Prognostic and predictive significance of MSI in stages Ⅱ/Ⅲ colon cancer

In colon cancer,classic disease staging remains the key prognosis and treatment determinant.Although adjuvant chemotherapy has an established role in stageⅢcolon cancer patients,in stageⅡit is still a subject of controversy due to its restriction to a small subgroup of patients with high-risk histopathologic features.Patients with stageⅡtumors form a highly heterogeneous group,with five-year relative overall survival rates ranging from 87.5%(ⅡA)to 58.4%(ⅡC).Identifying those for whom adjuvant chemotherapy would be appropriate and necessary has been challenging,and prognostic markers which could serve in the selection of patients more likely to recur or benefit from adjuvant chemotherapy are eagerly needed.The stronger candidate in this category seems to be microsatellite instability(MSI).The recently reported European Society for Medical Oncology guidelines suggest that MSI should be evaluated in stageⅡcolorectal cancer patients in order to contribute in treatment decisionmaking regarding chemotherapy administration.Thehypothetical predictive role of MSI regarding its response to 5-fluorouracil-based adjuvant chemotherapy has proven a much more difficult issue to address.Almost every possible relation between MSI and chemotherapy outcome has been described in the adjuvant colon cancer setting in the international literature,and the matter is far from being settled.In this current report we critically evaluate the prognostic and predictive impact of MSI status in patients with stageⅡand stageⅢcolon cancer patients.

Macroscopic appearance of TypeⅣand giant Type Ⅲ is a high risk for a poor prognosis in pathological stage Ⅱ/Ⅲ advanced gastric cancer with postoperative adjuvant chemotherapy

AIM To evaluate whether a high risk macroscopic appearance(Type Ⅳ and giant Type Ⅲ) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage Ⅱ/Ⅲ(p Stage Ⅱ/Ⅲ) gastric cancer.METHODS One hundred and seventy-two advanced gastric cancer(defined as pT2 or beyond) patients with p Stage Ⅱ/Ⅲ who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival(RFS)(35.7%) and overall survival(OS)(34%) than an average risk appearance(P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13^(th) Japanese Gastric Cancer Association(JGCA) pT(P = 0.01), but not with the 13^(th) JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13^(th) JGCA p Stage(P < 0.0001)and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified highrisk macroscopic appearance(P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13^(th) JGCA stage in p Stage Ⅱ/Ⅲ advanced gastric cancer.

Stage Ⅲ should be subclassified into Stage ⅢA and ⅢB in the American Joint Committee on Cancer(8^(th) Edition) staging system for pancreatic cancer

AIM To ascertain the prognostic role of the T4 and N2 category in stage Ⅲ pancreatic cancer according to the 8 th edition of the American Joint Committee on Cancer(AJCC) classification.METHODS Patients were collected from the Surveillance Epidemiology and End Results(SEER) database(2004-2013) and were divided into three groups: T(1-3)N2, T4 N(0-1), and T4 N2. Overall survival(OS) and disease-specific survival(DSS) of patients were evaluated by the Kaplan-Meier method. RESULTS For the first time, we found a significant difference in OS and DSS between T(1-3)N2/T4 N(0-1) and T4 N2 butnot between T(1-3)N2 and T4 N(0-1). A higher grading correlated with a worse prognosis in the T(1-3)N2 and T4 N2 groups.CONCLUSION Patients with stage T4 N2 had a worse prognosis than those with stage T(1-3)N2/T4 N(0-1) in the 8 th edition AJCC staging system for pancreatic cancer. We recommend that stage Ⅲ should be subclassified into stage ⅢA [T(1-3)N2/T4 N(0-1)] and stage ⅢB(T4 N2).

Effect of TCM Combined with Chemotherapy on Immune Function and Quality of Life of Patients with Non-small Cell Lung Cancer inStage Ⅲ-Ⅳ

Objective: To observe and compare the effect of traditional Chinese medicine (TCM) combined with chemotherapy (CT) on immune function and quality of life (QOL)of patients with non-small cell lung cancer (NSCLC) in stage Ⅲ-Ⅳ. Methods: One hundred cases with stage Ⅲ-Ⅳ NSCLC were randomly divided into two groups. The treated group (n=50) received CT combined with TCM, and the control group received CT alone. The percentage of T lymphocyte subset in peripheral blood and the change of natural killer (NK) cell count were observed after treatment. The QOL and tolerance of CT were also compared between the two groups after treatment. Results: In the treated group, CD3 cell count, CD4 cell count, CD4/ CDg ratio and NK cell activity were higher than those in control group, while CD8 cell count in the treated group was lower than that in the control group (P<0.05), and QOL and tolerance of CT in the treated group were also better (P<0.05). Conclusion: TCM combined with CT could raise the patients' ability in tolerating CT in stage Ⅲ-ⅣNSCLC.

Role of radiation therapy in the management of stage Ⅲ non-small cell lung cancers: current status and controversies

The treatment of stage Ⅲ non-small cell lung cancer(NSCLC) consisting of the heterogeneous stage subsets remains a challenge. Overall, it has been gradually recognized that radiation therapy(RT) plays a crucial role in the management of stage Ⅲ NSCLC. One superior sulcus tumors are the subset for which the trimodality treatments are clearly preferred. One subset of stage Ⅲ NSCLC has a minimal disease burden with microscopic p N2 disease or with discrete p N2 involvement identified preoperatively, thus technically could undergo a surgical resection. For the incidentally found p N2 disease after complete surgery(ⅢA-1, ⅢA-2), the value of postoperative radiotherapy(PORT) has been recognized by a reassessment based on new data. However, doubt persists regarding how to define the clinical target volume for PORT. For the discrete p N2 involvement identified preoperatively(a selected part of ⅢA-3), induction chemoradiation therapy(CRT) before surgery may yield a survival advantage, although the phase Ⅲ randomized trials in this issue are not conclusive. The other major subset of stage Ⅲ NSCLC is the infiltrative stage Ⅲ NSCLC with N2 or N3 nodal disease(ⅢA-3, ⅢA-4, and ⅢB), for which concurrent CRT is considered as the current standard of care. The potential role of radiation dose escalation/acceleration has been proposed; however, the optimal dose fractionation remains an important unresolved question. Additionally, the role of prophylactic cranial irradiation for stage Ⅲ patients with high risk of brain metastasis is worth of further assessment. Moreover, how to integrate molecular targeted therapy with RT, as well as whether they had a role in stage Ⅲ diseases, are other controversies actively under study in ongoing trials. This review specifically describes the updated role of RT in multimodal approach to treat stage Ⅲ NSCLC and the controversies regarding these results in various situations.

Yiqi Huoxue Decoction in the treatment of Qi and yin deficiency and stasis type diabetic nephropathy in stageⅢ and its effect on VEGF and TGF-β1

Objective:To observe the efficacy of Yiqi Huoxue Decoction in the treatment of patients with diabetic nephropathy(DN)stageⅢwith qi and yin deficiency and stasis and its effects on vascular endothelial growth factor(VEGF)and transforming growth factor-β(TGF-β1).Methods:Sixty patients with stage DN of Qi-yin deficiency and stasis type DN who were treated in the Endocrinology Department of the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine from September 2018 to December 2019 were selected as the research subjects.The remainder method was used to divide them into 30 cases in the observation group and 30 cases in the control group.Patients in both groups were referred to the guidelines and expert consensus for general treatment of DN(hypogl-ycemic,antihypertensive,lipid-lowering,etc.).The control group was given pancreatic kallikrein enteric-coated tablets orally once,120U,3 times a day,and the observation group was given The traditional Chinese medicine Yiqi Huoxue Decoction was taken orally,one dose daily,twice a day in the morning and evening;the two groups intervened continuously for 8 weeks.Detect blood FPG,PBG,HbA1c,β2-MG,BUN,SCr,VEGF,TGF-β1,and urine mALB and UACR levels before and after treatment,and calculate eGFR before and after treatment in both groups;observe changes in TCM syndrome scores in the two groups,Compare its clinical efficacy.Results:After 8 weeks of treatment,the total clinical effective rate of patients in the observation group was 93.3%,which was significantly different from the control group of 76.6%(P<0.05);the TCM syndrome scores in the observation group were significantly lower than those before treatment and in the control group(P<0.05);The levels of FPG,HbA1c,PPG,mALB,β2-MG,UACR,VEGF,and TGF-β1 in the observation group were significantly lower than those in the control group,with significant differences(P<0.05).The levels of SCr and BUN in the observation group were significantly lower.Compared with before treatment,eGFR increased,but there was no signi-ficant difference(P>0.05).Conclusion:Yiqi Huoxue Decoction for the treatment of patients with DN typeⅢqi-yin deficiency and stasis type,not only helps to lower blood sugar levels,improve TCM syndromes,but also can reduce early renal damage,reduce urine albumin,and delay kidney function It may be further worsened and has better safety.The mechanism may be related to reducing the levels of VEGF and TGF-β1,thereby delaying the fibrosis of tubulointerstitial scar and inhibi-ting glomerular capillary sclerosis.

Bushen Huoxue method combined with ACEI/ARB in treating diabetic kidney disease (stage Ⅲ):A meta-analysis and trial sequential analysis

Objective:To evaluate the efficiency of Bushen Huoxue method with ACEI/ARB in treating diabetic kidney disease(stageⅢ).Methods:A total of 8 major electronic databases(CNKI,WanFang,VIP,Sinomed,Pubmed,Embase,Cochrane Liberary,Web of Science)were retrieved since the establishment of the database to October 9,2019.Two reviewers extracted data,and assessed the methodological quality of the included studies.The analysis was made by Stata 15.0 and TSA 0.9 softwares.Results:A total of 10 RCT studies were obtained,including 711 patients with diabetic kidney disease of stageⅢ.Meta-analysis showed that the method of Bushen Huoxue with ACEI/ARB could reduce UAER[WMD=-31.24,95%CI(-42.98,-19.51)],β2-GM[WMD=-92.95,95%CI(-166.05,-19.85)],LDL-C[WMD=-0.19,95%CI(0.19,-0.30)].However,there were no significant effect for HbAlc[WMD=-0.08,95%CI(-0.17,-0.00)],Scr[WMD=-12.96,95%CI(-39.82,13.90)],BUN[WMD=-0.14,95%CI(-0.44,0.17)].The result of TSA indicated that the method of Bushen Huoxue with ACEI/ARB was effective in the treatment of diabetic kidney disease of stageⅢ.Conclusion:The study show that the method of Bushen Huoxue with ACEI/ARB can reduce urinary protein,renal tubular injury and LDL-C in patients with diabetic kidney disease of stageⅢ,and had no effect on HbAlc and renal function.But the conclusion of this study needs further research of high quality.

Unresectable stage Ⅲ non-small-cell lung cancer: Have we made any progress?

Lung cancer is responsible for the most cancer deaths worldwide with an incidence that is still rising. One third of patients have unresectable stage ⅢA or stage ⅢB disease. The standard of care for locally advanceddisease in patients with good performance status consists of combined modality therapy in particular concurrent chemoradiotherapy. But despite a lot of efforts done in the past, local control and survival of patients with unresectable stage Ⅲ non-small-cell lung cancer(NSCLC) remains poor. Improving outcomes for patients with unresectable stage Ⅲ NSCLC has therefore been an area of ongoing research. Research has focused on improving systemic therapy, improving radiation therapy or adding a maintenance therapy to consolidate the initial therapy. Also implementation of newer targeted therapies and immunotherapy has been investigated as well as the option of prophylactic cranial irradiation. This article reviews the latest literature on improving local control and preventing distant metastases. It seems that we have reached a plateau with conventional chemotherapy. Radiotherapy dose escalation did not improve outcome although increasing radiation dose-intensity with new radiotherapy techniques and the use of newer agents, e.g., immunotherapy might be promising. In the future well-designed clinical trials are necessary to prove those promising results.

The famous Chinese medicine doctor Xue Jing-Dong Taohong Siwu Decoction cured 1 case of primary liver cancer stage Ⅲa

Primary liver cancer is the most common malignant tumor of the liver.Surgery,intervention,radiotherapy,and chemotherapy are the main treatment methods in the early stage,and the basic principles of post-treatment are palliative treatment and symptomatic treatment.Xue Jing-Dong,a famous Chinese doctor,started from the etiology and pathogenesis of liver cancer,used the methods of promoting blood circulation to remove blood stasis,nourishing blood and replenishing liver,and applied Taohong Siwu Decoction based on long-term clinical experience to cure 1 case of primary liver cancer stage Ⅲa in two years.The patient’s survival period can be prolonged and the quality of life can be improved.The author begins with the diagnosis of stage Ⅲa liver cancer,western medicine treatment methods,and previous treatment experience of traditional Chinese medicine,and briefly describes the diagnosis and treatment of this patient.

The path toward prognostication and prediction in stage Ⅱ colon cancer

Currently,there are several newer biomarkers that may be clinically useful in colon cancer. This paper focuses on a few of these biomarkers,namely microsatellite instability,loss of heterozygosity at chromosome 18q(LOH18q) and multi-gene assays,and discusses the clinical evidence behind their predictive or prognostic abilities. The results show that although there have been several newer prognostic factors identified,such as LOH18 q and multi-gene assays,none of these factors can predict benefit from treatment. Therefore,ongoing prospective clinical trials are still needed to further assess the role and optimal use of these tests.

Xiaozhiling Four-Step Injection in Treating Hemorrhoids of Stages Ⅲ and Ⅳ -A Sclerotherapeutic Approach of Thrombosing Branches of Artery Rectalis Superior

Objectice: Traditional Chinese medicine has a long history of over 2, 000 years in treating piles,based on the principle 'Sore herbs can be stringent while the puckery can control prolapse', and a large amount of precious experience has been accumulated. Methods: Prepared mainly with such effective compositions as gallnut (Galla Chinensis) and alum, Xiaozhiling (XZL) was applied in treating piles of stages Ⅲ and Ⅳ. Fourstep injections were given at (1 ) the branches of artery rectalis superior (ARS), (2) the submucosa, (3) the mucous lamina propria, and (4) the sinous veins. The injection obliterated the ARS and made piles sclerosed, atrophied and finally disappear. Results: From 1987 to 1996, piles of stages Ⅲ and Ⅳ were treated of 21, 361 cases. Of all the cases, 21, 148 (99 % ) were cured, 203 (0. 95% ) improved and 10 (0. 05% ) ineffective for whom surgery was used. Of the 620 cases who were followed up 3 years after treatment, it recurred in only 6 cases (prolapse, 1 % ). Conclusion: This method summarized a relatively ideal non-operative approach in the treatment of piles of stages Ⅲ and Ⅳ.

A multivariate analysis of prognostic determinants for stages Ⅱ and Ⅲ colorectal cancer in 141 patients

Background Previous prognosis analyses of colorectal cancer （CRC） patients with stage Ⅱ and Ⅲ disease were done as separate categories. The purpose of this study was to analyze prognostic factors associated with survival in a group of patients who underwent radical resection of stages Ⅱ and Ⅲ CRC.Methods A retrospective review was performed for 141 consecutive stages Ⅱ and Ⅲ patients who had undergone radical resection of coloractal adenocarcinoma between May 2003 and November 2003. Univariate and multivariate analyses were performed to assess the effect of record variables on disease free survival and overall survival.Results The median follow-up time was 59 months, and the 3-and 5-year survival rates were 76% and 68%,respectively. Four factors were independently associated with a worse disease-free survival： diabetes （hazard ratio （HR） 2.338; 95% confidence interval （CI） 1.011-5.407）, expression of cyclooxygenase-2 （Cox-2） （HR 0.335; 95% CI 0.126-0.888）, expression of matrix metalloproteinases 2 （MMP-2） （FIR 0.233; 95% CI 0.101-0.541）, expression of vascular endothelial growth factor （VEGF） （HR 0.295; 95% CI 0.088-0.996）. Four factors were independently associated with a worse overall survival： lymph nodes metastasis （HR 1.67; 95% CI 1.29-2.14）, Cox-2 positive （HR 0.056; 95% CI 0.247-0.731）, MMP-2 positive （HR 0.398; 95% CI 0.190-0.836）, VEGF （HR 0.364; 95% CI 0.090-0.716）.Conclusions Diabetes, expression of Cox-2, MMP-2 and VEGF were independently associated with a worse diseasefree survival. Lymph nodes metastasis, expression of Cox-2, MMP-2 and high level of VEGF predicted a poor overall survival.

The clinical trial research of preoperative induced hypertension chemotherapy on the III staging cardia or fundus of stomach carcinoma

Objective： To observation the therapeutic effect and the adverse reaction of preoperative induced hypertension chemotherapy （IHC） on the Ⅲ staging cardia or fundus of stomach carcinoma. Methods： 49 cases of the Ⅲ staging cardia or fundus of stomach carcinoma were divided into two groups at random. The observation group included 19 cases and the control group included 30 cases. Every case used one cycle chemotherapy. The observation group （IHC group） used chemotherapy and AT Ⅱ. The control group （simple chemotherapy group） used simple chemotherapy. All cases of the two groups operated after 3 weeks rest. The specimen＇s DNA was analyzed by flow cytometry. Results： The effective power of observation group was 63.2% （12/19）, exairesis ratio was 84.2% （16/19）. The effective power of control group was 30% （9/30）, exairesis ratio was 63.3% （19/30）. DNA ploid determination： 13 cases were diploid and 5 cases were heteropioid in the observation group, 9 cases were diploid and 16 cases were heteroploid in the control group. The operative complications and risks of the two groups did not increase. Conclusion： IHC can increase the therapeutic effect of Ⅲ staging cardia or fundus of stomach carcinoma obviously. IHC is one of the chemotherapy methods that have good future, it has good value of clinic enlarge trial.