Application of pocket-first technique for implantation of totally implantable venous access ports.

BACKGROUND: While vascular puncture is always performed before making port pocket in the implantation of totally implantable venous access ports (TIVAP), some surgeons preferred to make port pocket first. This study seeks to verify the safety and feasibility for the pocket-first technique. METHODS: The study retrospectively reviewed 447 patients who undergone TIVAP implantation from July 2017 to November 2022. All the patients were divided into two groups based on vascular puncture first or making port pocket first. The general information, operation information and post-operative complications were reviewed and analyzed. RESULTS: All the operations were performed successfully. No difference was observed in the sex, age, height, weight, BMI, port location and total complication rate between the two groups. The operation time of the Puncture Group and the Pocket Group were 46.9 ± 22.4 min and 33.8 ± 13.6 min ( P<0.00001 ). In the patients of SCV approach, the operation time between the two groups were 37.4 ± 14.8 min and 33.5 ± 10.9 min ( P<0.05 ). Multivariate analysis showed the variable BMI and first procedure were independent prognostic factors for operation time. In the cases using SCV/AxV approach the variable first procedure was the only independent prognostic factor for operation time (P = 0.002). CONCLUSIONS: The pocket-first technique can be considered as a safe, feasible and convenient technique for TIVAP implantation. The time consuming is significantly shortened compared with the puncture-first technique and this advantage may be more obvious when using SCV/AxV approach.

Case Report: Complete pathological remission of human chorionic gonadotrophin-producing gallbladder carcinoma with multiple liver metastases after treatment with chemotherapy plus an immune checkpoint inhibitor.

Background: Gallbladder carcinoma (GBC) producing human chorionic gonadotrophin (HCG) is an extremely rare and highly invasive tumor with a poor prognosis. This unfavorable clinical outcome is partly due to the aggressive nature of the tumor and its insensitivity to chemotherapy. Case presentation: We herein report a case of primary GBC producing HCG with liver metastases in a 58-year-old woman. The patient presented with a markedly elevated ß-HCG level and a mass in the gallbladder with multiple liver metastases. A definitive diagnosis was obtained after a needle biopsy of the liver metastases, showing poorly differentiated carcinoma with large-scale necrosis and strong positivity of immunostaining for HCG in tumor cells. The patient received chemotherapy (gemcitabine plus capecitabine) combined with carrellizumab, an immune checkpoint inhibitor (ICI). Pathological complete response was achieved after eight courses of combined therapy, which was confirmed by pathological analysis of resected specimens. After surgery, two courses of chemotherapy plus ICIs were adopted again. Complete response remained for approximately 1 year up to the present. Tumor tissue was collected to perform immunostaining of PD-L1, whole-exome sequencing, and RNA-seq. Low-TMB (1.51 mut/Mb), MSS, and high PD-L1 expression (TPS ≥ 50%) were observed in the tumor. Besides, the dominant types of infiltrating immune cells were macrophage and CD4+ T cells. Compared to other gallbladder adenocarcinoma without HCG, the proportion of M1 macrophage was at a higher level and the gene sets of MYC targets v1 and PI3K/AKT/mTOR signaling were highly expressed in our case. To the best of our knowledge, this is the first case report of complete remission of HCG-producing gallbladder carcinoma with liver metastases after chemotherapy combined with an immune checkpoint inhibitor. Furthermore, this is also the first report that described the tumor genetic feature and tumor immune microenvironment atlas of HCG-producing GBC. Conclusion: chemotherapy plus an immune checkpoint inhibitor may provide a potentially curative option for gallbladder carcinoma with HCG production.

Construction and analysis of lncRNA-associated ceRNA network identified potential prognostic biomarker in gastric cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) are defined as non-coding RNA (ncRNA) with transcripts longer than 200 nucleotides with tissue specificity. Recently it has been found participate in cancer tumorigenesis and progression via transcriptional regulation, post-transcriptional regulation and epigenetic gene regulation. Competitive endogenous RNA (ceRNA) hypothesis assume that lncRNAs compete the target RNA by sponging the common miRNA response elements (MREs) to complete the post-transcriptional regulation. To explore the function and mechanisms of lncRNAs as ceRNAs in gastric cancer (GC), this study performed a genome-wide analysis. METHODS: The lncRNAs, mRNAs and microRNAs (miRNAs) profiles of 375 GC samples and 32 normal samples were obtained from The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) datasets. The data was standardized with a cross match in the miRBase (a database at http://www.mirbase.org/), which made 365 samples as the analysis objects. We identify differentially expressed RNAs (DERNAs), including differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed lncRNAs (DElncRNAs) by applying edge R package with thresholds of |log2FC| >2 and false discovery rate (FDR) <0.01. The potential RNAs for the gastric ceRNA network were screened out from the DERNAs based on "ceRNA hypothesis". The further construction of the network and analysis of its topological properties were performed by Cytoscape. Gene oncology (GO) function enrichment was analyzed by BINGO plugin of Cytoscape. Survival analysis was estimated according to Kaplan-Meier curve analysis. RESULTS: The constructed gastric ceRNA network involved 61 mRNAs, 44 lncRNAs and 22 miRNAs. Five lncRNAs out of the DElncRNAs, namely MIR100HG, MAGI2-AS3, AC080038.1, AC010478.1 and MEF2C-AS1, were found mostly involved in the network. The lncRNA AL139147 were detected negatively correlated with overall survival (log-rank, P<0.05). CONCLUSIONS: In conclusion, our study identified promising lncRNAs, which might be potential diagnostic biomarker and therapeutic targets and contribute to further understanding of the ceRNA pathogenesis in GC and guide for further investigation.

Schisandrin B inhibits cell proliferation and induces apoptosis in human cholangiocarcinoma cells.

Cholangiocarcinoma (CCA) is the second most common hepatic cancer with high resistance to current chemotherapies and extremely poor prognosis. The present study aimed to examine the effects of schisandrin B (Sch B) on CCA cells both in vitro and in vivo and to examine its underlying mechanism. We found that Sch B inhibited the viability and proliferation of CCA cells in a dose- and time-dependent manner as assessed by MTT and colony formation assays. The flow cytometric assay revealed G0/G1 phase arrest in the Sch B-treated HCCC-9810 and RBE cells. In addition, Sch B induced intrahepatic cholangiocarcinoma apoptosis as shown by the results of Annexin V/PI double staining. Rhodamine 123 staining revealed that Sch B decreased the mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Mechanistically, western blot analysis indicated that Sch B induced apoptosis by upregulating Bax, cleaved caspase-3, cleaved caspase-9 and cleaved PARP, and by downregulating cyclin D1, Bcl-2 and CDK-4. Moreover, Sch B significantly inhibited HCCC-9810 xenograft growth in athymic nude mice. In summary, these findings suggest that Sch B exhibited potent antitumor activities via the induction of CCA apoptosis and that Sch B may be a promising drug for the treatment of CCA.

Decreased levels of active SMAD2 correlate with poor prognosis in gastric cancer.

BACKGROUND: TGF-ß plays a dual role in the progression of human cancer. During the early stages of carcinogenesis, TGF-ß functions as a tumor suppressor. During the late stages of tumor development, however, TGF-ß can promote tumor growth and metastasis. A shift in Smad2/3 phosphorylation from the carboxy terminus to linker sites is a key event determining biological function of TGF-ß in colorectal and hepatocellular carcinoma. In the present study, we investigated the potential role of differential Smad2/3 phosphorylation in gastric adenocarcinoma. METHODOLOGY: Immunohistochemical staining with anti-P-Smad2/3C and P-Smad2/3L antibodies was performed on 130 paraffin-embedded gastric adenocarcinoma specimens. The relationship between P-Smad2/3C and P-Smad2/3L immunohistochemical score and clinicopathologic characteristics of patients was analyzed. Real time PCR was used to measure mRNA expression of Smad2 and Smad3 in cancer and surrounding non-tumor tissue. PRINCIPAL FINDINGS: No significant P-Smad2L and/or P-Smad3L positive staining was detected in the majority of specimens (positive staining in 18/130 samples). Positive P-Smad2/3L staining was not associated with a decrease in carboxyterminal phosphorylation staining. Loss of P-Smad2C remarkably correlated with depth of tumor infiltration and poor differentiation of cancer cells in patients with gastric cancer. No correlation was detectable between P-Smad3C and clinicopathologic characteristics of gastric adenocarcinoma. However, co-staining analysis revealed that P-Smad3C co-localised with α-SMA and collagen I in gastric cancer cells, indicating a potential link between P-Smad3C and epithelial-to-mesenchymal transition of cancer. Real time PCR demonstrated reduced mRNA expression of Smad2 in gastric cancer when compared with surrounding non-tumor tissue in 15/16 patients. CONCLUSIONS: Loss of P-Smad2C tightly correlated with cancer invasion and poor differentiation in gastric cancer. Contrary to colorectal and hepatocellular carcinoma, canonical carboxy-terminal phosphorylation, but not linker phosphorylation, of Smad2 is critical for gastric cancer.

Telomere shortening occurs early during gastrocarcinogenesis.

When telomeres are shortened to a critical length, they will initiate chromosomal instability (CIN) and may finally cause tumorigenesis. The purpose of the present study was to evaluate the shortened telomere as a potential biomarker for tumorigenesis in gastric carcinoma. The telomeres in matched cancer and adjacent noncancer mucosa samples from 86 gastric carcinoma patients were measured by real-time polymerase chain reaction (PCR). According to the International Union Against Cancer (UICC), tumor stages were classified into four groups: stage I (n = 23), stage II (n = 20), stage III (n = 23), and stage IV (n = 20). Telomere length decreased with aging in both adjacent noncancer mucosa and cancer tissue (r = -0.261 (P = 0.008) and r = -0.27 (P = 0.012), respectively). The telomere length of UICC stage I tumors was significantly shorter than the average telomere length in adjacent noncancer mucosa (P = 0.023). Telomere length increased gradually with increasing UICC stage (P = 0.032). The telomere length of UICC stage IV tumors was significantly longer, when compared to that in noncancer mucosa (P = 0.019) and stage I tumors (P = 0.002). In summary, telomere length undergoes shortening in early stage gastric carcinoma and lengthening in advanced gastric carcinoma. Additionally, telomere shortening may initiate the tumorigenesis of gastric carcinoma.

Acute cholecystitis immediately after radical gastrectomy: a report of three cases.

Acute cholecystitis is not a common complication of gastrectomy. Its clinical presentations and management strategies in old patients have not been well described in available literature. This report describes the clinical features, management strategies, and treatment outcome of acute cholecystitis immediately after gastrectomy. Acute cholecystitis immediately after gastrectomy in old patients has different clinical presentations, such as fever and high plasma C-reaction protein level. Abdominal computed tomography (CT) scan and ultrasonography showed acute cholecystitis in our cases, which was treated with antibiotics and ultrasound-guided percutaneous transhepatic gallbladder drainage (PTGD). The results indicate that abdominal CT scan and ultrasonography can effectively diagnose acute cholecystitis after gastrectomy, which can be effectively treated with antibiotics and PTGD.