Irreversible electroporation for metastatic pancreatic carcinoma with liver metastasis:What does the evidence say

Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.

Optimal sequential therapy using tyrosine kinase inhibitors as the first-line treatment in patients with metastatic renal cell carcinoma: A nationwide multicenter study

Objective:The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor(TKI)as the first-line therapy for patients with metastatic renal cell carcinoma(mRCC)in terms of overall survival(OS),progression-free survival(PFS),and rates of discontinuation and adverse effects during the treatment period.Methods:This is a retrospective,nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December 2017.We focused on patients at either“favorable”or“intermediate”risk according to the International mRCC Database Consortium criteria,and they were followed up(median 335 days).Finally,a total of 1409 patients were selected as the study population.We generated a Cox proportional hazard model adjusted for covariates,and the different therapy schemes were statistically tested in terms of OS as well as PFS.In addition,frequencies of discontinuation and adverse events were compared among the therapy schemes.Results:Of the primary patterns of treatment sequences(24 sequences),“sunitinib epazopanib”and“sunitinibeeverolimuseimmunotherapy”showed the most beneficial results in both OS and PFS with significantly lower hazards than“sunitinib”,which is the most commonly treated agent in Korea.Considering that the“TKIeTKI”structure showed relatively higher discontinuation rates with higher adverse effects,the overall beneficial sequence would be“sunitinibeeverolimuseimmunotherapy”.Conclusion:Among several sequential therapy starting with TKIs,“sunitinibeeverolimuse immunotherapy”was found to be the best scheme for mRCC patients with“favorable”or“intermediate”risks.

Secondary rectal linitis plastica caused by prostatic adenocarcinoma-magnetic resonance imaging findings and dissemination pathways:A case report

BACKGROUND Secondary rectal linitis plastica(RLP)from prostatic adenocarcinoma is a rare and poorly understood form of metastatic spread,characterized by a desmoplastic response and concentric rectal wall infiltration with mucosal preservation.This complicates endoscopic diagnosis and can mimic gastrointestinal malignancies.This case series underscores the critical role of magnetic resonance imaging(MRI)in identifying the distinct imaging features of RLP and highlights the importance of considering this condition in the differential diagnosis of patients with a history of prostate cancer.CASE SUMMARY Three patients with secondary RLP due to prostatic adenocarcinoma presented with varied clinical features.The first patient,a 76-year-old man with advanced prostate cancer,had rectal pain and incontinence.MRI showed diffuse prostatic invasion and significant rectal wall thickening with a characteristic"target sign"pattern.The second,a 57-year-old asymptomatic man with elevated prostatespecific antigen levels and a history of prostate cancer exhibited rectoprostatic angle involvement and rectal wall thickening on MRI,with positron emission tomography/computed tomography PSMA confirming the prostatic origin of the metastatic spread.The third patient,an 80-year-old post-radical prostatectomy,presented with refractory constipation.MRI revealed a neoplastic mass infiltrating the rectal wall.In all cases,MRI consistently showed stratified thickening,concentric signal changes,restricted diffusion,and contrast enhancement,which were essential for diagnosing secondary RLP.Biopsies confirmed the prostatic origin of the neoplastic involvement in the rectum.CONCLUSION Recognizing MRI findings of secondary RLP is essential for accurate diagnosis and management in prostate cancer patients.

Follicular carcinoma of the thyroid with a single metastatic lesion in the lumbar spine:A case report

BACKGROUND The bone is the second most common site of thyroid cancer metastasis,after the lung.Treatment options for bone metastasis of thyroid cancer include surgery,radioiodine therapy(RAIT),external radiation therapy,thyroid-stimulating hormone(TSH)inhibition,bisphosphonates,and small-molecule targeted therapies.In most cases,thyroid carcinoma is found in the thyroid tissue;reports of follicular thyroid carcinoma with a single metastasis to the lumbar spine are rare.CASE SUMMARY We report a case of bone metastasis as the only clinical manifestation of thyroid cancer.The patient was a 67-year-old woman with lumbar pain for 7 years and aggravation with intermittent claudication who had previously undergone partial thyroidectomy of a benign thyroid lesion.No abnormal nodules were found in the bilateral thyroid glands.However,imaging studies were consistent with a spinal tumor,and the lesion was diagnosed as a metastatic follicular carcinoma of thyroid origin.We adopted a multidisciplinary collaboration and comprehensive treatment approach.The patient underwent lumbar spine surgery,total resection of the thyroid,postoperative TSH suppression therapy,and RAIT.There were no complications associated with the operation,and the patient had good postoperative recovery.She has experienced no recurrence.CONCLUSION Follicular thyroid carcinoma is associated with early hematogenous metastasis,and the bone is a typical site of metastasis.Single bone metastasis is not a contraindication to medical procedures,and providing the appropriate therapy can result in better outcomes and quality of life for these patients.

Metastatic Carcinoma of the Uterine Cervix from Rectal Carcinoma: A Case Report and Review of the Literature

Primary adenocarcinomas of the uterine cervix account for 5% - 15% of all cervical malignancies, but secondary adenocarcinomas from extragenital cancers are rare. Only 35 cases have been reported in the literature since 1941. We report a 52-year-old Japanese woman who had been treated for rectal adenocarcinoma (Dukes C, stage IIIb) and who was diagnosed with primary uterine cervical carcinoma (FIGO stage Ib2) two years later. A radical hysterectomy was performed and the surgical specimen showed metastatic adenocarcinoma of the uterine cervix from rectal cancer without direct extension. Immunohistochemical staining was positive for cytokeratin 20 and CDX2, and negative for cytokeratin 7. Immunohistochemical staining is important for distinguishing between primary and secondary adenocarcinomas of the cervix, but histologic findings alone are not always adequate to establish the site of the primary lesion. The distinction between primary and secondary adenocarcinomas of the cervix is important for patient management and prognosis. Therefore, the possibility of metastatic adenocarcinoma should be considered whenever a diagnosis of adenocarcinoma of the cervix is received.

Metastatic Lobular Carcinoma of the Breast Presenting with Small Bowel Metastases:Case Report and Literature Review

Introduction: Invasive lobular carcinoma (ILC) is the second most common histologic type of breast cancer, representing 5% to 15% of invasive tumors. ILC tends to spread to bones, lungs, central nervous system, reproductive organs, and the gastrointestinal tract (GI tract). The most commonly affected organs in the GI tract are the stomach, small intestine, followed by colon and rectum. Case presentation: A 78-year-old woman who was referred to our institution after having a bowel obstruction that required a diagnostic laparoscopy where they identified an obstructing ulcerative lesion in the distal ileum that was managed with a segmental bowel resection. Pathology report showed an invasive lobular breast carcinoma that occluded 90% of the bowel lumen. A PET/CT scan revealed a left breast tumor with increased metabolism. The patient was staged as a clinical cT4b, cN0, cM1 left breast invasive lobular carcinoma (ER/PgR positive, HER-2 negative). She was managed with endocrine therapy with Letrozole (an eight-week course). A follow-up PET/CT showed a peritoneal hypermetabolic nodule adjacent to the previous ileal anastomosis. The lesion decreased in size and metabolic activity. In a multidisciplinary fashion, the endocrine therapy was extended for another three months. Another follow-up PET/CT scan was performed three months after the identification of the peritoneal implant that showed that the nodule increased in size and in metabolism. The lesion continued to decrease significantly in size and became metabolically inactivity. Due to the good breast response and the possibility that the ileal nodule could be a granuloma, she underwent an exploratory laparoscopy with excision of the peritoneal nodule, and a modified left radical mastectomy with immediate breast reconstruction (complex wound closure). The final pathology report of the nodule was negative for malignancy. She continued on endocrine therapy and underwent whole breast irradiation four weeks after the operation. Currently, she is free of disease with no evidence of local, regional, or distant recurrence, and she is still on endocrine therapy. Discussion: The time interval between primary breast cancer and gastrointestinal involvement may range from synchronous presentation to as long as 30 years. The clinical manifestations in GI lobular breast cancer metastasis may range from non-specific complaints to acute GI symptoms, such as a bowel obstruction. There are multiple controversies in the management of ILC. Systemic treatment should be initiated as soon as possible. Indications for postmastectomy radiotherapy are also controversial, given the propensity for multifocal/multicentric tumors and late recurrences, sometimes in atypical locations. Five years of postoperative adjuvant hormonal therapy is an option for women with poor prognosis. Remissions are observed in 32% to 53% of patients. Conclusion: Metastatic lobular carcinoma of the breast has a wide range of clinical presentations. Patients with a history of breast cancer who present with new GI tumors should have these lesions evaluated for evidence of metastasis through histopathologic and immunohistochemical analysis, this will allow for appropriate management. Currently, breast cancer management involves a multidisciplinary approach including surgery, radiotherapy, and systemic medical therapy, and the treatment must be tailored to the patient’s needs.

Comparison of efficacy, safety, and quality of life between sorafenib and sunitinib as first.line therapy for Chinese patients with metastatic renal cell carcinoma

Background: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma(mRCC) in China.This study aimed to compare the efficacy, safety, and quality of life(QoL) in Chinese mRCC patients treated with sorafenib and sunitinib as first-line therapy.Methods: Clinical data of patients with mRCC who received sorafenib(400 mg twice daily; 4 weeks) or sunitinib(50 mg twice daily; on a schedule of 4 weeks on treatment followed by 2 weeks off) were retrieved. Primary outcomes were overall survival(OS), progression-free survival(PFS), adverse events(AEs), and QoL(SF-36 scores), and secondary outcomes were associations of clinical characteristics with QoL.Results: Medical records of 184 patients(110 in the sorafenib group and 74 in the sunitinib group) were reviewed.PFS and OS were comparable between the sorafenib and sunitinib groups(both P > 0.05).The occurrence rates of leukocytopenia, thrombocytopenia, and hypothyroidism were higher in the sunitinib group(36.5% vs. 10.9%,P< 0.001; 40.5% vs. 10.9%, P < 0.001; 17.6% vs. 3.6%, P = 0.001), and that of diarrhea was higher in the sorafenib group(62.7% vs. 35.2%, P < 0.001). There was no significant difference in SF-36 scores between the two groups. Multivariate analysis indicated that role-physical and bodily pain scores were associated with the occurrence rate of grade 3 or 4 AEs(P = 0.017 and 0.005).Conclusions: Sorafenib has comparable efficacy and lower toxicity profile than sunitinib as first-line therapy for mRCC. Both agents showed no significant impact on QoL of patients.

Association of post.treatment hypoalbuminemia and survival in Chinese patients with metastatic renal cell carcinoma

Background:Hypoalbuminemia adversely affects the clinical outcomes of various cancers.The purpose of this study was to estimate the prognostic value of hypoalbuminemia 3-5 weeks after treatment in patients with metastatic renal cell carcinoma(mRCC) who received sorafenib or sunitinib as first-line treatment.Methods:In this single-center,retrospective study,we assessed the progression-free survival(PFS) and overall survival(OS) of 184 mRCC patients who received first-line sorafenib or sunitinib treatment.PFS and OS were compared between patients with post-treatment hypoalbuminemia(post-treatment albumin level <36.4 g/L) and those with normal post-treatment albumin level(albumin level≥36.4 g/L).The Memorial Sloan Kettering Cancer Center(MSKCC)risk model stratified mRCC patients into three risk categories.Prognostic values of all patient characteristics including MSKCC risk category were determined by using univariate and multivariate Cox regression models.Prognostic value was further determined using the Harrell concordance index and receiver operating characteristic curve analysis.Results:The median PFS and OS of the 184 patients were 11 months(95%confidence interval[CI]9-12 months)and 23 months(95%CI 19-33 months),respectively.Patients with post-treatment hypoalbuminemia had significantly shorter median PFS(6 months[95%CI 5-7 months]) and OS(11 months[95%CI 9-15 months]) than patients who had normal post-treatment albumin levels(PFS:12 months[95%CI 11-16 months],P < 0.001;OS:31 months[95%CI24-42 months],P < 0.001),respectively.Multivariate analysis showed that post-treatment hypoalbuminemia was an independent predictor of PFS(hazard ratio[HR],2.113;95%CI 1.390-3.212;P < 0.001) and OS(HR,2.388;95%CI 1.591-3.585;P < 0.001).Post-treatment hypoalbuminemia could also be combined with the MSKCC risk category for better prediction about OS.The model that included post-treatment hypoalbuminemia and MSKCC risk category improved the predictive accuracy for PFS and OS(c-index:0.68 and 0.73,respectively) compared with the basic MSKCC risk model(c-index:0.67 and 0.70,respectively).The prognostic values for PFS and OS of the integrated MSKCC risk model involving post-treatment hypoalbuminemia were significantly more accurate than the basic MSKCC risk model using likelihood ratio analysis(both P < 0.001).Conclusions:Post-treatment hypoalbuminemia can be considered an independent prognostic factor for patients with mRCC who undergo first-line treatment with tyrosine kinase inhibitors.Additionally,integrating post-treatment serum albumin level into the basic MSKCC risk model can improve the accuracy of this model in predicting patient overall survival and progression-free survival.

Evolution in the treatment of metastatic colorectal carcinoma of the liver

Metastatic colorectal cancer to the liver is associated with a uniform poor prognosis without treatment. Advances in therapy over the past decades have now allowed surgical resections of the liver to occur with a low morbidity and mortality. Improvements in chemotherapy regimes have paralleled technical improvements and now allow a new group of patients to become eligible for surgical resection. This chapter will review the recent advances in surgical and chemotherapeutic regimes in metastatic colorectal cancer to the liver.

Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma

This report describes a patient that developed recurrent metastatic hepatocellular carcinoma(HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed.

Relationship between apoptosis and invasive and metastatic potential of hepatocellular carcinoma

Objective: To study relationship between apoptosis and invasive and metastatic potential of hepatocellu- lar carcinoma (HCC). Methods: Apoptotic rate (AR), proliferative index (PI) and S-phase fraction (SPF) were measured by flow cytometry, and p170, p21 and nucleoside diphosphate kinase (ndpk) by strept avidin-biotin complex immunohistochemical technique in 57 pa- tients with HCC. Results: In this group, AR was 1.77% ±0.19%, SPF 12.55% ±0.68%, and PI 20.91% ±1.12% (r =-0.173). p170, p21 and ndpk positive rates were 61.36%, 68, 18%, 52.27% respectively in patients with a mean AR of ≤1.77%, and 23.08%, 38.46%, 84.62% respectively in patients with a mean AR of >1.77% (all P<0.05). In patients with positive tumor invasiveness and metastasis, nd- pk (+) was 43.75%, p21 (+) 75.00%, p170 (+) 65.63%, AR 1.12% ±0. 16%, PI 23.78% ±1.48%, and SPF 13.90 % ±0.99 %. In patients with negative invasiveness and metastasis, however, ndpk (+) was 80.00%, p21 (+) 44.00%, p170 (+) 36.00%, AR 2,32%±0.52%, PI 18.53% ±0.82% and SPF 11.43% ±0.70%. Conclusion: Apoptosis of HCC is negatively correla- ted with its invasive and metastatic potential or other factors as proliferative activity, p21, p170 and ndpk.

Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential

Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like metastatic model of human HCC in nude mice (LCI-D20) and a low metastatic model of human HCC in nude mice (LCI-D35) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding. Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-1 increased gradually following tumor progression in LCI-D20 model, and correlated with tumor size and AFP level. Phasic expression of tissue intercellular adhesion molecule-1 in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including anti-angiogenesis,antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vitro and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.

Review of the treatment of metastatic non small cell lung carcinoma:A practical approach

In recent years,as we have a better knowledge and understanding of the biology of non small cell lung carcinoma(NSCLC),which leads us to targeting biomarkers driving the NSCLC carcinogenesis and metastatic potential,we now have an increased number of options to offer our patients with NSCLC.We also realize the importance of distinguishing squamous and non squamous histology to guide our treatment decisions of NSCLC.The palliative care concomitant with therapies from the very start of the treatment also showed an impact on survival.This review examines the treatment options in all lines of therapy for metastatic NSCLC that have been approved in Canada,the United States,or Europe.

Update on the treatment of metastatic renal cell carcinoma

Metastatic renal cell cancer(mRCC)management has undergone a paradigm shift in recent decades.The first revolution came with the emergence of vascular endothelial growth factor inhibitors;there was a second wave with the unprecedented success of checkpoint inhibitors,and then the latest approach,which is becoming the new care standard in mRCC,of combining these two strategies in different ways.Updated results of Checkmate-214 after 42 mo of follow-up were consistent with previously published results showing the superiority of nivolumab/ipilimumab over sunitinib in progression free survival(PFS),overall survival(OS),and objective response rate(ORR)in intermediate and high-risk patients.However,several studies presented at the American Society of Clinical Oncology 2020 suggested that the best place,and so far,the only one for nivolumab/ipilimumab is the frontline setting.The update on Keynote-426 after 23 mo of follow-up showed no superiority of pembrolizumab/axitinib over sunitinib in favorable-risk mRCC,suggesting that it should no longer be the first line of choice in low-risk patients.Finally,the phase III Checkmate 9ER trial results revealed the superiority of nivolumab/cabozantinib vs sunitinib in PFS,OS,and ORR,providing a new first-line option among all International Metastatic RCC Database Consortium risk patients.Some phase II clinical trials also presented this year showed promising results with new combination therapies such as nivolumab/sitravatinib,cabozantinib/atezolizumab,and lenvatinib/pembrolizumab,providing promising grounds upon which to start phase III studies.In addition,other works are using novel therapeutic agents with different mechanisms of action,including telaglenastat(a glutaminase inhibitor),entinostat[an inhibitor of histone deacetylases(HDACs)],and olaparib and talazoparib,poly(ADP-ribose)polymerase inhibitors widely used in other tumors.However,some questions regarding mRCC management still need to be addressed,such as head-to-head comparisons between the current options,treatment sequencing,non-clear cell mRCC,and the role of biomarkers to ascertain the best treatment choice.

Metastatic sarcomatoid renal cell carcinoma to the mandible treated with Sorafenib

A case of metastatic sarcomatoid renal cell carcinoma to the mandible treated with Sorafenib is reported. A 76-year-old man consulted us for hyposthesia of the right lower lip. Panorama X-ray film showed a ra-diolucent lesion in the right mandibular body. A diagnosis of metastatic tumor to the mandible from the left kidney was made after evaluation by computed tomography and positron emission tomography, which also revealed multiple bone metastases. After radiotherapy for mandibular and thoracic lesions, nephrectomy was performed. Histological diagnosis was sarcomatoid renal cell carcinoma. Interferon therapy was performed but was not effective;therefore, a molecular targeted drug, Sorafenib, was administered. Sorafenib effectively inhibited the growth of oral and other metastatic lesions for 10 months. Quality of life was relatively well maintained with tolerable adverse effects. The patient survived for as long as 2 years after appearance of the first symptom.

Gemcitabine cures metastatic hepatic carcinoma and bone metastasis

We report a case of a 59-year-old gentleman who had suffered from low back pain for several months.Abdominal sonogram showed multiple heteroechoic nodules in the bilateral liver and an enlarged pancreatic head.Abdominal computer tomography(CT)favored pancreas head tumor with liver and bone metastasis.Endoscopic retrograde cholangiopancreatography(ERCP)disclosed pancreatic duct invasion over the distal portion of the pancreatic duct with prestenotic dilatation.Liver biopsy showed undifferentiated carcinoma.As suggested by the pathologist,the nasopharyngeal area was checked by the ear,nose and throat doctor,was negative and nasopharyngeal carcinoma was ex-cluded.Therefore,the patient was treated with Gemcitabine(1500 mg/wk),as the suggested treatment schedule,for 24 wk in opioid dependency program.Sequential abdominal CT during follow up showed the disappearance of liver metastasis and shrinkage of the pancreatic tumor.Repeated ERCP after treatment showed re-channelization of the pancreatic duct.During11 years of follow up,5 CT scans disclosed not only the disappearance of the hepatic tumor but also no cancer recurrence.Progressive shrinkage of pancreatic head was also noted.Therefore,we can say this malignant case was cured by monotherapy with gemcitabine.

Practice change in the management of metastatic urothelial carcinoma after ASCO 2020

Metastatic urothelial carcinoma(mUC)is an incurable and aggressive disease.In the past decades there have been few effective treatment options that have impacted the prognosis of mUC patients.However,in the last few years,several drugs have emerged as new treatment choices that are changing the therapeutic landscape of mUC.Immune checkpoint inhibitors(ICIs)and targeted agents are useful treatment strategies that have been incorporated into our clinical practice.Nevertheless,cisplatin-based chemotherapy is still the standard of care in the first-line of metastatic disease.The results of the JAVELIN Bladder 100 phase 3 trial were presented at ASCO 2020,this trial evaluated the role of avelumab,an ICI,as maintenance therapy in patients who had not progressed after first-line platinum-based chemotherapy.The trial met its primary endpoint demonstrating an overall survival benefit with avelumab maintenance.In addition,new drugs and combinations are being evaluated to improve the outcomes of second and subsequent lines.Fibroblast growth factor receptor(FGFR)inhibitors and immunotherapy combinations were some of the strategies presented at ASCO 2020 that have shown promising results.Finally,the development of predictive biomarkers that help us in the decision-making process will be one of the most important challenges in the next years.

Total En Bloc Spondylectomy for Lumbar Renal Cell Carcinoma and Review of the Literature

Introduction: Total en bloc spondylectomy (TES) is gaining increasing favour as a treatment of choice for cancers of the spine that are resistant to radiological and chemotherapeautic intervention such as renal cell carcinoma (RCC). Until recently, RCC of the lumbar spine has presented a surgical challenge due to anatomical and vascular constraints. The development of the combined posterior-anterior en bloc spondylectomy offers improved access to the lumbar region. This case report and review of the literature presents a combined posterior-anterior lumbar en bloc spondylectomy for RCC involving L3 vertebra, which we believe is the first reported in Australia. Methods: A 46-year-old male with a seven-year history of renal cell carcinoma resulting in a left nephrectomy presented with a lytic lesion involving the L3 vertebral body, extending to the epidural space and compressing the cauda equina and left L3 and L4 nerve roots on MRI. A literature review revealed ten previous cases of the posterior-anterior TES in the lumbar spine for cancerous lesions but none from Australia. Results: A posterior-anterior TES and L2-L4 fusion was performed to remove a cancerous renal cell carcinoma of L3 with wide margins. Blood loss was the major complication. The patient remains recurrence free at nineteen months post procedure. Conclusion: Despite being an aggressive and invasive procedure, TES is rapidly becoming the treatment of choice for curative and palliative care in select patients with isolated metastatic tumours of the lumbar spine.

Progress in targeted therapy for metastatic renal cell carcinoma

In recent years, with the deepening of research on the pathogenesis of renal cell carcinoma, anti-VEGF receptor inhibitors and mTOR inhibitors have been produced, making metastatic renal cell carcinoma into the era of targeted therapy. This article analyzes the latest research results at home and abroad. For patients with metastatic renal cell carcinoma, sunitinib and pizopanib are the first choice for targeted drugs. The drug dose starts from the standard dose, and the disease can be increased as appropriate when the disease progresses;When responding, it should be treated or reduced in time. When using an anti-VEGF inhibitor, the patient's blood pressure should be closely monitored. When the patient has high blood sugar or diabetes, anti-VEGF inhibitors should be preferred.

Study on the mechanism of"Sangu Decoction"in the treatment of bone metastatic carcinoma

Objective:To study the mechanism of"Sangu Decoction"in the treatment of bone metastatic carcinoma by network pharmacology.Methods:TCMSP,TCMID and TCM Database@Taiwan databases and literature search were used to screen the main effective components of drugs.Swiss Target and TCMSP databases were used to search the potential therapeutic targets of"Sangu Decoction".DisGeNet and Drugbank databases were used to search the genes of bone metastatic carcinoma.Drug action targets and disease genes were mapped.Cytoscape 3.8.1 software was used to visualize and screen out the core genes.GO and KEGG pathway analysis was performed on potential therapeutic targets.Results:There were 29 main active ingredients in"Sangu Decoction",which contained 413 target proteins.There are 773 disease targets of bone metastatic carcinoma,of which 112 are potential targets of"Sangu Decoction"for the treatment of bone metastatic carcinoma.Through GO and KEGG pathway analysis,it was found that"Sangu Decoction"exerted anti-cancer,inhibiting bone metastasis and immune regulation mechanism through TNF,ErbB,FoxO,PI3K-Akt,Toll-like Receptor,NOD-like Receptor,Rap1 and other signaling pathways in the treatment of bone metastatic carcinoma.The key genes of"Sangu Decoction"in treating bone metastatic carcinoma are VEGFA,AKT1,IL6,TP53,MAPK3,SRC,EGFR and CASP3 and so on.Conclusion:In this study,we constructed a a multi-level interaction"traditional Chinese medicine-compound-target-pathway"network through network pharmacology,and found that the mechanism of"Sangu Decoction"in the treatment of bone metastasis cancer involves multiple targets and pathways,which may be related to anti-cancer,inhibition of bone metastasis,regulation of immunity and so on.