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.

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.

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.

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.

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.

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.

Current status of yttrium-90 microspheres radioembolization in primary and metastatic liver cancer

Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy.Radioembolization with yttrium-90(^(90)Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy.The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with^(90)Y microspheres,from patient selection to follow up,both technically and clinically,are discussed in this paper.It describes the application and development of^(90)Y microspheres in the treatment of liver cancer.

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.

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.

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.

Evaluation of Lipid Peroxidation and Some Antioxidant Activities in Patients with Primary and Metastatic Liver Cancer

Abstract: HCC is the 6th most common cancer in the world. The main risk factors associated with HCC are hepatitis B (HBV) and hepatitis C viral infections and other factors that play a role in HCC development, include aflatoxin B1 (AFB1) cigarette smoking, and chronic inflammation. The aim of this study is to investigate lipid peroxidation and some antioxidant enzyme activities in patients with primary and metastatic liver cancer. For this purpose, 25 primary and metastatic liver cancer patients and 15 healthy controls were included in the study. In blood samples taken from the patient and control groups, the main product of lipid peroxidation MDA and SOD, GSH, GPx activity levels were examined. In result of study serum MDA level is higher and erythrocyte SOD, GSH, and GPx activities were found to be significantly lower in the patient group compared with the control group (p 0.05). As a result, liver cancer is associated with oxidative stress and antioxidant system weakens, which is an important indicator of oxidative stress, lipid peroxidation levels increased and promotes the tissue damage.

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.

Metastatic clear cell variant of hepatocellular carcinoma with an occult hepatic primary

Metastatic clear cell carcinomas are commonly seen in the kidney and lung. Clear cell variant of hepatocellular carci- noma is an uncommon tumour. Diagnosis is usually made by correlation of histopathology. tumour markers and im- munohistochemistry, especially HepPar 1. In this unusual case of metastatic clear cell carcinoma presenting as Sister Mary Joseph's nodule, no primary evidence was observed radiologically in the liver, but the level of alfa fetoprotein was markedly elevated. Metastatic clear cell carcinoma of the liver with an occult hepatic primary was diagnosed by immunohistochemical profile of the tumour.

Influence of primary tumor location and resection on survival in metastatic colorectal cancer

BACKGROUND Patients with right sided colorectal cancer are known to have a poorer prognosis than patients with left sided colorectal cancer, whatever the cancer stage. To this day, primary tumor resection(PTR) is still controversial in a metastatic, non resectable setting.AIM To explore the survival impact of PTR in patients with metastatic colorectal cancer(mCRC) depending on PTL.METHODS We retrospectively collected data from all consecutive patients treated for mCRC at the Centre Georges Francois Leclerc Hospital. Univariate and multivariate Cox proportional hazard regression models were used to assess the influence of PTR on survival. We then evaluated the association between PTL and overall survival among patients who previously underwent or did not undergo PTR. A propensity score was performed to match cohorts.RESULTS Four hundred and sixty-six patients were included. A total of 153(32.8%) patients had unresected synchronous mCRC and 313(67.2%) patients had resected synchronous mCRC. The number of patients with right colic cancer, left colic cancer and rectal cancer was respectively 174(37.3%), 203(43.6%) and 89(19.1%). In the multivariate analysis only PTL, PTR, resection of hepatic and or pulmonary metastases and the use of oxaliplatin, EGFR inhibitors or bevacizumab throughout treatment were associated to higher overall survival rates. Survival evaluation depending on PTR and PTL found that PTR improved the prognosis of both left and right sided mCRC. Results were confirmed by using a weighted propensity score.CONCLUSION In mCRC, PTR seems to confer a higher survival rate to patients whatever the PTL.

CSCO guidelines for metastatic colorectal cancer:personalized medicine in clinical practice

Colorectal cancer(CRC)is the second most common cancer in China,the morbidity and mortality rates of which are rapidly increasing1,2.Among newly-diagnosed CRC patients,20%have metastatic disease at the time of presentation and an additional 25%present with localized disease and will subsequently develop metastases3.The treatment of metastatic colorectal cancer(mCRC)is gradually moving towards the era of precision therapy,which involves guided treatment based on individual genetic characteristics4.Since the first edition of the Chinese Society of Clinical Oncology(CSCO)guidelines was published in 2017,the guidelines have been updated annually according to the latest clinical trial findings5-9.Herein we summarize how the CSCO guidelines enable tailor-made treatments of mCRC with different molecular characteristics(Figure 1).

Primary site resection is superior for incurable metastatic colorectal cancer

AIM:To investigate survival in patients treated with FOLFOX followed by primary site resection or palliative surgery for incurable metastatic colorectal cancer. METHODS:Between 2001 and 2009,a total of 98 patients with colorectal adenocarcinoma and non-resectable metastases were diagnosed and treated with the new systemic agent chemotherapy regimen FOLFOX. Primary site resection was carried out in 38 patients, creation of a colostomy or bypass without resection was carried out in 36 patients,and 23 were not operated on because of advanced disease.The survival times of patients in different groups were analyzed. RESULTS:There were no differences between the patients regarding their general condition,concurrent disease,or tumor stage according to AJCC classification.The median survivals of the three groups were 30.6,20.8,and 12.7 mo(log-rank P value<0.05),respectively.The postoperative complication rate was higher in the primary site resection group than in the palliative surgery group. CONCLUSION:The results indicate that there are benefits from primary site resection for incurable metastatic colorectal cancer with systemic chemotherapy.

“Oligometastatic pancreatic cancer”definition:The first step

Pancreatic ductal adenocarcinoma(PDAC)is nowadays the fourth leading cause of cancer-related death worldwide,but according to recent estimations it will become the second leading cause of cancer-related deaths in the USA up to 2030,following lung cancer.The implementation of neoadjuvant chemotherapy during recent years led to an increase of overall survival at 35 months in PDAC after R0 resection[1].However,pancreatic cancer has a particularity that makes it a real challenge for clinicians:only 20%of patients are diagnosed early enough to have a resectable pancreatic cancer,whereas 40%of patients present with locally advanced or non-resectable disease,while the rest present with distant metastases[2].Systemic chemotherapy plays the main role in metastatic PDAC treatment:polychemotherapy regimens such as FOLFIRINOX(folinic acid,5-fluorouracil,irinotecan and oxaliplatin)or combination of gemcitabine/nab-paclitaxel seemed to improve median overall survival from 6.8 to 11.1 months and 6.7 to 8.5 months,respectively[3].

Investigating Catalase and Carbonic Anhydrase Enzyme Activities and Levels of Certain Trace Elements and Heavy Metals in Patients with Primary and Metastatic Hepatic Carcinoma

Hepatocellular carcinoma (HCC) is among most common terminal cancer types in the world. Primary etiological factors include cirrhosis, hepatitis, aflatoxin and alcohol. The current study was conducted to determine cytosolic erythrocyte carbonic anhydrase and catalase enzyme activities and levels of some trace elements. For this purpose, 40 patients with primary and metastatic hepatic cancer and 29 healthy volunteers enrolled to the study. Catalase and carbonic anhydrase enzyme activities and serum trace element levels were measured in patient and control groups. In the current study, serum copper, magnesium, manganese and zinc levels were lower in the primary and metastatic hepatic cancer group in comparison with the control group (P < 0.05). In contrast, serum iron, cobalt, cadmium and lead levels were higher in the patient relative to the control group (P < 0.05). In comparison with the control group, the catalase level was lower in primary and metastatic cancer group, while the carbonic anhydrase level was higher in the cancer group (P < 0.05). Changes in levels of trace elements and anti-oxidant enzymes may be the factors which influence the development and progression of liver cancer. The carbonic anhydrase enzyme can be a useful indicator in the diagnosis of cancer. However, this issue warrants further investigation.

Stereotactic ablative body radiotherapy for oligometastatic inguinal lymph node in castrate resistant prostate cancer

Dear Editor,Introduction of prostate-specific membrane antigen positron-emission tomography/contrast-enhanced computed tomography(PSMA PET/CECT)for prostate cancer staging and follow-up have increased detection of metastases even in non-regional nodes,often in oligometastatic or oligorecurrent state[1].Some of these merit metastases-directed therapy(MDT)such as surgery or radiotherapy(RT)with curative intent.