49,960 study participants, revealing approximately 4 million coding variants (of which around 98.6% have a frequency of less than 1%). The data include 198,269 autosomal predicted loss-of-function (LOF) variants, a more than 14-fold increase compared to the imputed sequence. Nearly all genes (more than 97%) had at least one carrier with a LOF variant, and most genes (more than 69%) had at least ten carriers with a LOF variant. We illustrate the power of characterizing LOF variants in this population through association analyses across 1,730 phenotypes. In addition to replicating established associations, we found novel LOF variants with large effects on disease traits, including PIEZO1 on varicose veins, COL6A1 on corneal resistance, MEPE on bone density, and IQGAP2 and GMPR on blood cell traits. We further demonstrate the value of exome sequencing by surveying the prevalence of pathogenic variants of clinical importance, and show that 2% of this population has a medically actionable variant. Furthermore, we characterize the penetrance of cancer in carriers of pathogenic BRCA1 and BRCA2 variants. Exome sequences from the first 49,960 participants highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.

Abdominal cocoon with early postoperative small bowel obstruction: A case report and review of literature in China.

RATIONALE: Abdominal cocoon is a condition in which intestinal obstruction results from the encasement of part or whole of the small bowel by a thick fibrous membrane, giving the appearance of a cocoon. The preoperative diagnosis is difficult to be made and the treatment is still controversial. PATIENT CONCERNS: Here we describe the case of a 62-year-old male presented with a 24-h history of continual colicky abdominal pain, which was accompanied with nausea and vomiting. DIAGNOSIS: Accurate diagnosis of abdominal cocoon was made intraoperatively. INTERVENTIONS: Membrane excision and adhesiolysis were performed and the patient experienced early postoperative small bowel obstruction. Nasointestinal obstruction tube was then installed and bowel function was gradually recovered by the 20th postoperative day. OUTCOMES: The patient recovered well and was discharged from the hospital on the 30th postoperative day LESSONS:: Abdominal cocoon can occur at any age. The possibility of abdominal cocoon should also be considered in infertile patients. Imaging studies may be helpful to make the correct diagnosis, and surgery should be performed for patients with recurrent acute or chronic intestinal obstruction.

Target-specific delivery of oxaliplatin to HER2-positive gastric cancer cells in vivo using oxaliplatin-au-fe3o4-herceptin nanoparticles.

Gastric cancer is the fourth most common malignancy globally. In order to decrease the dosage and side effects of conventional chemotherapy, and achieve improved benefits from molecular targeted therapy, novel drug delivery systems were developed in the present study. Oxaliplatin-Au-Fe3O4-Herceptin® acts as a dual-functional nanoparticles (NPs) conjugate and possesses the capability of human epithelial growth factor receptor 2 (HER2) targeting and oxaliplatin delivery. The 8-20 nm Au-Fe3O4 were synthesized by decomposing iron pentacarbonyl on the surfaces of Au NPs in the presence of oleic acid and oleylamine. Following being coated with polyethylene glycol, the NPs possessed a ζ-potential of 13.8±1.6 mV and were demonstrated to exhibit no cytotoxicity when Fe concentration is <100 µg/ml via an MTS assay. Mass spectrometry analysis detected a peak at m/z 148,000, and Nuclear Magnetic Resonance indicated peaks at δ 3.51 (8.00H, s, 3-H), 2.97-3.02 (3.80H, t, 2-H) and 2.72-2.76 (3.72H, t, 1-H) following successful loading with Herceptin and oxaliplatin probes. A drug release assay via dialysis cassettes demonstrated that 25% of the oxaliplatin was released at pH 8.0, however >58% was released at pH 6.0 following 4 h incubation, indicating its pH-dependent release characteristic. The active targeting feature of oxaliplatin-Au-Fe3O4-Herceptin was verified in a subcutaneous xenograft mouse model containing SGC-7901 cells via detecting aggregated low intensity in T2-weighted magnetic resonance imaging, which was further confirmed by immunohistochemistry. Therefore, oxaliplatin-Au-Fe3O4-Herceptin is a promising multifunctional platform for simultaneous magnetic traceable and HER2 targeted chemotherapy for gastric cancer.

[Effects of siRNAs targeting CD97 immune epitopes on biological behavior in breast cancer cell line MDA-MB231].

OBJECTIVE: To investigate the effects of siRNAs targeting CD97 immune epitopes on proliferation, infiltration, apoptosis and cell cycle of breast cancer cells. METHODS: siRNA sequences targeting CD97EGF and CD97Stalk immune epitopes were designed according to Gene Bank NM_001025160.2 with smart siCatchTM siRNA design software. CD97siRNAs were transfected into MDA-MB231 cells in which CD97 was highly expressed. Highest sensitive CD97EGF and CD97Stalk siRNA were screened by Western blotting. Inverted microscope was used to observe the growth of CD97siRNAs-transfected MDA-MB231 cells; the proliferation activity of MDA-MB231 cells was detected by MTT method; the wound healing assay and Transwell migration test were performed to examine the migration and infiltration ability of CD97EGF and CD97Stalk siRNA-transfected MDA-MB231 cells; the effects of CD97EGF siRNA and CD97Stalk siRNA on cell apoptosis and cell cycle of MDA-MB231 cells were detected by TUNEL and flow cytometry. RESULTS: The growth and proliferation activity of CD97siRNAs-transfected MDA-MB231 cells were significantly lower than those in the control groups, and such differences were more significant in CD97Stalk siRNA-transfected group (all P<0.05); scratch test showed that the wound healing rate was lower in CD97siRNAs-transfected groups, especially in CD97Stalk siRNA-transfected group (all P<0.05); Transwell migration showed that the number of MDA-MB231 cells crossing through chambers were less in CD97siRNAs-transfected groups, especially in CD97Stalk siRNA-transfected group (all P<0.05); no significant difference in cell apoptosis was observed between CD97siRNAs-transfected groups and control groups; cell cycle detection showed that CD97siRNAs-transfected groups had less cells in G0/G1 phase and more cells in S phase compared with the control groups, and such effect on cell cycle was more marked in CD97Stalk siRNA-transfected group (all P<0.05). CONCLUSIONS: CD97 plays an important role in the cell growth, proliferation, migration and invasion of breast cancer MDA-MB231 cells, and compared with CD97EGF, CD97Stalk may have more effective inhibitory effects on cellular malignant behaviors.

Anatomic isolated caudate lobectomy: Is it possible to establish a standard surgical flow?

AIM: To establish the surgical flow for anatomic isolated caudate lobe resection. METHODS: The study was approved by the ethics committee of the Second Affiliated Hospital Zhejiang University School of Medicine (SAHZU). From April 2004 to July 2014, 20 patients were enrolled who underwent anatomic isolated caudate lobectomy at SAHZU. Clinical and postoperative pathological data were analyzed. RESULTS: Of the total 20 cases, 4 received isolated complete caudate lobectomy (20%) and 16 received isolated partial caudate lobectomy (80%). There were 4 cases with the left approach (4/20, 20%), 6 cases with the right approach (6/20, 30%), 7 cases with the bilateral combined approach (7/20, 35%), 3 cases with the anterior approach (3/20, 15%), and the hanging maneuver was also combined in 2 cases. The median tumor size was 5.5 cm (2-12 cm). The median intra-operative blood loss was 600 mL (200-5700 mL). The median intra-operative blood transfusion volume was 250 mL (0-2400 mL). The median operation time was 255 min (110-510 min). The median post-operative hospital stay was 14 d (7-30 d). The 1- and 3-year survival rates for malignant tumor were 88.9% and 49.4%, respectively. CONCLUSION: Caudate lobectomy was a challenging procedure. It was demonstrated that anatomic isolated caudate lobectomy can be done safely and effectively.

Effects of targeted CD97 immune epitopes small interference RNA on cellular biological behaviors in MDA-MB231 malignant breast cancer cell line.

Two CD97 immune epitopes, CD97EGF (epidermal growth factor domain) and CD97Stalk (stalk domain), have different distribution patterns in malignant epidermal tumors. However, little is known about the effect of CD97EGF and CD97Stalk immune epitopes in breast cancer metastasis. To explore the effects on cell proliferation, infiltration, apoptosis, and the cell cycle, we used small interfering RNA (siRNA) against CD97EGF and CD97Stalk immune epitopes to knock down CD97 in MDA-MB231 breast cancer cells. Compared with controls, CD97 knockdown caused decreased cell growth, proliferation, migration, infiltration, and altered distribution of the percentage of cells in G0/G1 and S phase. We suggest that the potential mechanism of CD97EGF and CD97Stalk immune epitopes on the biological behaviors of MDA-MB231 breast cancer cells may be related to the altered number of N-terminal glycosylation sites, which influence the stability and signaling intensity of CD97 heterodimers.

Clinical treatment of gastrinoma: A case report and review of the literature.

Gastrinoma is a gastrin-secreting tumor that is associated with Zollinger-Ellison syndrome. The majority of cases occur in the pancreas, followed by the duodenum. Early diagnosis is difficult due to the relative rarity of the tumor and the lack of specific symptoms. In the current study, a 68-year-old female patient presented at the Second Affiliated Hospital, Zhejiang University (Hangzhou, China) due to intermittent abdominal pain and watery diarrhea. The patient was treated by surgical resection and was pathologically diagnosed with a well-differentiated pancreatic neuroendocrine tumor (gastrinoma; grade 1). No evidence of recurrence was observed during 1 year of follow-up. Furthermore, a review of the Chinese literature was performed, which analyzed an additional 17 published cases of gastrinoma. The tumor size ranged between 0.5×0.5 cm and 7.5×6.3×5.1 cm. The pancreas was the most common site of occurrence, accounting for 72% (13/18) of cases, followed by the duodenum (28%; 5/18). The most common initial symptom was abdominal pain (89%; 16/18), followed by diarrhea (56%; 10/18). In 18 cases, including the present case and 17 previous cases, the level of gastrin ranged between 137 and 1,550 pg/ml (normal range, 5-100 pg/ml). Of the 17 previous cases, 11 patients underwent surgery and 6 patients received conservative therapy due to metastasis or patient choice. Overall, gastrinoma remains a rare disease. Complete removal of the lesion is the standard curative treatment and conservative treatment is only recommended for patients unsuitable for surgery or for those with widespread metastasis.

Identification of serologic biomarkers for predicting microvascular invasion in hepatocellular carcinoma.

Microvascular invasion (MVI) of hepatocellular carcinoma (HCC) is a major risk factor for early recurrence and poor survival after curative surgical therapies. However, MVI can only be diagnosed by pathological examination following resection. The aim of this study is to identify serologic biomarkers for predicting MVI preoperatively to help facilitate treatment decisions. We used the sero-proteomic approach to identify antigens that induce corresponding antibody responses either specifically in the serum from MVI (+) patients or from MVI (-) patients. Six antigens were subsequently identified as HSP 70, HSP 90, alpha-enolase (Eno-1), Annexin A2, glutathione synthetase and beta-actin by mass spectrometry. The antibodies titers in sera corresponding to four of these six antigens were measured by ELISA and compared between 35 MVI (+) patients and 26 MVI (-) patients. The titers of anti-HSP 70 antibodies were significantly higher in MVI (-) patients than those in MVI (+) patients; and the titers of anti-Eno-1 antibodies were significantly lower in MVI (-) patients than those in MVI (+) patients. The results were subjected to multivariate analysis together with other clinicopathologic factors, suggesting that antibodies against HSP 70 and Eno-1 in sera are potential biomarkers for predicting MVI in HCC prior to surgical resection. These biomarkers should be further investigated as potential therapeutic targets.

CD97 promotion of gastric carcinoma lymphatic metastasis is exosome dependent.

BACKGROUND: CD97 knockdown impairs the metastatic capacity of SGC-7901 gastric cancer cells. However, the role of CD97 in the distant lymphatic premetastatic niche formation of gastric cancer remains unknown. METHODS: Exosomes and the soluble fraction were isolated from SGC-L (an SGC-7901-cell-derived highly lymphatic metastatic cell line) and CD97-knockdown (SGC-L/CD97-kd) cells, and were co-cultured with gastric cancer cells. The metastatic capacity of the two cell lines was evaluated in vitro and in a footpad lymph node metastasis mouse model. Premetastatic-niche-formation-related proteins were examined immunohistochemically. RESULTS: CD97 expression was ninefold higher in SGC-L cells than in SGC-7901 cells. In vitro, exosomes or conditioned medium from the SGC-L cells enhanced cell proliferation (20 % increase) and invasion (30 % increase) as compared with that from SGC-L/CD97-kd cells (p < 0.01). Intrafootpad injections of SGC-L, but not SGC-L/CD97-kd exosomes or conditioned medium, strongly promoted SGC-L and SGC-L/CD97-kd cell accumulation in the draining lymph nodes (p < 0.01) and increased CD55, CD44v6, α5ß1, CD31, epithelial cell adhesion molecule, and CD151 expression. Although the SGC-L/CD97-kd exosomes alone were insufficient for promotion of metastasis, they were partly aided by the SGC-L-cell-derived soluble fraction. CONCLUSIONS: The CD97 small isoform promotes SGC-L cell lymphatic metastasis exosome dependently, and aided by the soluble fraction, the exosome-dependent CD97 plays a pivotal role in premetastatic niche formation.

Management of retroperitoneal liposarcoma: A case report and review of the literature.

Retroperitoneal liposarcoma is a rare tumor with an incidence of 2.5 per million individuals. Early diagnosis is difficult as there is an absence of specific clinical presentations. The present case study reports a patient diagnosed with retroperitoneal liposarcoma who was treated by complete surgical resection and relapsed 3 months following the surgery. In addition, the clinical data of 14 patients with retroperitoneal liposarcoma were reviewed and analyzed. The mean age of the 14 patients at presentation was 54.1 (range, 36-73 years) and 5/14 patients experienced recurrence, ranging between 1 and 10 times. Of the 12 cases that reported histological subtypes, 7 were well-differentiated liposarcoma, 2 were dedifferentiated liposarcoma, 2 were myxoid liposarcoma and 1 was mixed subtype. All the patients underwent complete resection and 5 received combined multiple organs resection (3 nephrectomy, 1 sigmoid colon and 1 multiple visceral organs). However, no patients received chemotherapy or radiotherapy. In conclusion, retroperitoneal liposarcoma is a rare disease with a high rate of recurrence. Complete resection is the predominant treatment and combined resection of adjacent organs is occasionally necessary.

CD97 promotes gastric cancer cell proliferation and invasion through exosome-mediated MAPK signaling pathway.

AIM: To investigate the mechanism underlying the promoting role of CD97 in gastric cancer cell proliferation and invasion. METHODS: Two types of exosomes released by gastric cancer cells with high (SGC/wt) or low (SGC/kd) CD97 expression were isolated by ultracentrifugation and identified by electron microscopy and western blot analysis. The influences of the two exosomes on gastric cancer cell proliferation and invasion were investigated by proliferation and Matrigel invasion assays. Exosomal miRNAs were subsequently isolated from the two samples and their miRNA profiles were compared via microarray assay analysis. Reverse transcription-quantitative real-time polymerase chain reaction was used to validate the microarray assay. Target genes of the differently expressed microRNAs were predicted based on five independent algorithms and were then subjected to gene oncology enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. After identifying the pathway that was the most likely altered, tumor cells were treated with the two exosomes at different concentrations, and the pathway activation was identified through western blot analysis. RESULTS: Exosomes isolated from SGC/wt cells significantly promoted tumor cell proliferation in a dose-dependent manner in vitro. SGC/wt exosomes also significantly elevated the invasiveness of both SGC/wt (129.67 ± 8.327 vs 76.00 ± 5.292, P < 0.001) and SGC/kd (114.52 ± 9.814 vs 45.73 ± 4.835, P < 0.001) cells as compared to the exosomes released by SGC/kd cells. Microarray assay of the two exosomes revealed that 62 miRNAs were differently regulated with a signal intensity of > 500 and a false discovery rate < 0.05. The following KEGG analysis defined the MAPK signaling pathway as the most likely candidate pathway that regulated tumor cell proliferation and invasion. Through western blot analysis, significant up-regulations of phosphorylated MAPKs, including extracellular signal-regulated kinase, Jun NH2-terminal kinase, and p38 mitogen-activated protein kinase, were detected in a dose-dependent manner in the SGC/wt exosomes treated groups, confirming activation of the MAPK signaling pathway stimulated by SGC/wt exosomes. CONCLUSION: CD97 promotes gastric cancer cell proliferation and invasion in vitro through exosome-mediated MAPK signaling pathway, and exosomal miRNAs are probably involved in activation of the CD97-associated pathway.

Management of differentiated thyroid carcinoma with bone metastasis: a case report and review of the Chinese literature.

Differentiated thyroid carcinoma (DTC) is a common malignancy. The general treatments are thyroidectomy of the affected lobe along with lymphadenectomy. However, bone metastasis is rare in DTC compared with other malignancies and the management of metastasis foci is still controversial. Here we present a case of follicular thyroid carcinoma with the 6th cervical vertebra body metastasis successfully treated by total thyroidectomy, cervical corpectomy, and internal fixation, followed by hormone replacement therapy and radioiodine therapy. Eleven additional patients diagnosed as thyroid carcinoma with bone metastasis collected from Chinese literature between January 1996 and December 2013 were also reviewed. The mean age of the 12 patients at presentation was (53.9±9.2) years (rang, 42-72 years) and the male to female ratio was 1:2. Nine cases received total/near-total thyroidectomy or lobectomy while the other three patients refused for personal reasons. The interventions for bone metastasis were one-stage operation (9/12), I(131) adjuvant therapy (3/12), chemotherapy (1/12), and no intervention (1/12). During the follow-up, two patients died of metastatic carcinoma recurrence, one died of multiple organ metastasis, and one with an unknown reason. We conclude that the management of thyroid carcinoma with bone metastasis needs multidisciplinary cooperation. Surgical resection is still the first choice for cure, while the combined one-stage operation on the primary and metastatic sites followed by hormone replacement therapy and radioiodine therapy is an applicable treatment.

HER-2 overexpression and survival in colorectal cancer: a meta-analysis.

OBJECTIVE: Numerous studies examining the relationship between human epidermal growth factor receptor 2 (HER-2) overexpression and survival in patients with colorectal cancer (CRC) have yielded controversial results. We therefore performed a meta-analysis more precisely to estimate its prognostic value. METHODS: Published studies investigating the effect of HER-2 overexpression on CRC survival were identified; the hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) were pooled in terms of disease-specific or overall survival. RESULTS: Eleven studies were included in the meta-analysis. The pooled data showed that HER-2 overexpression was negatively related to CRC survival (HR=1.10, 95% CI: 0.77-1.44). Subgroup analyses regarding test method and study quality also demonstrated little association between HER-2 overexpression and CRC survival (HR=0.89, 95% CI: 0.50-1.29; HR=0.90, 95% CI: 0.43-1.37, respectively). CONCLUSIONS: Regardless of several limitations, our study suggested that HER-2 overexpression probably had little impact on CRC survival.

Colonic interposition between the liver and left diaphragm - management of Chilaiditi syndrome: A case report and literature review.

Chilaiditi syndrome refers to a medical condition that is indicated by the presence of Chilaiditi sign, the radiological observation of a colonic interposition between the liver and the diaphragm, and is associated with other clinical symptoms. Chilaiditi syndrome is a rare entity and therefore, is often misdiagnosed in clinical practice, however, it may be accompanied by a series of severe complications, such as bowel obstruction and perforation. The current study describes a 47-year-old male who presented with repeated abdominal pain and acute intestinal obstruction. The patient was diagnosed with Chilaiditi syndrome via radiological observation and was cured by conservative treatment. The clinical data of seven additional patients with Chilaiditi syndrome, which was reported in the Chinese literature between January 1990 and January 2013, were also collected. The pathogenesis, clinical manifestation, diagnosis and treatment of this syndrome have been reviewed and analyzed. The current study may be useful to familiarize clinical practitioners with Chilaiditi syndrome, in order to avoid a misdiagnosis during clinical treatment.