Adjuvant therapy for hepatocellular carcinoma:Dilemmas at the start of a new era

Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.

New method of local adjuvant therapy with bicarbonate Ringer’s solution for tumoral calcinosis: A case report

BACKGROUND Tumoral calcinosis is a condition characterized by deposits of calcium phosphate crystals in extra-articular soft tissues,occurring in hemodialysis patients.Calcium phosphate crystals are mainly composed of hydroxyapatite,which is highly infilt-rative to tissues,thus making complete resection difficult.An adjuvant method to remove or resolve the residual crystals during the operation is necessary.CASE SUMMARY A bicarbonate Ringer’s solution with bicarbonate ions(28 mEq/L)was used as the adjuvant.After resecting calcium phosphate deposits of tumoral calcinosis as much as possible,while filling with the solution,residual calcium phosphate deposits at the pseudocyst wall can be gently scraped by fingers or gauze in the operative field.A 49-year-old female undergoing hemodialysis for 15 years had swelling with calcium deposition for 2 years in the shoulders,bilateral hip joints,and the right foot.A shoulder lesion was resected,but the calcification remained and early re-deposition was observed.Considering the difficulty of a complete rection,we devised a bicarbonate dissolution method and excised the foot lesion.After resection of the calcified material,the residual calcified material was washed away with bicarbonate Ringer’s solution.CONCLUSION The bicarbonate dissolution method is a new,simple,and effective treatment for tumoral calcinosis in hemodialysis patients.

Research Progress of Drug Therapy for Diabetes

Diabetes is mainly a series of symptoms of glucose metabolism disorder caused by relative or absolute insufficiencies of insulin.Most patients are accompanied by protein,fat,water and electrolyte disorders,including diabetes type 1 and diabetes type 2,of which diabetes type 2 accounts for more than 90%.The incidence rate of diabetes is high,the course of disease is long,and it is difficult to cure.Most patients need long-term medication.This study analyzed the clinical manifestations and predisposing factors of diabetes,and explored the progress of drug treatment of diabetes,which is summarized as follows.

Observation on the Clinical Effect of Applying Venetoclax Combined with Demethylation Drug Therapy in Patients with Acute Myeloid Leukemia

Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P > 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.

Efficacy and safety of anlotinib as an adjuvant therapy in hepatocellular carcinoma patients with a high risk of postoperative recurrence

Objective:Hepatocellular carcinoma(HCC)has a high rate of postoperative recurrence and lacks an effective treatment to prevent recurrence.This study aims to investigate the efficacy and safety of anlotinib in postoperative adjuvant therapy for HCC patients with high-risk recurrence factors.Methods:For this multicenter,retrospective study,we recruited 63 HCC patients who received either anlotinib(n=27)or transcatheter arterial chemoembolization(TACE)(n=36)from six research centers in China between March 2019 and October 2020.The primary endpoint was disease-free survival(DFS)and the secondary endpoints were overall survival(OS)and safety.Results:In this study,the median follow-up time was 25.9 and 26.8 months in the anlotinib and TACE groups,respectively.There was no significant difference in the median DFS between the anlotinib[26.8 months,95%confidence interval(95%CI):6.8-NE]and TACE groups(20.6 months,95%CI:8.4-NE).The 12-month OS rates in the anlotinib and TACE groups were 96.3%and 97.2%,respectively.In the anlotinib group,19 of 27patients(70.4%)experienced treatment-emergent adverse events,with the most common events(≥10%)being hypertension(22.2%)and decreased platelet count(22.2%).Conclusions:The results indicate that anlotinib,as a new,orally administered tyrosine kinase inhibitor,has the same efficacy as TACE,and side effects can be well controlled.

Comparative effectiveness of several adjuvant therapies after hepatectomy for hepatocellular carcinoma patients with microvascular invasion

BACKGROUND For resectable hepatocellular carcinoma(HCC),radical hepatectomy is commonly used as a curative treatment.However,postoperative recurrence significantly diminishes the overall survival(OS)of HCC patients,especially with microva-scular invasion(MVI)as an independent high-risk factor for recurrence.While some studies suggest that postoperative adjuvant therapy may decrease the risk of recurrence following liver resection in HCC patients,the specific role of adju-vant therapies in those with MVI remains unclear.AIM To conduct a network meta-analysis(NMA)to evaluate the efficacy of various adjuvant therapies and determine the optimal adjuvant regimen.METHODS A systematic literature search was conducted on PubMed,EMBASE,and Web of Science until April 6,2023.Studies comparing different adjuvant therapies or comparing adjuvant therapy with hepatectomy alone were included.Hazard ratios(HRs)with 95%confidence intervals were used to combine data on recurrence free survival and OS in both pairwise meta-analyses and NMA.RESULTS Fourteen eligible trials(2268 patients)reporting five different therapies were included.In terms of reducing the risk of recurrence,radiotherapy(RT)[HR=0.34(0.23,0.5);surface under the cumulative ranking curve(SUCRA)=97.7%]was found to be the most effective adjuvant therapy,followed by hepatic artery infusion chemotherapy[HR=0.52(0.35,0.76);SUCRA=65.1%].Regarding OS improvement,RT[HR:0.35(0.2,0.61);SUCRA=93.1%]demonstrated the highest effectiveness,followed by sorafenib[HR=0.48(0.32,0.69);SUCRA=70.9%].INTRODUCTION Hepatocellular carcinoma(HCC)is the sixth most common malignant tumor in the world and ranks third in terms of worldwide malignant tumor mortality rates in 2020[1].Curative treatments for HCC include ablation,radical hepatectomy,and liver transplantation.However,ablation is suitable only for early-stage HCC patients,who represent a small percentage of the overall HCC population.Although liver transplantation serves as the optimal treatment for HCC patients,the scarcity of donor organs restricts the availability of this procedure.Therefore,hepatectomy is the most commonly employed curative treatment for resectable HCC.Unfortunately,the 5-year recurrence rate for patients who undergoing hepatectomy ranges from 50%to 70%[2,3].Recurrence of HCC is associated with several risk factors[4],including single nodule>5 cm,vascular invasion,and multiple nodules.Among these factors,microvascular invasion(MVI)is an independent risk factor for recurrence.MVI is defined as the presence of cancer cells in the lumen of endothelium-lined vessels,typically in the small branches of the portal and hepatic veins of the paracancerous liver tissue,visible only under the microscope[5].Previous studies have shown that among HCC patients who underwent hepatectomy,those with MVI had a higher risk of recurrence and shorter overall survival(OS)than those without MVI[6].Several studies have indicated that adjuvant therapy following curative hepatectomy can prevent recurrence and improve OS in HCC patients with MVI.These postoperative adjuvant therapies include transarterial chemoembolization(TACE)[7],sorafenib[8],hepatic artery infusion chemotherapy(HAIC)[9],and radiotherapy(RT)[10].However,the existing studies mostly compare individual adjuvant therapy with hepatectomy alone.Direct or indirect comparisons between the various adjuvant therapies are lacking.Therefore,we performed the network meta-analysis(NMA)to compare the relative efficacy of each adjuvant therapy to determine the optimal treatment.

The current role of neoadjuvant/adjuvant/chemoprevention therapy in partial hepatectomy for hepatocellular carcinoma:a systematic review

BACKGROUND: Following curative treatment for hepatocellular carcinoma (HCC), 50%-90% of postoperative death is due to recurrent disease. Intra-hepatic recurrence is frequently the only site of recurrence. Thus, any neoadjuvant or adjuvant therapy, which can decrease or delay the incidence of intra-hepatic recurrence, or any cancer chemoprevention which can prevent a new HCC from developing in the liver remnant, will improve the results of liver resection. This article systematically reviewed the current evidence of neoadjuvant, adjuvant, and chemoprevention in partial hepatectomy of HCC. DATA SOURCES: Studies were identified by searching MEDLINE and PubMed databases for articles from January 1990 to November 2008 using the keywords 'hepatocellular carcinoma', 'hepatectomy', 'adjuvant therapy', 'neoadjuvant therapy', and 'regional therapy'. Additional papers and book chapters were identified by a manual search of the references from the key articles. RESULTS: Neoadjuvant transarterial chemoembolization or adjuvant regional transarterial chemotherapy embolization+systemic chemotherapy did not add benefit. Both adjuvant transarterial radioembolization with (131)I-lipiodol and adjuvant systemic interferon showed promising results. However, there were only a limited number of such studies. CONCLUSIONS: Further randomized controlled studies need to be carried out. Currently, there is no consensus on a standard neoadjuvant/adjuvant/chemoprevention therapy in partial hepatectomy for HCC.

Prognostic evaluation of postoperative adjuvant therapy for operable cervical cancer:10 years'experience of National Cancer Center in China

Objective： The aim of this study was to investigate the prognostic factors and to evaluate the impact of adjuvant therapy on clinical outcome for early-stage cervical cancer. Methods： The clinical-pathological data of all 1,335 patients with the International Federation of Gynecology and Obstetrics （FIGO） Ib-[Ia cervical cancer treated with primary radical surgery at the Chinese National Cancer Center between May 2007 and Dec 2013 were retrospectively reviewed. The median follow-up was 70 months. Results： Of all the patients, 61.6% of the cases received adjuvant therapy, with 5-year disease-free survival （DFS） of 92.1% and 5-year overall survival （OS） of 95.0%. In multivariate analysis, differentiation of G3 （P〈0.05）, lymph node metastasis （LNM, P〈0.05） and lymphovascular space invasion （LVSI, P〈0.05） were independent predictors for OS, while LNM （P〈0.05）, deep stroma invasion （DSI, P〈0.05） and LVSI （P〈0.05） were independent factors for DFS. The samples were stratified by histologic type, and cervical squamous cell carcinoma （SCC） was found to share the same independent factors except for differentiation of OS. As to patients with cervical adenocarcinoma/adenosquamons carcinoma （AC/ASC）, differentiation was the independent predictor of OS （P〈0.05）; and LVSI of DFS （P〈0.05）. Of 236 patients with high-risk factors, there was no significant difference in survival between concurrent chemoradiotherapy （CCRT, n=195）, radiotherapy （RT, n=24）, and chemotherapy （CT, n=17）. Among the 190 patients with LNM who underwent CCRT, 124 cases showed improved DFS after sequential CT （P=0.118）, with a recurrence rate decrease of 14%, though the difference was not statistically significant. Patients with single intermediate-risk factors like DSI or LVSI were found to partially benefit from adjuvant therapy, but the difference was not statistically significant. Conclusions： LNM, LVSI, DSI and differentiation were found to be independent prognostic factors for operable cervical cancer. Aggressive postoperative adjuvant therapy based on single risk factors in Chinese National Cancer Center could benefit survival. CCRT＋CT outperformed CCRT in high-risk patients. For patients with single non-high-risk factor, the role of adjuvant therapy needs to be further discussed.

Estimating survival benefit of adjuvant therapy based on a Bayesian network prediction model in curatively resected advanced gallbladder adenocarcinoma

BACKGROUND The factors affecting the prognosis and role of adjuvant therapy in advanced gallbladder carcinoma(GBC)after curative resection remain unclear.AIM To provide a survival prediction model to patients with GBC as well as to identify the role of adjuvant therapy.METHODS Patients with curatively resected advanced gallbladder adenocarcinoma(T3 and T4)were selected from the Surveillance,Epidemiology,and End Results database between 2004 and 2015.A survival prediction model based on Bayesian network(BN)was constructed using the tree-augmented na?ve Bayes algorithm,and composite importance measures were applied to rank the influence of factors on survival.The dataset was divided into a training dataset to establish the BN model and a testing dataset to test the model randomly at a ratio of 7:3.The confusion matrix and receiver operating characteristic curve were used to evaluate the model accuracy.RESULTS A total of 818 patients met the inclusion criteria.The median survival time was 9.0 mo.The accuracy of BN model was 69.67%,and the area under the curve value for the testing dataset was 77.72%.Adjuvant radiation,adjuvant chemotherapy(CTx),T stage,scope of regional lymph node surgery,and radiation sequence were ranked as the top five prognostic factors.A survival prediction table was established based on T stage,N stage,adjuvant radiotherapy(XRT),and CTx.The distribution of the survival time(>9.0 mo)was affected by different treatments with the order of adjuvant chemoradiotherapy(cXRT)>adjuvant radiation>adjuvant chemotherapy>surgery alone.For patients with node-positive disease,the larger benefit predicted by the model is adjuvant chemoradiotherapy.The survival analysis showed that there was a significant difference among the different adjuvant therapy groups(log rank,surgery alone vs CTx,P<0.001;surgery alone vs XRT,P=0.014;surgery alone vs cXRT,P<0.001).CONCLUSION The BN-based survival prediction model can be used as a decision-making support tool for advanced GBC patients.Adjuvant chemoradiotherapy is expected to improve the survival significantly for patients with node-positive disease.

Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2(HER2)-positive early-stage breast cancer: A real-world retrospective study in Chinese patients

Objective: To assess the long-term effectiveness and safety of trastuzumab in adjuvant therapy for Chinese patients with early-stage human epidermal growth factor 2(HER2)-positive breast cancer in a real-world setting.Methods: This retrospective observational study analyzed the medical records of HER2-positive breast cancer patients between 2000 and 2012 at the Chinese Academy of Medical Sciences. Patients who received adjuvant chemotherapy alone or adjuvant chemotherapy followed by/combined with trastuzumab were included. The Kaplan-Meier method was used to estimate disease-free survival(DFS) and overall survival(OS). Hazard ratios(HR) and 95% confidence intervals(95% CI) were calculated using the Cox regression model.Results: Of the 1,348 patients analyzed, 909 received chemotherapy alone and 439 received chemotherapy plus trastuzumab. The 3-year, 5-year and 10-year DFS rates were 83.70%, 76.38% and 68.94%, respectively, in the chemotherapy-alone cohort, and 90.21%, 86.19% and 83.45% in the chemotherapy plus trastuzumab cohort. The3-year, 5-year and 10-year OS rates were 96.10%, 91.40% and 81.88% in the chemotherapy-alone cohort, and98.17%, 94.91% and 90.01% in the chemotherapy plus trastuzumab cohort. The chemotherapy plus trastuzumab group had a significantly lower risk of disease recurrence and death than the chemotherapy-alone group(DFS:HR=0.50, 95% CI, 0.37-0.68;P<0.001;OS: HR=0.53, 95% CI, 0.34-0.81;P=0.004) after adjusting for covariates.In the 439 patients treated with trastuzumab, multivariate analysis suggested that lymph node positivity, higher T stages, and hormone receptor-negative status were significantly associated with higher risks of disease recurrence,and lymph node positivity and hormone receptor-negative status were significantly associated with higher risks of death. Grade 3/4 adverse events(incidence ≥1%) were more common in patients receiving trastuzumab(54.44% vs.15.73%).Conclusions: Early-stage HER2-positive breast cancer patients treated with trastuzumab plus adjuvant chemotherapy have a significant survival benefit compared with chemotherapy-alone in real-world settings. Lymph node positivity, hormone receptor-negative status, and higher T stages may be associated with higher risks of recurrence, and effective therapy for patients with these factors is required.

Early prediction of pathological outcomes to neoadjuvant chemotherapy in breast cancer patients using automated breast ultrasound

Objective： Early assessment of response to neoadjuvant chemotherapy （NAC） for breast cancer allows therapy to be individualized. The optimal assessment method has not been established. We investigated the accuracy of automated breast ultrasound （ABUS） to predict pathological outcomes after NAC. Methods： A total of 290 breast cancer patients were eligible for this study. Tumor response after 2 cycles of chemotherapy was assessed using the product change of two largest perpendicular diameters （PC） or the longest diameter change （LDC）. PC and LDC were analyzed on the axial and the coronal planes respectively. Receiver operating characteristic （ROC） curves were used to evaluate overall performance of the prediction methods. Youden＇s indexes were calculated to select the optimal cut-off value for each method. Sensitivity, specificity, positive and negative predictive values （PPV and NPV） and the area under the ROC curve （AUC） were calculated accordingly.Results： ypT0/is was achieved in 42 patients （14.5%） while ypT0 was achieved in 30 patients （10.3%） after NAC. All four prediction methods （PC on axial planes, LDC on axial planes, PC on coronal planes and LDC on coronal planes） displayed high AUCs （all〉0.82）, with the highest of 0.89 [95% confidence interval （95% CI）, 0.83-0.95] when mid-treatment ＆BUS was used to predict final pathological complete remission （pCR）. High sensitivities （85.7%-88.1%） were observed across all four prediction methods while high specificities （81.5%-85.1%） were observed in two methods used PC. The optimal cut-off values defined by our data replicate the WHO and the RECIST criteria. Lower AUCs were observed when mid-treatment ABUS was used to predict poor pathological outcomes. Conclusions：ABUS is a useful tool in early evaluation of pCR after NAC while less reliable when predicting poor pathological outcomes.

Adjuvant hormone therapy after radical prostatectomy in highrisk localized and locally advanced prostate cancer: First multicenter, observational study in China

Objective: Potential of combined androgen blockade(CAB) has not been explored extensively in Chinese males with prostate cancer(PCa). Therefore, this study evaluated the 2-year prostate-specific antigen(PSA) recurrence rate and quality of life(Qo L) in patients with high-risk localized and locally advanced PCa receiving adjuvant hormone therapy(HT) after radical prostatectomy(RP).Methods: This prospective, multicenter, observational study conducted in 18 centers across China enrolled patients with high-risk factor(preoperative PSA>20 ng/m L or Gleason score >7) or locally advanced PCa. Different adjuvant HT were administered after RP according to investigator’s decision in routine clinical practice.Relationship of baseline and postoperative characteristics was assessed with recurrence rate. PSA recurrence rate and Functional Assessment of Cancer Therapy-Prostate(FACT-P) Qo L scores were recorded at 12 months and 24 months. Kaplan-Meier analysis was used to construct the PSA recurrence rate during follow-up.Results: A total of 189 patients(mean age: 66.9±6.5 years) were recruited, among which 112(59.3%) patients showed serum PSA>20 ng/m L preoperatively. The highest postoperative pathological advancement noticed was from clinical T2(c T2) to pathological T3(p T3)(43.9%) stage. The majority of the patients(66.1%) received CAB as adjuvant HT, for a median duration of 20.0 months. The least recurrence(15.2%) was noticed in patients treated with CAB, followed by those treated with luteinizing hormone-releasing hormone agonist(LHRHa)(16.1%), and antiandrogen(19.0%), with non-significant difference noted among the groups. None of the baseline or postoperative characteristics was related with PSA recurrence in our study. The 24-month FACT-P Qo L score of119 patients treated for >12 months showed significant improvement above baseline compared with those treated for ≤12 months.Conclusions: Adjuvant CAB therapy after RP showed reduction trend in 2-year PSA recurrence rate in highrisk Chinese patients with localized and locally advanced PCa, compared with adjuvant anti-androgens(AA) or LHRHa therapy. Further long-term therapy(>12 months) significantly improved Qo L compared to short-term HT therapy, suggesting the beneficial effect of long-term CAB therapy in improving Qo L.

Advances in adjuvant systemic therapy for non-small-cell lung cancer

Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies.

Development and controversies of adjuvant therapy for pancreatic cancer

BACKGROUND: Pancreatic cancer is an aggressive malignancy with a dismal prognosis. Radical surgery provides the only chance for a cure with a 5-year survival rate of 7%-25%. An effective adjuvant therapy is urgently needed to improve the surgical outcome. This review describes the current status of adjuvant therapy for pancreatic cancer, and highlights its controversies. DATA SOURCES: A Medline database search was performed to identify relevant articles using the keywords 'pancreatic neoplasm', and 'adjuvant therapy'. Additional papers were identified by a manual search of the references from the key articles. RESULTS: Eight prospective randomized controlled trials (RCTs) on the use of adjuvant chemotherapy and chemoradiation for pancreatic cancer could be identified. The results for adjuvant regimens based on systemic 5-fluorouracil with or without external radiotherapy were conflicting. The recent two RCTs on gemcitabine based regimen gave promising results. CONCLUSIONS: Based on the available data, no standard adjuvant therapy for pancreatic cancer can be established yet. The best adjuvant regimen remains to be determined in large-scale RCTs. Future trials should use a gemcitabine based regimen.

Advances in postoperative adjuvant therapy for primary liver cancer

Hepatocellular carcinoma(HCC)is a highly heterogeneous,invasive,and conventional chemotherapy-insensitive tumor with unique biological characteristics.The main methods for the radical treatment of HCC are surgical resection or liver transplantation.However,recurrence rates are as high as 50%and 70%at 3 and 5 years after liver resection,respectively,and even in Milan-eligible recipients,the recurrence rate is approximately 20%at 5 years after liver transplantation.Therefore,reducing the postoperative recurrence rate is key to improving the overall outcome of liver cancer.This review discusses the risk factors for recurrence in patients with HCC radical surgical resection and adjuvant treatment options that may reduce the risk of recurrence and improve overall survival,including local adjuvant therapy(e.g.,transcatheter arterial chemoembolization),adjuvant systemic therapy(e.g.,molecular targeted agents and immunotherapy),and other adjuvant therapies(e.g.,antiviral and herbal therapy).Finally,potential research directions that may change the paradigm of adjuvant therapy for HCC are analyzed.

Curative effect of ganglioside sodium for adjuvant therapy on acute severe craniocerebral injury

Objective: To study the effect of adjuvant therapy of ganglioside sodium on intracranial pressure (ICP), partial pressure of brain tissue oxygen (PbtO2), nerve injury molecules, nerve protection molecules and indexes of oxidative stress in patients with acute severe craniocerebral injury. <br> Methods: Forty-seven patients with severe craniocerebral injury treated in the emergency department of our hospital during the period time from December 2012 to October 2015 were selected for retrospective analyses. They were divided into the ganglioside group and the normal treatment group according to the usage of ganglioside sodium in the process of the emergency treatment. At days 1, 3, 5 and 7 before and after treatment, theICP and PbtO2 in patients of the two groups were measured. After 7 days of treatment, the nerve injury molecules, nerve protection molecules and the indexes of oxidative stress in serum of the patients of the two groups were determined. <br> Results: At days 1, 3, 5 and 7 before and after treatment, theICP in patients of the ganglioside group were all significantly lower than those of the normal treatment group, while the PbtO2 were all significantly higher than those of normal treatment group. After 7 days of treatment, the contents of serum methane dicarboxylic aldehyde, advanced oxidation protein products, 8-hydroxy-2'-deoxyguanosine urine, S100β, glial fibrillary acidic portein, neuron specific enolase, myelin basic protein, neuroglobin and ubiquitin carboxyl-terminal hydrolase L1 in patients of the ganglioside group were notably lower than those of the normal treatment group, while the contents of superoxidase dismutase, glutathione peroxidase, catalase, nerve growth factor and brain derived neurotrophic factor were significantly higher than those of the normal treatment group. <br> Conclusions: The adjuvant therapy of ganglioside sodium in patients with severe craniocerebral injury can effectively reduceICP, improve PbtO2 and alleviate the injuries of neurons and glial cells caused by oxidative stress.

Current status of the adjuvant therapy in uterine sarcoma: A literature review

Uterine sarcomas (US) are rare mesenchymal tumours accounting approximately for 3%–7% of all uterine cancers. Histologically, US are classified into mesenchymal tumours or mixed epithelial and mesenchymal tumours. The group of mesenchymal tumours includes uterine leiomyosarcoma (uLMS, 65% of cases), endometrial stromal sarcoma (ESS, 21%)– traditionally divided into low grade (LG-ESS) and high grade–undifferentiated uterine sarcoma (5%) and other rare subtypes such as alveolar or embryonal rhabdomyosarcoma. Despite the fact that several drugs demonstrated clinical activity in advanced or metastatic settings, the role of postoperative therapy in US remains controversial. In this review, we have summarised the current state of the art, including the chief trials on adjuvant treatment modalities in US, especially focusing on uLMS, LG-ESS and other rare histotypes.

Pathological response measured using virtual microscopic slides for gastric cancer patients who underwent neoadjuvant chemotherapy

BACKGROUND Although pathological response is a common endpoint used to assess the efficacy of neoadjuvant chemotherapy (NAC) for gastric cancer, the problem of a low rate of concordance from evaluations among pathologists remains unresolved. Moreover, there is no globally accepted consensus regarding the optimal evaluation. A previous study based on a clinical trial suggested that pathological response measured using digitally captured virtual microscopic slides predicted patients’ survival well. However, the pathological concordance rate of this approach and its usefulness in clinical practice were unknown. AIM To investigate the prognostic utility of pathological response measured using digital microscopic slides in clinical practice. METHODS We retrospectively evaluated pathological specimens of gastric cancer patients who underwent NAC followed by surgery and achieved R0 resection between March 2009 and May 2015. Residual tumor area and primary tumor beds were measured in one captured image slide, which contained the largest diameter of the resected specimens. We classified patients with < 10% residual tumor relative to the primary tumorous area as responders, and the rest as non-responders;we then compared overall survival (OS) and relapse-free survival (RFS) between these two groups. Next, we compared the prognostic utility of this method using conventional Japanese criteria. RESULTS Fifty-four patients were evaluated. The concordance rate between two evaluators was 96.2%. Median RFS of 25 responders and 29 non-responders was not reached (NR) vs 18.2 mo [hazard ratio (HR)= 0.35, P = 0.023], and median OS was NR vs 40.7 mo (HR = 0.3, P = 0.016), respectively. This prognostic value was statistically significant even after adjustment for age, eastern cooperative oncology group performance status, macroscopic type, reason for NAC, and T- and Nclassification (HR = 0.23, P = 0.018). This result was also observed even in subgroup analyses for different macroscopic types (Borrmann type 4/non-type 4) and histological types (differentiated/undifferentiated). Moreover, the adjusted HR for OS between responders and non-responders was lower in this method than that in the conventional histological evaluation of Japanese Classification of Gastric Carcinoma criteria (0.23 vs 0.39, respectively). CONCLUSION The measurement of pathological response using digitally captured virtual microscopic slides may be useful in clinical practice.

Advances in Drug Therapy for Alzheimer’s Disease

Alzheimer’s disease(AD)is a chronic neurodegenerative disease that mainly causes dementia.It is a serious threat to the health of the global elderly population.Considerable money and effort has been invested in the development of drug therapy for AD worldwide.Many drug therapies are currently under development or in clinical trials,based on two known mechanisms of AD,namely,Aβtoxicity and the abnormal Tau hyperphosphorylation.Numerous drugs are also being developed for other AD associated mechanisms such as neuroinflammation,neurotransmitter imbalance,oxidative damage and mitochondrial dysfunction,neuron loss and degeneration.Even so,the number of drugs that can successfully improve symptoms or delay the progression of the disease remains very limited.However,multi-drug combinations may provide a new avenue for drug therapy for AD.In addition,early diagnosis of AD and timely initiation of treatment may allow drugs that act on the early pathological processes of AD to help improve the symptoms and prevent the progression of the condition.

Fertility-sparing surgeries without adjuvant therapy through term pregnancies in a patient with low-grade endometrial stromal sarcoma:A case report

BACKGROUND Low-grade endometrial stromal sarcoma(LGESS)is a rare indolent tumor with a favorable prognosis.With the importance of improving quality of life recognized,fertility-sparing surgery may be an option for those young women.However,most of the reports suggested that stage IA patients might be candidates for fertility-sparing surgery,and adjuvant hormonal treatment was considered a feasible adjuvant therapy for reducing the recurrence risk of patients with LGESS and hysterectomy was recommended after the completion of pregnancy and delivery.CASE SUMMARY A 28-year-old pregnant woman diagnosed with stage IB LGESS was treated by fertility-sparing surgery when term cesarean section delivery was performed.Without any adjuvant treatment,she had the other successful term pregnancy and cesarean section 45 mo after first fertility-sparing surgery.Moreover,only hysteroscopic resection was performed to retain fertility again even when the tumor recurred after 6 years.So far the patient’s fertility and disease-free status have remained for more than 8 years without any adjuvant therapy despite local resection of the sarcoma.And the two babies were in good health.CONCLUSION For young patients with stage I LGESS,it seems that repeated fertility-sparing surgeries could be performed even after two term deliveries and the tumor recurrence,and it might be attempted without adjuvant therapy but the counseling should be considered as mandatory.