Genitourinary small-cell carcinoma： 11-year treatment experience

The predictive factors of prognosis and treatment strategies for small-cell carcinoma （SCC） of the urinary tract are controversial. This study was aimed to investigate the clinical experience and management of patients with SCC of the urinary tract. We collected data of patients who were diagnosed with genitourinary SCC （GSCC） between 2002 and 2013 and were treated in the Fudan University Shanghai Cancer Center. A total of 18 patients were diagnosed with GSCC of which 10 originated from the prostate, seven from the bladder and one from the adrenal gland. The mean follow-up time was 15.5 months and progression-free survival （PFS） was 9.3 months. Primary tumor resection was attempted in 13 of 18 patients （72.2%） in whom radical surgery was performed in six of 14 （42.9%） limited disease patients. Most of the patients （13, 72.2%） received cisplatin-based chemotherapy. Patients who had normal lactic dehydrogenase （LDH） levels showed a significantly higher median PFS and overall survival （OS） compared with patients with high LDH levels （P = 0,030, P = 0.010）. Patients with limited disease treated with a radical operation experienced a non-significant （P = 0,211） longer PFS compared with patients who were not treated, but this reached statistical significance after analyzing OS （P = 0.211, P = 0.039）. Our patients showed a poor prognosis as reported previously. Serum LDH levels beyond the normal range indicate a poor prognosis. For GSCC patients who are diagnosed with limited disease, radical surgery is strongly recommended along with cisplatin-based chemotherapy,

A Novel Peptide from T-Cell Leukemia Translocation-Associated Gene (TCTA) Protein Inhibits Proliferation of a Small-Cell Lung Carcinoma

In 2009, we demonstrated that a peptide, which we named “Peptide A”, derived from the extracellular domain of T-cell leukemia translocation-associated gene (TCTA) protein, inhibited both RANKL-induced human osteoclastogenesis and pit formation of mature human osteoclasts. Here, we examined the effect of Peptide A on the cell proliferation of cell lines of small-cell lung carcinoma, breast cancer, and prostate cancer: RERF-LC-MA, MCF-7, and PC-3, respectively. Peptide A inhibited the proliferation of RERF-LC-MA, but not MCF-7 or PC-3. TCTA protein was immunohistologically detected in RERF-LC-MA and MCF-7. Thus, Peptide A may provide a novel strategy for the therapy of the patients with small-cell lung carcinoma, especially with bone metastasis. In addition, Peptide A may be useful for the treatment of various cancer patients with bone metastasis.

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.

Small-cell neuroendocrine carcinoma of the prostate： are heterotransplants a better experimental model？

Small-cell neuroendocrine carcinoma of the prostate （SCNCP） is an uncommon type of prostate cancer. However, it is of clinical importance because it is one of the most aggressive tumors of the prostate with a very poor prognosis. There exist few artificially cultured tumor cell lines to study SCNCE Then, another approach to that study consists in the use of fresh tumor tissue obtained from patients and its heterotransplantation into host mice. The purpose of this review is to integrate data from more than 20 years of heterotransplantation research in the study of small-cell neuroendocrine carcinoma of the prostate （SCNCP）. Heterotransplantation has provided data regarding the histopathology, karyotype, DNA content, cell cycle frequency, tumor markers, androgen receptor expression, metastasis and take rate of this prostate disease. When possible, comparisons between original in situ specimens removed from patients and heterotransplanted tissue from host mice have been made. There are advantages, as well as limitations, that have been identified for SCNCP heterotransplants versus xenotransplantation of cultured cells. Overall, heterotransplanted tumors are better than conventional tumor xenografts at retaining tumor morphology, pathology, secretory activity and expression of tumor markers of the patient＇s original specimen. Furthermore, heterotransplanted tissue preserves the three-dimensional tumor architecture of the prostate to maintain critical stromal-epithelial cell interactions.

Relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma

Objective:To study the relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma.Methods:A total of 297 patients from July 2009 to May 2013 were chosen as objects.EGFR gene mutation were detected with fluorescence quantitative PCR.Relevance of EGFR gene mutation with clinical and pathological features was analyzed,and the prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was compared.Results:In 297 patients.136(45.79%) showed EGFR gene mutation.EGFR gene mutation had no significant relevance with age.gender,smoking history,family history of cancer and clinical stage(P>0.05);there was significant relevance between EGFR gene mutation and blood type,pathologic types,differentiation and diameter of cancer(P<0.05).The difference between prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was statistical significance(P<0.05).Conclusions:EGFR gene mutation has significant relevance with pathological features,the prognosis of EGFRmutant-paticnts is better than that of EGFR- wide type-patients.

Inhibitory Effect of MiR-449b on Cancer Cell Growth and Invasion through LGR4 in Non-Small-Cell Lung Carcinoma

Non-small-cell lung carcinoma （NSCLC） is one of the most frequently diagnosed malignancies worldwide. Previous studies have shown that microRNA-449b （miR-449b） functions as a tumor suppressor in many cancers. However, the role of miR- 449b in NSCLC is still unknown. In the present study, miR-449b was significantly down- regulated in NSCLC samples and cell lines. Bioinformatics analysis revealed that 3＇-UTR region of leucine rich repeat containing G protein-coupled receptor 4 （LGR4） mRNA had putative complementary sequences to miR-449b, which was further confirmed by the luciferase assay. Western blotting showed that restoration of miR-449b in NSCLC cells decreased the expression of LGR4. Interestingly, over-expression of miR-449b inhibited growth and invasion of NSCLC cells in vitro. Furthermore, ectopic expression of LGR4 reversed miR-449b-suppressed proliferation and invasion of NSCLC cells. Therefore, the data of the present study demonstrate that miR-449b inhibits tumor cell growth and invasion by targeting LGR4 in NSCLC.

Small-cell neuroendocrine carcinoma of the rectum—a rare tumor type with poor prognosis:A case report and review of literature

BACKGROUND Small-cell neuroendocrine carcinoma(SNEC)of the rectum is a rare tumor associated with poor prognosis.CASE SUMMARY We report a case of a 77-year-old male who came into our hospital because of blood with his stool.An endoscopy revealed a cauliflower-like neoplasm in his rectum.Imaging examination showed that the lesion in the upper rectum was likely rectal cancer,and there was no evidence of metastasis.The patient was treated with surgery.Pathological examination confirmed SNEC of the rectum and an R0 resection was achieved.However,1 mo after the operation,the patient developed intestinal and ureteral obstructions due to peritoneal metastases.Finally,the patient died from renal failure.CONCLUSION SNEC of the rectum is a high-grade carcinoma with an aggressive phenotype,and surgery should be cautiously considered.

Small-Cell Carcinoma of Prostate:A Case Report and Literature Review

One case of small-cell carcinoma（SCC） of prostate was identified at Shangyu people＇s hospital.This 70-year-old male had a prior diagnosis of prostatic adenocarcinoma when he was first admitted to the hospital and received anti-androgen treatment.9 months later,he was readmitted to the hospital and was diagnosed as SCC through biopsy.The article was written to evaluate the clinical and pathological characteristics and treatment of SCC of prostate.

Small-cell carcinoma of the prostate with negative CD56,NSE,Syn,and CgA indicators:A case report

BACKGROUND Small-cell carcinoma of the prostate(SCCP)is a clinically rare malignant tumor,accounting for<1%of all prostate tumors.However,negativity for all SCCP neuroendocrine markers is rare.Herein,we report a case of SCCP with completely negative neuroendocrine markers and explore its clinicopathologic features,thus improving the understanding of its clinical diagnosis and management.CASE SUMMARY We report the case of a 48-year-old patient with SCCP negative for common sensitive neuroendocrine-staining indicators.Dysuria was the first symptom,and rectal examination revealed a hard prostate,palpable nodules,diffuse prostate enlargement,no pressure pain,no blood staining in the finger sleeve,1.33 ng/mL total prostate-specific antigen level,and a free-to-total prostate-specific antigen ratio of 0.21 ng/mL.Ultrasound suggested a prostate size of 5.3 cm×5.8 cm×5.6 cm,and magnetic resonance imaging suggested prostate cancer.The lower posterior bladder wall,rectal mesentery,and bilateral seminal vesicles were invaded,with multiple lymph node metastases in the pelvis.A whole-body bone scan suggested an abnormally active multiple bone metabolism and possible bone metastases.Head and lungs computed tomography revealed no significant nodal shadow.Following a pathological diagnosis of SCCP after a prostate puncture,with negative indicators of common sensitive neuroendocrine staining,chemotherapy was administered;the patient died 4-5 mo after SCCP diagnosis.CONCLUSION SCCP is a rare disease characterized by atypical clinical symptoms,limited treatment options,a short survival period,and a poor prognosis.

Accuracy of endoscopic ultrasound-guided needle aspiration specimens for molecular diagnosis of non-small-cell lung carcinoma

BACKGROUND Endoscopic ultrasonography-guided fine-needle aspiration(EUS-FNA)and endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)are highly sensitive for diagnosing and staging lung cancer.In recent years,targeted therapy has shown great significance in the treatment of non-small cell lung carcinoma(NSCLC).Using these minimally invasive techniques to obtain specimens for molecular testing will provide patients with a more convenient diagnostic approach.AIM To evaluate the feasibility and accuracy of tissue samples obtained using EUSFNA and EBUS-TBNA for molecular diagnosis of NSCLC.METHODS A total of 83 patients with NSCLC underwent molecular testing using tissues obtained from EUS-FNA or EBUS-TBNA at the Tianjin Medical University Cancer Hospital from January 2017 to June 2019.All enrolled patients underwent chest computed tomography or positron emission tomography/computed tomography prior to puncture.We detected abnormal expression of EGFR,KRAS,MET,HER2,ROS1 and anaplastic lymphoma kinase protein.Two patients failed to complete molecular testing due to insufficient tumor tissue.The clinical features,puncture records,molecular testing results and targeted treatment in the remaining 81 patients were summarized.RESULTS In a total of 99 tissue samples obtained from 83 patients,molecular testing was successfully completed in 93 samples with a sample adequacy ratio of 93.9%(93/99).Biopsy samples from two patients failed to provide test results due to insufficient tumor tissue.In the remaining 81 patients,62 cases(76.5%)were found to have adenocarcinoma,11 cases(13.6%)had squamous cell carcinoma,3 cases(3.7%)had adenosquamous carcinoma and 5 cases(6.2%)had NSCLC-not otherwise specified.The results of molecular testing showed EGFR mutations in 21 cases(25.9%),KRAS mutations in 9 cases(11.1%),ROS-1 rearrangement in 1 case(1.2%)and anaplastic lymphoma kinase-positive in 5 cases(6.2%).Twentyfour patients with positive results received targeted therapy.The total effectiveness rate of targeted therapy was 66.7%(16/24),and the disease control rate was 83.3%(20/24).CONCLUSION Tissue samples obtained by EUS-FNA or EBUS-TBNA are feasible for the molecular diagnosis of NSCLC and can provide reliable evidence for clinical diagnosis and treatment.

Atezolizumab and bevacizumab combination in advanced hepatocellular carcinoma patients:The imperative for safety assessment studies

Hepatocellular carcinoma(HCC)is the most prevalent cancer of the hepatobiliary tract and the third leading cause of cancer-related mortality worldwide.Atezolizumab and bevacizumab combination is currently considered among the frontline treatment modalities for advanced unresectable HCC.Most studies examining this combination were focused on evaluating its effectiveness.Despite numerous case reports documenting some side effects,there is a limited number of large-scale studies assessing these side effects.In this article,we comment on the case report by Park et al published recently,reporting a fatal intra-tumoral hemorrhage in a patient with HCC who received systemic therapy in the form of the combination of atezolizumab and bevacizumab.

Dysregulation of genes involved in the long-chain fatty acid transport in pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United States.As for other types of tumors,such as colorectal cancer,aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC development and progression.AIM To identify the possible involvement of lipid metabolism in PDAC by analyzing in tumoral and non-tumoral tissues the expression level of the most relevant genes involved in the long-chain fatty acid(FA)import into cell.METHODS A gene expression analysis of FASN,CD36,SLC27A1,SLC27A2,SLC27A3,SLC27A4,SLC27A5,ACSL1,and ACSL3 was performed by qRT-PCR in 24 tumoral PDAC tissues and 11 samples from non-tumoral pancreatic tissues obtained via fine needle aspiration or via surgical resection.The genes were considered significantly dysregulated between the groups when the p value was<0.05 and the fold change(FC)was≤0.5 and≥2.RESULTS We found that three FA transporters and two long-chain acyl-CoA synthetases genes were significantly upregulated in the PDAC tissue compared to the non-tumoral tissue:SLC27A2(FC=5.66;P=0.033),SLC27A3(FC=2.68;P=0.040),SLC27A4(FC=3.13;P=0.033),ACSL1(FC=4.10;P<0.001),and ACSL3(FC=2.67;P=0.012).We further investigated any possible association between the levels of the analyzed mRNAs and the specific characteristics of the tumors,including the anatomic location,the lymph node involvement,and the presence of metastasis.A significant difference in the expression of SLC27A3(FC=3.28;P=0.040)was found comparing patients with and without lymph nodes involvement with an overexpression of this transcript in 17 patients presenting tumoral cells in the lymph nodes.CONCLUSION Despite the low number of patients analyzed,these preliminary results seem to be promising.Addressing lipid metabolism through a broad strategy could be a beneficial way to treat this malignancy.Future in vitro and in vivo studies on these genes may offer important insights into the mechanisms linking PDAC with the long-chain FA import pathway.

Development of a nomogram for overall survival in patients with esophageal carcinoma:A prospective cohort study in China

BACKGROUND Esophageal carcinoma(EC)presents a significant public health issue in China,with its prognosis impacted by myriad factors.The creation of a reliable prog-nostic model for the overall survival(OS)of EC patients promises to greatly advance the customization of treatment approaches.AIM To create a more systematic and practical model that incorporates clinically significant indicators to support decision-making in clinical settings.METHODS This study utilized data from a prospective longitudinal cohort of 3127 EC patients treated at Chongqing University Cancer Hospital between January 1,2018,and December 12,2020.Utilizing the least absolute shrinkage and selection operator regression alongside multivariate Cox regression analyses helped pinpoint pertinent variables for constructing the model.Its efficacy was assessed by concordance index(C-index),area under the receiver operating characteristic curve(AUC),calibration curves,and decision curve analysis(DCA).RESULTS Nine variables were determined to be significant predictors of OS in EC patients:Body mass index(BMI),Karnofsky performance status,TNM stage,surgery,radiotherapy,chemotherapy,immunotherapy,platelet-to-lymphocyte ratio,and albumin-to-globulin ratio(ALB/GLB).The model demonstrated a C-index of 0.715(95%CI:0.701-0.729)in the training cohort and 0.711(95%CI:0.689-0.732)in the validation cohort.In the training cohort,AUCs for 1-year,3-year,and 5-year OS predictions were 0.773,0.787,and 0.750,respectively;in the validation cohort,they were 0.772,0.768,and 0.723,respectively,illustrating the model's precision.Calibration curves and DCA verified the model's predictive accuracy and net benefit.CONCLUSION A novel prognostic model for determining the OS of EC patients was successfully developed and validated to help clinicians in devising individualized treatment schemes for EC patients.

Scapular metastasis from acinic cell carcinoma of parotid gland:A case report

BACKGROUND Acinic cell carcinoma(ACC)is a malignant epithelial neoplasm that commonly occurs in the parotid gland.It is known to have a high recurrence rate and the potential to metastasize to the lung or cervical lymph nodes.However,few cases of ACC with bone metastasis have been reported in the medical literature.CASE SUMMARY The clinical significance of this case report lies in the unique site of occurrence of the metastasis:To the best of our knowledge,this report is the only literature documenting ACC arising in a shoulder mass.CONCLUSION Unusual presentations of uncommon malignancies can present diagnostic challenges for both surgeons and histopathologists.It is important to be aware of these rare occurrences in order to provide the best possible treatment for patients.

TRIPLET combined with microwave ablation:A novel treatment for advanced hepatocellular carcinoma

This editorial comments on a study by Zuo et al.The focus is on the efficacy of he-patic arterial infusion chemotherapy combined with camrelizumab and apatinib(the TRIPLET regimen),alongside microwave ablation therapy,in treating advanced hepatocellular carcinoma(HCC).The potential application of this combination therapy for patients with advanced HCC is evaluated.

WNT/β-catenin-M2 macrophage interplay as a target for therapy against hepatocellular carcinoma:Role of Calculus bovis

Liver cancer,and in particular hepatocellular carcinoma(HCC)is a disease of rising prevalence and incidence.To date,definitive treatment options include either surgical excision or ablation of the affected area.With increasing research on several pathways that could be involved in the progression of HCC,new elements within these pathways emerge as potential targets for novel therapies.The WNT/β-catenin pathway favors the presence of M2 tumor-associated macrophages which in turn promote tumor growth and metastasis.The inhibition of this pathway is considered a good candidate for such targeted therapeutic interventions.Interestingly,as Huang et al show in their recently published article,Calculus bovis which is used in traditional Chinese medicine can exert an inhibitory effect on theβ-catenin pathway and become a potential candidate for targeted pharmacotherapy against liver cancer.

Advanced hepatocellular carcinoma treatment strategies:Are transarterial approaches leading the way?

Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,with advanced stages posing significant treatment challenges.Al-though hepatic arterial infusion chemotherapy(HAIC)has emerged as a promising modality for treating advanced HCC,particularly in Asian clinical practice,its adoption in Western medicine remains limited due to a lack of large-scale randomized controlled trials.This editorial reviews and comments on the meta-analysis conducted by Zhou et al,which evaluates the efficacy and safety of HAIC and its combination strategies for advanced HCC.The authors performed a comprehensive meta-analysis of various clinical trials and cohort studies comparing HAIC and its combinations to other first-line treatments,such as sorafenib and transarterial chemoembolization(TACE).In this work,HAIC showed significantly better results regarding overall survival and progression-free survival compared to sorafenib or TACE alone and their combination.HAIC in combination with lenvatinib,ablation,programmed cell death 1 inhibitors,and radiotherapy further enhanced patient outcomes,indicating a synergistic effect.This editorial focuses on the critical role of multimodal treatment strategies in managing advanced HCC.It advocates for a paradigm shift towards integrated treatment approaches to enhance survival rates and improve the quality of life in patients with advanced HCC.

Transarterial chemoembolization combined with lenvatinib and sintilimab vs lenvatinib alone in intermediate-advanced hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is the most common form of liver cancer that has limited treatment options and a poor prognosis.Transarterial chemoembolization(TACE)is the first-line treatment for intermediate-stage HCC but can induce tumour hypoxia,thereby promoting angiogenesis.Recent studies suggested that combining TACE with anti-angiogenic therapies and immunotherapy might im-prove efficacy.Lenvatinib,a tyrosine kinase inhibitor,has demonstrated superior outcomes compared to sorafenib,while immune checkpoint inhibitors such as sintilimab show potential when combined with TACE.However,the efficacy and safety of TACE combined with lenvatinib and sintilimab(TACE+SL)compared to TACE with lenvatinib alone(TACE+L)in patients with intermediate-ad-vanced HCC has not yet been investigated.AIM To evaluate the efficacy and safety of TACE+SL therapy in comparison to TACE+L therapy in patients with intermediate-advanced HCC.METHODS A retrospective analysis was performed on patients with intermediate-advanced HCC who received TACE plus lenvatinib with or without sintilimab between September 2019 and September 2022.Baseline characteristics were compared,and propensity score matching was applied.Overall survival(OS),progression-free survival(PFS),and objective response rate(ORR)were evaluated between the two groups,and adverse events were analyzed.RESULTS The study included 57 patients,with 30 in the TACE+SL group and 27 in the TACE+L group.The TACE+SL group demonstrated significantly improved median PFS and OS compared to the TACE+L group(PFS:14.1 months vs 9.6 months,P=0.016;OS:22.4 months vs 14.1 months,P=0.039),along with a higher ORR(70.0%vs 55.6%).After propensity score matching,30 patients were included,with the TACE+SL group again showing longer median PFS and a trend toward improved OS(PFS:14.6 months vs 9.2 months,P=0.012;OS:23.9 months vs 16.3 months,P=0.063),and a higher ORR(73.3%vs 53.3%).No severe adverse events were reported.CONCLUSION TACE+SL demonstrated superior outcomes in terms of OS and PFS,compared to TACE+L.These findings suggest that the addition of sintilimab might enhance the therapeutic response in patients with intermediate-advanced HCC.

Targeted gene sequencing and bioinformatics analysis of patients with gallbladder neuroendocrine carcinoma:A case report

BACKGROUND Gallbladder neuroendocrine carcinoma(NEC)represents a subtype of gallbladder malignancies characterized by a low incidence,aggressive nature,and poor prognosis.Despite its clinical severity,the genetic alterations,mechanisms,and signaling pathways underlying gallbladder NEC remain unclear.CASE SUMMARY This case study presents a rare instance of primary gallbladder NEC in a 73-year-old female patient,who underwent a radical cholecystectomy with hepatic hilar lymphadenectomy and resection of liver segments IV-B and V.Targeted gene sequencing and bioinformatics analysis tools,including STRING,GeneMANIA,Metascape,TRRUST,Sangerbox,cBioPortal and GSCA,were used to analyze the biological functions and features of mutated genes in gallbladder NEC.Twelve mutations(APC,ARID2,IFNA6,KEAP1,RB1,SMAD4,TP53,BTK,GATA1,GNAS,and PRDM3)were identified,and the tumor mutation burden was determined to be 9.52 muts/Mb via targeted gene sequencing.A protein-protein interaction network showed significant interactions among the twelve mutated genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to assess mutation functions and pathways.The results revealed 40 tumor-related pathways.A key regulatory factor for gallbladder NEC-related genes was identified,and its biological functions and features were compared with those of gallbladder carcinoma.CONCLUSION Gallbladder NEC requires standardized treatment.Comparisons with other gallbladder carcinomas revealed clinical phenotypes,molecular alterations,functional characteristics,and enriched pathways.

Antiviral therapy for hepatitis B virus infection is beneficial for the prognosis hepatocellular carcinoma

In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV infection.HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic cells.In addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral infection.The loss of immune cell function caused by HBV infection ultimately leads to HCC.Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.