Antibody-platinum (IV) prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma.

Antibody-drug conjugates (ADCs) are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells, thereby attracting considerable attention in precise oncology therapy. Cetuximab (Cet) is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma (cSCC); however, its anti-tumor activity is limited to a single use. Cisplatin (CisPt) shows good curative effects; however, its adverse effects and non-tumor-targeting ability are major drawbacks. In this study, we designed and developed a new ADC based on a new cytotoxic platinum (IV) prodrug (C8Pt(IV)) and Cet. The so-called antibody-platinum (IV) prodrugs conjugates, named Cet-C8Pt(IV), showed excellent tumor targeting in cSCC. Specifically, it accurately delivered C8Pt(IV) into tumor cells to exert the combined anti-tumor effect of Cet and CisPt. Herein, metabolomic analysis showed that Cet-C8Pt(IV) promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells, thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum (IV) prodrugs conjugates.

Safety and feasibility of minimally invasive gastrectomy after neoadjuvant immunotherapy for locally advanced gastric cancer: a propensity score-matched analysis in China.

Background: The effect of neoadjuvant immunotherapy on minimally invasive gastrectomy (MIG) for locally advanced gastric cancer (LAGC) remains controversial. This study aimed to compare short-term outcomes between MIG after neoadjuvant chemo-immunotherapy (NICT-MIG) and MIG after neoadjuvant chemotherapy alone (NCT-MIG), and determine risk factors for post-operative complications (POCs). Methods: This retrospective study included clinicopathologic data from 193 patients who underwent NCT-MIG or NICT-MIG between January 2020 and February 2023 in the Department of General Surgery, Chinese People's Liberation Army General Hospital First Medical Center (Beijing, China). Propensity score-matched analysis at a ratio of 1:2 was performed to reduce bias from confounding patient-related variables and short-term outcomes were compared between the two groups. Results: The baseline characteristics were comparable between 49 patients in the NICT-MIG group and 86 patients in the NCT-MIG group after propensity score matching. Objective and pathologic complete response rates were significantly higher in the NICT-MIG group than in the NCT-MIG group (P < 0.05). The overall incidence of treat-related adverse events, intraoperative bleeding, operation time, number of retrieved lymph nodes, time to the first flatus, post-operative duration of hospitalization, overall morbidity, and severe morbidity were comparable between the NCT-MIG and NICT-MIG groups (P > 0.05). By multivariate logistic analysis, estimated blood loss of >200 mL (P = 0.010) and prognostic nutritional index (PNI) score of <45 (P = 0.003) were independent risk factors for POCs after MIG following neoadjuvant therapy. Conclusions: Safety and feasibility of NICT were comparable to those of NCT in patients undergoing MIG for LAGC. Patients with an estimated blood loss of >200 mL or a PNI score of <45 should be carefully evaluated for increased POCs risk.

Comparison of Clinical Characteristics, Therapy, and Short-Term Prognosis between Blunt and Penetrating Abdominal Trauma: A Multicentric Retrospective Cohort Study.

Objective: Large-scale studies on the characteristics and management of abdominal trauma in megacities in China are lacking. The aim of this study was to analyze and present the clinical patterns and treatment status of abdominal trauma in regional medical centers. Methods: Cases of abdominal trauma treated at seven medical centers in Beijing from 2010 to 2021 were collected. Clinical information about age, sex, injury cause, geographic distribution, abbreviated injury scale/injury severity score (AIS/ISS) value, injury-hospital time, preoperative time, surgically identified organ injuries, type of surgery, causes of reoperation and 90-day mortality was included in this study. Clinical characteristics, treatment methods, and short-term prognoses (90-days survival) were compared between blunt abdominal trauma (BAT) and penetrating abdominal trauma (PAT) cases. Non-normally distributed data are described as medians (IQR), and the Mann‒Whitney U test was performed; qualitative data were analyzed using the X2 test. Univariate and multivariate survival analyses were performed by the Cox proportional hazards model. Results: A total of 553 patients (86.98% male) with a median age of 36.50 (27.00-48.00) years were included. The BAT group had a significantly higher proportion of serious injury (P=0.001), lower initial hemoglobin level (P=0.001), and a lower laparoscopy surgery rate (P=0.044) compared to the PAT group. Additionally, more BAT cases were from the area around Beijing (P=0.008) and a longer injury-regional hospital time (10.47 (5.18-22.51) hours vs. 7.00 (3.80-15.38) hours, P=0.001). In the hollow viscus injury subgroup, the BAT group had a significantly longer injury-regional hospital time and preoperative time compared to the PAT group (injury-regional hospital time: 10.23 (6.00-21.59) hours vs. 7.07 (3.99-13.85) hours, P=0.002; preoperative time: 3.02 (2.01-5.58) hours vs. 2.81 (1.85-3.63) hours, P=0.047). The overall 90-day mortality was 11.9%, and longer injury-regional hospital time (HR: 1.01, 95% CI: 1.00-1.02, P=0.008), receipt of ICU treatment (HR: 4.69, 95% CI: 2.54-8.65, P=0.001), and severe ISSs (ISS > 25 vs. ISS < 16, HR: 2.78, 95% CI: 1.38-5.601, P=0.004) had a worse impact on survival. Conclusion: More patients with BAT were transferred to higher-level hospital, leading to significantly longer prehospital and preoperation time. In the subgroup of hemodynamically stable individuals, more patients with BAT experienced hollow viscus injuries. For those patients, aggressive diagnostic laparoscopic exploration may be beneficial. Patients with longer injury-regional hospital intervals, the need for ICU care, and higher injury severity scores (ISSs) suffered from worse prognoses.

KAT8-catalyzed lactylation promotes eEF1A2-mediated protein synthesis and colorectal carcinogenesis.

Aberrant lysine lactylation (Kla) is associated with various diseases which are caused by excessive glycolysis metabolism. However, the regulatory molecules and downstream protein targets of Kla remain largely unclear. Here, we observed a global Kla abundance profile in colorectal cancer (CRC) that negatively correlates with prognosis. Among lactylated proteins detected in CRC, lactylation of eEF1A2K408 resulted in boosted translation elongation and enhanced protein synthesis which contributed to tumorigenesis. By screening eEF1A2 interacting proteins, we identified that KAT8, a lysine acetyltransferase that acted as a pan-Kla writer, was responsible for installing Kla on many protein substrates involving in diverse biological processes. Deletion of KAT8 inhibited CRC tumor growth, especially in a high-lactic tumor microenvironment. Therefore, the KAT8-eEF1A2 Kla axis is utilized to meet increased translational requirements for oncogenic adaptation. As a lactyltransferase, KAT8 may represent a potential therapeutic target for CRC.

Mitochondrial genomes provide insights into the Euholognatha (Insecta: Plecoptera).

BACKGROUND: Euholognatha is a monophyletic group within stoneflies comprised by a superfamily Nemouroidea and a family Scopuridae. Based on morphological data, the family-level phylogenetic relationships within Euholognatha are widely accepted, but there is still controversy among different molecular studies. To better understand the phylogeny of all six extant euholognathan families, we sequenced and analyzed seven euholognathan mitogenomes. RESULTS: The sequence heterogeneity analysis observed a low degree of compositional heterogeneity in euholognathan mitogenomes. Meanwhile, leuctrid mitogenomes were more heterogeneous than other euholognathan families, which may affect the phylogenetic reconstruction. Phylogenetic analyses with various datasets generated three topologies. The Leuctridae was recovered as the earliest branching lineage, and the sister relationship of Capniidae and Taeniopterygidae was supported by most tree topologies and FcLM analyses. When separately excluding sparsely sampled Scopuridae or high heterogeneity leuctrid taxa, phylogenetic analyses under the same methods generated more stable and consistent tree topologies. Finally, based on the results of this study, we reconstructed the relationships within Euholognatha as: Leuctridae + (Scopuridae + ((Taeniopterygidae + Capniidae) + (Nemouridae + Notonemouridae))). CONCLUSION: Our research shows the potential of data optimizing strategies in reconstructing phylogeny within Euholognatha and provides new insight into the phylogeny of this group.

Total versus proximal gastrectomy for proximal gastric cancer after neoadjuvant chemotherapy: a multicenter retrospective propensity score-matched cohort study.

BACKGROUND: This study aimed to analyze and compare the short-term and long-term outcomes of proximal gastrectomy (PG) and total gastrectomy (TG) in patients with locally advanced proximal gastric cancer (GC) following neoadjuvant chemotherapy (NACT). METHOD: A multicenter retrospective cohort study and propensity score matching (PSM) were employed. The authors examined 367 patients with proximal GC who received NACT followed by PG ( n =164) or TG ( n =203) at two Chinese medical institutions between December 2009 and December 2022. Clinical and pathological parameters, postoperative complications, and 5-year overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups. The dissection status and metastasis rate of each lymph node station were assessed. RESULTS: After PSM, 80 patients were enrolled in both TG and PG group, and baseline characteristics were comparable between the groups (all P >0.05). The TG group had a higher total number of lymph nodes retrieved ( P <0.001) and longer operative time ( P =0.007) compared to the PG group. The incidence of Clavien-Dindo grade II or higher postoperative complications was similar between the TG group (21.3%, 17/80) and the PG group (17.5%, 14/80) ( P =0.689). The 5-year OS rates were 68.4 for the PG group and 66.0% for the TG group ( P =0.881), while the 5-year RFS rates were 64.8 and 61.9%, respectively ( P =0.571), with no statistically significant differences. Metastasis rates at lymph node stations #4d, #5, #6, and #12a were notably low in the TG group, with values of 2.74, 0.67, 1.33, and 1.74%, respectively. CONCLUSION: For proximal GC patients following NACT, PG maintains comparable curative potential and oncological efficacy to TG, making it a safe option.

Five-year long-term comparison of robotic and laparoscopic gastrectomy for gastric cancer: a large single-center cohort study.

BACKGROUND: Robotic gastrectomy (RG) has been reported to be technically feasible and safe for patients with gastric cancer. However, 5-year long-term survival and recurrence outcomes for advanced gastric cancer have rarely been reported. This study aimed to compare the long-term oncologic outcomes between RG and laparoscopic gastrectomy (LG) for gastric cancer. METHODS: The general clinicopathological data of 1905 consecutive patients who underwent RG and LG were retrospectively collected at the Chinese People's Liberation Army General Hospital between November 2011 and October 2017. Propensity score matching (PSM) was used to match groups. The primary endpoints were 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: After PSM, a well-balanced cohort of 283 patients in the RG group and 701 patients in the LG group were included in the analysis. The 5-year cumulative DFS rates were 67.28% in the robotic group and 70.41% in the laparoscopic group. The 5-year OS rate was 69.01% in the robotic group and 69.58% in the laparoscopic group. No significant differences in Kaplan-Meier survival curves for DFS (HR = 1.08, 95% CI 0.83-1.39, Log-rank P = 0.557) and OS (HR = 1.02, 95% CI 0.78-1.34, Log-rank P = 0.850) were observed between the 2 groups. In the subgroup analyses for potential confounding variables, there were no significant differences in 5-year DFS and 5-year OS survival between the 2 groups (P > 0.05), except for patients with pathological stage III and pathological stage N3 (P < 0.05). CONCLUSION: For patients with early gastric cancer, robotic and laparoscopic approaches have similar long-term survival. For patients with advanced gastric cancer, further studies need to be conducted to assess the long-term survival outcomes of RG.

L-kynurenine induces NK cell loss in gastric cancer microenvironment via promoting ferroptosis.

BACKGROUND: Natural killer (NK) cells play a major role in body's fighting against various types of cancers. Their infiltration in the tumor microenvironment (TME) of gastric cancer (GC) are significantly decreased, which has been reported as a robust prognostic marker. However, the causes leading to NK cells loss in GC TME remains poorly understood. METHODS: We constructed a non-contact co-culturing system and humanized xenograft tumor mice model to detect the influence of GC microenvironment on NK-92 or primary human NK cells viability by flow cytometry. Then through using the specific inhibitors for different types of cell death and examining the surrogate markers, we confirmed ferroptosis in NK cells. Inspired by the accidental discoveries, we constructed a NK-92 cell strain with high expression of GPX4 and treated the humanized xenograft tumor mice model with the NK-92 cells. RESULTS: We found L-KYN, mainly generated through indoleamine 2, 3-dioxygenase (IDO) from GC cells, impaired NK cells viability in TME. Further analysis revealed L-KYN induced ferroptosis in NK cells via an AHR-independent way. Moreover, we found NK cells with higher GPX4 expression showed resistance to L-KYN induced ferroptosis. Based on this, we generated GPX4 over-expressed NK-92 cells, and found these cells showed therapeutic potential towards GC. CONCLUSIONS: Our study revealed a novel mechanism to explain the decline of NK cell number in GC TME. Notably, we also developed a potential immunotherapy strategy, which might be beneficial in clinical treatment in the future.

Relative efficacy of prophylactic strategies for postthyroidectomy hypocalcemia: a systematic review and network meta-analysis.

BACKGROUND: Routine prophylaxis for at-risk patients may reduce the occurrence of postoperative hypocalcemia but is not widely adopted due to a lack of evidence on the efficacy of available prophylactic strategies. In this study, we compared the relative efficacy of prophylactic strategies for postthyroidectomy hypocalcemia with a systematic review and network meta-analysis. METHODS: PubMed, Embase, and Cochrane Library were searched, covering the period from 1980 to May 2022, for randomized controlled trials (RCTs) comparing calcium, vitamin D 3 , activated vitamin D 3 , teriparatide, steroids, and magnesium with placebo or each other in patients receiving total or completion thyroidectomy. Involved RCTs reporting symptomatic or biochemical hypocalcemia. The primary outcome was symptomatic hypocalcemia, defined as circumoral tingling, and Chvostek and Trousseau signs. The secondary outcome was biochemical hypocalcemia. Risk of bias was assessed using the Cochrane risk of bias assessment tool for randomized trials. Pooled estimates were calculated using a random-effects inverse-variance weighting model. The network meta-analysis was performed under the frequentist framework. This meta-analysis was registered on the PROSPERO (International prospective register of systematic reviews) (CRD42022299982). RESULTS: Twenty-seven RCTs comprising 3382 patients are included. Prophylactic strategies of teriparatide, oral calcium plus vitamin D 3 , and oral calcium plus activated vitamin D 3 are superior to placebo in reducing symptomatic hypocalcemia. Teriparatide emerged as the most effective strategy for symptomatic hypocalcemia [relative risk (RR): 0.18; 95% CI: 0.03-0.98], followed by oral calcium plus activated vitamin D 3 (RR: 0.42; 95% CI: 0.25-0.73) and oral calcium plus vitamin D 3 (RR: 0.43; 95% CI: 0.26-0.71). Evidence on monotherapy with either oral calcium or vitamin D 3 in reducing symptomatic hypocalcemia is insufficient. Intravenous calcium and oral calcium are effective in reducing biochemical hypocalcemia. CONCLUSIONS: This network meta-analysis provides information on the relative efficacy of current prophylactic strategies for postthyroidectomy hypocalcemia. Teriparatide performed better than other interventions and would seem appropriate for deployment among high-risk populations.

Multilevel proteomic analyses reveal molecular diversity between diffuse-type and intestinal-type gastric cancer.

Diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer (IGC) are the major histological types of gastric cancer (GC). The molecular mechanism underlying DGC and IGC differences are poorly understood. In this research, we carry out multilevel proteomic analyses, including proteome, phospho-proteome, and transcription factor (TF) activity profiles, of 196 cases covering DGC and IGC in Chinese patients. Integrative proteogenomic analysis reveals ARIDIA mutation associated with opposite prognostic effects between DGC and IGC, via diverse influences on their corresponding proteomes. Systematical comparison and consensus clustering analysis identify three subtypes of DGC and IGC, respectively, based on distinct patterns of the cell cycle, extracellular matrix organization, and immune response-related proteins expression. TF activity-based subtypes demonstrate that the disease progressions of DGC and IGC were regulated by SWI/SNF and NFKB complexes. Furthermore, inferred immune cell infiltration and immune clustering show Th1/Th2 ratio is an indicator for immunotherapeutic effectiveness, which is validated in an independent GC anti-PD1 therapeutic patient group. Our multilevel proteomic analyses enable a more comprehensive understanding of GC and can further advance the precision medicine.

Development of HPLC-MS/MS assay for quantitation of ensartinib in human plasma and its application to a pharmacokinetics study in Chinese patients.

Ensartinib is a novel anaplastic lymphoma kinase (ALK) inhibitor with potent activity against a broad range of known crizotinib-resistant ALK mutations and is developed to treat patients with non-small-cell lung cancer. This study was the first to develop and validate a rapid and sensitive HPLC-MS/MS method for the determination of ensartinib in human plasma. The plasma samples were extracted using liquid extraction, and chromatographic separation was performed using a Phenomenex, Luna phenyl-hexyl column (50 × 2.0 mm, 5 µm). Electrospray ionization in positive-ion mode and multiple reaction monitoring were used to monitor ion transitions at m/z 561.3 → 257.1 (ensartinib) and 565.2 → 261.2 (internal standard: X-396-d4), respectively. The method yielded excellent linearity in the range of 0.5-500 ng/ml with the lowest quantification of 0.5 ng/ml. Both intra- and inter-run precisions (relative standard deviation %) were less than 15%, with accuracy (relative error %) between ±15%. Extraction recovery, matrix effect, selectivity, and stability were also validated and found to be satisfactory. Finally, the validated method was successfully applied in a phase I clinical study of ensartinib in Chinese subjects with advanced ALK-positive non-small-cell lung cancer.

The cause analysis of benign uretero-ileal anastomotic stricture after radical cystectomy and urinary diversion.

Background: Benign uretero-ileal anastomotic stricture (UIAS) is a major complication following radical cystectomy (RC) and ileal orthotopic bladder substitution, and it can occur in combination with other complications. But risk factors for patients with UIAS have not been well described. Material and methods: We retrospectively reviewed 198 patients treated with RC for bladder cancer from 2014 to 2019 at the Zhejiang Provincial People's Hospital. Patient demographic and clinical variables were examined to determine the risk factors associated with UIAS by univariate and multivariate logistic regression analysis. Results: A total of 180 patients into the group standards and in all 360 uretero-ileal anastomoses. Among the above cases, 22 patients developed UIAS, including 10 cases of left UIAS, nine cases of right UIAS, and three cases of bilateral UIAS. There was no difference in demographic, operative, or perioperative variables between patients with and without UIAS. In a multivariate analysis, after adjusting for gender, age, surgical methods, and underlying diseases, intraoperative or postoperative blood transfusion (HR = 0.144, P <0.01), postoperative urinary tract infection (HR = 3.624, P <0.01), and extracorporeal bladder anastomosis (HR = 3.395, P = 0.02) significantly increased the risk of UIAS. Conclusions: In our experience, intraoperative or postoperative blood transfusion, postoperative urinary tract infection, and extracorporeal neobladder anastomoses increased the risk of UIAS after radical cystectomy and ileal orthotopic bladder substitution surgery. Further studies with larger samples are necessary to validate this result.

Defining the impact of platelet-to-lymphocyte ratio on patient survival with gastric neuroendocrine neoplasm: a retrospective cohort analysis.

BACKGROUND: Gastric neuroendocrine neoplasm (g-NEN) is a rare but heterogeneous neoplasm, with an increasing incidence yearly. Conventional prognostic markers of g-NEN remain limited which could only be detected after surgery. There is an urgent need to explore new prognostic markers for g-NEN patients. This study aimed to investigate the prognostic value of platelet-to-lymphocyte, ratio (PLR) and the association between PLR and body mass index (BMI) in patients with gastric neuroendocrine neoplasms (g-NEN). METHODS: A retrospective cohort of patients with g-NEN from January 2001 through June 2016 was examined. The prognostic significance of PLR was determined by multiple regression analysis in different models. Stratified analysis was performed to examine the prognostic value of PLR at different BMI levels. RESULTS: In total, 238 patients were enrolled. Those with higher PLRs tended to undergo open surgery, had larger tumor sizes, were diagnosed more frequently with neuroendocrine carcinoma, and had higher tumor grades. PLR was significantly associated with the survival of patients with g-NEN. With PLR increased per standard deviation, the all-cause mortality risk of patients with g-NEN increased by 67%, 63%, and 54% in the crude (HR = 1.67, 95% CI 1.32-2.12, P < 0.001), minimally adjusted (HR = 1.63, 95% CI 1.28-2.08, P < 0.001), and fully adjusted (HR = 1.54, 95% CI 1.202-1.98, P = 0.001) models, respectively. Patients with higher PLR (quartile 4, ≥ 187) had a 1.8-fold increase in all-cause mortality risk compared with those with lower PLR (quartile 1-3, < 187). Furthermore, there was a significant interaction effect between BMI subgroups and PLR in predicting the survival of patients with g-NEN (PLR regarded as a continuous variable: all P for interaction < 0.05 in the crude, minimally adjusted, and fully adjusted models; PLR regarded as a categorical variable: P for interaction < 0.05 in the fully adjusted model). Patients with g-NEN with the characteristics of higher PLR (quartile 4, ≥ 187) and non-obesity (BMI < 25 kg/m2) had worse survival than others (P < 0.05). CONCLUSION: The inflammation marker PLR has an independent prognostic value for patients with g-NENs, and high PLR combined with non-obesity increases the mortality risk of these patients.

LASTR is a novel prognostic biomarker and predicts response to cancer immunotherapy in gastric cancer.

Gastric cancer (GC), a malignant tumor of digestive tract, is characterized by a high death rate. Thus, it is of particular importance to clarify the mechanisms of GC and gain new molecular targets for the sake of preventing and treating GC. It was reported that long non-coding RNAs (IncRNAs) are prognostic factors to cancer. Ferroptosis refers to a process of programmed cell death dependent on iron. This study sets out to investigate the expression and function of ferroptosis-related lncRNA (FRlncRNA) in GC. TCGA datasets offered RNA-seq data for 375 GC patients and clinical data for 443 GC patients. Based on Pearson's correlation analysis, we studied their expression and identified the FRlncRNAs. Differentially expressed prognosis related to FRlncRNA were determined with the help of the Wilcoxon test and univariate Cox regression analysis. To evaluate the accuracy of the prognostic capacity, researchers used the Kaplan-Meier technique, as well as univariate and multivariate Cox regression and receiver operating characteristic (ROC) curve studies. We also carried out the real-time PCR and CCK8 assays to examine the expression and function of FRlncRNA. In this study, we identified 50 ferroptosis-related DEGs which were involved in tumor progression. In addition, we identified 33 survival-related FRlncRNAs. Among them, lncRNA associated with SART3 regulation of splicing(LASTR) was confirmed to be highly expressed in GC specimens compared to non-tumor specimens in this cohort. Survival assays illuminated that the high LASTR expression predicted a shorter overall survival and progression-free survival of GC patients. Based on multivariate Cox regression analyses, it was confirmed that the GC had a worse chance of surviving the disease overall if their tumors expressed LASTR, which was an independent prognostic indication. Then, Loss-of-function tests showed that knocking down LASTR had a significant effect on reducing the proliferation of GC cells. Finally, we found that the expression of LASTR was negatively associated with CD8 T cells, T cells, Th17 cells, and T helper cells. Overall, our findings identified a novel survival-related FRlncRNA, LASTR which possibly can serve as a novel prognostic biomarker predicting response to cancer immunotherapy and therapeutic target for GC patients.

Complex q-rung orthopair fuzzy Frank aggregation operators and their application to multi-attribute decision making.

The complex q-rung orthopair fuzzy sets (Cq-ROFSs) can serve as a generalization of q-rung orthopair fuzzy sets (q-ROFSs) and complex fuzzy sets FS (CFSs). Cq-ROFSs provide more freedom for people handling uncertainty and vagueness by the truth and falsity grades on the condition that the sum of the q-powers of the real part and imaginary part is within the unit interval. Further, Frank operational laws are an extended form of Archimedes' T mode and Archimedes' S mode and Frank aggregation operators have a certain parameter which makes them more flexible and more generalized than many other aggregation operators in the process of information fusion. The objectives of this paper are to extend the Frank operations to the complex q-rung orthopair fuzzy environment and to introduce their score function and accuracy function. Meanwhile, some complex q-rung fuzzy Frank aggregation operators are developed, such as the complex q-rung orthopair fuzzy Frank weighted averaging (Cq-ROFFWA) operator, the complex q-rung orthopair fuzzy Frank weighted geometric (Cq-ROFFWG) operator, and the complex q-rung orthopair fuzzy Frank ordered weighted averaging (Cq-ROFFOWA) operator, and their special cases are discussed. In addition, an innovative MADM method is introduced according to the propounded operators to deal with multi-attribute decision-making problems under the complex q-rung orthopair fuzzy environment. Consequently, the practicability and effectiveness of the created methods are proposed by parameter exploration and comparative analysis.

Can a single-port robot be safely used for robotic total gastrectomy for advanced gastric cancer? First experience using the da Vinci SP platform.

Background: Many studies have shown the operative feasibility and safety of robotic gastrectomy. Surgeons are pursuing single-port (SP) surgery to leverage the advantages of minimally invasive gastrectomy. The purpose of this study was to describe technical considerations and short-term outcomes from the first reported SP robotic total gastrectomy (RTG) using the da Vinci SP platform. Methods: A 75-year-old patient with a body-mass index of 19.8 kg/m2 and clinical stage III cancer (cT3N+M0) underwent SP RTG on 22 January 2022 at the Department of General Surgery, the Chinese PLA General Hospital. All procedures were performed successfully using the da Vinci SP robotic platform. Results: The SP RTG was successfully performed with D2 lymphadenectomy including No. 10 lymph-nodes dissection and extracorporeal Roux-en-Y anastomosis. Except for subcutaneous emphysema, no severe adverse events occurred during the operation. According to a visual analogue scale (VAS), the subjective feeling of post-operative pain was given a VAS score of 3 of 10 on Post-Operative Day 1 (POD 1), 1 of 10 on POD 3, and 1 of 10 on POD 7. We removed the gastric tube on POD 2 and advised sipping water, a liquid diet, and a soft diet on PODs 2, 4, and 6, respectively. The patient was discharged without any complications on POD 8. Conclusion: RTG is technically feasible and safe using the da Vinci SP robotic platform. To our knowledge, this is the first study using the da Vinci SP platform in RTG for advanced gastric cancer in elderly patients. To verify its superior operative outcomes, further clinical trials are needed.

The prognosis of different distant metastases pattern in malignant tumors of the adrenal glands: A population-based retrospective study.

INTRODUCTION: The present existing data on the association of metastatic sites and prognosis of patients with metastatic adrenal malignancy are limited. This study aims to investigate the impact of different distant metastases pattern on the survival of patients with adrenal malignancy. METHODS: A dataset from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 18 Registries (2000-2017) was selected for a retrospective metastatic adrenal malignancy cohort study. There was information on distribution of metastatic lesions in bone, brain, liver, and lung in the SEER database. Kaplan-Meier analysis and nomogram analyses were applied to compare the survival distribution of cases. Univariate and multivariate cox regression models were used to analyze survival outcomes. RESULTS: From the SEER database, a total of 980 patients with primary metastatic adrenal malignancy from 2010 to 2017 were enrolled in this cohort study. Based on the initial metastatic sites, 42.3%, 38.4%, 30.5%, and 4.9% of patients were found bone, liver, lung, and brain metastasis, respectively. Patients who had a single site of distant metastases accounted for 52.6% (515/980) and had a better overall survival (OS) and cancer-specific survival (CSS) (both P < 0.001). In contrast with the tumor arising from the cortex, the tumor from the medulla showed better survival outcomes in both OS and CSS (P < 0.001). CONCLUSION: Different histological types possess various metastatic features and prognostic values. Understanding these differences may contribute to designing targeted pre-treatment assessment of primary metastatic adrenal malignancy and creating a personalized curative intervention.

The prognosis and clinicopathological features of different distant metastases patterns in renal cell carcinoma: analysis based on the SEER database.

Existing data on the prognosis and clinicopathological features of patients with metastatic renal cell carcinoma (mRCC) are limited. This study aims to investigate the prognostic value and clinicopathological features of different metastatic sites in patients with mRCC. A dataset from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database consisting of 18 registries (1973-2015) was selected for a retrospective mRCC cohort study. Information was included on the metastatic sites in lung, bone, liver, and brain. Kaplan-Meier analysis was applied to compare the survival distribution. Univariate and multivariate Cox regression models were used to analyze survival outcomes. From the SEER database, a total of 10,410 patients with primary mRCC from 2010 to 2015 were enrolled in this cohort study. Analysis indicated that 54.9%, 37.7%, 19.5%, and 10.4% of patients were found to have lung, bone, liver, and brain metastasis, respectively. There was a significantly higher risk for sarcomatoid RCC patients to develop liver metastasis as compared to patients with clear cell RCC. The median survival for patients with lung, bone, liver, or brain metastasis was 7 months, 7 months, 4 months, and 5 months, respectively. Various clinicopathological features and prognostic values are associated with different metastatic sites. Understanding these differences may enable targeted pre-treatment assessment of primary mRCC and personalized curative intervention for patients.

Proteomics provides individualized options of precision medicine for patients with gastric cancer.

While precision medicine driven by genome sequencing has revolutionized cancer care, such as lung cancer, its impact on gastric cancer (GC) has been minimal. GC patients are routinely treated with chemotherapy, but only a fraction of them receive the clinical benefit. There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy. Here, we carried out retrospective analyses of 1,020 formalin-fixed, paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC. We identified two proteomic subtypes: the chemo-sensitive group (CSG) and the chemo-insensitive group (CIG) in the discovery set. The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (64.2% vs. 49.6%; Cox P-value=0.002), whereas no such improvement was observed in CIG (50.0% vs. 58.6%; Cox P-value=0.495). We validated these results in an independent validation set. Further, differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC. A prospective study is warranted to test these findings for future GC patient care.

Could neoadjuvant chemotherapy increase postoperative complication risk of laparoscopic total gastrectomy? A mono-institutional propensity score-matched study in China.

BACKGROUND: The potential survival benefit of neoadjuvant chemotherapy (NC) in patients with advanced gastric cancer has been widely recognized. With the development of minimally invasive surgery, which is represented by laparoscopy, the effect of NC on the safety of laparoscopic gastrectomy remains to be further explored. AIM: To compare the short-term outcomes of laparoscopic total gastrectomy (LTG) after NC (NC-LTG) with LTG alone. METHODS: A total of 92 patients who underwent NC-LTG and 381 patients who received LTG alone at the Chinese PLA General Hospital between September 2015 and September 2020 were retrospectively included in our study. We used propensity-score matching (PSM) to balance baseline bias. After 1:1 PSM, 73 patients were included in each group with no statistically significant difference in baseline characteristics. RESULTS: The NC-LTG group exhibited a longer operation time (244.10 ± 48.13 min vs 225.74 ± 45.33 min, P = 0.019) and increased intraoperative blood loss [150 (100-300) mL vs 100 (100-200) mL, P = 0.011] compared to the LTG group. The 30-d postoperative morbidity of the NC-LTG group was 20.5% (15/73), and that of the LTG group was 13.7% (10/73). There were no significant differences in 30-d severe complication rates or anastomotic leakage rates. Subgroup analysis showed that the patients with pTNM (pathological tumor-node-metastasis classification) T0N0-II in the NC-LTG group underwent a longer operation than the LTG group, while no significant difference was found in any perioperative index for the pTNM III patients. A multivariate analysis showed that an operation time longer than 240 min was an independent risk factor (odds ratio = 3.021, 95% confidence interval: 1.160-7.868, P = 0.024), while NC was not an independent risk factor for postoperative complications in LTG. CONCLUSION: Despite a longer operation time and more blood loss after NC-LTG, which indicate surgical difficulty, NC-LTG exhibits acceptable short-term outcomes compared to LTG, suggesting the safety and feasibility of NC-LTG.