Retracted: Expression of Long Non-Coding RNA (lncRNA) Small Nucleolar RNA Host Gene 1 (SNHG1) Exacerbates Hepatocellular Carcinoma Through Suppressing miR-195.

Retracted, due to breach of publishing guidelines, following the identification of non-original and manipulated figure images. Reference: Hui Zhang, Dong Zhou, Mingang Ying, Minyong Chen, Peng Chen, Zhaoshuo Chen, Fan Zhang: Expression of Long Non-Coding RNA (lncRNA) Small Nucleolar RNA Host Gene 1 (SNHG1) Exacerbates Hepatocellular Carcinoma Through Suppressing miR-195. Med Sci Monit, 2016; 22: 4820-4829. DOI: 10.12659/MSM.898574.

Effect of Laparoscopic vs Open Distal Gastrectomy on 3-Year Disease-Free Survival in Patients With Locally Advanced Gastric Cancer: The CLASS-01 Randomized Clinical Trial.

Importance: Laparoscopic distal gastrectomy is accepted as a more effective approach to conventional open distal gastrectomy for early-stage gastric cancer. However, efficacy for locally advanced gastric cancer remains uncertain. Objective: To compare 3-year disease-free survival for patients with locally advanced gastric cancer after laparoscopic distal gastrectomy or open distal gastrectomy. Design, Setting, and Patients: The study was a noninferiority, open-label, randomized clinical trial at 14 centers in China. A total of 1056 eligible patients with clinical stage T2, T3, or T4a gastric cancer without bulky nodes or distant metastases were enrolled from September 2012 to December 2014. Final follow-up was on December 31, 2017. Interventions: Participants were randomized in a 1:1 ratio after stratification by site, age, cancer stage, and histology to undergo either laparoscopic distal gastrectomy (n = 528) or open distal gastrectomy (n = 528) with D2 lymphadenectomy. Main Outcomes and Measures: The primary end point was 3-year disease-free survival with a noninferiority margin of -10% to compare laparoscopic distal gastrectomy with open distal gastrectomy. Secondary end points of 3-year overall survival and recurrence patterns were tested for superiority. Results: Among 1056 patients, 1039 (98.4%; mean age, 56.2 years; 313 [30.1%] women) had surgery (laparoscopic distal gastrectomy [n=519] vs open distal gastrectomy [n=520]), and 999 (94.6%) completed the study. Three-year disease-free survival rate was 76.5% in the laparoscopic distal gastrectomy group and 77.8% in the open distal gastrectomy group, absolute difference of -1.3% and a 1-sided 97.5% CI of -6.5% to ∞, not crossing the prespecified noninferiority margin. Three-year overall survival rate (laparoscopic distal gastrectomy vs open distal gastrectomy: 83.1% vs 85.2%; adjusted hazard ratio, 1.19; 95% CI, 0.87 to 1.64; P = .28) and cumulative incidence of recurrence over the 3-year period (laparoscopic distal gastrectomy vs open distal gastrectomy: 18.8% vs 16.5%; subhazard ratio, 1.15; 95% CI, 0.86 to 1.54; P = .35) did not significantly differ between laparoscopic distal gastrectomy and open distal gastrectomy groups. Conclusions and Relevance: Among patients with a preoperative clinical stage indicating locally advanced gastric cancer, laparoscopic distal gastrectomy, compared with open distal gastrectomy, did not result in inferior disease-free survival at 3 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01609309.

Diabetes Increases Morbidities of Colonic Diverticular Disease and Colonic Diverticular Hemorrhage: A Systematic Review and Meta-Analysis.

Colonic diverticular disease (CDD) and colonic diverticular hemorrhage (CDH) are the most common disorders in hospital admissions and outpatient health clinic visits. However, risk factors of CDD and CDH are complicated and need to be discussed. Diabetes mellitus (DM) has been related with CDD and CDH, but the associations remain ambiguous. Therefore, we performed a literature search for studies involving the associations among DM, morbidity of CDD, and incidence of CDH. Relative risks or odds ratios with their corresponding 95% confidence intervals (CIs) were combined and weighted to produce summary effect size. Sensitivity analysis and subgroup analysis were further performed. We selected 17 studies that involved a total of 8212 patients with diabetes, 381,579 controls without diabetes. We found that patients with DM had approximately 1.201 times higher CDD morbidity in prospective studies (95% CI, 1.135-1.270) with no significant heterogeneity (Q = 0.42, P = 0.519, I = 0%). DM was associated with a 52.8% increase in risk of CDH (95% CI, 14%-104%); we did not find significant heterogeneity among these studies (Q = 12.94, P = 0.114, I = 38.2%). This meta-analysis confirms that DM is an important risk factor for morbidities of CDD and CDH.

Expression of Long Non-Coding RNA (lncRNA) Small Nucleolar RNA Host Gene 1 (SNHG1) Exacerbates Hepatocellular Carcinoma Through Suppressing miR-195.

BACKGROUND Aberrant expression of lncRNA has been suggested to have an association with tumorigenesis. Our study was designed to reveal the underlying connection between lncRNA SNHG1 and hepatocellular carcinoma (HCC) pathogenesis. MATERIAL AND METHODS A total of 122 pairs of HCC tissues (case group) and matched adjacent non-tumor liver tissues (control group) were collected for this study. RT-PCR and in situ hybridization were conducted to investigate differences in lncRNA SNHG1 expression between the case and control group. The expression levels of lncRNA SNHG1 and miR-195 in HepG2 cells transfected with SNHG1-mimic and SNHG1-inhibitor were measured by RT-PCR. The proliferation, invasion, and migration status of HepG2 cells after transfection were assessed through MTT assay, wound healing assay, and Transwell assay, respectively. Whether miR-195 is a direct downstream target of lncRNA SNHG1 was verified by both bioinformatics target gene prediction and dual-luciferase report assay. RESULTS The expression level of lncRNA SNHG1 was remarkably upregulated in HCC tissues and cell lines compared with normal tissues and cell lines. High expression of lncRNA SNHG1 contributed to the downregulation of miR-195 in HepG2 cells. Also, lncRNA SNHG1 exacerbated HCC cell proliferation, invasion, and migration in vitro through the inhibition of miR-195. This suggests that miR-195 is a direct downstream target of lncRNA SNHG1. CONCLUSIONS lncRNA SNHG1 may contribute to the aggravation of HCC through the inhibition of miR-195.

Histological characterisation and prognostic evaluation of 62 gastric neuroendocrine carcinomas.

AIM OF THE STUDY: To determine the significance of expression of synaptophysin, chromogranin A, and Ki-67 and their association with clinicopathological parameters, and to find out the possible prognostic factors in gastric neuroendocrine carcinoma (G-NEC). MATERIAL AND METHODS: We investigated the immunohistochemical features and prognosis of 62 G-NECs, and evaluated the association among expressions of synaptophysin, chromogranin A, and Ki-67, clinicopathological variables, and outcome. RESULTS: Chromogranin A expression was found more commonly in small-cell NECs (9/9, 100%) than in large-cell NECs (27/53, 51%) (p = 0.008). No statistical significance was found in Ki-67 (p = 0.494) or synaptophysin (p > 0.1) expression between NEC cell types. Correlation analyses revealed that Ki-67 expression was significantly associated with mid-third disease of stomach (p = 0.005) and vascular involvement (p = 0.006), and had a trend of significant correlation with tumour relapse (p = 0.078). High expression of chromogranin A was significantly associated with histology of small-cell NECs (p = 0.008) and lesser tumour greatest dimension (p = 0.038). The prognostic significance was determined by means of Kaplan-Meier survival estimates and log-rank tests, and as a result, early TNM staging and postoperative chemotherapy were found to be correlated with longer overall survival (p < 0.05). Univariate analysis revealed associations between poor prognosis in NECs and several factors, including high TNM staging (p = 0.048), vascular involvement (p = 0.023), relapse (p = 0.004), and microscopic/macroscopic residual tumour (R1/2, p < 0.001). In a multivariate analysis, relapse was identified as the sole independent prognostic factor. CONCLUSIONS: No significant correlation between survival and expression of synaptophysin, chromogranin A, or Ki-67 has been determined in G-NECs. Our study indicated that early diagnosis, no-residual-tumour resection, and postoperative chemotherapy were possible prognostic factors.

Diabetes and risk of anastomotic leakage after gastrointestinal surgery.

BACKGROUND: Anastomotic leakage (AL) is one of the most common and lethal complications in gastrointestinal surgery. However, the relationship between AL risk and diabetes mellitus (DM) remains ambiguous. This meta-analysis was to evaluate the association between DM and AL risk in patients after gastrointestinal resection. METHODS: Odds ratios (OR) estimate with their corresponding 95% confidence intervals (CIs) were combined and weighted to produce pooled OR using the fixed-effects model. Relative risks were calculated in subgroup analysis of prospective studies. We calculated publication bias by Begg rank correlation test and Egger linear regression test. RESULTS: DM was significantly and independently associated with an increased risk of AL morbidity in colorectal patients, 1.661 times in total patients (95% CIs = 1.266-2.178), 1.995 times in a subgroup of case-control studies, 1.581 times in cohort investigations, 1.688 times in retrospective trials, and 1.562 times in prospective designs. After adjusting for the factor of obesity and/or body mass index in the subgroup analyses of colorectal surgery, DM patients without obesity experienced a significantly increased risk of AL (OR = 1.572, 95% CIs = 1.112-2.222). Furthermore, when obesity had not been adjusted, DM patients endured a dramatical increase of AL incidence (OR = 1.812, 95% CIs = 1.171-2.804). Perforation incidence after gastric resection showed borderline association with DM (OR = 2.170, 95% CIs = 0.956-4.926). CONCLUSIONS: The present meta-analysis provides strong evidence for the first time that DM is significantly and independently associated with an increased risk of AL mortality in colorectal surgery.

Antitumor Effects and Related Mechanisms of Penicitrinine A, a Novel Alkaloid with a Unique Spiro Skeleton from the Marine Fungus Penicillium citrinum.

Penicitrinine A, a novel alkaloid with a unique spiro skeleton, was isolated from a marine-derived fungus Penicillium citrinum. In this study, the isolation, structure and biosynthetic pathway elucidation of the new compound were described. This new compound showed anti-proliferative activity on multiple tumor types. Among them, the human malignant melanoma cell A-375 was confirmed to be the most sensitive. Morphologic evaluation, apoptosis rate analysis, Western blot and real-time quantitative PCR (RT-qPCR) results showed penicitrinine A could significantly induce A-375 cell apoptosis by decreasing the expression of Bcl-2 and increasing the expression of Bax. Moreover, we investigated the anti-metastatic effects of penicitrinine A in A-375 cells by wound healing assay, trans-well assay, Western blot and RT-qPCR. The results showed penicitrinine A significantly suppressed metastatic activity of A-375 cells by regulating the expression of MMP-9 and its specific inhibitor TIMP-1. These findings suggested that penicitrinine A might serve as a potential antitumor agent, which could inhibit the proliferation and metastasis of tumor cells.

ADAM17 is associated with EMMPRIN and predicts poor prognosis in patients with uterine cervical carcinoma.

Metalloproteinase activities of a disintegrin and metalloproteinase 17 (ADAM17), amphiregulin (AREG), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMPs) are involved in tumor biology. In patients with uterine cervical carcinoma, the expression and prognostic significance of ADAM17 remain to be fully elucidated. The expression of ADAM17, AREG, EMMPRIN, phospho-epidermal growth factor receptor (p-EGFR), phospho-extracellular signal-regulated kinase (p-ERK), MMP-2, and MMP-9 was assessed by immunohistochemistry and/or Western blotting from cervical carcinoma cell lines, SiHa and HeLa cells, and cervical carcinoma tissues. AREG activity was measured by ELISA assay. The correlation of ADAM17, AREG, EMMPRIN, and MMP-9 expression with patients' survival rates was assessed by Kaplan-Meier and Cox regression analyses. RNA interference (RNAi) experiment was performed using small interfering mRNA to ADAM17 and EMMPRIN. ADAM17, EMMPRIN, and MMP-9 protein content was overexpressed in cervical carcinoma tissues compared with normal cervical tissues (P < 0.05). Strong expression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly associated with stages, lymph node metastasis, differentiation, and parametrium invasion (P < 0.05). Overexpression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly correlated with short progression-free survival and overall survival (P < 0.05). Multivariate analysis suggested that lymph node metastasis, parametrium invasion, and ADAM17 expression were independent prognostic indicators for cervical cancer. ADAM17 RNAi decreased EMMPRIN, p-EGFR, p-ERK, MMP-2, and MMP-9 proteins in SiHa and HeLa cells. ELISA assay revealed that AREG activity was stimulated by ADAM17 and was reversed by ADAM17 RNAi in SiHa and HeLa cells. Our data suggest that the increased expression of ADAM17 in cervical cancer is significantly associated with aggressive progression and poor prognosis. ADAM17 may be a molecular marker for predicting the progression and prognosis in cervical cancer.

Effects of CO2 pneumoperitoneum on the expression of thymidine kinase 1 and Ki67 in colorectal carcinoma cells.

BACKGROUND: To investigate thymidine kinase 1(TK-1) and Ki67 expression levels of human colorectal carcinoma cells line SW480 after exposure to a simulated laparoscopic carbon dioxide (CO2) pneumoperitoneum environment at different pressures and lengths of exposure time. METHODS: The effects of the simulated laparoscopic CO2 pneumoperitoneum environment at different CO2 pressures (6, 9, 12, and 15 mmHg) and exposure times (2 and 4 h) on TK-1 and Ki67 of SW480 cells were assessed by flow cytometry and reverse transcription (RT-PCR). Cells cultured in a standard environment were used as the control group (at 37 °C, 5% CO2). RESULTS: In this study, TK-1 and Ki67 in SW480 cells tended to decrease with the increase of CO2 pressure and exposure time. Significantly lower expression levels were observed at 0 and 24 h of culture after exposure to both at 12 and 15 mmHg, as compared with the control group at 6 and 9 mmHg (p < 0.05). The expression of TK-1 and Ki67 levels increased up to a plateau of the control group after 48 and 72 h (p > 0.05). With the CO2 pneumoperitoneum exposure time prolonging, the expression of TK-1 and Ki67 levels in 12 or 15 mmHg was lower than in 2 h (p < 0.05). In the same exposure time, the transcription level of TK-1 and Ki67 decreased significantly in 12 and 15 mmHg CO2 pneumoperitoneum groups (p < 0.05) and returned to the basal level of control group after being cultivated for 48 h (p > 0.05). In the same pressure, the difference of TK-1 mRNA between the groups of 2 and 4 h was also significant. CONCLUSION: The expression levels of TK-1 and Ki67 were suppressed temporarily after the continuous CO2 insufflation in higher pressure (at 12 and 15 mmHg). The higher the pressure of CO2 insufflation, the more the inhibiting effects of TK-1 and Ki67 will be. The longer the time of CO2 insufflation, the more significantly their expression decreased.

Real-time optical diagnosis for surgical margin in low rectal cancer using multiphoton microscopy.

BACKGROUND: Multiphoton microscopy (MPM), based on advances in the field of nonlinear optics and femtosecond lasers, has been shown to provide detailed real-time information on tissue architecture and cell morphology in live tissue. The purpose of this study was to evaluate the feasibility of using MPM to make real-time optical diagnoses for surgical margins in low rectal cancers. METHODS: Thirty fresh, unfixed, and unstained full-thickness surgical margins of low rectal cancers underwent MPM examination and then went through intraoperative frozen procedures and routine pathological procedures. MPM images were compared with the gold standard hematoxylin-eosin (H-E) stained images. RESULTS: MPM images were acquired by two channels: broadband autofluorescence from cells and second harmonic generation (SHG) from tissue collagen. Peak multiphoton signal intensity was detected in mucosa excited at 800 nm. There were significant differences between negative surgical margins and positive surgical margins under MPM examination. In negative surgical margins, MPM revealed regular tissue architecture and cell morphology, including a typical foveolar pattern with central, round crypt openings, and glands lined by epithelial and goblet cells. SHG signals could be detected around the glands. In positive surgical margins, MPM demonstrated irregular tubular structures, reduced stroma, and cellular and nuclear pleomorphisms. Cancer cells were characterized by an irregular size and shape, enlarged nuclei, and an increased nuclear-cytoplasmic ratio. SHG signals were significantly decreased in positive surgical margins compared with negative surgical margins. MPM images were comparable to H-E stained images. CONCLUSIONS: We demonstrated the feasibility of using MPM to make real-time optical diagnoses for surgical margins in low rectal cancer. With the miniaturization and integration of colonoscopy or probes, MPM has the potential to provide real-time noninvasive optical diagnosis for surgical margins in low rectal cancer in the near future.

Oncologic outcomes of laparoscopy-assisted gastrectomy for advanced gastric cancer: a large-scale multicenter retrospective cohort study from China.

BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) has been indicated to be safe, feasible, and oncologically efficacious for the treatment of early gastric cancer by both retrospective and prospective studies. Although some reports have demonstrated that LAG was also a safe and technically feasible procedure for advanced gastric cancer (AGC), its oncologic outcomes have not yet been confirmed in a multicenter, large-scale study. The aim of this study was to evaluate the oncologic outcomes of LAG for AGC on a multicenter basis in China. METHODS: Data of 1,184 consecutive patients with locally AGC who underwent LAG with curative intent between February 2003 and December 2009 were collected from the Chinese Laparoscopic Gastrointestinal Surgery Study group database and retrospectively analyzed. Survival rates were estimated by the Kaplan-Meier method. Risk factors for recurrence and survival were evaluated by Cox regression models. RESULTS: Postoperatively, 121 patients (10.2%) experienced complications, and 1 patient died (0.1%). Median follow-up was 12 months. Recurrence was observed in 185 patients (16.7%), including hematogenous (31 patients), peritoneal (52), locoregional (25), distant lymph node (LN) (8), mixed (63), and uncertain (6) recurrences. The cumulative 3-year overall survival and disease-free survival rates were 75.3 and 69.0%, respectively. The 3-year overall survival and disease-free survival rates were 89.7 and 88.9% for stage I tumors, 85.0 and 77.0 % for stage II, 60.5 and 59.3% for stage III. Independent risk factors for recurrence were tumor size > 40 mm, intraoperative blood transfusion, and advanced tumor stage. For survival, age > 65 years, tumor size > 40 mm, and advanced tumor stage were independent risk factors. CONCLUSIONS: In addition to being safe and technically feasible, LAG for locally AGC could also yield acceptable short-term oncologic outcomes.

The marine fungal metabolite, dicitrinone B, induces A375 cell apoptosis through the ROS-related caspase pathway.

Dicitrinone B, a rare carbon-bridged citrinin dimer, was isolated from the marine-derived fungus, Penicillium citrinum. It was reported to have antitumor effects on tumor cells previously; however, the details of the mechanism remain unclear. In this study, we found that dicitrinone B inhibited the proliferation of multiple tumor types. Among them, the human malignant melanoma cell, A375, was confirmed to be the most sensitive. Morphologic evaluation, cell cycle arrest and apoptosis rate analysis results showed that dicitrinone B significantly induced A375 cell apoptosis. Subsequent observation of reactive oxygen species (ROS) accumulation and mitochondrial membrane potential (MMP) reduction revealed that the apoptosis induced by dicitrinone B may be triggered by over-producing ROS. Further studies indicated that the apoptosis was associated with both intrinsic and extrinsic apoptosis pathways under the regulation of Bcl-2 family proteins. Caspase-9, caspase-8 and caspase-3 were activated during the process, leading to PARP cleavage. The pan-caspase inhibitor, Z-VAD-FMK, could reverse dicitrinone B-induced apoptosis, suggesting that it is a caspase-dependent pathway. Our data for the first time showed that dicitrinone B inhibits the proliferation of tumor cells by inducing cell apoptosis. Moreover, compared with the first-line chemotherapy drug, 5-fluorouracil (5-Fu), dicitrinone B showed much more potent anticancer efficacy, suggesting that it might serve as a potential antitumor agent.

Mouse embryonic stem cell-derived thymic epithelial cell progenitors enhance T-cell reconstitution after allogeneic bone marrow transplantation.

We have reported that mouse embryonic stem cells (mESCs) can be selectively induced in vitro to differentiate into thymic epithelial cell progenitors (TEPs). When placed in vivo, these mESC-derived TEPs differentiate into cortical and medullary thymic epithelial cells, reconstitute the normal thymic architecture, and enhance thymocyte regeneration after syngeneic BM transplantation (BMT). Here, we show that transplantation of mESC-derived TEPs results in the efficient establishment of thymocyte chimerism and subsequent generation of naive T cells in both young and old recipients of allo-geneic BM transplant. GVHD was not induced, whereas graft-versus-tumor activity was significantly enhanced. Importantly, the reconstituted immune system was tolerant to host, mESC, and BM transplant donor antigens. Therefore, ESC-derived TEPs may offer a new approach for the rapid and durable correction of T-cell immune deficiency after BMT, and the induction of tolerance to ESC-derived tissue and organ transplants. In addition, ESC-derived TEPs may also have use as a means to reverse age-dependent thymic involution, thereby enhancing immune function and decreasing infection rates in the elderly.

Laparoscopic vs Open Distal Gastrectomy for Locally Advanced Gastric Cancer: Five-Year Outcomes From the CLASS-01 Randomized Clinical Trial.

Importance: It is not clear whether laparoscopic and open distal gastrectomy produce similar outcomes among patients with locally advanced gastric cancer. Data from a multicenter, randomized clinical trial (Chinese Laparoscopic Gastrointestinal Surgical Study [CLASS]-01) showed that laparoscopic distal gastrectomy did not result in inferior disease-free survival at 3 years compared with open distal gastrectomy. Objective: To report 5-year overall survival data from the CLASS-01 trial of laparoscopic vs open distal gastrectomy among patients with locally advanced gastric cancer. Design, Setting, and Patients: This was a noninferiority, open-label, randomized clinical trial conducted at 14 centers in China. A total of 1056 eligible patients with clinical stage T2, T3, or T4a gastric cancer without bulky nodes or distant metastases were enrolled from September 12, 2012, to December 3, 2014. Final follow-up was on December 31, 2019. Interventions: Participants were randomized in a 1:1 ratio after stratification by site, age, cancer stage, and histologic features to undergo either laparoscopic distal gastrectomy (n = 528) or open distal gastrectomy (n = 528) with D2 lymphadenectomy. Main Outcomes and Measures: The 5-year overall survival rates were updated to compare laparoscopic distal gastrectomy with open distal gastrectomy. All analyses were performed on an intention-to-treat basis. In addition, per-protocol and as-treated analyses were performed for overall survival. Results: Data from 1039 patients (726 men [69.9%]; mean [SD] age, 56.2 [10.7] years) who received curative therapy were analyzed. At 5 years, the overall survival rates were 72.6% in the laparoscopic distal gastrectomy group and 76.3% in the open distal gastrectomy group (log-rank P = .19; hazard ratio, 1.17; 95% CI, 0.93-1.48; P = .19). After comparison for competing risk events, gastric cancer-related deaths (hazard ratio, 1.14; 95% CI, 0.87-1.49; P = .34) and deaths from other causes (hazard ratio, 1.23; 95% CI, 0.74-2.05; P = .42) did not differ significantly between groups. Overall rates of survival did not differ significantly between groups with each tumor stage. Conclusions and Relevance: This study found that laparoscopic distal gastrectomy with D2 lymphadenectomy performed by experienced surgeons in high-volume specialized institutions resulted in similar 5-year overall survival compared with open distal gastrectomy among patients with locally advanced gastric cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT01609309.

Guidelines for Diagnosis and Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus in China (2021 Edition).

Portal vein tumor thrombus (PVTT) is very common and it plays a major role in the prognosis and clinical staging of hepatocellular carcinoma (HCC). We have published the first version of the guideline in 2016 and revised in 2018. Over the past several years, many new evidences for the treatment of PVTT become available, especially for the advent of new targeted drugs and immune checkpoint inhibitors which have further improved the prognosis of PVTT. So, the Chinese Association of Liver Cancer and Chinese Medical Doctor Association revised the 2018 version of the guideline to adapt to the development of PVTT treatment. Future treatment strategies for HCC with PVTT in China would depend on new evidences from more future clinical trials.

Chinese Expert Consensus on Immunotherapy for Hepatocellular Carcinoma (2021 Edition).

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. Most HCC patients are first diagnosed at an advanced stage, and systemic treatments are the mainstay of treatment. Summary: In recent years, immune checkpoint inhibitors have made a breakthrough in the systemic treatment of middle-advanced HCC, breaking the single therapeutic pattern of molecular-targeted agents. To better guide the clinical treatment for effective and safe use of immunotherapeutic drugs, the Chinese Association of Liver Cancer and Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the "Chinese Clinical Expert Consensus on Immunotherapy for Hepatocellular Carcinoma (2021)" based on current clinical studies and clinical medication experience for reference in China. Key Messages: The consensus contained 17 recommendations, including the preferred regimen for first- and second-line immunotherapy, evaluation and monitoring before/during/after treatment, management of complications, precautions for special patients, and potential population for immunotherapy.

A pilot study of using multiphoton microscopy to diagnose gastric cancer.

BACKGROUND: Using a combination of autofluorescence from cells and second-harmonic generation (SHG) signal from collagen, multiphoton microscopy (MPM) imaging can provide detailed real-time information on tissue architecture and cellular morphology in live tissue without administration of exogenous contrast agents. The purpose of this study is to evaluate the feasibility of using MPM to histologically diagnose gastric cancer by using fresh, unfixed, unstained gastric specimens, compared with gold-standard hematoxylin-eosin (H-E)-stained histopathology. METHODS: A pilot study was performed between June 2009 and December 2009. Ten cases with gastric carcinoma confirmed by preoperative endoscopic biopsy underwent radical gastrectomy. The fresh specimen was opened, and a piece of cancer tissue and a piece of normal tissue each with a size of 1-1.5 cm across and 0.2 cm in thickness were taken and snap-frozen. A 5-µm slide was sectioned for MPM examination, and the remainder of the tissue went through routine histopathological procedure. MPM images and H-E-stained images were compared by the same attending pathologist. RESULTS: MPM images were acquired by two channels: broadband autofluorescence from cells, and SHG from tissue collagen. Peak multiphoton autofluorescence intensity was detected in mucosa excited at 800 nm. Cancer cells, characterized by irregular size and shape, enlarged nuclei, and increased nuclear-to-cytoplasmic ratio, were identified by MPM images, which were confirmed by H-E-stained images. Regular architectures of gastric pits and gastric glands in the normal tissue of the same specimens were clearly revealed by MPM images, which were comparable to H-E-stained images. CONCLUSIONS: It is feasible to use MPM to diagnose gastric cancer by "optical biopsy." With miniaturization and integration of endoscopy, MPM has the potential to provide real-time histological diagnosis without invasive biopsy for gastric cancer in the future.

Floating cells with stem cell properties in gastric cell line SGC-7901.

AIMS: To obtain floating spheres from the adherent gastric cancer cell line SGC-7901 and to analyze the properties of the spheres. METHODS: Serum-free medium was applied to cultured SGC-7901 cells. Limiting dilution assay, tumor formation assay, microarray analysis, and real-time fluorescent quantitative PCR were used to test the stem cell properties of the spheres. RESULTS: A subpopulation of SGC-7901 cells formed floating spheres in serum-free medium. These cells showed enhanced tumorigenic ability and also highly expressed certain stem-cell-associated proteins. CONCLUSIONS: We successfully propagated floating spheres with stem cell properties in the SGC-7901 gastric cell line.

[Advantage of perisplenic hilar lymph node dissection by laparoscopy-assisted total gastrectomy (D2) over conventional open total gastrectomy for advanced gastric cancer].

OBJECTIVE: To compare the number of harvested perisplenic hilar lymph nodes by laparoscopy-assisted total gastrectomy (LATG) and conventional open total gastrectomy (OTG) for advanced upper and middle gastric cancer. METHODS: Three hundred twelve patients with advanced gastric cancer treated in a single institution between Sept 2008 and Jan 2011 were included in this study. They were divided into two groups: the LATG group and OTG (D2) group. All the surgical operations were performed by one surgeon or under his supervision. The lymph node clearance outcomes of the patients treated by those two surgical procedures were analyzed. RESULTS: The harvested lymph node numbers of the two groups were (29.57 ± 9.62) and (29.38 ± 11.22) respectively, statistically with no significant difference (P = 0.875). The numbers of lymph node dissected around the splenic area in the LATG group and OTG group (Section 10, 11 group) were (2.01 ± 1.34) and (1.33 ± 1.11), respectively, indicating a significant difference (P = 0.000). The numbers of lymph nodes dissected around the celiac region (Section 7, 8, 9, 11p and 12a(2) group) were (7.90 ± 3.41) and (7.22 ± 2.65), respectively, with a non-significant difference (P = 0.050). There were also no significant differences while comparing with the numbers of lymph nodes dissected in the cardiac area (group 1, 2), pyloric region (5, 6 group) and the greater and lesser omentum area (group 3 and 4) between the two groups (P = 0.605, P = 0.248, P = 0.262). CONCLUSION: Short-term results of this study indicate that laparoscopy-assisted total gastrectomy (D2) is better than conventional open surgery in perisplenic hilar lymph node dissection.

Serum thymidine kinase 1 correlates to clinical stages and clinical reactions and monitors the outcome of therapy of 1,247 cancer patients in routine clinical settings.

BACKGROUND: Thymidine kinase 1 in serum (STK1) has been found to be a reliable proliferation marker in clinical trials. In this study, we examined the significance of STK1 in routine clinical settings. METHODS: The concentration of STK1 was determined by a sensitive dot blot ECL assay. The STK1 value was correlated to clinical stage and reactions and used for monitoring the outcome of surgery and/or multidrug chemotherapy of 1,247 patients with five different types of carcinomas (lung, esophagus, gastric, head and neck, and thyroid) in routine clinical settings. RESULTS: The STK1 values correlated with the clinical stage in patients with lung, esophagus, thyroid, and gastric carcinomas. After treatment, STK1 declined in all tumor groups after treatments (P < 0.01). The STK1 was low (<2 pM) or decreasing during treatment in patients with clinical reactions of complete response (CR) or partial response (PR), but high (>2 pM) or increasing in patients with stable disease (SD) or progressive disease (PD), some of them showing metastasis. STK1 also reflected the differences in clinical reactions when surgery and chemotherapy were compared. CONCLUSION: We concluded that the concentration of TK1 in serum correlates to clinical stages and clinical reactions and monitors the effect of tumor therapies, not only in controlled clinical trials, but also in routine clinical settings.