Goal-directed therapy in intraoperative fluid and hemodynamic management

Intraoperative fluid management is pivotal to the outcome and success of surgery, especially in high-risk proce- dures. Empirical formula and invasive static monitoring have been traditionally used to guide intraoperative fluid management and assess volume status. With the awareness of the potential complications of invasive procedures and the poor reliability of these methods as indicators of volume status, we present a case scenario of a patient who underwent major abdominal surgery as an example to discuss how the use of minimally invasive dynamic monitoring may guide intraoperative fluid therapy.

Use of Early Goal-Directed Therapy in the Emergency Department before and after the Sepsis Trilogy

The management of sepsis evolved recently with the publication of three large trials (referred to as the sepsis trilogy) investigating the efficacy of early goal-directed therapy (EGDT). Our goal was to determine if the publication of these trials has influenced the use of EGDT when caring for patients with severe sepsis and septic shock in the emergency department (ED). In February 2014, we surveyed a sample of board-certified emergency medicine physicians regarding their use of EGDT in the ED. A follow-up survey was sent after the publication of the sepsis trilogy. Data was analyzed using 95% confidence intervals to determine if there was a change in the use of EGDT following the publication of the above trials. Subgroup analyses were also performed with regard to academic affiliation and emergency department volume. Surveys were sent to 308 and 350 physicians in the pre-and post-publication periods, respectively. Overall, ED use of EGDT did not change with publication of the sepsis trilogy, 48.7% (CI 39.3% - 58.2%) before and 50.5% (CI 40.6% - 60.3%) after. Subgroup analysis revealed that academic-affiliated EDs significantly decreased EGDT use following the sepsis trilogy while nonacademic departments significantly increased EGDT use. Use of EGDT was significantly greater in community departments versus academic departments following the publication of the sepsis trilogy. There was no change overall in the use of EGDT protocols when caring for patients with severe sepsis and septic shock, but subgroup analyses revealed that academic departments decreased their use of EGDT while community departments increased use of EGDT. This may be due to varying rates of uptake of the medical literature between academic and community healthcare systems.

Simplified Intraoperative Goal-Directed Therapy Using the FloTrac/Vigileo System: An Analysis of Its Usefulness and Safety

Purpose: We investigated whether the simplified intraoperative Goal-Directed Therapy (GDT) could improve the factors affecting medical costs, and contribute in standardizing intraoperative fluid management. Methods: The enrolled patients underwent esophagectomy, pancreatoduodenectomy, or aortic stent grafting in 2012, and between March 2013 and October 2014. We conducted a comparison study on the effects of GDT, between the before-GDT historical control group (n = 100) and GDT group (n = 100). The hemodynamic indices used for control group patients were conventional: Blood pressure, heart rate, and urine output. For GDT group, additionally, we used stroke volume variation (SVV) and stroke volume index (SVI). The primary outcomes were the length of intensive care unit (ICU) stay and hospital stay (LOS). Regression analysis was used to identify factors affecting LOS. The secondary outcomes were the albumin use, the fluid amount administered, and the variation in the fluid administration rate. Results: The control and GDT groups comprised 96 and 99 patients, respectively. The patient characteristics were similar. The length of ICU stay was significantly shorter (2.1 ± 2.1 days vs. 2.8 ± 1.9 days, P = 0.0009) and LOS was shorter but without statistical significance (24.5 ± 17.7 days vs. 27.7 ± 20.1 days, P = 0.21) in the GDT group than in the control group. The fluid amount administered and the presence/ absence of albumin use were factors affecting LOS. The variation of the fluid administration rate was significantly lower in the GDT group. Conclusion: The simplified GDT may contribute to the improvement of medical economics and standardize the fluid management.

The effect of intraoperative goal-directed fluid therapy in patients under anesthesia for gastrointestinal surgery

BACKGROUND Intraoperative fluid management is an important aspect of anesthesia mana-gement in gastrointestinal surgery.Intraoperative goal-directed fluid therapy(GDFT)is a method for optimizing a patient's physiological state by monitoring and regulating fluid input in real-time.AIM To evaluate the efficacy of intraoperative GDFT in patients under anesthesia for gastrointestinal surgery.METHODS This study utilized a retrospective comparative study design and included 60 patients who underwent gastrointestinal surgery at a hospital.The experimental group(GDFT group)and the control group,each comprising 30 patients,received intraoperative GDFT and traditional fluid management strategies,respectively.The effect of GDFT was evaluated by comparing postoperative recovery,com-plication rates,hospitalization time,and other indicators between the two patient groups.RESULTS Intraoperative blood loss in the experimental and control groups was 296.64±46.71 mL and 470.05±73.26 mL(P<0.001),and urine volume was 415.13±96.72 mL and 239.15±94.69 mL(P<0.001),respectively.The postoperative recovery time was 5.44±1.1 days for the experimental group compared to 7.59±1.45 days(P<0.001)for the control group.Hospitalization time for the experimental group was 10.87±2.36 days vs 13.65±3 days for the control group(P<0.001).The visual analogue scale scores of the experimental and control groups at 24 h and 48 h INTRODUCTION Gastrointestinal surgery is one of the most common procedures in the field of general surgery[1],involving the stomach,intestines,liver,pancreas,spleen,and other internal abdominal organs[2,3].With advancements in surgical technology and anesthesia methods,the safety and success rates of surgery have significantly improved[4,5].However,intraop-erative fluid management remains a critical challenge[6].Traditional fluid management strategies often rely on experience and basic physiological parameters,which may lead to excessive or insufficient fluid input,thereby affecting postoperative recovery and complication rates.Intraoperative goal-directed fluid therapy(GDFT)is an emerging fluid management strategy that dynamically adjusts fluid input volume by monitoring the patient's hemodynamic parameters in real-time to optimize the patient's physiological state[7,8].GDFT has shown superiority in many surgical fields;however,its application in gastrointestinal surgery requires further research and verification[9,10].The application of intraoperative GDFT in clinical settings has gradually increased in recent years[11,12].Studies have demonstrated that GDFT can optimize tissue perfusion and oxygenation by precisely controlling fluid input and reducing the occurrence of postoperative complications[13,14].For example,in cardiac and major vascular surgeries,GDFT significantly reduced the incidence of postoperative acute kidney injury and cardiovascular events[15,16].Similarly,in abdominal surgery,GDFT effectively reduced postoperative infections and expedited recovery[17].However,studies on the utilization of GDFT in gastrointestinal surgery are relatively limited and they are confounded by contradictory findings[18].Traditional fluid management strategies typically rely on estimating fluid input volume based on the patient's weight,preoperative status,and basic physiological parameters[19].However,this method lacks real-time dynamic adjustment,which may result in either insufficient or excessive fluid input,consequently affecting postoperative recovery.Insufficient fluid input can lead to hypovolemia and inadequate tissue perfusion,whereas excessive fluid input can cause tissue edema and postoperative complications,such as pulmonary edema and heart failure.GDFT involves dynamically adjusting fluid input volume by monitoring the patient's hemodynamic parameters in real-time,such as cardiac output,pulse pressure variability,and central venous pressure.Commonly used monitoring equipment include esophageal Doppler and pulse wave profile analyzers[20].These devices provide real-time hemo-dynamic data to assist anesthesiologists in tailoring fluid therapy to a patient's specific condition.Firstly,the patient's volume responsiveness is assessed by preloading fluid;secondly,fluid input volume is dynamically adjusted based on real-time monitoring data;finally,vasoactive and inotropic drugs are administered in combination to further optimize the patient’s hemodynamic status.Through personalized fluid management,GDFT can more accurately maintain intraop-erative hemodynamic stability and reduce complications[21].Gastrointestinal surgery involves procedures on multiple organs,often requiring prolonged operative times and extensive tissue trauma,which presents challenges for intraop-erative fluid management.Surgical procedures can lead to significant bleeding and fluid loss,requiring prompt and effective fluid replenishment.In addition,the slow recovery of gastrointestinal function after surgery and susceptibility to complications such as intestinal obstruction and delayed gastric emptying elevate the necessity for postoperative fluid management.

Hepatic Perfusion Alterations in Septic Shock Patients： Impact of Early Goal-directed Therapy

Background： Early goal-directed therapy （EGDT） has become an important therapeutic management in early salvage stage of septic shock. However, splenic organs possibly remained hypoperfused and hypoxic despite fluid resuscitation. This study aimed to evaluate the effect of EGDT on hepatic perfusion in septic shock patients. Methods： A prospective observational study was carried out in early septic shock patients who were admitted to Intensive Care Unit within 24 h after onset and who met all four elements of the EGDT criteria after treatment with the standard EGDT procedure within 6 h between December 1, 2012 and November 30, 2013. The hemodynamic data were recorded, and oxygen metabolism and hepatic functions were monitored. An indocyanine green clearance test was applied to detect the hepatic perfusion. The patients＇ characteristics were compared before treatment （TO）, immediately after EGDT （T 1 ）, and 24 h after EGDT （T2）. This study is registered at ClinicalTrials.org, NCT02060773. Results： Twenty-one patients were included in the study; however, the hepatic perfusion data were not included in the analysis for two patients： therefore, 19 patients were eligible for the study. Hemodynamics data, as monitored by pulse-indicator continuous cardiac output, were obtained from 16 patients. There were no significant differences in indocyanine green plasma disappearance rate （ICG-PDR） and 15-min retention rate （Rl 5） at TO （ 11.9 ±5.0%/min and 20.0 ±13.2%）, T1 （ 11.4 ± 5.1%/min and 23.6 ± 14.9%）, and T2 （ 11.0 ±4.5%/rain and 23.7 ± 15.3%） （all P 〉 0.05）. Both of the alterations of ICG-PDR and R l 5 showed no differences at TO, T1, and T2 in the patients of different subgroups that achieved different resuscitation goal numbers when elected （P 〉 0.05）.

Intraoperative Goal-Directed Therapies in Femoral and Pelvic Osteotomies in Children and In-Hospital Postoperative Outcomes

Background: Femoral and pelvic osteotomies are potential hemorrhagic interventions where transfusion requirements can be necessary. Objective: We undertook a secondary analysis of patients who underwent femoral and pelvic osteotomy in the initial cohort. The objective of this secondary analysis was to describe intraoperative and postoperative outcomes and to describe intraoperative management in these patients in terms of blood product management and fluid and hemodynamic therapy with the aim of implementing optimization management protocols for postoperative outcome improvement. Methods: A secondary analysis of patients who underwent femoral and pelvic osteotomy surgery was included in the initial retrospective study. Results: There were eighteen patients with a mean age of 104 ± 47.1 months. Four (22.2%) patients had intraoperative and/or postoperative complications. One patient (5.6%) had an intraoperative hemorrhagic shock, two patients (11.1%) had postoperative neurologic failure, and one patient (5.6%) had postoperative wound sepsis. The transfusion rate was 50% in nine patients. Conclusion: Femoral and pelvic osteotomies are interventions where blood, transfusion and fluid requirements can be increased;thus, this implies the necessity of a global patient blood management protocol with point-of-care tests and fluid- and hemodynamic-guided protocols with validated tools in children for intraoperative and postoperative outcome optimization.

Scoliosis in Children: Impact of Goal-Directed Therapies on Intraoperative and Postoperative Outcomes

Background: Scoliosis is among interventions with high postoperative complication rates due to the characteristics of the surgery, where blood loss, transfusion and fluid requirements can be increased. A monocentric retrospective observational study was undertaken earlier to determine predictors of intraoperative and postoperative outcomes in surgical patients. In this initial cohort, there were patients who underwent scoliosis surgery, and a secondary analysis to describe outcomes in these patients was realized and presented here. Objective: To describe intraoperative and postoperative outcomes in patients under 18 years old in scoliosis surgery included in the initial study and to propose improvement and implementation measures. Methods: A secondary analysis of patients undergoing scoliosis surgery from 1 January 2014 to 17 May 2017 was undertaken in our institution—Necker Enfants Malades university hospital. The study was approved by the Ethics Committee. Results: There were 116 patients with a mean age of 147.5 ± 40.2 months. Twenty-eight patients (24.1%) presented intraoperative and/or postoperative complications. The most common intraoperative complication was hemorrhagic shock in 3 patients (2.6%). The most common postoperative organ failure was neurologic in seven patients (6%), respiratory in 3 patients (2.6%), cardio-circulatory in 2 patients (1.7%) and renal failure in 1 patient (0.9%). The most common postoperative infection was surgical wound sepsis in 8 patients (6.9%), urinary sepsis in 3 patients (2.6%), and abdominal sepsis and septicemia in 2 patients (1.7%). 12 patients (10.3%) had reoperations. Fifty-six patients (48.3%) had intraoperative transfusion. There was no in-hospital mortality. Conclusion: The portion of patients with intraoperative and or postoperative complications was 24.1%, integrating goal-directed therapies in this surgical setting could improve postoperative outcomes.

Intraoperative Blood Pressure Lability Acts as a Key Mediator in the Impacts of Goal-Directed Fluid Therapy on Postoperative Complications in Patients Undergoing Major Spine Surgery

Objective Although goal-directed fluid therapy(GDFT)has been proven to be effective in reducing the incidence of postoperative complications,the underlying mechanisms remain unknown.The aim of this study was to examine the mediating role of intraoperative hemodynamic lability in the association between GDFT and the incidence of postoperative complications.We further tested the role of this mediation effect using mean arterial pressure,a hemodynamic indicator.Methods This secondary analysis used the dataset of a completed nonrandomized controlled study to investigate the effect of GDFT on the incidence of postoperative complications in patients undergoing posterior spine arthrodesis.We used a simple mediation model to test whether there was a mediation effect of average real variability between the association of GDFT and postoperative complications.We conducted mediation analysis using the mediation package in R(version 3.1.2),based on 5,000 bootstrapped samples,adjusting for covariates.Results Among the 300 patients in the study,40%(120/300)developed postoperative complications within 30 days.GDFT was associated with fewer 30-day postoperative complications after adjustment for confounders(odds ratio:0.460,95%CI:0.278,0.761;P=0.003).The total effect of GDFT on postoperative complications was-0.18(95%CI:-0.28,-0.07;P<0.01).The average causal mediation effect was-0.08(95%CI:-0.15,-0.04;P<0.01).The average direct effect was-0.09(95%CI:-0.20,0.03;P=0.17).The proportion mediated was 49.9%(95%CI:18.3%,140.0%).Conclusions The intraoperative blood pressure lability mediates the relationship between GDFT and the incidence of postoperative complications.Future research is needed to clarify whether actively reducing intraoperative blood pressure lability can prevent postoperative complications.

Goal-directed fluid therapy in gastrointestinal cancer surgery:A prospective randomized study

Objective:To investigate the effects of perioperative goal-directed fluid therapy(GDFT)on intraoperative fluid balance,postoperative morbidity,and mortality.Methods:This is a prospective randomized study,and 90 patients who underwent elective open gastrointestinal cancer surgery between April 2017 and May 2018 were included.Patients were randomized into 2 groups that received liberal fluid therapy(the LFT group,n=45)and goal-directed fluid therapy(the GDFT group,n=45).Patients’Colorectal Physiologic and Operative Severity Score for the enUmeration of Mortality and Morbidity(CR-POSSUM)physiological score,Charlson Comorbidity Index(CCI),perioperative vasopressor and inotrope use,postoperative AKIN classification,postoperative intensive care unit(ICU)hospitalization,hospital stay,and 30-day mortality were recorded.Results:The volume of crystalloid used perioperatively and the total volume of fluid were significantly lower in the GDFT group compared to the LFT group(P<0.05).CR-POSSUM physiological score and CCI were significantly higher in the GDFT group(P<0.05).Although perioperative vasopressor and inotrope use was significantly higher in the GDFT group(P<0.05),postoperative acute kidney injury development was not affected.Postoperative mortality was determined to be similar in both groups(P>0.05).Conclusion:Although GDFT was demonstrated to be a good alternative method to LFT in open gastrointestinal cancer surgery,and it can prevent perioperative fluid overload,and the postoperative results are comparable in the two groups.

Effect of Goal-Directed Fluid Therapy on Lung Function, Cognitive Function and Inflammatory Response in Patients Undergoing Radical Esophageal Cancer Surgery under One-Lung Ventilation

Objective: To explore the effects of goal-directed fluid therapy (GDFT) on lung function, cognitive function and inflammatory response in patients undergoing radical esophageal cancer surgery under one-lung ventilation. Methods: Sixty-seven patients undergoing radical esophageal cancer surgery were divided into GDFT group (GDFT therapy) and control group (conventional liquid therapy). The changes in patients’ pulmonary function, cognitive function and inflammatory response were evaluated. Results: Both alveolar-arterial oxygen partial pressure difference [P(A-a)O2] and respiratory index (RI) increased at one-lung ventilation for 30 minutes (T2) and decreased at one-lung ventilation for 60 minutes (T3), and after surgery (T4) in the two groups, and the GDFT group was lower than the control group (P < 0.05);theoxygenation index (OI) of the two groups decreased at T2, T3, and T4 compared with that at T1 (before one-lung ventilation), and the GDFT group was higher than the control group (P < 0.05). At T4 and T5, the tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), central nervous system specific protein (S100β), and neuron specific enolase (NSE) in the GDFT group were lower compared to the control group (P < 0.05), while interleukin-10 (IL-10) was higher compared to the control group (P < 0.05);the incidence of perioperative neurocognitive disorder (PND) in the GDFT group was lower than that in the control group (P < 0.05). Conclusion: GDFT can help prevent lung injury during radical esophageal cancer surgery under one-lung ventilation, reduce the body’s inflammatory response, and reduce the incidence of perioperative cognitive disorder to a certain extent.

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

Optimizing care for gastric cancer with overt bleeding:Is systemic therapy a valid option?

Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB.Using propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.

Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.

Neoadjuvant therapy for pancreas cancer: Past lessons and future therapies

Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgeryfirst strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.

When combination therapy isn't working: Emerging therapies for the management of inflammatory bowel disease

Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs such as 5-aminosalicylates and immunomodulators, the therapeutic effect is not universal leaving many people searching for options. The development of newer agents has benefited from advances in the understanding of the pathophysiology of the disease. Uncontrolled activation of the acquired immune system has an important role, and lymphocytes, cytokines, and adhesion molecules are broadly targeted for therapeutic intervention. There is increasing evidence of an important role of the innate immune system and the intestinal epithelium, and the therapeutic paradigm is also shifting from immunosuppression to the reinforcement of the intestinal barrier, and modification of the disease process. In this review, we explore the limitation of current therapy as well as mechanisms of actions of new drugs and the efficacy and adverse events from data from clinical trials.

Loco-regional therapies for patients with hepatocellular carcinoma awaiting liver transplantation: Selecting an optimal therapy

Hepatocellular carcinoma(HCC) is a common, increasingly prevalent malignancy. For all but the smallest lesions, surgical removal of cancer via resection or liver transplantation(LT) is considered the most feasible pathway to cure. Resection- even with favorable survival- is associated with a fairly high rate of recurrence, perhaps since most HCCs occur in the setting of cirrhosis. LT offers the advantage of removing not only the cancer but the diseased liver from which the cancer has arisen, and LT outperforms resection for survival with selected patients. Since time waiting for LT is time during which HCC can progress, locoregional therapy(LRT) is widely employed by transplant centers. The purpose of LRT is either to bridge patients to LT by preventing progression and waitlist dropout, or to downstage patients who slightly exceed standard eligibility criteria initially but can fall within it after treatment. Transarterial chemoembolization and radiofrequency ablation have been the most widely utilized LRTs to date, with favorable efficacy and safety as a bridge to LT(and for the former, as a downstaging modality). The list of potentially effective LRTs has expanded in recent years, and includes transarterial chemoembolization with drug-eluting beads, radioembolization and novel forms of extracorporal therapy. Herein we appraise the various LRT modalities for HCC, and their potential roles in specific clinical scenarios in patients awaiting LT.

Advances in radiotherapy and targeted therapies for rectal cancer

The last decade witnessed a significant progress in understanding the biology and immunology of colorectal cancer alongside with the technical innovations in radiotherapy.The stepwise implementation of intensitymodulated and image-guided radiation therapy by means of megavolt computed tomography and helical tomotherapy enabled us to anatomically sculpt dose delivery,reducing treatment related toxicity.In addition,the administration of a simultaneous integrated boost offers excellent local control rates.The novel challenge is the development of treatment strategies for medically inoperable patient and organ preserving approaches.However,distant control remains unsatisfactory and indicates an urgent need for biomarkers that predict the risk of tumor spread.The expected benefit of target?ed therapies that exploit the tumor genome alone is so far hindered by high cost techniques and pharmaceuticals,hence hardly justifying rather modest improvements in patient outcomes.On the other hand,the immune landscape of colorectal cancer is now better clarified with regard to the immunosuppressive network that promotes immune escape.Both N2 neutrophils and myeloid-derived suppressor cells(MDSC)emerge as useful clinical biomarkers of poor prognosis,while the growing list of anti-MDSC agents shows promising ability to boost antitumor T-cell immunity in preclinical settings.Therefore,integration of genetic and immune biomarkers is the next logical step towards effective targeted therapies in the context of personalized cancer treatment.

Combining chemotherapy and targeted therapies in metastatic colorectal cancer

Colorectal cancer remains one of the major causes of cancer death worldwide. During the past years, the development of new effective treatment options has led to a considerable improvement in the outcome of this disease. The advent of agents such as capecitabine, irinotecan, oxaliplatin, cetuximab and bevacizumab has translated into median survival times in the range of 2 years. Intense efforts have focused on identifying novel agents targeting specific growth factor receptors, critical signal transduction pathways or mediators of angiogenesis. In addition, several clinical trials have suggested that some of these molecularly targeted drugs can be safely and effectively used in combination with conventional chemotherapy. In this article we review various treatment options combining cytotoxic and targeted therapies currently available for patients with metastatic colorectal cancer.

Revolutionizing gastric cancer treatment:The potential of immunotherapy

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of literature

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.