Comparison of Physical Therapy Follow-Up of Patients with Operated and Non-Operated Lumbar Spinal Stenosis According to the Nottingham Health Profile-Pain Scale

Background: Lumbar spinal stenosis (LSS) continues to be a major problem in societies, causing job loss and lowering quality of life. There are two types of treatment methods, physical therapy and surgery. If patients with LSS avoid treatment, they are likely to experience neurological deterioration in later years. Objective: The study aimed to evaluate the effect of physical therapy applied after decompression surgery or the effect of only applied physical therapy in patients with lumbar spinal stenosis. Materials and Methods: The results of the physical therapy follow-up of patients who had surgery and did not have surgery due to lumbar spinal stenosis between July 2014 and December 2019 were compared with each other. All patients received physical therapy for 6 months. Included were 42 patients who underwent decompression surgery due to LSS; 56 patients were not operated. Clinical outcomes were measured using the Nottingham Health Profile-Pain (NHP-Pain) scale at the initial, first, third and sixth months. The results were compared statistically. Results: The age of the operated patients was 54.69 ± 8.42 (39 - 71), while the non-operated patients were 59.16 ± 14.04 (34 - 83). There was no significant difference in the statistical comparison (p = 0.053). While the body mass index (BMI) of the operated patients was 29.43 ± 4.99 (21 - 40), the BMI of the non-operated patients was 28.84 ± 4.62 (22 - 42). There was no significant difference in the statistical comparison (p = 0.552). The scores of a 6-month physical therapy follow-up of patients were evaluated according to the NHP-pain scale. The values of patients who underwent surgery, initial - 1st month (p < 0.001), 1st month - 3rd month (p = 0.028), 3rd month - 6th month (p = 0.389) follow-up of the intervals were compared statistically. The values of non-operated patients, initial - 1st month (p = 0.008), 1st month -3rd month (p = 0.013), 3rd month - 6th month (p = 0.025) were compared statistically. Patients with and without surgery had significantly different initial pain scores (p < 0.001). Conclusions: The NHP-Pain scores of the patients undergoing physical therapy with the operation were shown to provide more significant improvement than the group receiving only the physical therapy. Patients with LSS should be treated with an operation to obtain the maximum benefit of physical therapy.

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.

P300 change and cognitive behavioral therapy in subjects with Internet addiction disorder A 3-month follow-up study

Event-related potential studies of cognitive function in addiction behaviors have focused on the P300 event-related potential component. The current study investigated the association between P300 component and Internet addiction disorder. We found that individuals with Internet addiction disorder exhibited significantly longer P300 latencies than controls （N2： P = 0.035; P3a： P = 0.031 P3b： P = 0.043） and similar P300 amplitudes compared to control participants. After 3 months of cognitive behavioral therapy, P300 latencies decreased significantly in the P3a and P3b （P3a： P = 0.045; P3b： P = 0.062）. These results suggest that deficits in cognitive function may be involved in Internet addiction disorder, and that clinical psychological treatment may be effective.

Combined therapy with bevacizumab and photodynamic therapy for myopic choroidal neovascularization: A oneyear follow-up controlled study

AIMTo evaluate the efficacy and safety of a combined treatment for myopic choroidal neovascularization (CNV) using photodynamic therapy (PDT) and intravitreal bevacizumab and to compare it with intravitreal bevacizumab monotherapy.

Prognostic value of plasma Epstein-Barr virus DNA level during posttreatment follow-up in the patients with nasopharyngeal carcinoma having undergone intensity-modulated radiotherapy

Background: The value of Epstein-Barr virus(EBV) DNA assay during posttreatment follow-up of the patients with nasopharyngeal carcinoma(NPC) presenting with different pretreatment plasma EBV DNA levels remains unclear. In the present study, we aimed to evaluate the prognostic value of plasma EBV DNA assay during posttreatment followup in the patients with NPC who have undergone intensity-modulated radiotherapy.Methods: The medical records of 385 NPC patients treated with intensity-modulated radiotherapy between November 2009 and February 2012 were reviewed. All patients underwent plasma EBV DNA assays before treatment, within3 months after treatment, and then every 3-12 months during posttreatment follow-up period. The recurrence rates for patients with different pretreatment and posttreatment follow-up plasma EBV DNA levels were analyzed.Results: Of the 385 patients, 267(69.4%) had detectable pretreatment plasma EBV DNA(> 0 copy/mL) and 93(24.2%) had detectable posttreatment EBV DNA during a median follow-up of 52.8 months(range 9.3-73.8 months).Detectable EBV DNA during posttreatment follow-up was found in 14.4%(17/118) and 28.5%(76/267) of patients with undetectable and detectable pretreatment EBV DNA, respectively, and was significantly associated with tumor recurrence in both patient groups. EBV DNA was detectable in 12.8%(40/313) of patients who remained disease-free,56.4%(22/39) of patients with locoregional recurrence alone, and 93.9%(31/33) of patients with distant metastasis as the first recurrence event(P < 0.001); 6.5%(19/292) of patients with undetectable EBV DNA and 57.0%(53/93) of patient with detectable EBV DNA during posttreatment follow-up experienced tumor recurrence. Compared with other cut-off values, the cut-off value of 0 copy/mL for EBV DNA during posttreatment follow-up had the highest area under the ROC curve(AUC) value(0.804,95% confidence interval 0.741-0.868) for predicting tumor recurrence(sensitivity, specificity, and accuracy: 73.6%, 87.2%, and 84.7%, respectively).Conclusion: Plasma EBV DNA level during posttreatment follow-up is a good marker for predicting distant metastasis but not locoregional recurrence in the patients with NPC irrespective of the pretreatment EBV DNA levels.

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.

A clinical and long-term follow-up study of perioperative sequential triple therapy for gastric cancer

INTRODUCTIONAlthough the long-term postoperative survival rateof gastric cancer(GC) patients has been improvedsignificantly since the local dissection of lymph nodewas widely used in China,yet the low curativeresection rate and the high recurrence rate fromperitoneal and hepatic metastases hinder it fromfurther improvement.To alter the currentunsatisfactory status of GC treatment,a

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.

Does ‘super-responder’ patients to cardiac resynchronization therapy still have indications for neuro-hormonal antagonists? Evidence from long-term follow-up in a single center

Background Whether cardiac resynchronization therapy super-responders (CRT-SRs) still have indications for neuro-hormonal antagonists or not remains uninvestigated.Methods We reviewed clinical data from 376 patients who underwent CRT implantation in Fuwai Hospital from 2009 to 2015 and followed up to 2017.CRT-SRs were defined by an improvement of the New York Heart Association functional class and left ventricular ejection fraction to ≥ 50% in absolute values at 6-month follow-up.All CRT-SRs were assigned into two groups on the basis of whether persistently receiving neuro-hormonal antagonists (NHA)(defined as angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers and β-blockers) after 6-month follow-up and then we compared long-term outcome.Results A total of 60 patients met criteria for super-response.One of thirteen (7.7%) CRT-SRs without NHA had all-cause death,which also occurred in 2 of 47 (4.3%) in CRT-SRs with NHA (P = 0.526).However,3 of 13 (23.1%) CRT-SRs without NHA had heart failure (HF) hospitalization,1 of 47 (2.1%) CRT-SRs with NHA had this endpoint (P = 0.040).Besides,subgroup analysis indicated that,for ischemic etiology group,CRT-SRs receiving NHA had considerably lower incidence of HF hospitalization than those without NHA (0 vs.75%,P = 0.014),which was not observed in non-ischemic etiology group (2.6% vs.0,P = 1.000) during long-term follow-up.Conclusions Our study found that for ischemic etiology,compared with CRT-SRs with NHA,CRT-SRs without NHA were associated with a higher risk of HF hospitalization.However,for non-ischemic etiology,we found that CRT-SRs with NHA or without NHA at follow-up were associated with similar outcomes,which needed further investigation by prospective trials.

Long-term follow-up of cumulative incidence of hepatocellular carcinoma in hepatitis B virus patients without antiviral therapy

BACKGROUND China has a high prevalence of hepatitis B virus(HBV),but most chronic hepatitis B(CHB)patients do not receive standardized antiviral therapy.There are few relevant reports addressing the outcomes of the large number of CHB patients who do not receive antiviral therapy.AIM To observe the outcomes of long-term follow-up of patients with CHB without antiviral treatment.METHODS This study included 362 patients with CHB and 96 with hepatitis B cirrhosis without antiviral treatment and with only liver protection and anti-inflammatory treatment from 1993 to 1998.The median follow-up times were 10 and 7 years,respectively.A total of 203 CHB and 129 hepatitis B cirrhosis patients receiving antiviral therapy were selected as the control groups.The median follow-up times were 8 and 7 years,respectively.Kaplan-Meier curves were used to analyze the cumulative incidence of hepatocellular carcinoma(HCC),and the Cox regression model was used to analyze the risk factors for HCC.RESULTS Among the patients in the non-antiviral group,16.9%had spontaneous decreases(HBeAg)seroconversion.In the antiviral group,87.2%of patients had undetectable HBV DNA,and 52%showed HBeAg seroconversion.Among CHB and hepatitis B cirrhosis patients,the cumulative incidence rates of HCC were 14.9%and 53.1%,respectively,in the non-antiviral group and were 10.7%and 31.9%,respectively,in the antiviral group.There was no difference between the two groups regarding the CHB patients(P=0.842),but there was a difference between the groups regarding the hepatitis B cirrhosis patients(P=0.026).The cumulative incidence rates of HCC were 1.6%and 22.3%(P=0.022)in the groups with and without spontaneous HBeAg seroconversion,respectively.The incidence rates of HCC among patients with and without spontaneous declines in HBV DNA to undetectable levels were 1.6%and 19.1%,respectively(P=0.051).There was no difference in the cumulative incidence of HCC between the two groups regarding the patients with drug-resistant CHB(P=0.119),but there was a significant difference between the two groups regarding the patients with cirrhosis(P=0.004).The Cox regression model was used for regression of the corrected REACH-B score,which showed that alanine aminotransferase>400 U/L,history of diabetes,and family history of liver cancer were risk factors for HCC among men aged>40 years(P<0.05).Multifactorial analysis showed that a family history of HCC among men was a risk factor for HCC.CONCLUSION Antiviral therapy and non-antiviral therapy with liver protection and antiinflammatory therapy can reduce the risk of HCC.Antiviral therapy may mask the spontaneous serological response of some patients during CHB.Therefore,the effect of early antiviral therapy on reducing the incidence of HCC cannot be overestimated.

An eighteen-month follow-up study on the effects of Intravitreal Dexamethasone Implant in diabetic macular edema refractory to anti-VEGF therapy

AIM： To evaluate the long-term efficacy and safety of dexamethasone implants in subjects affected by diabetic macular edema（DME） resistant to anti-vascular endothelial growth factor（VEGF） therapy.METHODS： Thirty-two DME patients were enrolled.A700 microgram slow release Intravitreal Dexamethasone Implant（Ozurdex~） was placed in the vitreous cavity.All patients were followed for 18 mo.Best-corrected visual acuity（BCVA） measured with Early Treatment Diabetic Retinopathy Study（ETDRS） and central macular thickness（CMT） exams were carried out at baseline（T0）and after 1（T1）,3（T3）,4（T4）,6（T6）,9（T9）,12（T12）,15（T15）,and 18mo（T18） post injection. RESULTS： Repeated measures ANOVA showed an effect of treatment on ETDRS（P〈0.0001）.Post hoc analyses revealed that ETDRS values were significantly increased at T1,T3,T4,T9,and T15（P 〈0.001） as compared to baseline value（T0）.At T6,T12,and T18,ETDRS values were still statistically higher than baseline（P〈0.001 vs T0）.However,at these time points,we observed a trend to return to baseline conditions.ANOVA also showed an effect of treatment（P 〈0.0001）.CMT decreased significantly at T1,T3,T4,T9,and T15（P〈0.001）.At T6（P〈0.01）,T12 and T18（P〈0.001） CMT was also significantly lower than T0 although a trend to return to the baseline conditions was also observed.CONCLUSION： Our findings demonstrate that Intravitreal Dexamethasone Implant is a good option to improveBCVA and CMT in DME patients resistant to anti-VEGF therapy.Our data also show that the use of drugs administered directly into the vitreous allows achieving appropriate and long-lasting concentration at the site of disease without systemic side effects.

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.

Endoscopic stent therapy in patients with chronic pancreatitis:A 5-year follow-up study

AIM:This study analyzed clinical long-term outcomes after endoscopic therapy,including the incidence and treatment of relapse. METHODS:This study included 19 consecutive patients(12 male,7 female,median age 54 years)with obstructive chronic pancreatitis who were admitted to the 2nd Medical Department of the Technical University of Munich.All patients presented severe chronic pancreatitis(stageⅢ°)according to the Cambridge classification.The majority of the patients suffered intermittent pain attacks.6 of 19 patients had strictures of the pancreatic duct;13 of 19 patients had strictures and stones.The first endoscopic retrograde pancreatography(ERP)included an endoscopic sphincterotomy, dilatation of the pancreatic duct,and stent placement.The first control ERP was performed 4 wk after the initial intervention,and the subsequent control ERP was performed after 3 mo to re-evaluate the clinical and morphological conditions.Clinical follow-up was performed annually to document the course of pain and the management of relapse.The course of pain was assessed by a pain scale from 0 to 10.The date and choice of the therapeutic procedure were documented in case of relapse. RESULTS:Initial endoscopic intervention was successfully completed in 17 of 19 patients.All 17 patients reported partial or complete pain relief after endoscopic intervention.Endoscopic therapy failed in 2 patients. Both patients were excluded from further analysis.One failed patient underwent surgery,and the other patient was treated conservatively with pain medication.Seventeen of 19 patients were followed after the successful completion of endoscopic stent therapy.Three of 17 patients were lost to follow-up.One patient was not avail-able for interviews after the 1st year of follow-up.Two patients died during the 3rd year of follow-up.In both patients chronic pancreatitis was excluded as the cause of death.One patient died of myocardial infarction, and one patient succumbed to pneumonia.All three patients were excluded from follow-up analysis.Followup was successfully completed in 14 of 17 patients.4 patients at time point 3,2 patients at time point 4,3 patients at time point 5 and 2 patients at time point 6 and time point 7 used continuous pain medication after endoscopic therapy.No relapse occurred in 57%(8/14) of patients.All 8 patients exhibited significantly reduced or no pain complaints during the 5-year follow-up.Seven of 8 patients were completely pain free 5 years after endoscopic therapy.Only 1 patient reported continuous moderate pain.In contrast,7 relapses occurred in 6 of the 14 patients.Two relapses were observed during the 1st year,2 relapses occurred during the 2nd year,one relapse was observed during the 3rd year,one relapse occurred during the 4th year,and one relapse occurred during the 5th follow-up year.Four of these six patients received conservative treatment with endoscopic therapy or analgesics.Relapse was conservatively treated using repeated stent therapy in 2 patients.Analgesic treatment was successful in the other 2 patients. CONCLUSION:57%of patients exhibited long-term benefits after endoscopic therapy.Therefore,endoscopic therapy should be the treatment of choice in patients being inoperable or refusing surgical treatment.

p53 gene therapy in combination with transcatheter arterial chemoembolization for HCC:One-year follow-up

AIM:To evaluate the efficacy and safety of combination therapy with recombinant adenovirus p53 injection (rAdp53) and transcatheter hepatic arterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC).METHODS:A total of 82 patients with advanced HCC treated only with TACE served as control group.Another 68 patients with HCC treated with TACE in combination with recombinant adenovirus-p53 injection served as p53 treatment group.Patients were followed up for 12 mo.Safety and therapeutic effects were evaluated according to the improvement in clinical symptoms,leukocyte count,Karnofsky and RECIST criteria.Survival rate was calculated with Kaplan-Meier method.RESULTS:The total effective rate was 58.3% for p53 treatment group,and 26.5% for control group (P < 0.05).The incidence of gastrointestinal symptoms was lower in p53 treatment group than in control group (P < 0.05).The 3-,6-and 12-mo survival rates were significantly higher for p53 treatment group than for control group (P < 0.01).The combination treatment was well tolerated with such adverse events as fever (51.5%,P=0.006) and pain of muscles and joints (13.2%,P=0.003),which were significantly higher than the chemotherapy.Except for these minor adverse effects,no severe vector-related complications were identified.With respect to the efficacy,patients in p53 treatment group had less gastrointerestinal symptoms (P=0.062),better improvement in tumor-related pain (P=0.003),less downgrade of leukocyte counts (P=0.003) and more upgrade of Karnofsky performance score (P=0.029) than those in control group.The total effective rate (CR + PR) for p53 treatment group and control group was 58.3% and 26.5%,respectively,with distributions of different effect in two groups (P=0.042).The survival rates were 89.71%,76.13%,and 43.30% for p53 treatment group,and 68.15%,36.98%,and 24.02% for control group,respectively,3,6 and 12 mo after treatment,suggesting that the survival rates are significantly higher for p53 treatment group than for control group (P=0.0002).CONCLUSION:The rAd-p53 gene therapy in combination with TACE is a safe and effective treatment modality for advanced HCC.

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.

Fifty-Year-Follow-up Results Compared with Shorter Follow-up of Breast Cancer Patients Undergoing Radical Mastectomy with or without Adjuvant Radiotherapy

Background: To evaluate the effect of follow-up length on the outcome of breast cancer patients, we compared the 50- and 25-year follow-up results in terms of cure rate, overall mortality and mortalities from breast cancer, second cancer, and benign diseases. Methods: 763 patients treated for breast cancer between February 1953 and September 1976, were followed up until December 2014. They were divided into two cohorts;earlier cohort exclusively underwent radical mastectomy plus adjuvant radiotherapy, while later cohort had radical mastectomy alone. Assuming that in all patients follow-up was terminated at 50 or 25 years after diagnosis, likelihood ratio test and stratified Log-rank tests were performed to evaluate the differences in cure rate and overall survival between the two cohorts. Results: During the 50 years, radical mastectomy alone compared with radical mastectomy plus adjuvant radiotherapy is associated with a significantly higher cure rate, and higher survivals regardless of whether the death was from breast cancer, second cancer, benign causes or any causes. However, if follow-up information is limited to 25 years, the advantage of radical mastectomy alone is partly offset and the survival difference between the two cohorts becomes less significant. Conclusion: Radiotherapy to breast cancer may adversely affect not only mortality from breast cancer, but mortalities unrelated to breast cancer. Since such deaths occur later, they may fail to be detected unless follow-up is long enough. Thus, deleterious effects of radiotherapy may be underestimated. Exceedingly long follow-up is required to accurately estimate the cure rate and the long-term effect of radiotherapy.

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.