Safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant chemotherapy combined with immunotherapy / 中华胃肠外科杂志

Objective: To investigate the safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy. Methods: Between November 2020 and April 2021, patients with locally advanced gastric cancer who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology were prospectively enrolled in this study. Inclusion criteria were: (1) patients who signed the informed consent form voluntarily before participating in the study; (2) age ranging from 18 to 75 years; (3) patients staged preoperatively as cT3-4N+M0 by the TNM staging system; (4) Eastern Collaborative Oncology Group score of 0-1; (5) estimated survival of more than 6 months, with the possibility of performing R0 resection for curative purposes; (6) sufficient organ and bone marrow function within 7 days before enrollment; and (7) complete gastric D2 radical surgery. Exclusion criteria were: (1) history of anti-PD-1 or PD-L1 antibody therapy and chemotherapy; (2) treatment with corticosteroids or other immunosuppre- ssants within 14 days before enrollment; (3) active period of autoimmune disease or interstitial pneumonia; (4) history of other malignant tumors; (5) surgery performed within 28 days before enrollment; and (6) allergy to the drug ingredients of the study. Follow-up was conducted by outpatient and telephone methods. During preoperative SOX chemotherapy combined with PD-1 inhibitor immunotherapy, follow-up was conducted every 3 weeks to understand the occurrence of adverse reactions of the patients; follow-up was conducted once after 1 month of surgical treatment to understand the adverse reactions and survival of patients. Observation indicators were: (1) condition of enrolled patients; (2) reassessment after preoperative therapy and operation received (3) postoperative conditions and pathological results. Evaluation criteria were: (1) tumor staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system; (2) tumor regression grading (TRG) of pathological results were evaluated with reference to AJCC standards; (3) treatment-related adverse reactions were evaluated according to version 5.0 of the Common Terminology Criteria for Adverse Events; (4) tumor response was evaluated by CT before and after treatment with RECIST V1.1 criteria; and (5) Clavien-Dindo complication grading system was used for postoperative complications assessment. Results: A total of 30 eligible patients were included. There were 25 males and 5 females with a median age of 60.5 (35-74) years. The primary tumor was located in the gastroesophageal junction in 12 cases, in the upper stomach in 8, in the middle stomach in 7, and in the lower stomach in 3. The preoperative clinical stage of 30 cases was III. Twenty-one patients experienced adverse reactions during neoadjuvant chemotherapy combined with immunotherapy, including four cases of CTCAE grade 3-4 adverse reactions resulting in bone marrow suppression and thoracic aortic thrombosis. All cases of adverse reactions were alleviated or disappeared after active symptomatic treatment. Among the 30 patients who underwent surgery, the time from chemotherapy combined with immunotherapy to surgery was 28 (23-49) days. All 30 patients underwent laparoscopic radical gastrectomy, of which 20 patients underwent laparoscopic-assisted radical gastric cancer resection; 10 patients underwent total gastrectomy for gastric cancer, combined with splenectomy in 1 case and cholecystectomy in 1 case. The surgery time was (239.9±67.0) min, intraoperative blood loss was 84 (10-400) ml, and the length of the incision was 7 (3-12) cm. The degree of adenocarcinoma was poorly differentiated in 18 cases, moderately differentiated in 12 cases, nerve invasion in 11 cases, and vascular invasion in 6 cases. The number lymph nodes that underwent dissection was 30 (17-58). The first of gas passage, the first postoperative defecation time, the postoperative liquid diet time, and the postoperative hospitalization time of 30 patients was 3 (2-6) d, 3 (2-13) d, 5 (3-12) d, and 10 (7-27) d, respectively. Postoperative complications occurred in 23 of 30 patients, including 7 cases of complications of Clavien-Dindo grade IIIa or above. Six patients improved after treatment and were discharged from hospital, while 1 patient died 27 days after surgery due to granulocyte deficiency, anemia, bilateral lung infection, and respiratory distress syndrome. The remaining 29 patients had no surgery-related morbidity or mortality within 30 days of discharge. Postoperative pathological examination showed TRG grades 0, 1, 2, and 3 in 8, 9, 4, and 9 cases, respectively, and the number of postoperative pathological TNM stages 0, I, II, and III was 8, 7, 8, and 7 cases, respectively. The pCR rate was 25.0% (8/32). Conclusion: Laparoscopic surgery after neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy for locally advanced gastric cancer is safe and feasible, with satisfactory short-term efficacy. Early detection and timely treatment of related complications are important.

No Causal Link between Phosphodiesterase Type 5 Inhibition and Melanoma

PURPOSE: To examine the association between phosphodiesterase type 5 (PDE5) inhibitor use and melanoma by 1) conducting a systematic review of observational studies; and 2) determining if low PDE5A gene expression in human melanoma correlated with decreased overall survival. MATERIALS AND METHODS: A systematic search of observational studies examining the association between PDE5 inhibitor use and melanoma was performed through ClinicalTrials.gov, the Cochrane Library, EMBASE, PubMed, and Web of Science databases, and seven eligible studies were identified. PDE5A gene expression was analyzed with RNA sequencing data from 471 human melanoma samples obtained from The Cancer Genome Atlas. RESULTS: Four studies reported a positive association between PDE5 inhibitor use and melanoma, and three studies found no correlation. RNA sequencing data analysis revealed that under-expression of the PDE5A gene did not impact clinical outcomes in melanoma. CONCLUSIONS: There is currently no evidence to suggest that PDE5 inhibition in patients causes increased risk for melanoma. The few observational studies that demonstrated a positive association between PDE5 inhibitor use and melanoma often failed to account for major confounders. Nonetheless, the substantial evidence implicating PDE5 inhibition in the cyclic guanosine monophosphate (cGMP)-mediated melanoma pathway warrants further investigation in the clinical setting.

Pre-treatment with rapamycin protects hematopoiesis against radiation injury

Background: Protection of hematopoietic system has become a primary goal in the development of novel medical countermeasures against ionization radiation and radiotherapy. This study was to explore the role of rapamycin in normal tissues against radiation

Materials and Methods: Mice were pretreated with rapamycin by i.p. every other day for five times before 5 Gy or 8.5 Gy gamma-ray whole body irradiation. Blood cell counts, HE staining of bone marrow and liver, bone marrow transplantation, CFU of spleen were used to measure the damage of hematopoiesis and extramedullary hemopoietic organs. Regular karyotype analysis and expression of gamma-H2AX [by flow cytometry and western blot] were used to measure DNA damage. Rad 50 and DNA Lig 4 expression by western blot were to see the DNA repair ability

Results: The decrease of red blood cells and platelet induced by radiation were alleviated by pretreatment with rapamycin [d 7,15, p<0.01], and the long-term restoration of white blood cells, lymphocytes and bone marrow were enhanced in rapamycin pretreatment group [d 30,40,70, p<0.05]. The transplantation experiment also indicates that the long-term reconstitution in lethally irradiated recipient mice was improved in rapamycin group [p<0.05]. The hepatocellular injury by radiation was also reduced and the colony formation numbers of spleen after irradiation was improved in rapamycin group [p<0.05]. Karyotype analysis indicates that rapamycin protected bone marrow cells from chromosome mutation. Furthermore, expression of DNA repair proteins Rad 50 and DNA Lig 4 was enhanced and DNA damage marker gamma-H2AX was reduced in mice exposed to radiation by rapamycin pretreatment

Conclusion: Rapamycin pretreatment mitigates hematopoietic system from radiation injury in both bone marrow and extramedullary hematopoietic organs by improving genomic stability and increasing survival of hematopoietic stem and progenitor cells [HSPCs]

Application of computed tomography and magnetic resonance imaging fusion images for delineating gross tumor volume in three-dimensional conformal radiotherapy of nasopharyngeal carcinoma

Background: To evaluate computed tomography [CT] and magnetic resonance imaging [MRI] fusion images for delineating gross tumor volume [GTV] in three-dimensional conformal radiotherapy [3D-CRT] of nasophanrygeal carcinoma [NPC], and compare treatment outcomes between CT- and CT+MRI-based targets

Materials and Methods: A total of 120 NPC patients treated with 3D-CRT were included, in which, 60 each were treated with CT-based and 60 with CT+MRI fusion targets. We explored the clinical application of CT+MRI fusion targets and compared the 1-, 3-, and 5-year survival and relapse rates between both targets

Results: The clinical characteristics and treatment factors were well balanced. The differences in public volume using CT alone in the CT+MRI [Group A] and the CT arm [Group B] were not significant [33.6+/-2.18 vs. 34.3+/-2.98, P > 0.05]. The public volumes of GTV in the two arms were 49.48+/-2.46 cm[3] and 33.6+/-2.18 cm[3] respectively [P < 0.05]. CT+MR fusion images did not influence the one-, three-, and 5-year survival rates [100% vs. 98.3%, 85.0% vs. 81.2%, and 73.3% vs. 68.3%, respectively]. The three- and 5-year out-of-field progression was reduced in the CT+MRI arm. However, only the difference in 3-year out-of-field relapse rate was significant [3.3% vs. 13.3%; P < 0.05]. The incidence of acute toxicities was similar between groups

Conclusion: The variability in GTV delineation in NPC was ascribed to intermodality and not interobserver variability. CT+MR fusion images likely reduced the 3-year out-of-field relapse rate

A novel, minimally-invasive technique of cartilage repair in the human knee using arthroscopic microfracture and injections of mesenchymal stem cells and hyaluronic acid--a prospective comparative study on safety and short-term efficacy

<p><b>INTRODUCTION</b>Most current cell-based cartilage repair techniques require some form of scaffolds and 2 separate surgical procedures. We propose a novel, scaffold-less technique of cartilage repair in the human knee that combines arthroscopic microfracture and outpatient intra-articular injections of autologous bone marrow-derived mesenchymal stem cells (MSCs) and hyaluronic acid (HA).</p><p><b>MATERIALS AND METHODS</b>Seventy matched (age, sex, lesion size) knees with symptomatic cartilage defects underwent cartilage repair with the proposed technique (n = 35) or an open technique (n = 35) in which the MSCs were implanted beneath a sutured periosteal patch over the defect. Prospective evaluation of both groups were performed using the International Cartilage Repair Society (ICRS) Cartilage Injury Evaluation Package, which included questions from the Short-Form (SF-36) Health Survey, International Knee Documentation Committee (IKDC) subjective knee evaluation form, Lysholm knee scale, and Tegner activity level scale. Postoperative magnetic resonance imaging (MRI) evaluation was also performed at 1 year for most patients.</p><p><b>RESULTS</b>There were no clinically significant adverse events reported through the course of our study. At the fi nal follow-up (mean = 24.5 months), there was significant improvement in mean IKDC, Lysholm, SF-36 physical component score and visual analogue pain scores in both treatment groups.</p><p><b>CONCLUSION</b>In the short term, the results of this novel technique are comparable to the open procedure with the added advantages of being minimally invasive and requiring only a single operation under general anaesthesia. Its safety has been validated and its efficacy is currently being evaluated in an ongoing randomised controlled trial.</p>

Anemia prevalence among pregnant women and birth weight in five areas in China

To investigate the current prevalence of anemia among pregnant women in different areas of China and the association with birth weight and educational level. A total of 6,413 women aged 24-37 in the third trimester of pregnancy from five areas were randomly selected from all gravidas who gave birth in the hospitals from 1999 to 2003. blood hemoglobin concentration [Hb] was measured by the cyanomethemoglobin method; Hb<110 g/l was considered as anemia. The overall prevalence of anemia was 58.6%, ranging from 48.1 to 70.5% in the five areas. There was a significant difference in the prevalence of anemia between women who have mental jobs and those who have physical jobs [52.3 vs. 61.1%, p<0.01]. The prevalence of anemia depended on the level of education: with 52.9, 62.4 and 66.5%, for college, secondary school and primary education, respectively, and the difference was statistically significant [p=0.005]. results showed that higher birth weight was associated with Hb concentrations ranging from 90 to 140 g/l, whereas lower birth weight occurred below 80 g/l and above 140 g/l Hb. The prevalence of anemia in Chinese pregnant women was high both in rural areas and towns. Area of residence, education level and type of job influenced the prevalence of anemia. Low maternal Hb concentrations influenced birth weight