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.

Coordination of distinctive pesticide adjuvants and atomization nozzles on droplet spectrum evolution for spatial drift reduction

Pesticide adjuvants,as crop protection products,have been widely used to reduce drift loss and improve utilization efficiency by regulating droplet spectrum.However,the coordinated regulation mechanisms of adjuvants and nozzles on droplet spectrum remain unclear.Here,we established the relationship between droplet spectrum evolution and liquid atomization by investigating the typical characteristics of droplet diameter distribution near the nozzle.Based on this,the regulation mechanisms of distinctive pesticide adjuvants on droplet spectrum were clarified,and the corresponding drift reduction performances were quantitively evaluated by wind tunnel experiments.It shows that the droplet diameter firstly shifts to the smaller due to the liquid sheet breakup and then prefers to increase caused by droplet interactions.Reducing the surface tension of sprayed liquid facilitates the uniform liquid breakup and increasing the viscosity inhibits the liquid deformation,which prolong the atomization process and effectively improve the droplet spectrum.As a result,the drift losses of flat-fan and hollow cone nozzles are reduced by about 50%after adding organosilicon and vegetable oil adjuvants.By contrast,the air induction nozzle shows a superior anti-drift ability,regardless of distinctive adjuvants.Our findings provide insights into rational adjuvant design and nozzle selection in the field application.

TRIANGLE operation,combined with adequate adjuvant chemotherapy,can improve the prognosis of pancreatic head cancer:A retrospective study

BACKGROUND The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein,celiac axis-common hepatic artery,and superior mesenteric artery to improve patient prognosis.Although previously promising in patients with locally advanced pancreatic ductal adenocarcinoma(PDAC),data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy(PD).AIM To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable PDAC.METHODS This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023,with or without the TRIANGLE operation.Patients were divided into the PD_(TRIANGLE)and PD_(non-TRIANGLE)groups.Surgical and survival outcomes were compared between the two groups.Adequate adjuvant chemotherapy was defined as adjuvant chemotherapy≥6 months.RESULTS The PD_(TRIANGLE)and PD_(non-TRIANGLE) groups included 52 and 55 patients,respectively.There were no significant differences in the baseline characteristics or perioperative indexes between the two groups.Furthermore,the recurrence rate was lower in the PD_(TRIANGLE) group than in the PD_(non-TRIANGLE) group(48.1%vs 81.8%,P<0.001),and the local recurrence rate of PDAC decreased from 37.8%to 16.0%.Multivariate Cox regression analysis revealed that PD_(TRIANGLE)(HR=0.424;95%CI:0.256-0.702;P=0.001),adequate adjuvant chemotherapy≥6 months(HR=0.370;95%CI:0.222-0.618;P<0.001)and margin status(HR=2.255;95%CI:1.252-4.064;P=0.007)were found to be independent factors for the recurrence rate.CONCLUSION The TRIANGLE operation is safe for PDAC patients undergoing PD.Moreover,it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.

Optimal extent of lymphadenectomy improves prognosis and guides adjuvant chemotherapy in esophageal cancer: A propensity scorematched analysis

BACKGROUND The optimal extent of lymphadenectomy in esophageal squamous cell carcinoma(ESCC)patients remained debatable.AIM To explore the ideal number of cleared lymph nodes in ESCC patients undergoing upfront surgery.METHODS In this retrospective,propensity score-matched study,we included 1042 ESCC patients who underwent esophagectomy from November 2008 and October 2019.Patients who underwent neoadjuvant therapy were excluded.We collected pa-tients’clinicopathological features and information regarding lymph nodes,in-cluding the total number of resected lymph nodes(NRLN),and pathologically diagnosed positive lymph nodes(RPLN).SPSS and R software were used for statistical analysis.RESULTS Among the included 1042 patients,two cohorts:≤21(n=664)and>21 NRLN(n=378)were identified.The final prognostic model included four variables:T stage,N,venous thrombus,and the number of removed lymph nodes.Among them,NRLN>21 was determined as an independent prognosticator after surgery for esophageal cancer(hazards regression=0.66,95%confidence interval:0.50-0.87,P=0.004).A nomogram was created based on the regression coefficients of the variables in the final model.In the training cohort,the predictive model dis-played an uncorrected five-year overall survival C-index of 0.659,with a bootstrap-corrected C-index of 0.654.In the subgroup analysis,adjuvant chemotherapy was beneficial in the subgroup with NRLN>21 and RPLN≤0.16 and NRLN≤21 and RPLN>0.16.CONCLUSION NRLN>21 was an independent prognostic factor after ESCC surgery.The combination of NRLN and RPLN may provide a reference for adjuvant chemotherapy use in potential beneficiaries.

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.

Adjuvant chemotherapy for isolated resectable colorectal lung metastasis: A retrospective study using inverse probability treatment weighting propensity analysis

BACKGROUND The benefit of adjuvant chemotherapy(ACT)for patients with no evidence of disease after pulmonary metastasis resection(PM)from colorectal cancer(CRC)remains controversial.AIM To assess the efficacy of ACT in patients after PM resection for CRC.METHODS This study included 96 patients who underwent pulmonary metastasectomy for CRC at a single institution between April 2008 and July 2023.The primary end-point was overall survival(OS);secondary endpoints included cancer-specific survival(CSS)and disease-free survival(DFS).An inverse probability of treat-ment-weighting(IPTW)analysis was conducted to address indication bias.Sur-vival outcomes compared using Kaplan-Meier curves,log-rank test,Cox regre-ssion and confirmed by propensity score-matching(PSM).RESULTS With a median follow-up of 27.5 months(range,18.3-50.4 months),the 5-year OS,CSS and DFS were 72.0%,74.4%and 51.3%,respectively.ACT had no significant effect on OS after PM resection from CRC[original cohort:P=0.08;IPTW:P=0.15].No differences were observed for CSS(P=0.12)and DFS(P=0.68)between the ACT and non-ACT groups.Multivariate analysis showed no association of ACT with better survival,while sublobar resection(HR=0.45;95%CI:0.20-1.00,P=0.049)and longer disease-free interval(HR=0.45;95%CI:0.20-0.98,P=0.044)were associated with improved survival.CONCLUSION ACT does not improve survival after PM resection for CRC.Further well-designed randomized controlled trials are needed to determine the optimal ACT regimen and duration.

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.

Predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa squamous cell lung cancer:A retrospective analysis

BACKGROUND Lung cancer(LC)is a global medical,social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms.LC is characterized by an aggressive course,and in the presence of disease recurrence risk factors,patients,even at an early stage,may be indicated for adjuvant therapy to improve survival.However,combined treatment does not always guarantee a favorable prognosis.In this regard,establishing predictors of LC recurrence is highly important both for determining the optimal treatment plan for the patients and for evaluating its effectiveness.AIM To establish predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa lung squamous cell carcinoma(LSCC).METHODS A retrospective case-control cohort study included 69 patients with LSCC who underwent radical surgery at the Orenburg Regional Clinical Oncology Center from 2009 to 2018.Postoperatively,all patients received adjuvant chemotherapy.Histological samples of the resected lung were stained with Mayer's hematoxylin and eosin and examined under a light microscope.Univariate and multivariate analyses were used to identify predictors associated with the risk of disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with a high risk of disease recurrence and those with a low risk of disease recurrence.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.Differences were considered to be significant at P<0.05.RESULTS The following predictors of a high risk of disease recurrence in patients with stage IIb-IIa LSCC were established:a low degree of tumor differentiation[odds ratio(OR)=7.94,95%CI=1.08-135.81,P=0.049];metastases in regional lymph nodes(OR=5.67,95%CI=1.09-36.54,P=0.048);the presence of loose,fine-fiber connective tissue in the tumor stroma(OR=21.70,95%CI=4.27-110.38,P=0.0002);and fragmentation of the tumor solid component(OR=2.53,95%CI=1.01-12.23,P=0.049).The area under the curve of the predictive model was 0.846(95%CI=0.73-0.96,P<0.0001).The sensitivity,accuracy and specificity of the method were 91.8%,86.9%and 75.0%,respectively.In the group of patients with a low risk of LSCC recurrence,the 1-,2-and 5-year disease-free survival(DFS)rates were 84.2%,84.2%and 75.8%,respectively,while in the group with a high risk of LSCC recurrence the DFS rates were 71.7%,40.1%and 8.2%,respectively(P<0.00001).Accordingly,in the first group of patients,the 1-,2-and 5-year overall survival(OS)rates were 94.7%,82.5%and 82.5%,respectively,while in the second group of patients,the OS rates were 89.8%,80.1%and 10.3%,respectively(P<0.00001).CONCLUSION The developed method allows us to identify a group of patients at high risk of disease recurrence and to adjust to ongoing treatment.

Pharmacological adjuvants for diabetic vitrectomy surgery

Diabetic vitrectomy is a highly intricate surgical procedure performed during the advanced stages of diabetic retinopathy(DR).It is used to treat conditions such as tractional or combined retinal detachment,vitreous hemorrhage,and subhyaloid hemorrhage,which are all severe manifestations of proliferative DR.The results of the surgery are uncertain and variable.Vitreoretinal surgery has made significant progress since the early stages of vitrectomy.In the past ten years,advancements in intravitreal pharmacotherapy have emerged,offering new possibilities to improve the surgical results for our patients.Within the realm of medical terminology,an"adjunct"refers to a pharmaceutical or substance employed to aid or expedite the primary therapeutic intervention for a particular ailment.Their introduction has broadened the range of therapeutic choices that are accessible prior to,during,and following surgical procedures.This review article will specifically analyze the pharmacological adjuncts used in diabetic vitrectomy surgery,with a focus on their role in facilitating or aiding specific steps of the procedure.The implementation of this system of categorization offers benefits to the surgeon by allowing them to foresee potential difficulties that may occur during the surgical procedure and to choose the appropriate pharmacological agent to effectively tackle these challenges,thus enhancing surgical success rates.

Clinical,pathological,and adjuvant chemotherapy use differences among microsatellite unstable and microsatellite stable colon cancers

Background:Colon cancers are categorized into mismatch repair deficient/microsatellite unstable(MSI-H)and mismatch repair proficient/microsatellite stable(MSS)cancers.This study aims to compare the disease char-acteristics and trends in the utilization of cancer therapies across different age groups and stages in these two groups.Methods:MSI-H and MSS colon adenocarcinomas from 2010 to 2016 were identified using the National Can-cer Database.We compared patient and disease characteristics between the two groups and evaluated the use of adjuvant chemotherapy across age groups and cancer stages.Within MSI-H and MSS groups,we conducted a land-mark analysis after propensity score matching for adjuvant chemotherapy versus no chemotherapy to determine its effect on survival.Results:Of the 542,368 patients that met inclusion criteria,120,751(22%)had mismatch repair results avail-able-out of these 96,928(80%)had MSS colon cancers while 23,823(19.7%)had MSI-H cancers.MSI-H disease had a bimodal age distribution(<40 years=22%;≥75 years=26%)and was frequent among females(22%)and non-Hispanic Whites(20%).Among those<65 years,15%of low-risk stage 2 MSI-H patients and 40%of high-risk stage 2 MSI-H patients received adjuvant chemotherapy.More than two-thirds of stage 3 patients<65 years received adjuvant chemotherapy in both groups.After conducting propensity-score matching for age,gender,and co-morbidities,we found that adjuvant chemotherapy use had a trend towards lower overall survival(OS)in low-risk stage 2 MSI-H(HR=1.8[95%CI,0.8-4.02])and high-risk stage 2 MSI-H(HR=1.42[95%CI,0.96-2.12])groups.Adjuvant chemotherapy significantly improved OS in stage 3 colon cancer patients irrespective of microsatellite status or risk category of disease.Conclusions:MSI-H colon cancer had bimodal age distribution.Among stage 2 MSI-H patients<65 years,a notable proportion received adjuvant chemotherapy.Among MSI-H stage 2 patients,adjuvant chemotherapy use was associated with lower survival while it significantly improved survival for stage 3 patients,irrespective of MSI status.

Immune Effect of Combination of Universal Molecular Adjuvant and IBDV Subunit

In order to evaluate the immune effect of the protein expressed by the universal vector pET-mLTA-CTLA-4 plus IBDV subunit, the fusion protein mLTA-CTLA-4 was expressed and purified. Protein toxicity tests were carried out on rabbits.The VP2 gene of infectious bursal virus was amplified by RT-PCR, and lately used for pET-VP2 construction. Ten-day-old free healthy chickens were chosen for a grouped test, including the mLTA-CTLA-4（at different doses） plus VP2 groups, IBDV living vaccine group and control group. Serum and mucosal samples were collected regularly and the neutralization titers of IgG and IgA were assayed, while an animal protection test was conducted to determine the protection rate. The results showed that the protein m LTA-CTLA-4 was non-toxic and its protection rate was100%. IgG or IgA levels in the IBDV vaccine group were slightly higher than those in recombinant protein groups. These results indicated that the recombinant protein mLTA-CTLA-4 could be applied with IBDV subunit vaccine to protect chickens from infection.

Immunological Adjuvant Function of Aluminium Phosphate and Chicken IL-18 in NDV F Gene Vaccine

[Objective] This study aimed to investigate the immunological adjuvant function of aluminium phosphate and chicken IL-18 in NDV F gene vaccine. [Method] The vaccine （0.2 ml） containing aluminum phosphate adjuvant （90 μg）, pcDNA/F （200μg）, and pcDNA/chlL-18 （200 μg） was prepared. The 7 d old chick- ens to be tested were randomly divided into six groups （12 chickens in each group） and immunized through intramuscular injection with inactivated Newcastle disease vaccines, pcDNA/F＋pcDNA/chlL-18＋phosphate aluminum, pcDNA/F, pcDNA/F.＋pcDNA/ chlL-18, pcDNA/F＋aluminum phosphate, and physiological saline respectively; the secondary immunization was conducted with the same dose when the chickens were 21 d old. Their blood was sampled 0, 7, 14, 21, 28 d after first immunization. Anti- body titer was detected with ELISA and T cell transformation rate was measured with MIT. Experimental chicken will be challenged with 30 LD50 NDV virulence 28 d after first immunization. [Result] The survival rate of the chickens immunized with pcDNA/F＋aluminium phosphate＋pcDNA/chlL-18 achieved 8/12, higher than that of those immunized with pcDNA/F 4/12 and pcDNA/F＋pcDNA/chlL-18 （6/12）. The NDV antibody titer of the chickens immunized with pcDNA/F＋ aluminum phosphate, pcD- NA/F＋pcDNA/chlL-18 and pcDNA/F＋pcDNA/chlL-18＋aluminum phosphate is not differ- ent （P〉0.05）, but significantly lower than that of the chickens immunized with tradi- tional vaccine （P〈0.05）. The T cell transformation rate of the chickens immunized with pcDNA/F＋pcDNA/chlL-18＋aluminium phosphate was obviously higher than that of the chickens immunized with pcDNA/F （P〈0.05）. The T cell transformation rates of chickens immunized with pcDNA/F and the traditional vaccine showed no signifi- cant difference （P〉0.05）. [Conclusion] Combination of aluminium phosphate and pcD- NA/chlL-18 can significantly enhance the immune effect of NDV F gene vaccine.

Adjuvant chemotherapy for resected colorectal cancermetastases:literature review and meta-analysis

Surgical resection is the only option of cure for patients with metastatic colorectal cancer(CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy after surgical resection of CRC metastases despite the lower level of evidence(based on the quality of studies in this setting). However, there is still no standard treatment and the effective role of an adjuvant therapy remains controversial. The aim of this review is to report the state-of-art of systemic chemotherapy and regional chemotherapy with hepatic arterial infusion in the management of patients after resection of metastases from CRC, with a literature review and meta-analysis of the relevant randomized controlled trials.

Adjuvant chemotherapy with paclitaxel and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma

Objective： No standard postoperative adjuvant chemotherapy has ever been established in node-positive esophageal squamous cell carcinoma （ESCC）. This is a study to explore the effect of postoperative paelitaxel （PTX） and cisplatin （DDP） in lymph node-positive, completely resected thoracic ESCC patients. Methods： We conducted a prospective phase II trial. Patients had pathologically node-positive thoracic ESCC with negative margins. Outcomes of disease-free survival （DFS） and overall survival （OS） were compared with a matched historical control cohort. The postoperative chemotherapy regimen consisted of 4 to 6 cycles of PTX 150 mg/m2 administered intravenously on d 1 followed by DDP 50 mg/m2 on d 2 every 14 d. Results： Forty-three patients were accrued from December 2007 to May 2012 at Cancer Hospital of Chinese Academy of Medical Sciences for adjuvant chemotherapy. The historical control group consisted of 80 patients who received complete resection but no adjuvant chemotherapy during the same period of time. Of the 43 patients with adjuvant chemotherapy, 37 （86.0%） patients completed 4 to 6 cycles of chemotherapy. The 3-year DFS rates were 56.3% in the adjuvant group and 34.6% in the control group （P=0.006）. The 3-year OS rates were 55.0% in the adjuvant group and 37.5% in the control group （P=0.013）. Multivariate analysis revealed that postoperative chemotherapy was the significant predictor for improved OS （P=0.005）. Conclusions： Biweekly adjuvant PTX and DDP might improve 3-year DFS and OS in lymph node-positive, curatively resected thoracic ESCC patients. These conclusions warrant further study in randomized phase III clinical trials.

Adjuvant effects of saponins on animal immune responses

Vaccines require optimal adjuvants including immunopotentiator and delivery systems to offer long term protection from infectious diseases in animals and man. Initially it was believed that adjuvants are responsible for promoting strong and sustainable antibody responses. Now it has been shown that adjuvants influence the isotype and avidity of antibody and also affect the properties of cell-mediated immunity. Mostly oil emulsions, lipopolysaccharides, polymers, saponins, liposomes, cytokines, ISCOMs (immunostimulating complexes), Freund’s complete adjuvant, Freund’s incomplete adjuvant, alums, bacterial toxins etc., are common adjuvants under investigation. Saponin based adjuvants have the ability to stimulate the cell mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity. In the present study the importance of adjuvants, their role and the effect of saponin in immune system is reviewed.

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.

Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.

Adjuvant chemotherapy for gastric cancer:Current evidence and future challenges

Gastric cancer still represents one of the major causes of cancer mortality worldwide.Patients survival is mainly related to stage,with a high proportion of patients with metastatic disease at presentation.Thus,the cure rate largely depend upon surgical resection.Despite the additional,albeit small,benefit of adjuvant chemotherapy has been clearly demonstrated,no general consensus has been reached on the best treatment option.Moreover,the narrow therapeutic index of adjuvant chemotherapy(i.e.,limited survival benefit with considerable toxicity)requires a careful assessment of expected risks and benefits for individual patients.Treatment choices vary widely based on the different geographic areas,with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States.In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses.The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery;the same Authors also showed that disease free survival may be used as a surrogate end-point for overall survival.We finally discuss future research issues such as the need of economic evaluations,development of prognostic or predictive biomarkers,and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment.

Adjuvants to local anesthetics: Current understanding and future trends

Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by itsduration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids(dexamethasone), anti-inflammatory agents(parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action(tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability(liposomal, microspheres and cyclodextrin systems) and further studies with other drugs(adenosine, neuromuscular blockers, dextrans).

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.