Treatment-induced neuroendocrine prostate cancer and de novo neuroendocrine prostate cancer:Identification,prognosis and survival,genetic and epigenetic factors

Neuroendocrine prostate cancer(NEPC)shows an aggressive behavior compared to prostate cancer(PCa),also known as prostate adenocarcinoma.Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer.NEPC may arise de novo or develop following androgen deprivation therapy(ADT).NEPC that arise following ADT has the nomenclature“treatmentemerging/induced NEPC(t-NEPC)”.t-NEPC would be anticipated in castration resistant prostate cancer(CRPC)and metastatic PCa.t-NEPC is characterized by low or absent androgen receptor(AR)expression,independence of AR signaling,and gain of neuroendocrine phenotype.t-NEPC is an aggressive metastatic tumor,develops from PCa in response to drug induced ADT,and shows very short response to conventional therapy.t-NEPC occurs in 10%-17%of patients with CRPC.De novo NEPC is rare and is accounting for less than 2%of all PCa.The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated.Sphingosine kinase 1 plays a significant role in t-NEPC development.Although neuroendocrine markers:Synaptophysin,chromogranin A,and insulinoma associated protein 1(INSM1)are expressed in t-NEPC,they are non-specific for diagnosis,prognosis,and follow-up of therapy.t-NEPC shows enriched genomic alteration in tumor protein P53(TP53)and retinoblastoma 1(RB1).There are evidences suggest that t-NEPC might develop through epigenetic evolution.There are genomic,epigenetic,and transcriptional alterations that are reported to be involved in development of t-NEPC.Knock-outs of TP53 and RB1 were found to contribute in development of t-NEPC.PCa is resistant to immunotherapy,and at present there are running trials to approach immunotherapy for PCa,CRPC,and t-NEPC.

Erdafitinib and checkpoint inhibitors for first-line and second-line immunotherapy of hepatic,gastrointestinal,and urinary bladder carcinomas:Recent concept

Cancer immunotherapy is administered for first-line,second-line,neoadjuvant,or adjuvant treatment of advanced,metastatic,and recurrent cancer in the liver,gastrointestinal tract,and genitourinary tract,and other solid tumors.Erdafitinib is a fibroblast growth factor receptor(FGFR)inhibitor,and it is an adenosine triphosphate competitive inhibitor of FGFR1,FGFR2,FGFR3,and FGFR4.Immune checkpoint inhibitors are monoclonal antibodies that block programmed cell death protein 1(PD-1)and its ligand that exert intrinsic antitumor mechanisms.The promising results of first-line treatment of advanced and metastatic urothelial carcinoma with PD-1 blockades with single or combined agents,indicate a new concept in the treatment of advanced,metastatic,and recurrent hepatic and gastrointestinal carcinomas.Cancer immunotherapy as first-line treatment will improve overall survival and provide better quality of life.Debate is arising as to whether to apply the cancer immunotherapy as first-line treatment in invasive carcinomas,or as second-line treatment in recurrent or metastatic carcinoma following the standard chemotherapy.The literature in the field is not definite,and so far,there has been no consensus on the best approach in this situation.At present,as it is described in this editorial,the decision is applied on a case-by-case basis.

Lower urinary tract dysfunction in pediatrics progress to kidney disease in adolescents:Toward precision medicine in treatment

Newborn infants who had neurogenic bladder dysfunction(NBD)have a normal upper urinary tract at birth.Most of them will develop deterioration of renal function and chronic kidney disease if they do not receive proper management.Children with NBD can develop renal damage at adolescence or earlier,which is due to high detrusor pressures resulted from poor compliance of the bladder,detrusor overactivity against a closed sphincter or detrusor sphincter dyssynergia.To preserve renal function and prevent deterioration of the kidneys,NBD must be treated immediately after being diagnosed.Over the last few years there was great progress in the treatment of children with the NBD.We searched PubMed and the Cochrane Library for peer-reviewed articles published in any language up to March 10,2021,using the search term“neurogenic bladder children.”Our search excluded diagnosis,pathophysiology,surgical treatment of spinal cord injury and spina bifida.The research identified the effectiveness of treatment regimens targeting prevention of chronic kidney disease and the indications of kidney transplantation.The results of the research showed that NBD in children should be diagnosed early in life,and the child should receive the proper management.The literature search concluded that the management of NBD in children would be personalized for every case and could be changed according to response to treatment,side effects,child compliance,availability of treatment modality and costs of treatment.The objectives of the study are to present the different options of management of NBD in children and the selection of the proper method in a personalized manner.

Multidisciplinary basic and clinical research of acute kidney injury with COVID-19:Pathophysiology,mechanisms,incidence,management and kidney transplantation

Acute kidney injury(AKI)linked to coronavirus disease 2019(COVID-19)has been identified in the course of the disease.AKI can be mild or severe and that is dependent on the presence of comorbidities and the severity of COVID-19.Among patients who had been hospitalized with COVID-19,some were admitted to intensive care unit.The etiology of AKI associated with COVID-19 is multifactorial.Prevention of severe AKI is the prime task in patients with COVID-19 that necessitates a battery of measurements and precautions in management.Patients with AKI who have needed dialysis are in an increased risk to develop chronic kidney disease(CKD)or a progression of their existing CKD.Kidney transplantation patients with COVID-19 are in need of special management to adjust the doses of immunosuppression drugs and corticosteroids to guard against graft rejection but not to suppress the immune system to place the patient at risk of developing a COVID-19 infection.Immunosuppression drugs and corticosteroids for patients who have had a kidney transplant has to be adjusted based on laboratory results and is individualized aiming at the protection of the transplanted from rejection.

Enhanced recovery after surgery:Progress in adapted pathways for implementation in standard and emerging surgical settings

The concept of enhanced recovery after surgery(ERAS)has been practiced for decades and has been implemented in numerous surgical specialties.ERAS is a global surgical quality improvement initiative,and it is an element in the field of perioperative care.ERAS had shown significant clinical outcomes,patientreported satisfaction,and improvements in medical service cost.ERAS has been developed for specific surgical procedures,but with the fast progress of newly introduced surgical procedures,the original ERAS have been developed and modified.Recently appearing Topics and future research trends encompass ERAS protocols for other types of surgery and the enhancement of perioperative status,including but not limited to pediatric surgery,laparoscopic and robotic assisted surgery,bariatric surgery,thoracic surgery,and renal transplantation.The elements and pathways of ERAS have been developed with the introduction of up-to-date methodologies in the pre-operative,operative,and post-operative pathways.ERAS costs are higher than traditional care,but the patient’s clinical outcome and satisfaction are higher.ERAS is in progress in the fields of anesthetic tasks,pediatric surgery,and organ transplantation.Although ERAS has shown significant clinical outcomes,there are needs to modify the protocol for specific cases,hospital facilities,resources,and nurses training on elements of ERAS.Several challenges and limitations exist in the implementation of ERAS that deserve consideration,it includes:Frailty,maximizing nutrition,prehabilitation,treating preoperative anemia,and enhancing ERAS adoption globally are all included.