Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy

Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.

Improving the utility of locally differentially private protocols for longitudinal and multidimensional frequency estimates

This paper investigates the problem of collecting multidimensional data throughout time(i.e.,longitudinal studies)for the fundamental task of frequency estimation under Local Differential Privacy(LDP)guarantees.Contrary to frequency estimation of a single attribute,the multidimensional aspect demands particular attention to the privacy budget.Besides,when collecting user statistics longitudinally,privacy progressively degrades.Indeed,the“multiple”settings in combination(i.e.,many attributes and several collections throughout time)impose several challenges,for which this paper proposes the first solution for frequency estimates under LDP.To tackle these issues,we extend the analysis of three state-of-the-art LDP protocols(Generalized Randomized Response–GRR,Optimized Unary Encoding–OUE,and Symmetric Unary Encoding–SUE)for both longitudinal and multidimensional data collections.While the known literature uses OUE and SUE for two rounds of sanitization(a.k.a.memoization),i.e.,L-OUE and L-SUE,respectively,we analytically and experimentally show that starting with OUE and then with SUE provides higher data utility(i.e.,L-OSUE).Also,for attributes with small domain sizes,we propose Longitudinal GRR(L-GRR),which provides higher utility than the other protocols based on unary encoding.Last,we also propose a new solution named Adaptive LDP for LOngitudinal and Multidimensional FREquency Estimates(ALLOMFREE),which randomly samples a single attribute to be sent with the whole privacy budget and adaptively selects the optimal protocol,i.e.,either L-GRR or L-OSUE.As shown in the results,ALLOMFREE consistently and considerably outperforms the state-of-the-art L-SUE and L-OUE protocols in the quality of the frequency estimates.

Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma:A population-based study

BACKGROUND Gastric signet ring cell carcinoma(GSRC)represents a specific subtype of gastric cancer renowned for its contentious epidemiological features,treatment principles,and prognostic factors.AIM To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC(LAGSRC)after surgery.METHODS The annual rates of GSRC incidence and mortality,covering the years 1975 to 2019,were extracted from the Surveillance,Epidemiology,and End Results(SEER)database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software.The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates.The Cox regression model was used to explore the independent prognostic factors for overall survival(OS).The risk factors extracted were used to establish a prognostic nomogram.RESULTS The overall incidence of GSRC increased dramatically between 1975 and 1998,followed by a significant downward trend in incidence after 1998.In recent years,there has been a similarly optimistic trend in GSRC mortality rates.The trend in GSRC showed discrepancies based on age and sex.Receiver operating characteristic curves,calibration curves,and decision curve analysis for 1-year,3-year,and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram.The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system.CONCLUSION The model we established can aid clinicians in the early prognostication of LAGSRC patients,resulting in improved clinical outcomes by modifying management strategies and patient health care.

Prediction of pathological complete response and prognosis in locally advanced rectal cancer

BACKGROUND Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide.Neoadjuvant chemoradiotherapy(nCRT)is standard for locally advanced rectal cancer(LARC).Except for pathological examination after resection,it is not known exactly whether LARC patients have achieved pathological complete response(pCR)before surgery.To date,there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes.AIM To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC.METHODS Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed.Patients were categorized into pCR and non-pCR groups.Univariate analysis(using the χ^(2) test or Fisher’s exact test)and logistic multivariate regression analysis were used to study clinical predictors affecting pCR.The 5-year disease-free survival(DFS)and overall survival(OS)rates were calculated using Kaplan-Meier analysis,and differences in survival curves were assessed with the log-rank test.RESULTS Univariate analysis showed that pretreatment carcinoembryonic antigen(CEA)level,lymphocyte-monocyte ratio(LMR),time interval between neoadjuvant therapy completion and total mesorectal excision,and tumor size were correlated with pCR.Multivariate results showed that CEA≤5 ng/mL(P=0.039),LMR>2.73(P=0.023),and time interval>10 wk(P=0.039)were independent predictors for pCR.Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates(94.7%vs 59.7%,P=0.002)and 5-year OS rates(95.8%vs 80.1%,P=0.019)compared to the non-pCR group.Tumor deposits(TDs)were significantly correlated with shorter DFS(P=0.002)and OS(P<0.001).CONCLUSION Pretreatment CEA,LMR,and time interval contribute to predicting nCRT efficacy in LARC patients.Achieving pCR demonstrates longer DFS and OS.TDs correlate with poor prognosis.

Programmed cell death 1 inhibitor sintilimab plus concurrent chemoradiotherapy for locally advanced pancreatic adenocarcinoma

BACKGROUND Pancreatic adenocarcinoma,a malignancy that arises in the cells of the pancreas,is a devastating disease with unclear etiology and often poor prognosis.Locally advanced pancreatic cancer,a stage where the tumor has grown significantly but has not yet spread to distant organs,presents unique challenges in treatment.This article aims to discuss the current strategies,challenges,and future directions in the management of locally advanced pancreatic adenocarcinoma(LAPC).AIM To investigate the feasibility and efficacy of programmed cell death 1(PD-1)inhibitor sintilimab plus concurrent chemoradiotherapy for LAPC.METHODS Eligible patients had LAPC,an Eastern cooperative oncology group performance status of 0 or 1,adequate organ and marrow functions,and no prior anticancer therapy.In the observation group,participants received intravenous sintilimab 200 mg once every 3 wk,and received concurrent chemoradiotherapy(concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-140 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression,death,or unacceptable toxicity).In the control group,participants only received concurrent chemoradiotherapy.From April 2020 to November 2021,64 participants were finally enrolled with 34 in the observation group and 30 in the control group.RESULTS Thirty-four patients completed the scheduled course of chemoradiotherapy,while 32(94.1%)received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation group.Thirty patients completed the scheduled course of chemoradiotherapy in the control group.Based on the Response Evaluation Criteria in Solid Tumors guidelines,the analysis of the observation group revealed that a partial response was observed in 11 patients(32.4%),stable disease was evident in 19 patients(55.9%),and 4 patients(11.8%)experienced progressive disease;a partial response was observed in 6(20.0%)patients,stable disease in 18(60%),and progressive disease in 6(20%)in the control group.The major toxic effects were leukopenia and nausea.The incidence of severe adverse events(AEs)(grade 3 or 4)was 26.5%(9/34)in the observation group and 23.3%(7/30)in the control group.There were no treatment-related deaths.The observation group demonstrated a significantly longer median overall survival(22.1 mo compared to 15.8 mo)(P<0.05)and progression-free survival(12.2 mo vs 10.1 mo)(P<0.05)in comparison to the control group.The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group(P>0.05).CONCLUSION Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients,and warrants further investigation.

Minimally invasive pelvic exenteration for primary or recurrent locally advanced rectal cancer:A glimpse into the future

Surgeons have grappled with the treatment of recurrent and T4b locally advanced rectal cancer(LARC)for many years.Their main objectives are to increase the overall survival and quality of life of the patients and to mitigate postoperative complications.Currently,pelvic exenteration(PE)with or without neoadjuvant treatment is a curative treatment when negative resection margins are achieved.The traditional open approach has been favored by many surgeons.However,the technological advancements in minimally invasive surgery have radically changed the surgical options.Recent studies have demonstrated promising results in postoperative complications and oncological outcomes after robotic or laparoscopic PE.A recent retrospective study entitled“Feasibility and safety of minimally invasive multivisceral resection for T4b rectal cancer:A 9-year review”was published in the World Journal of Gastrointestinal Surgery.As we read this article with great interest,we decided to delve into the latest data regarding the benefits and risks of minimally invasive PE for LARC.Currently,the small number of suitable patients,limited surgeon experience,and steep learning curve are hindering the establishment of minimally invasive PE.

Evaluation of oxaliplatin and tigio combination therapy in locally advanced gastric cancer

BACKGROUND Locally advanced gastric cancer(LAGC)is a common malignant tumor.In recent years,neoadjuvant chemotherapy has gradually become popular for the treatment of LAGC.AIM To investigate the efficacy of oxaliplatin combined with a tigio neoadjuvant chemotherapy regimen vs a conventional chemotherapy regimen for LAGC.METHODS Ninety patients with LAGC were selected and randomly divided into control and study groups with 45 patients in each group,according to the numerical table method.The control group was treated with conventional chemotherapy,and the study group was treated with oxaliplatin combined with tigio-neoadjuvant che-motherapy.The primary outcome measures were the clinical objective response rate(ORR)and surgical resection rate(SRR),whereas the secondary outcome measures were safety and Karnofsky Performance Status score.RESULTS The ORR in the study group was 80.00%,which was significantly higher than that of the control group(57.78%).In the study group,SRR was 75.56%,which was significantly higher than that of the control group(57.78%).There were 15.56%adverse reactions in the study group and 35.56%in the control group.These differences were statistically significant between the two groups.CONCLUSION The combination of oxaliplatin and tigio before surgery as neoadjuvant chemotherapy for patients with LAGC can effectively improve the ORR and SRR and is safe.

Efficacy evaluation and survival analysis of the combination of oxaliplatin plus Teysuno (SOX) with immune checkpoint inhibitors in the conversion therapy of locally advanced gastric cancer

Background:The efficacy of combining immune checkpoint inhibitors(ICIs)with chemotherapy in neoadjuvant therapy for locally advanced gastric cancer has been explored.However,limited research exists on its effectiveness in conversion therapy,and its superiority over standalone chemotherapy remains to be elucidated.This study aims to investigate the efficacy and survival outcomes of patients treated with ICIs in combination with conversion therapy for locally advanced gastric cancer.Methods:Retrospective data from patients with locally advanced gastric cancer treated with either oxaliplatin+S-1(SOX)alone or in combination with ICIs in conversion therapywere collected.Clinical andpathological characteristics,disease-free survival,andefficacy assessments in nonoperable patients were compared between the 2 treatment groups.Efficacy was further evaluated through dynamic changes in serum markers,and patients’quality of life was assessed using the QLQ-STO22(Gastric Cancer–Specific Quality of Life Questionnaire)quality-of-life measurement scale.Results:A total of 140 patients underwent conversion therapy:80 in the SOX alone group and 60 in the SOX combined with the ICIs group.There were no significant differences in baseline characteristics between the 2 groups.Compared with the SOX alone group,the SOX combined with ICIs group exhibited a higher conversion rate(83.3%vs 75%,P=0.23),R0 resection rate(90.0%vs 83.3%,P=0.31),pathological complete response(pCR)rate(18%vs 5%,P=0.02),median disease-free survival(21.4 vs 16.9 months,P=0.007),the objective response rate in nonoperable patients(60%vs 40%,P=0.301),and median progression-free survival time(7.9 vs 5.7 months,P=0.009).The QLQ-STO22 quality-of-life assessment revealed statistically significant improvements in pain,swallowing difficulties,and dietary restrictions in the combination therapy group compared with those in the monotherapy group.The enhanced efficacy of immune combination with SOX is evident,as demonstrated by the significantly prolonged surgical duration in operated patients(206.6±26.6 min vs 197.8±19.8 min,P=0.35)and intraoperative blood loss(158.9±21.2 mL vs 148.9±25.1 mL,P=0.59).No significant differences were observed in postoperative complications.Conclusions:Compared with the SOX conversion therapy regimen,SOX combined with ICIs demonstrated higher conversion rates,R0 resection rates,pathological response rates,and disease-free survival without increasing surgical difficulty or complications.Nonoperable patients also experienced longer progression-free survival and objective response rates.

Current Status and Research Progress of Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer

Gastric cancer is one of the most common malignant tumours worldwide, with a high degree of malignancy and a poor prognosis. While early gastric cancer can be cured by surgical treatment, locally advanced gastric cancer requires neoadjuvant therapy to shrink the tumour, suppress potential metastases, achieve down-staging, and provide patients with the opportunity for radical surgery to prolong their survival. This article reviews the current status and progress of neoadjuvant chemotherapy for locally advanced gastric cancer.

Clinical implication of naive and memory T cells in locally advanced cervical cancer:A proxy for tumor biology and short-term response prediction

Background:This study was designed to investigate the feasibility of tumor-infiltrating immune cells with different phenotypic characteristics for predicting short-term clinical responses in patients with locally advanced cervical cancer(LACC).Methods:Thirty-four patients who received concurrent chemoradiotherapy and twenty-one patients who merely underwent radiotherapy were enrolled in this study.We retrospectively analyzed the T cell markers(i.e.,CD3,CD4,CD8),memory markers(i.e.,CD45,CCR7),and differentiation markers(i.e.,CD27)in the peripheral blood and tumor tissues of patients with LACC before treatment based on flow cytometry.We also analyzed the relationship of T cell subsets between peripheral blood and tumor tissues,and their correlation with complete response or partial response.Results:The percentage of central memory CD8^(+)TCM(CD8^(+)CD45RA^(−)CD27^(+)CCR7^(+))cells in LACC patients was significantly lower than that of the control group.The percentage of CD8^(+)TN in the peripheral blood of LACC patients was significantly higher than that of tumor tissues.CD8^(+)TEM in the peripheral blood was significantly lower than that of tumor tissues.The percentage of CD8^(+)TN and CD8^(+)TCM in human papillomavirus(HPV)positive samples was significantly higher than that of HPV-negative samples.Similarly,the percentage of CD8^(+)TCM in tumor tissues was significantly higher in cancer tissue samples with lymph nodes compared with those without.Conclusion:A higher proportion of CD4^(+)TCM and a lower proportion of CD8^(+)TN in the tumor microenvironment of LACC may contribute to the therapy response prediction.

Advances in translational therapy for locally advanced gastric cancer

Translational therapy refers to a combination of chemotherapy,radiotherapy,targeted therapy,and immunotherapy for patients with advanced gastric cancer who are initially unable to undergo R0 resection.This treatment can achieve partial or complete remission of the unresectable tumors to meet the criteria for R0 resection,thus enabling the patients to prolong their survival time and improve their quality of life.In gastric cancer,translational therapy has been tried and improved.At present,there are a large number of patients with locally advanced gastric cancer in China,and the selection of suitable patients for transla-tional therapy to prolong objective survival and improve survival quality is one of the hot spots in the field of gastric cancer research.

Developments and challenges in neoadjuvant therapy for locally advanced pancreatic cancer

Pancreatic ductal adenocarcinoma(PDAC)remains a significant public health challenge and is currently the fourth leading cause of cancer-related mortality in developed countries.Despite advances in cancer treatment,the 5-year survival rate for patients with PDAC remains less than 5%.In recent years,neoadjuvant therapy(NAT)has emerged as a promising treatment option for many cancer types,including locally advanced PDAC,with the potential to improve patient outcomes.To analyze the role of NAT in the setting of locally advanced PDAC over the past decade,a systematic literature search was conducted using PubMed and Web of Science.The results suggest that NAT may reduce the local mass size,promote tumor downstaging,and increase the likelihood of resection.These findings are supported by the latest evidence-based medical literature and the clinical experience of our center.Despite the potential benefits of NAT,there are still challenges that need to be addressed.One such challenge is the lack of consensus on the optimal timing and duration of NAT.Improved criteria for patient selection are needed to further identify PDAC patients likely to respond to NAT.In conclusion,NAT has emerged as a promising treatment option for locally advanced PDAC.However,further research is needed to optimize its use and to better understand the role of NAT in the management of this challenging disease.With continued advances in cancer treatment,there is hope of improving the outcomes of patients with PDAC in the future.

Genome-wide investigation to assess copy number variants in the Italian local chicken population

Background Copy number variants(CNV)hold significant functional and evolutionary importance.Numerous ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure of livestock.High-density chips have enabled the detection of CNV with increased resolution,leading to the identification of even small CNV.This study aimed to identify CNV in local Italian chicken breeds and investigate their distribution across the genome.Results Copy number variants were mainly distributed across the first six chromosomes and primarily associated with loss type CNV.The majority of CNV in the investigated breeds were of types 0 and 1,and the minimum length of CNV was significantly larger than that reported in previous studies.Interestingly,a high proportion of the length of chromosome 16 was covered by copy number variation regions(CNVR),with the major histocompatibility complex being the likely cause.Among the genes identified within CNVR,only those present in at least five animals across breeds(n=95)were discussed to reduce the focus on redundant CNV.Some of these genes have been associated to functional traits in chickens.Notably,several CNVR on different chromosomes harbor genes related to muscle development,tissue-specific biological processes,heat stress resistance,and immune response.Quantitative trait loci(QTL)were also analyzed to investigate potential overlapping with the identified CNVR:54 out of the 95 gene-containing regions overlapped with 428 QTL associated to body weight and size,carcass characteristics,egg production,egg components,fat deposition,and feed intake.Conclusions The genomic phenomena reported in this study that can cause changes in the distribution of CNV within the genome over time and the comparison of these differences in CNVR of the local chicken breeds could help in preserving these genetic resources.

Deep brain implantable microelectrode arrays for detection and functional localization of the subthalamic nucleus in rats with Parkinson’s disease

The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.

Synchronization coexistence in a Rulkov neural network based on locally active discrete memristor

At present, many neuron models have been proposed, which can be divided into discrete neuron models and continuous neuron models. Discrete neuron models have the advantage of faster simulation speed and the ease of understanding complex dynamic phenomena. Due to the properties of memorability, nonvolatility, and local activity, locally active discrete memristors(LADMs) are also suitable for simulating synapses. In this paper, we use an LADM to mimic synapses and establish a Rulkov neural network model. It is found that the change of coupling strength and the initial state of the LADM leads to multiple firing patterns of the neural network. In addition, considering the influence of neural network parameters and the initial state of the LADM, numerical analysis methods such as phase diagram and timing diagram are used to study the phase synchronization. As the system parameters and the initial states of the LADM change, the LADM coupled Rulkov neural network exhibits synchronization transition and synchronization coexistence.

Dynamical analysis,geometric control and digital hardware implementation of a complex-valued laser system with a locally active memristor

In order to make the peak and offset of the signal meet the requirements of artificial equipment,dynamical analysis and geometric control of the laser system have become indispensable.In this paper,a locally active memristor with non-volatile memory is introduced into a complex-valued Lorenz laser system.By using numerical measures,complex dynamical behaviors of the memristive laser system are uncovered.It appears the alternating appearance of quasi-periodic and chaotic oscillations.The mechanism of transformation from a quasi-periodic pattern to a chaotic one is revealed from the perspective of Hamilton energy.Interestingly,initial-values-oriented extreme multi-stability patterns are found,where the coexisting attractors have the same Lyapunov exponents.In addition,the introduction of a memristor greatly improves the complexity of the laser system.Moreover,to control the amplitude and offset of the chaotic signal,two kinds of geometric control methods including amplitude control and rotation control are designed.The results show that these two geometric control methods have revised the size and position of the chaotic signal without changing the chaotic dynamics.Finally,a digital hardware device is developed and the experiment outputs agree fairly well with those of the numerical simulations.

Chemotherapy-free radiotherapy combined with immune checkpoint inhibitors:a new regimen for locally advanced non-small cell lung cancer?

Maintenance immunotherapy after concurrent chemoradiotherapy remains the standard therapeutic approach in patients with unresectable locally advanced non-small cell lung cancer(LA-NSCLC).The efficacy of pembrolizumab without chemotherapy in stage IV NSCLC has incited interest in similar approaches for LA-NSCLC.Several recent investigations involving the synergistic potential of immunotherapy combined with radiotherapy(i RT)have generated encouraging results.This review discusses the existing studies and prospective directions of chemotherapy-free i RT strategies in unresectable LA-NSCLC.Although the initial findings of chemotherapy-free i RT strategies have shown promising efficacy,we must consider the methodologic limitations of current studies and the myriad of challenges that accompany the implementation of chemotherapy-free i RT.These challenges include determining the optimal dose and fractionation,precise target volume delineation,and identification of additional suitable patient cohorts.Furthermore,the feasibility of chemotherapy-free i RT as a novel treatment modality for select patients with LA-NSCLC is contingent upon validation through randomized phase III trials.

Comparison between upfront surgery and neoadjuvant chemotherapy in patients with locally advanced gastric cancer:A systematic review

BACKGROUND Gastric cancer(GC)is a major health concern worldwide.Surgical resection and chemotherapy is the mainstay treatment for gastric carcinoma,however,the optimal approach remains unclear and should be different in each individual.Chemotherapy can be administered both pre-and postoperatively,but a multidisciplinary approach is preferred when possible.This is particularly relevant for locally advanced GC(LAGC),as neoadjuvant chemotherapy(NAT)could potentially lead to tumor downsizing thus allowing for a complete resection with curative intent.Even though the recent progress has been impressive,European and International guidelines are still controversial,thus attenuating the need for a more standardized approach in the management of locally advanced cancer.AIM To investigate the effects of NAT on the overall survival(OS),the disease-free survival(DFS),the morbidity and the mortality of patients with LAGC in comparison to upfront surgery(US).METHODS For this systematic review,a literature search was conducted between November and February 2023 in PubMed,Cochrane Library and clinicaltrials.gov for studies including patients with LAGC.Two independent reviewers conducted the research and extracted the data according to predetermined inclusion and exclusion criteria.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to form the search strategy and the study protocol has been registered in the International Prospective Register of Systematic Reviews.RESULTS Eighteen studies with 4839 patients with LAGC in total were included in our systematic review.Patients were separated into two groups;one receiving NAT before the gastrectomy(NAT group)and the other undergoing upfront surgery(US group).The OS ranged from 41.6%to 74.2%in the NAT group and from 30.9%to 74%in the US group.The DFS was also longer in the NAT group and reached up to 80%in certain patients.The complications related to the chemotherapy or the surgery ranged from 6.4%to 38.1%in the NAT group and from 5%to 40.5%in the US group.Even though in most of the studies the morbidity was lower in the NAT group,a general conclusion could not be drawn as it seems to depend on multiple factors.Finally,regarding the mortality,the reported rate was higher and up to 5.3%in the US group.CONCLUSION NAT could be beneficial for patients with LAGC as it leads to better OS and DFS than the US approach with the same or even lower complication rates.However,patients with different clinicopathological features respond differently to chemotherapy,therefore currently the treatment plan should be individualized in order to achieve optimal results.

Efficacy and safety of laparoscopic vs open gastrectomy after neoadjuvant therapy for locally advanced gastric cancer

BACKGROUND Laparoscopic gastrectomy(LG)is widely accepted as a minimally invasive approach for the treatment of early gastric cancer.However,its role in locally advanced gastric cancer(LAGC)after neoadjuvant therapy(NAT)remains controversial.This study aimed to compare the efficacy and safety of LG vs open gastrectomy(OG)after NAT for the treatment of LAGC.AIM To compare the efficacy and safety of LG vs OG after NAT for LAGC.METHODS We conducted a prospective study of 76 patients with LAGC who underwent NAT followed by LG(n=38)or OG(n=38)between 2021 and 2023.The primary endpoint was overall survival(OS),and the secondary endpoints were diseasefree survival(DFS),surgical complications,and quality of life(QOL).RESULTS The two groups had comparable baseline characteristics,with a median follow-up period of 24 mo.The 3-year OS rates in the LG and OG groups were 68.4%and 60.5%,respectively(P=0.42).The 3-year DFS rates in the LG and OG groups were 57.9%and 50.0%,respectively(P=0.51).The LG group had significantly less blood loss(P<0.001),a shorter hospital stay(P<0.001),and a lower incidence of surgical site infection(P=0.04)than the OG group.There were no significant differences in other surgical complications between the groups,including anastomotic leakage,intra-abdominal abscess,or wound dehiscence.The LG group had significantly better QOL scores than the OG group regarding physical functioning,role functioning,global health status,fatigue,pain,appetite loss,and body image at 6 months postoperatively(P<0.05).CONCLUSION LG after NAT is a viable and safe alternative to OG for the treatment of LAGC,with similar survival outcomes and superior short-term recovery and QOL.LG patients had less blood loss,shorter hospitalizations,and a lower incidence of surgical site infections than OG patients.Moreover,the LG group had better QOL scores in multiple domains 6 mo postoperatively.Therefore,LG should be considered a valid option for patients with LAGC who undergo NAT,particularly for those who prioritize postoperative recovery and QOL.

Assessment of earthquake location uncertainties for the design of local seismic networks

The ability to estimate earthquake source locations,along with the appraisal of relevant uncertainties,is paramount in monitoring both natural and human-induced micro-seismicity.For this purpose,a monitoring network must be designed to minimize the location errors introduced by geometrically unbalanced networks.In this study,we first review different sources of errors relevant to the localization of seismic events,how they propagate through localization algorithms,and their impact on outcomes.We then propose a quantitative method,based on a Monte Carlo approach,to estimate the uncertainty in earthquake locations that is suited to the design,optimization,and assessment of the performance of a local seismic monitoring network.To illustrate the performance of the proposed approach,we analyzed the distribution of the localization uncertainties and their related dispersion for a highly dense grid of theoretical hypocenters in both the horizontal and vertical directions using an actual monitoring network layout.The results expand,quantitatively,the qualitative indications derived from purely geometrical parameters(azimuthal gap(AG))and classical detectability maps.The proposed method enables the systematic design,optimization,and evaluation of local seismic monitoring networks,enhancing monitoring accuracy in areas proximal to hydrocarbon production,geothermal fields,underground natural gas storage,and other subsurface activities.This approach aids in the accurate estimation of earthquake source locations and their associated uncertainties,which are crucial for assessing and mitigating seismic risks,thereby enabling the implementation of proactive measures to minimize potential hazards.From an operational perspective,reliably estimating location accuracy is crucial for evaluating the position of seismogenic sources and assessing possible links between well activities and the onset of seismicity.