[Clinicopathological features and prognosis of early-onset gastric cancer: a large-scale retrospective real-world study].

Objective: To clarify the clinicopathological features, prognosis, and recurrence pattern of early-onset gastric cancer (EOGC). Methods: Using data from the gastric cancer database of Zhongshan Hospital, Fudan University, we performed a retrospective, large-scale, real-world study of 5046 patients with gastric cancer who had undergone redical or palliative gastrectomy from January 2013 to December 2018, including 425 patients with EOGC (age ≤45 years) and 4621 controls. All those patients were pathologically confirmed adenocarcinoma with complete follow-up of five years. Residue gastric cancer and patients without complete clinical or follow-up data were excluded. We used a combination of outpatient and telephone follow-up, ending in October 2022 (median duration of follow-up 60 months), and compared the clinicopathological features and prognosis of the two groups. Results: The clinicopathological features of EOGC included female predominance (61.1% [262/425 vs. 26.3% [1217/4621], χ2=234.215, P<0.001), fewer comorbidities (31.3% [133/425] vs. 58.5% [2703/4621], χ2=34.378, P<0.001), poorer differentiation (90.6% [385/425] vs. 78.2% [3614/4621], χ2=30.642, P<0.001), higher proportion of diffuse type (53.9% [229/425] vs. 18.3% [846/4621], χ2=274.474, P<0.001), higher proportion of T4 stage (44.7% [190/425] vs. 37.5% [1733/4621], χ2=17.535, P=0.001), more lymph node metastases (60.5% [257/425] vs. 53.9% [2491/4621], χ2=6.764, P=0.009), and higher proportion of pathological stage III/IV (47.5% [202/425] vs. 42.4% [1959/4621], χ2=4.093, P=0.043). The 5-year overall survival rates of the EOGC and control groups were 55.1% and 49.1%, respectively. Overall survival was significantly better in the EOGC than in the control group (P<0.001). According to subgroup analysis, the prognosis of pathological stage I/II/III EOGC was better than that of the control group. Recurrence rates were similar in the two groups, whereas patients with EOGC had a higher proportion of peritoneal recurrence (7.8% [33/425] vs. 3.2% [146/4621], χ2=23.741, P<0.001) and a lower proportion of distant metastasis (4.9% [21/425] vs. 8.3% [385/4621], χ2=6.247, P=0.012). Conclusion: EOGC has unique clinicopathological features and recurrence patterns and resectable EOGC has a better prognosis, suggesting that patients with EOGC should be actively treated with the focus on preventing peritoneal recurrence.

[Construction and validation of a nomogram model of early related factors for hepatic insufficiency after hemihepatectomy].

Objectives: To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model. Methods: This was a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method,patients were randomly divided into a model group(n=166) and a validation group(n=41) according to an 4︰1 ratio. There were 118 males and 48 females in the modeling group,with an age (M(IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (rang: 25.0~81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the risk of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,followed by internal and external validation of the model. Results: Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT,D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set,and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model(P=0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806,suggesting that the model had a good generalization prediction ability. Conclusions: The levels of ALT,D-dimer,and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.

[Clinicopathological and molecular diagnostic features of early-onset gastric cancer: a study based on data from a single-center dedicated gastric cancer database].

Objective: To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies. Methods: In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups. Results: The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ2=5.442,P<0.001). HER-2 and Epstein-Barr virus positivity rates did not differ significantly between the two groups. Conclusion: Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.

Efficacy of Oral SERDs in the treatment of ER+, HER2 - metastatic breast cancer, a stratified analysis of the ESR1 wild type and mutant subgroups.

BACKGROUND: Oral SERDs are a novel drug class that have been developed to counteract resistance due to ESR1 mutations. Several SERDs have emerged from phase 2 and 3 trials, with the FDA limiting approval for Elacestrant to patients with ESR1mt tumours despite PFS benefit in the overall population. However, questions remain on whether patients with ESR1wt tumours stand to benefit from oral SERDs. PATIENTS AND METHODS: Manuscripts and conference presentations of Randomised Controlled Trials were extracted after a systematic search of Embase, PubMed and Cochrane from inception until January 21,2023. RCTs investigating the efficacy of oral SERDs versus endocrine therapy for ER positive, HER2 negative advanced breast cancer, and which reported the Kaplan Meier (KM) curves of PFS in the overall and ESR1 mutant (ESR1mt) population were selected. A graphical reconstructive algorithm was applied to estimate time-to-event outcomes from reported KM curves in all overall and ESR1mt cohorts. A bipartite matching algorithm, KMSubtraction, was used to derive survival data for unreported (ESR1wt) subgroups. An individual patient data (IPD) meta-analysis was then pursued, pooling data by ESR1 mutation status in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane Guidelines for IPD. RESULTS: The randomized clinical trials ACELERA, AMEERA-3, EMERALD and SERENA-2 were included, totalling 1290 patients. In the pooled analysis of the overall cohort, PFS benefit was observed with oral SERDs when compared with treatment of physicians choice (TPC) (HR 0.783, 95%CI 0.681-0.900, p<0.001). In the ESR1mt subgroup, oral SERDs demonstrated improved PFS (HR 0.557, 95%CI 0.440-0.705, p<0.001) compared to TPC. In the ESR1wt subgroup, oral SERDs demonstrated no significant PFS benefit (HR 0.944, 95%CI 0.783-1.138, p=0.543) when compared to TPC. CONCLUSIONS: The results of this IPD meta-analysis suggests that PFS benefit in the overall population is mainly driven by the ESR1mt subgroup.

[Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy].

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.

[Clinical and genetics characteristics of adult-onset cerebrotendinous xanthomatosis: analysis of a Chinese pedigree].

Objective: Clinical manifestations, imaging findings, pathologic features, and genetic mutations of Chinese adult patients with cerebrotendinous xanthomatosis (CTX) were analyzed in order to achieve a greater understanding of CTX that can improve early detection, diagnosis, and treatment. Methods: Clinical data including medical history, neurologic and auxiliary examinations, imaging findings, and genetic profile were collected for an adult patient with CTX admitted to the Sixth Medical Center of Chinese People's Liberation Army General Hospital in August 2020. Additionally, a systematic review of genetically diagnosed Chinese adult CTX cases reported in major databases in China and other countries was performed and age of onset, first symptoms, common signs and symptoms, pathologic findings, imaging changes, and gene mutations were analyzed. Results: The proband was a 39-year-old female with extensive, early-onset nervous system manifestations including cognitive dysfunction and ataxia. Systemic lesions included juvenile cataract and a tendon mass. Cranial magnetic resonance imaging revealed cerebral atrophy, symmetric white matter changes predominantly in the pyramidal tract, and lesions in the cerebellar dentate nucleus. A novel homozygous mutation in the sterol-27-hydroxylase (CYP27A1) gene (c.1477-2A>C) was identified. There were no family members with similar clinical presentation although some were carriers of the c.1477-2A>C mutation. The patient showed a good response to deoxycholic acid treatment. Totally there were 56 cases of adult CTX patients in China, mostly in East China (31/56, 55.4%), at a male-to-female ratio of 1.8 to 1. Multiple organs and tissues including nervous system, tendon, lens, lung, and skeletal muscle were affected in these cases. The most common neurologic manifestations were cognitive dysfunction (44/52, 84.6%) and ataxia (44/51, 86.3%). The cases were characterized by early onset, chronic progressive damage of multiple systems, long disease course, and delayed diagnosis, making the disease difficult to manage clinically and resulting in poor prognosis. The 2 most common genetic mutations in Chinese adult CTX patients were c.1263+1G>A and c.379C>T. Exon 2 of the CYP27A1 gene was identified as a mutation hot spot. Conclusions: Chinese adult patients with CTX have complex clinical characteristics, a long diagnostic cycle, and various CYP27A1 gene mutations. Early diagnosis and intervention can improve the prognosis of these patients.

[Identification and functional analysis of combined oxidative phosphorylation deficiency 28 gene mutation].

Objective: To report a case of combined oxidative phosphorylation deficiency 28 (COXPD28) in China, identified the pathogenic mutation and explored the pathogenic mechanism preliminarily. Methods: The clinical characteristics of a patient with COXPD28 were retrospectively analyzed and the pathogenic mutations were identified by mitochondrial gene sequencing and whole exome sequencing. The wild-type and mutant plasmids of pathogenic genes were constructed, and effect of mutation on protein expression by quantitative real-time PCR (qPCR) and Western blot were evaluated. Statistical methods mainly used one-way ANOVA and LSD test. Results: A 21 year old female patient presented with lactic acid poisoning due to repeated chest distress and wheezing since childhood. The sequencing of the whole exon group gene found that solute carrier family 25 member 26 (SLC25A26) gene had a compound heterozygous mutation (c.34G>C, p.A12P; c.197C>A, p.A66E), which was the first report in China. In vitro function test showed that the expression levels of SLC25A26 mRNA and S-adenosylmethionine carrier (SAMC) protein in cells transfected with SLC25A26 mutant plasmid were significantly lower than those transfected with wild type plasmid. The p.A66E mutant plasmid reduced the expression level of SLC25A26 mRNA and SAMC protein to 6% and 26% of wild type plasmids respectively (both P<0.001), while p.A12P mutant plasmid decreased to 62% and 82% of wild type plasmids respectively (P<0.001, P=0.044). When the double mutant (p.A66E+p.A12P) plasmids were co-transfected, the expression levels of SLC25A26 mRNA and SAMC protein decreased to 47% and 57% of the wild type plasmids, respectively (P<0.001, P=0.001). Conclusion: The pathogenic mutation gene of this patient with COXPD28 is SLC25A26 gene mutation (p.A66E, p.A12P), which causes the decrease of SLC25A26 expression level, mitochondrial oxidative phosphorylation dysfunction, and induces COXPD28.

[Establishment of a platelet production model by bone marrow cavity transplantation of mouse primary megakaryocytes].

Objective: To establish an intramedullary transplantation model of primary megakaryocytes to evaluate the platelet-producing capacity of megakaryocytes and explore the underlying regulatory mechanisms. Methods: Donor megakaryocytes from GFP-transgenic mice bone marrow were enriched by magnetic beads. The platelet-producing model was established by intramedullary injection to recipient mice that underwent half-lethal dose irradiation 1 week in advance. Donor-derived megakaryocytes and platelets were detected by immunofluorescence staining and flow cytometry. Results: The proportion of megakaryocytes in the enriched sample for transplantation was 40 to 50 times higher than that in conventional bone marrow. After intramedullary transplantation, donor-derived megakaryocytes successfully implanted in the medullary cavity of the recipient and produce platelets, which showed similar expression of surface markers and morphology to recipient-derived platelets. Conclusion: We successfully established an in vivo platelet-producing model of primary megakaryocytes using magnetic-bead enrichment and intramedullary injection, which objectively reflects the platelet-producing capacity of megakaryocytes in the bone marrow.

[All-inside subtalar arthroscopy through three portals combined with rafting screws technique for the treatment of the calcaneal fractures of Sanders â ¡ and â ¢].

Objective: To investigate the surgical technology and clinical efficacy of using the all-inside subtalar arthroscopy through three portals combined with rafting screws technique for the treatment of the calcaneal fractures of Sanders Ⅱ and Ⅲ. Methods: The clinical data of 33 patients (33 feet) with intra-articular displaced calcaneal fractures treated by modified all-inside arthroscopic from March 2017 to March 2019 at Department of Orthopedics,Xuzhou Central Hospital were retrospectively analyzed.There were 19 male patients,and 14 female patients,aged (32.6±11.3) years(range:20 to 55 years). According to the Sanders classification,there were 12 cases of type Ⅱ and 21 cases of type Ⅲ. The duration from injury to surgery was (101.2±32.1) hours(range:6 to 140 hours).The preoperative visual analogue scale (VAS) was 6.4±2.9 (range: 4 to 8); The preoperative American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scale and the SF-36 score was 63.3±11.8 (range:50 to 75) and 94.8±9.1 (range:70 to 105) respectively.All the patients were managed with the all-side subtalar arthroscopy through three portals combined with rafting screws technique.The incision healing,reduction of fracture,and fracture healing were recorded.The VAS,AOFAS ankle-hindfoot scale,and SF-36 score were used to assess the pain and functional outcomes.Repeated-measurement was used to compare the scores before and after surgery. Results: The time of operation was (69.7±10.4) minutes (range:40 to 110 minutes). All patients did not undergo bone grafting.The incision healed in one stage without complications of skin sensory and peroneal tendon injury.All patients were followed up for 24 months.At the last follow-up,all the patients were satisfied with the hindfoot alignment,function,and hindfoot appearance.Postoperative calcaneal imaging indicators (calcaneal length,calcaneal width,calcaneal height,Bohler angle and Gissane angle) were significantly improved compared with those before surgery (P<0.01).There was no statistically significant difference in the imaging indexes of calcaneus at 1 day,1 year and 2 years after surgery,indicating no loss of fracture reduction (all P>0.05).The VAS,AOFAS ankle-hindfoot scale,and SF-36 score were 1.5±0.4 (range: 0 to 2),94.0±6.5 (range:90 to 100),and 119.1±7.2 (range:105 to 130),respectively,which were better than those before surgery (all P>0.05).According to the AOFAS scoring system,27 cases were excellent,4 cases were good, 2 cases were fair,and the excellent and good rate was 94.0%. Conclusion: All-inside subtalar arthroscopy through three portals combined with rafting screws technique for the treatment of the calcaneal fractures of Sanders Ⅱ and Ⅲ provides precise reduction,reliable fixation,satisfactory function and limited complications,which is an alternative method.

Octyl cyanoacrylate skin adhesive with or without subcuticular suture for skin closure after implantable venous port placement for oncology patients: a propensity-score matching analysis.

AIM: To compare peri-operative outcomes of skin closure with octyl cyanoacrylate (OCA) skin adhesive (Dermabond) with or without subcuticular sutures after deep dermal suturing for implantable venous port placement closure. MATERIALS AND METHODS: Seven hundred and ninety-two single-lumen implantable venous port insertions for chemotherapy were reviewed from September 2019 to March 2021 in a retrospective single-centre study. Propensity-score matching by a 1:1 nearest neighbour algorithm was conducted to control for confounding baseline differences. Distances were determined by logistic regression. Propensity-score matching was performed based on the following variables: age at procedure, gender, race, operator's seniority, use of anchoring polypropylene suture (PROLENE), port model, and volume of intra-operative local analgesia. The primary outcome was wound dehiscence at the first follow-up (∼1 week). RESULTS: The 792 port insertions were conducted in 302 males (38.1%), median age 63 years (IQR: 54-69). Of the 656 wounds closed with subcuticular sutures and skin adhesive, 136 were matched in a 1:1 fashion against procedures closed without a subcuticular suture. No significant differences were demonstrated in pain scores, bleeding, swelling, bruising, fever, wound dehiscence, and discharge at postoperative day 1 (POD1) and at first follow-up between the groups (all p>0.05). Of note, no significant differences in wound dehiscence at first follow-up was found in both unmatched (p=0.133) and matched cohorts (McNemar-Bowker's χ2 = 1.167, p=0.761). CONCLUSION: These findings suggest that the omission of subcuticular sutures during implantable venous port closure may not compromise peri-operative outcomes when OCA skin adhesives were used.

[Stereotactic body radiation therapy for patients with lung and liver oligometastases from colorectal cancer: a phase â ¡ trial].

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.

[Laparoscopic proximal gastrectomy and lymph node resection in adenocarcinoma of the esophagogastric junction].

The proportion of adenocarcinoma of the esophagogastric junction (AEG) in gastric cancer is gradually increasing. Due to the unique anatomical structure and biological characteristics of the tumor at this site, AEG has a certain degree of complexity in many aspects of diagnosis and treatment, which brings difficulties to the operation method, the selection of the resection range, the lymph node dissection and the treatment decision-making. Therefore, AEG has always been the focus of academic debate. With the development of minimally invasive surgery in recent years, laparoscopic technology has been increasingly mature and widely used in the treatment of gastrointestinal tumors. Compared with distal gastric cancer, the minimally invasive treatment of AEG is in a lagging state, and there are also a series of problems that have not yet reached a consensus. This article reviews and summarizes the recent research progress in two aspects: proximal gastrectomy for AEG and lymph node dissection. Laparoscopic-assisted proximal gastrectomy is safe for early proximal gastric cancer and has a long-term survival outcome not inferior to total gastrectomy, but the surgical indications must be strictly selected. Abdominal lymph node metastasis of AEG is mainly in group 1, 2, 3, and 7, and mediastinal lymph node metastasis is closely related to the length of the infiltrated esophagus. The abdominal transhiatal (TH) approach can obtain a sufficient number of harvested lymph node, and has good safety and efficacy, which is the first-choice of surgical approach for early AEG. The results of the CLASS-10 clinical trial can provide a higher level of evidence for laparoscopic mediastinal lymph node dissection. Laparoscopic surgery for AEG should be carried out in experienced medical center based on clinical research.

[Clinical and molecular pathological features of uterine inflammatory myofibroblastic tumor].

Objective: To evaluate the clinical and molecular pathologic features of uterine inflammatory myofibroblastic tumor (UIMT). Methods: Six UIMT cases collected at Department of Pathology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University from 2019 to 2020. They were analyzed for their general characteristics and clinicopathologic features. ALK rearrangements were detected by fluorescence in situ hybridization. Results: The age of the six patients ranged from 14 to 65 years, the tumors ranged in size from 2.5 to 6.0 cm. The masses were intramural or submucosal in location. Most of them (4/6) were white with yellow foci, and two (2/6) were white with tan foci. Other features noted included a soft or firm appearance. The fasciitis-like pattern of UIMT had myxoid stroma around the spindle cells and inflammatory cells. The ganglion-like pattern showed either fascicular or storiform architecture with diffuse growth. Nuclear atypia was mild or moderate. Mitoses ranged from 2 to 4 per 10 high-power fields. Five tumors were ALK-positive with granular cytoplasmic staining by immunohistochemistry. ALK rearrangements were detected in five cases but was absent in one case. Conclusions: UIMT is an intermediate grade soft tissue tumor, a minority may present with extrauterine spread and/or recurrence. The tumors are composed of spindled cells. The main differentials include smooth muscle tumors and endometrial stromal tumors and their morphology may overlap with that of UIMT. Immunohistochemical positivity for ALK or FISH testing for ALK rearrangements can help in the diagnosis.

[The value of morphological characteristics of cervical adenocarcinoma biopsy tissue in predicting tumor invasion pattern and prognosis].

Objective: To evaluate the pathologic findings from biopsy samples to predict the status of nodal metastasis for patients with usual cervical adenocarcinoma. Methods: The 32-pair samples of cervical adenocarcinoma specimens (32 cervical biopsies and 32 hysterectomies with staging) from 2013 to 2019 were selected for retrospective study in Shanghai first Maternal and infant Health Care Hospital Affiliated to Tongji University. The correlation between histopathologic features including necrotic tumor debris (NTD), nuclear grade, mitotic count and pattern-based classification system and the status of lymph node metastasis was evaluated. Results: Tumor invasive patterns of cervical adenocarcinoma, as described previously, could be discerned in hysterectomy/staging specimens, but not in cervical biopsies. Because the biopsy tissues were small, only 14(14/32, 43.8%) cases could be classified according to pattern of invasion, and the concordance rate with resected specimens was 37.5%. NTD (9/19) and grade 3 nuclei (11/19) were positively correlated with invasive pattern C and nodal metastases (P<0.05). Moreover, when NTD and (or) nuclear grade were evaluated at the same time, the sensitivity for type C infiltration was higher. Conclusions: Evaluation of NTD and nuclear grade in biopsies for cervical adenocarcinoma provides good predictive value for lymph node metastasis. It is helpful for patient stratification and management andto avoid unnecessary staging procedures. However, multicenter studies and prospective clinical trials are necessary to confirm the findings before clinical application can be considered.

[Disease burden of liver cancer in China: an updated and integrated analysis on multi-data source evidence].

Objective: To analyze the disease burden of liver cancer in China. Methods: Based on eight data sources, including the series of Chinese Cancer Registry Annual Report, three national death cause surveys in China, China Health Statistical Yearbook, China Death Cause Surveillance Datasets, GLOBOCAN, Cancer Incidence in Five Continents (CI5), WHO Mortality Database and the Global Burden of Disease (GBD), the information on incidence, mortality and disability-adjusted life year (DALY) of liver cancer, were extracted for the analysis on the past, current and future disease burden caused by liver cancer in China. Results: 1) Past situation: The long-term data from 1973 to 2012 reported by the CI5 showed that in urban populations in China (taking Shanghai as an example), the incidence rate of liver cancer in males and females decreased by 41.3% and 36.3%, respectively, and that in rural areas (taking Qidong as an example) decreased by 32.3% and 12.2%, respectively. The Chinese Cancer Registry Annual Reports showed that the national incidence and mortality rates of liver cancer decreased by 8.1% and 12.8% respectively from 2005 to 2015. The Joinpoint analysis based on the data from the China Health Statistics Yearbook also showed a declining trend: the average annual percentage change of liver cancer mortality in China from 2002 to 2017 was -3.0% (P<0.05), and that in rural areas was -3.1% (P<0.05). 2) Current status: GLOBOCAN estimates that the rates of incidence, mortality and prevalence of liver cancer in China in 2018 were 18.3 per 100 000, 17.1 per 100 000 and 10.8 per 100 000, respectively. According to the latest annual report, the incidence and mortality rates of liver cancer in cancer registration areas in 2015 were 17.6 per 100 000 and 15.3 per 100 000, respectively, and both increased with age. The mortality rate was similar to that reported in 2017 (16.7 per 100 000) by the China Death Cause Surveillance Datasets, and the male to female ratio of live cancer deaths was estimated as 3.1. The GBD 2017 reports that the DALYs caused by liver cancer in China reached 11 153.0 thousand in 2017 (accounting for 53.7% of the global DALYs) and hepatitis B virus infection was always the leading cause. 3) Prediction: The GLOBOCAN 2018 predicts that, by 2040, the number of liver cancer cases and deaths in China would reach 591 000 and 572 000 (with an increase of 50.5% and 54.9%, respectively, compared with those in 2018), with a more significant increase in people over 70 years old. 4) Economic burden: According to the literature review of economic burden data on liver cancer, the direct medical expenditure per patient with liver cancer generally showed a rising trend. Conclusions: Multiple data sources indicate that the incidence and mortality rates of liver cancer in populations in China decreased in the past decades, indicating the effect of population interventions. However, the population-level disease burden are still substantial, and comprehensive intervention strategies need to be continually strengthened and optimized, especially the primary and secondary prevention.

Effects of oxaliplatin on inflammation and intestinal floras in rats with colorectal cancer.

OBJECTIVE: The aim of this study was to investigate the effects of oxaliplatin on intestinal floras, inflammation level, apoptosis-related gene expressions and oxidative stress in rats with colorectal cancer. MATERIALS AND METHODS: A total of 30 adult Sprague-Dawley (SD) rats were selected as research objects and were divided into control group, model group and oxaliplatin group. Rats in control group were raised normally, without any treatment. Rats in model group were subcutaneously injected with dimethylhydrazine (25 mg/kg) to establish the model of colorectal cancer. Meanwhile, rats in oxaliplatin group were injected with oxaliplatin (15 mg/kg) once every 2 weeks for 12 consecutive weeks. Peripheral blood, intestinal tumor tissues and feces were collected from rats. In addition, inflammatory indexes [tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), interleukin-4 (IL-4) and IL-1ß], oxidative stress indexes [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and total antioxidant capacity (T-AOC)], expressions of apoptosis-related genes [apoptotic protease activating factor-1 (Apaf1), Caspase-9, Survivin and B-cell lymphoma-2 (Bcl-2)] and intestinal floras were detected. RESULTS: The abundance of microorganisms such as Sphaerobacterales, Adlercreutzia and Coriobacterium glomerans increased significantly in the intestines in control group (p<0.05). However, the abundance of Bifidobacterium, Rikenellaceae and Paraprevotella in the intestines was obviously higher in model group (p<0.05). Oxaliplatin group exhibited remarkably higher abundance of such microorganisms as Cyanobacteria, Alistipes and Metascardovia in rat intestines (p<0.05). The content of Alistipes was the highest in oxaliplatin group, followed by control group and model group, and the difference was statistically significant (p<0.05). The levels of serum TNF-α, CRP and IL-1ß were remarkably higher in model group than those in control group (p<0.05). Oxaliplatin group exhibited notably lower levels of serum TNF-α, CRP and IL-1ß (p<0.05) and higher IL-4 level than model group (p<0.05). The content of serum CAT, SOD, GSH and T-AOC was markedly elevated in model group compared with control group (p<0.05). However, it was significantly reduced in oxaliplatin group in comparison with model group (p<0.05). Compared with control group, model group had distinctly lower expressions of Apaf1, Caspase-9 and Survivin but an evidently higher expression level of Bcl-2 in tumor tissues (p<0.05). Moreover, the expressions of Apaf1, Caspase-9 and Survivin were clearly higher, while that of Bcl-2 was prominently lower in tumor tissues in oxaliplatin group than model group (p<0.05). CONCLUSIONS: Oxaliplatin exerts significant effects on the inflammation, oxidative stress, apoptosis-related genes and intestinal floras in rats with CRC.

LncRNA SNHG16 drives proliferation, migration, and invasion of lung cancer cell through modulation of miR-520/VEGF axis.

OBJECTIVE: Long non-coding RNAs (lncRNAs) have been shown to have important effects on various biological behavior of human diseases. Although increasing lncRNAs have been explored in human cancers, there are still countless lncRNA to be mined. The purpose of this study was to investigate the effect of lncRNA SNHG16 on the proliferation and metastasis of lung cancer cells. PATIENTS AND METHODS: RT-qPCR was used to analyze the expression patterns of SNHG16, miR-520 and VEGF. MTT and transwell methods were used to detect the effect of SNHG16 on cell migration. The association between SNHG16, miR-520 and VEGF was analyzed by bioinformatics analysis and Dual-Luciferase verification reporter analysis. Finally, lung cancer cells have demonstrated the role of SNHG16-miR-520-VEGF in the cell biological behavior axis. RESULTS: Compared with normal cells, SNHG16 is highly expressed in lung cancer cells. Silent SNHG16 has a negative effect on the migration of lung cancer cells. CONCLUSIONS: LncRNA SNHG16 as ceRNA up-regulates VEGF in lung cancer cells by binding to miR-520. LncRNA SNHG16 as ceRNA promotes the migration of lung cancer cells by regulating the miR-520/VEGF axis.

[Pleural effusion as the first manifestation of pleural isolated myeloid sarcoma: a case report and literature review].

Objective: To analyze the clinic features of isolated myeloid sarcoma (IMS) involving the pleural cavity. Methods: A case of pleural isolated myeloid sarcoma (PIMS) with pleural effusion as the first manifestation was described. The related cases in literatures were reviewed with"myeloid sarcoma"and"pleural effusions"as the keywords to search China HowNet, Wanfang database and PubMed database. Results: A 59-year-old man complained of right chest pain for 2 months and worsening pain with distress and shortness of breath for 2 weeks. The chest CT scan showed pleural effusion on the right side. Flow cytometric analysis of pleural fluid showed that a population of blasts with CD34 expressing was 37.6% of the total nucleated cells. The pleural biopsy through medical thoracoscopy indicated lymphoproliferative lesions by pathological examination. Immunohistochemistry was performed on pleural histological sections and cell blocks of pleural effusions, which showed CD34 and CD117 positive expression. The diagnosis of PIMS was finally made. Two literature papers with 2 complete cases were found and reviewed. The 3 cases were analyzed. There were 2 males and 1 female. The age was 59, 51, 56 years respectively. One case was a patient with 3 weeks of right upper quadrant and epigastric pain, nausea, and weight loss. Cytological examination of the pleural fluid showed numerous poorly differentiated malignant cells. Histology from an open laparotomy in duodenal biopsies, gallbladder, and mesenteric lymph nodes supported the diagnosis of IMS. The other case was a patient with 6 weeks of dyspnea and a large swelling in the upper vestibular region. Thoracentesis showed 82% myeloid blasts in the pleural fluid. A gingival biopsy showed a diffuse infiltration by cells with a blastic appearance and supported IMS. Conclusion: PIMS was a very rare cause of pleural effusions. The cytological and histopathological evidences were useful to diagnose IMS involving the pleural cavity.

Grape-seed polyphenols inhibit AAA in mice via regulation of macrophage polarization.

AIM: Abdominal aortic aneurysm (AAA) is characterized by macrophage polarization, and at present, no drug therapy is available. Although grape-seed polyphenols (GSP) showed an anti-AAA effect, the role of GSP in the phenotype shift in macrophages remains unknown. METHOD: The main phenolic compounds in GSP were determined by LC-MS. Male C57BL/6 mice were divided into four equal groups, namely sham group, CaPO4 group, CaPO4+GSP low-dose group, and CaPO4+GSP high-dose group. GSP was administered intragastrically after CaPO4 application. Molecular expressions were histologically evaluated and analyzed by various staining assays and FACS. RESULTS: GSP administration inhibited CaPO4-induced AAA formation, which correlated with a decrease in macrophage infiltration and retainment of vascular smooth muscle layer as compared to those in the CaPO4 group. FACS assay showed that the GSP administration dose-dependently decreased the CD54 expression (low-dose group: 11.4 ± 2.1 % and high-dose group: 4.8 ± 1.4 % vs 23.2 ± 3.6 %; p < 0.05 and p < 0.01, respectively) and increased the CD206 expression of F4/80-positive cells in GSP-administered groups as compared with that in CaPO4-injured aortas in the CaPO4 group (low-dose group: 22.4 ± 3.3 % and high-dose group: 26.7 ± 4.2 % vs 8.1 ± 1.3 %; p < 0.05 and p < 0.01, respectively). CONCLUSIONS: GSP could be a pharmacologically potent agent in the treatment of AAA (Tab. 1, Fig. 3,Ref. 20). Text in PDF www.elis.sk Keywords: grape-seed polyphenols, abdominal aortic aneurysm, macrophage, inflammatory, polarization.

Inhibitory effect of the Notch pathway-inhibitor DAPT on invasion and metastasis of tongue cancer via lncRNA-KAT14 regulation.

OBJECTIVE: We aimed to identify a reliable biomarker for tongue squamous cell carcinoma (TSCC), the most common oral cancer with no established biomarkers, to predict prognosis and to select the optimal treatment. MATERIALS AND METHODS: To investigate whether DAPT exhibited antitumor functions, CAL-27 and SCC-9 cells were treated with DAPT (5 µM or 10 µM) for different times. Further, qRT-PCR was used to determine the mRNA expression levels of lncRNA-KAT14 after treatment with DAPT or si-KAT14 and both combined. Moreover, the treated cells were cultured for different times to investigate their antitumor function. The Wound-healing and Transwell assay were carried out to evaluate the migration and invasion viability of cancer cells, respectively. Finally, the Western blots were performed to determine the expression of EMT-related proteins after transfection with si-KAT14 or treatment with DAPT to investigate the effects of DAPT on EMT-related proteins. RESULTS: Proliferation was inhibited after treatment with DAPT, and the expression of lncRNA-KAT14 was upregulated. To investigate the correlation of DAPT and lncRNA-KAT14 on the metastasis and invasion in tongue cancer, the following cellular processes were assessed: proliferation, invasion, and migration ability. The Western blots were used to determine the expression of E-cadherin, N-cadherin, Vimentin, and Snail, showing that DAPT or lncRNA-KAT14 suppressed all these processes, inducing a decreased expression of N-cadherin, Vimentin, and Snail, and increased expression of E-cadherin, compared with the control group. Once transfection with si-KAT14 occurred, the evaluated cellular processes were enhanced, being this attenuated by the treatment with DAPT. CONCLUSIONS: Our results suggest that DAPT suppresses invasion and metastasis of tongue cancer by regulating lncRNA-KAT14.