Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1

BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab treatment.Programmed cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.AIM To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of PD-L1.METHODS This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.RESULTS A total of 124 patients was included in this analysis.Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy.While 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line chemotherapy.The numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),respectively.The results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

Metastatic clear cell sarcoma of the pancreas:A sporadic cancer

Primary or secondary clear cell sarcoma of the pancreas is an exceedingly rare and aggressive disease.In addition to pathology,molecular analysis is pivotal in differential diagnosis,especially with malignant melanoma.A key aspect in identifying clear cell sarcoma is specific genetic alterations,notably the translocation of t(12;22)(q13;q13),a diagnostic hallmark of this sarcoma subtype,which is absent in malignant melanoma.Treatment of primary clear cell sarcoma of the pancreas is the same as that for adenocarcinoma.

Emerging role of liquid biopsy in rat sarcoma virus mutated metastatic colorectal cancer:A case report

BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.

Prognostic role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with non-metastatic and metastatic prostate cancer:A meta-analysis and systematic review

Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratified in non-metastatic and metastatic diseases.Methods: A literature search process was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. In our meta-analysis, the pooled event rate estimated and the pooled hazard ratio were calculated using a random effect model.Results: Forty-two articles were selected for our analysis. The pooled risk difference for non-organ confined PCa between high and low NLR cases was 0.06 (95% confidence interval [CI]: −0.03-0.15) and between high and low PLR cases increased to 0.30 (95% CI: 0.16-0.43). In non-metastatic PCa cases, the pooled hazard ratio for overall mortality between high and low NLR was 1.33 (95% CI: 0.78-1.88) and between high and low PLR was 1.47 (95% CI: 0.91-2.03), whereas in metastatic PCa cases, between high and low NLR was 1.79 (95% CI: 1.44-2.13) and between high and low PLR was 1.05 (95% CI: 0.87-1.24).Conclusion: The prognostic values of NLR and PLR in terms of PCa characteristics and responses after treatment show a high level of heterogeneity of results among studies. These two ratios can represent the inflammatory and immunity status of the patient related to several conditions. A higher predictive value is related to a high NLR in terms of risk for overall mortality in metastatic PCa cases under systemic treatments.

Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer

Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This study investigates whether the limited e±cacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the e±cacy.A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives(HpD-PDT).The anti-tumor effect of HpD-PDT was observed,as well as CD4þT,CD8þT and calreticulin(CRT)by immunohistochemistry and immunofluorescence.Immune checkpoints on T cells were analyzed byflow cytometry after HpD-PDT.When combining PDT with immune checkpoint inhibitors,the antitumor effect and immune effect were assessed.For HpD-PDT at 100 mW/cm2 and 40,60 and 80 J/cm2,primary tumors were suppressed and CD4þT,CD8þT and CRT were elevated;however,distant tumors couldn't be inhibited and survival could not be prolonged.Immune checkpoints on T cells,especially PD1 and LAG-3 after HpD-PDT,were upregulated,which may explain the reason for the limited HpD-PDT effect.After PDT combined with anti-PD1 antibody,but not with anti-LAG-3 antibody,both the primary and distant tumors were signi-cantly inhibited and the survival time was prolonged,additionally,CD4þT,CD8þT,IFN-þCD4þT and TNF-þCD4þT cells were signi-cantly increased compared with HpD-PDT.HpD-PDT could not combat metastatic breast cancer.PD1 and LAG-3 were upregulated after HpD-PDT.Anti-PD1 antibody,but not anti-LAG-3 antibody,could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.

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.

Vascular endothelial growth factor pathway’s influence on bevacizumab efficacy in metastatic colorectal cancer treatment

In this article,an article published in the World Journal of Gastrointestinal Oncology,which focuses on whether the expression of programmed death-ligand 1(PD-L1)affects the effectiveness of chemotherapy regimens,including bevacizumab,in treating patients with colorectal cancer(CRC).Through neutralization of vascular endothelial growth factor(VEGF),bevacizumab inhibits tumor angiogenesis,impairing neovascularization and thereby depriving the tumor of essential nutrients and oxygen.Conversely,PD-L1 binding to VEGF receptor 2 promotes angiogenesis,supporting tumor vasculature.The interplay between these pathways complicates the assessment of bevacizumab’s efficacy in cancer therapy,notably in CRC,where VEGF and PD-L1 significantly affect treatment response.This review examines metastatic CRC treatment strategies,focusing on bevacizumab’s mechanism of action and the role of PD-L1 in this therapeutic context.

Clear cell sarcoma of the pancreas,an unusual cancer with unusual metastatic site or unusual primary site?

Clear cell sarcoma(CCS)is a type of malignant tumor that can arise from tendons and aponeuroses.This malignant proliferation of cells with melanocytic lineage normally occurs in young patients,and it is normally identified in extremities.However,different sites including gastrointestinal organs are also described.Due difficulties in the molecular and histopathology evaluation,the diagnosis is often confused with malignant melanoma.Most cases are treated with surgical resection,but overall,the prognosis is poor.In this editorial,we will discuss a very interesting case of CCS identified in the pancreas.We will discuss the literature and controversies in the management of this type of cancer.Furthermore,we will address molecular strategies to be incorporated in those cases to better understand the primary location of the tumor.Finally,future perspectives of the field and new strategies of treatment will be described.

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.

Immunotherapy for metastatic gastric cancer

This editorial discusses the article written by Chen et al that was published in the latest edition of the World Journal of Gastrointestinal Surgery.The current study found that programmed cell death 1 ligand 1(PD-L1)expression is considered as one of the pan-cancer biomarkers of immune checkpoint inhibitors(ICIs)treatment response.Four molecular subtypes are widely used to guide and evaluate the prognosis and diagnosis and treatment of gastric cancer(GC)patients.Clinical trials of ICI treatment including Nivolumab,Pembrolizumab,Avelumab have been conducted for metastatic GC(mGC).The effects of various single agent ICIs on mGC therapy varied.ICIs combined with chemotherapy can indeed bring survival benefits to patients with mGC.Combining ICIs with chemotherapy can give more patients the chance of surgery in the treatment of GC transformation.However,not all PD-L1 positive patients can benefit from it.It is urgent to find better biomarkers to predict the response of ICIs for more precise clinical treatment.

Therapeutic strategies targeting the epidermal growth factor receptor signaling pathway in metastatic colorectal cancer

More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and deaths.Overall,colorectal ranks third in incidence,but second in mortality.More than half of the patients are in advanced stages at diagnosis.Treatment options are complex because of the heterogeneity of the patient population,including different molecular subtypes.Treatments have included conventional fluorouracil-based chemotherapy,targeted therapy,immunotherapy,etc.In recent years,with the development of genetic testing technology,more and more targeted drugs have been applied to the treatment of CRC,which has further prolonged the survival of metastatic CRC patients.

Successful cetuximab rechallenge in metastatic colorectal cancer:A case report

BACKGROUND Metastatic colorectal cancer(mCRC)treatment has been evolving and increasingly driven by tumor biology and gene expression analysis.Rechallenge with epidermal growth factor receptor(EGFR)inhibitors(anti-EGFR)represents a promising strategy for patients with RAS wild-type(RAS-wt)mCRC and circulating tumor DNA has emerged as a potential selection strategy.Herein,we report the case of a RAS-wt mCRC patient who had a successful response to cetuximab rechallenge.CASE SUMMARY Our patient was diagnosed with stage IV RAS-wt,microsatellite-stable rectosigmoid junction adenocarcinoma.He was started on first-line treatment with FOLFIRI and cetuximab and achieved partial response,allowing for a left hepatectomy(R0),followed by post-operative chemotherapy and an anterior resection;progression-free survival(PFS)of 16 months was obtained.Due to hepatic and nodal relapse,second-line treatment with FOLFOX and bevacizumab was started with partial response;metastasectomy was performed(R0),achieving a PFS of 11 months.After a 15 months anti-EGFR-free interval,FOLFIRI and cetuximab were reintroduced upon disease progression,again with partial response and a PFS of 16 months.Following extensive hepatic relapse,cetuximab was reintroduced and a marked clinical and analytical improvement was seen,after only one cycle.RASwt status was confirmed on circulating tumor DNA.The patient’s overall survival exceeded 5 years.CONCLUSION Our case provides real-world data to support cetuximab rechallenge in later lines of RAS-wt mCRC treatment.

Comparative effectiveness of immunotherapy and chemotherapy in patients with metastatic colorectal cancer stratified by microsatellite instability status

BACKGROUND Immunotherapy have demonstrated promising outcomes in patients with high microsatellite instability(MSI)(MSI-H)metastatic colorectal cancer.However,the comparative effectiveness of Immunotherapy and chemotherapy for patients with low MSI(MSI-L),and microsatellite stable(MSS)metastatic colorectal cancer remains unclear.AIM To investigate immunotherapy vs chemotherapy for treatment of MSI-L/MSS metastatic colorectal cancer,and to evaluate the success of immunotherapy against chemotherapy in managing MSI-H metastatic colorectal cancer during a follow-up of 50 months.METHODS We conducted a retrospective cohort study using the National Cancer Database(NCDB)to evaluate the overall survival(OS)of patients with metastatic colorectal cancer treated with immunotherapy or chemotherapy.The study population was stratified by MSI status(MSI-H,MSI-L,and MSS).Multivariable Cox proportional hazard models were used to assess the association between treatment modality and OS,adjusting for potential confounders.RESULTS A total of 21951 patients with metastatic colorectal cancer were included in the analysis,of which 2358 were MSI-H,and 19593 were MSI-L/MSS.In the MSI-H cohort,immunotherapy treatment(n=142)was associated with a significantly improved median OS compared to chemotherapy(n=860).After adjusting for potential confounders,immunotherapy treatment remained significantly associated with better OS in the MSI-H cohort[adjusted hazard ratio(aHR):0.57,95%confidence interval(95%CI):0.43-0.77,P<0.001].In the MSS cohort,no significant difference in median OS was observed between immunotherapy treatment and chemotherapy(aHR:0.94,95%CI:0.69-1.29,P=0.715).CONCLUSION In this population-based study using the NCDB,immunotherapy treatment was associated with significantly improved OS compared to chemotherapy in patients with MSI-H metastatic colorectal cancer,but not in those with MSI-L/MSS metastatic colorectal cancer.Further studies are warranted to determine the optimal therapeutic approach for patients with MSI-L/MSS metastatic colorectal cancer.

Cohort study on the treatment of BRAF V600E mutant metastatic colorectal cancer with integrated Chinese and western medicine

BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohort study on mCRC conducted by our team,it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal cancer.Therefore,we further explored the survival benefits in the population with BRAF V600E mutant mCRC.AIM To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal cancer.METHODS A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December 2022.The patients were divided into two cohorts.RESULTS A total of 34 cases were included,with 23 in Chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,respectively.Subgroup analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(P<0.05).CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.

Transcriptomic Analysis of Metastatic Colorectal Tumor with Low Mutational Burden

Objective:To identify potential drug targets for metastasis colorectal cancer(CRC)patients with low mutational burden by examining differences in immune-related gene expression.Methods:For this study,623 samples were collected from The Cancer Genome Atlas(TCGA)database,comprising tumor mutational burden(TMB),RNA sequencing(RNA-Seq),and clinical data.Differential gene expression analysis,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of the identified genes were conducted using the R package.Additionally,a comparative analysis of immune infiltrating cell composition in metastatic and non-metastatic groups was performed.Hub genes,exhibiting high levels of interaction,were selected using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database.The Drug Gene Interaction Database(DGIdb)was then utilized to estimate drugs targeting the identified hub genes.Results:The transcriptome data of 326 colorectal cancer patients with low TMB were analyzed,comprising 58 patients with metastasis and 268 patients without metastasis.Among the differential expression in 1,111 genes for patients with metastasis compared to those without metastasis,733 genes were upregulated,and 378 genes were downregulated.KEGG and GO enrichment analysis indicated significant differences in gene expression in CRC metastatic patients with low TMB compared to non-metastasis patients with low TMB.Enriched pathways included humoral immune response,immunoglobulin production,and regulation of AMPA receptor activity.Two genes related to interleukin-12 were identified through secondary enrichment for immune-related genes.Analysis of tumor-infiltrating immune cell data revealed significant differences in memory-activated T cell CD4 and T cell CD8.Conclusions:This analysis of RNA sequencing data and immune-filtrating cell data revealed significant differences between metastatic colorectal cancer patients with low TMB and their non-metastatic counterparts.These distinctions suggest the possibility of identifying more effective drugs or therapies for metastatic colorectal cancer patients with low TMB.

Survival Rate and Factors Influencing It in Triptorelin-Castrated Metastatic Prostate Cancer Patients

Background: Most newly diagnosed prostate cancers in Benin are metastatic diseases and patients are reluctant to undergo orchiectomy. Still, chemical androgen deprivation therapy is not always available and not every patient can afford it. Thus, it will be interesting to evaluate the results of that therapy in the country. Objective: To analyze the survival rate and factors influencing it in metastatic prostate cancer patients who underwent triptorelin-based androgen deprivation therapy at the former Military Teaching Hospital of Cotonou from January 1, 2012, to December 31, 2022. Patients and Method: Metastatic prostate cancer patients received intragluteal injections of triptorelin 11.25 mg every 3 months. We retrospectively collected follow-up data from the patients’ medical records. By means of the software StataTM version 15, we performed a descriptive analysis of qualitative data. We used Kaplan-Meir method to estimate the overall survival rate in the whole cohort and in specific subgroups of patients. We compared survival rates by using the log-rank test. Results: 68 metastatic prostate cancer patients aged 47-86 years (mean = 69.9) with initial PSA ranging from 24.25 to 6334 ng/mL (mean = 666.1) started triptorelin-based castration. The tumor grade in 21 (33.3%), 14 (22.2%), 15 (23.8), 8 (12.7%), and 5 (7.9%) patients was respectively ISUP grade groups 5, 4, 3, 2, and 1. 15 (22.1%), 4 (5.9%), 2 (2.9%), 1 (1.5%), 11 (16.2%), and 7 (10.3%) patients respectively had hypertension, diabetes mellitus, peptic ulcer, asthma, unilateral or bilateral hydronephrosis, and paralysis. The mean nadir PSA level was 22.5 ng/mL (range: 0.01-220.25). The mean time to nadir PSA level was 8.9 months (range: 3-57). The overall survival rate was 42.6%. There was no significant survival difference between age groups (p = 0.475), relating to the presence of diabetes or hypertension (p = 0.757) or to the presence of paralysis or hydronephrosis (p = 0.090). The initial PSA level exerted no significant impact on patients’ survival (p = 0.461). Neither did the time to PSA nadir (p = 0.263). The PSA nadir less than 4 ng/mL (p = 0.005) and the PSA nadir less than 4 ng/mL achieved in 12 months or less (p = 0.002) were predictive of longer survival rate. The difference in survival rate through the ISUP grade groups was not significant (p = 0.061). Conclusion: The overall survival rate was 42.6% at 5 years. Achieving PSA nadir of less than 4 ng/mL in less than 12 months of castration was predictive of longer survival rate in triptorelin-castrated metastatic prostate cancer patients.

Exploring the Need and Strategy for Intraoperative Freezing to Identify Metastatic Adenocarcinoma of the Lungs

Objective: To explore the necessity and strategy of intraoperative freezing to identify primary and metastatic adenocarcinoma of the lung. Methods: This study retrospectively analyzes the impact of failing to make a definitive diagnosis of metastatic adenocarcinoma of the lung on the clinical surgical approach in four cases of intraoperative freezing. It also examines the reasons for this failure and reviews the relevant literature. Results: All 4 cases of intraoperative freezing were diagnosed as invasive adenocarcinoma, and none of them made a definitive diagnosis of metastatic adenocarcinoma. Conclusion: It is difficult to confirm the diagnosis of metastatic adenocarcinoma of the lung by intraoperative frozen section, and the combination of patient history, rapid immunohistochemistry, and histological morphology of intraoperative frozen section for its identification can guide the surgeon to adjust the surgical approach in time and provide evidence for the establishment of surgical protocols for reference.

Simultaneously metastatic cholangiocarcinoma and small intestine cancer from breast cancer misdiagnosed as primary cholangiocarcinoma:A case report

BACKGROUND Cholangiocarcinoma and small intestine cancer are common clinical malignancies,but metastatic cholangiocarcinoma and small intestine cancer are rare,especially simultaneous metastatic cholangiocarcinoma and small intestine cancer from breast cancer.Since the clinical presentation of metastatic cholangiocarcinoma and small intestine cancer does not differ from primary tumor,it may lead to misdiagnosis preoperatively.CASE SUMMARY A 66-year-old woman was admitted to our hospital for further treatment due to abdominal pain and jaundice.Abdominal magnetic resonance imaging and magnetic resonance cholangiopancreatography showed an occupying lesion of the bile duct,considering a high possibility of primary bile duct tumor.Therefore,we performed a radical bile duct cancer surgery and cholecystectomy,and multiple tumors in the small intestine were found and removed during the surgery process.Postoperative pathology showed metastatic bile duct cancer and small intestine cancer from tumors in other parts.The patient underwent a right total mastectomy and axillary lymph node dissection because of right breast cancer 2 years ago.Combining with the immunohistochemical results,the patient was finally diagnosed as metastatic cholangiocarcinoma and metastatic small intestine cancer from breast cancer.Postoperatively,the patient received four cycles of chemotherapy and targeted therapy with docetaxel,capecitabine and trastuzumab.Unfortunately,the patient eventually died from tumor progression,thoracoabdominal infection,and sepsis 5 mo after surgery.CONCLUSION Simultaneous metastatic cholangiocarcinoma and small intestine cancer from breast cancer are rare and the prognosis is extremely poor.Improving preoperative diagnostic accuracy is beneficial to avoid excessive surgical treatment.Treatment should be aimed at relieving biliary obstruction and abdominal pain,and then supplemented with chemotherapy and targeted therapy to control tumor progression and prolong the patient’s life.

Systemic treatment for metastatic colorectal cancer

Significant progress has been achieved in the treatment of metastatic colorectal cancer(mCRC)patients during the last 20 years.There are currently numerous treatments available for the first-line treatment of mCRC.Sophisticated molecular technologies have been developed to reveal novel prognostic and predictive biomarkers for CRC.The development of next-generation sequencing and wholeexome sequencing,which are strong new tools for the discovery of predictive molecular biomarkers to facilitate the delivery of customized treatment,has resulted in tremendous breakthroughs in DNA sequencing technology in recent years.The appropriate adjuvant treatments for mCRC patients are determined by the tumor stage,presence of high-risk pathologic characteristics,microsatellite instability status,patient age,and performance status.Chemotherapy,targeted therapy,and immunotherapy are the main systemic treatments for patients with mCRC.Despite the fact that these novel treatment choices have increased overall survival for mCRC,survival remains optimal for individuals with non-metastatic disease.The molecular technologies currently being used to support our ability to practice personalized medicine;the practical aspects of applying molecular biomarkers to regular clinical practice;and the evolution of chemotherapy,targeted therapy,and immunotherapy strategies for the treatment of mCRC in the front-line setting are all reviewed here.

Fecal transplantation in patient with metastatic melanoma refractory to immunotherapy:A case report

BACKGROUND Immunotherapy has revolutionized the treatment of metastatic melanoma,but a significant proportion of patients still experience treatment resistance.Fecal microbiota transplantation(FMT)has emerged as a potential strategy to overcome immunotherapy resistance by modulating the gut microbiome.CASE SUMMARY We present a case report of a 57-year-old male with metastatic melanoma refractory to immunotherapy who received FMT in combination with antiprogrammed death-ligand 1(PD-L1)immunotherapy(pembrolizumab).After failing multiple lines of treatment,the patient underwent a single FMT procedure by colonoscopy using fecal material from a female metastatic melanoma donor who successfully responded to immunotherapy.Following FMT,the patient demonstrated a response with decreased subcutaneous disease and subsequently underwent surgery to remove the residual disease.Despite a subsequent recurrence in the small bowel that was resected,the patient remained on pembrolizumab without evidence of melanoma recurrence at the time of writing.CONCLUSION The favorable clinical and long-lasting effect we saw in our patient without significant toxicity suggests that this procedure should be considered in similar patients with immunotherapy refractory melanomas.