Prolonged hyperthermic intraperitoneal chemotherapy duration with 90 minutes cisplatin might increase overall survival in gastric cancer patients with peritoneal metastases

BACKGROUND Advanced gastric cancer with synchronous peritoneal metastases(GC-PM)is associated with a poor prognosis.Although cytoreductive surgery with hyperthermic intraperitoneal chemotherapy(CRS-HIPEC)is a promising approach,only a limited number of Western studies exist.AIM To investigate the clinicopathological outcomes of patients who underwent CRSHIPEC for GC-PM.METHODS A retrospective analysis of patients with GC-PM was conducted.All patients were seen at the Department of General and Visceral Surgery,Hospital Barmherzige Brüder,Regensburg,Germany between January 2011 and July 2021 and underwent CRS-HIPEC.Preoperative laboratory results,the use of neoadjuvant trastuzumab,and the details of CRS-HIPEC,including peritoneal carcinomatosis index,completeness of cytoreduction,and surgical procedures were recorded.Disease-specific(DSS),and overall survival(OS)of patients were calculated.RESULTS A total of 73 patients were included in the study.Patients treated with neoadjuvant trastuzumab(n=5)showed longer DSS(P=0.0482).Higher white blood cell counts(DSS:P=0.0433)and carcinoembryonic antigen levels(OS and DSS:P<0.01),and lower hemoglobin(OS and DSS:P<0.05)and serum total protein(OS:P=0.0368)levels were associated with shorter survival.Longer HIPEC duration was associated with more advantageous median survival times[60-min(n=59):12.86 mo;90-min(n=14):27.30 mo],but without statistical difference.To obtain additional data from this observation,further separation of the study population was performed.First,propensity score-matched patient pairs(n=14 in each group)were created.Statistically different DSS was found between patient pairs(hazard ratio=0.2843;95%confidence interval:0.1119-0.7222;P=0.0082).Second,those patients who were treated with trastuzumab and/or had human epidermal growth factor receptor 2 positivity(median survival:12.68 mo vs 24.02 mo),or had to undergo the procedure before 2016(median survival:12.68 mo vs 27.30 mo;P=0.0493)were removed from the original study population.CONCLUSION Based on our experience,CRS-HIPEC is a safe and secure method to improve the survival of advanced GC-PM patients.Prolonged HIPEC duration may serve as a good therapy for these patients.

Role and function of granin proteins in diabetes mellitus

The granin glycoprotein family consists of nine acidic proteins;chromogranin A(CgA),chromogranin B(CgB),and secretogranin II–VIII.They are produced by a wide range of neuronal,neuroendocrine,and endocrine cells throughout the human body.Their major intracellular function is to sort peptides and proteins into secretory granules,but their cleavage products also take part in the extracellular regulation of diverse biological processes.The contribution of granins to carbohydrate metabolism and diabetes mellitus is a recent research area.CgA is associated with glucose homeostasis and the progression of type 1 diabetes.WE-14,CgA10-19,and CgA43-52 are peptide derivates of CgA,and act as CD4+or CD8+autoantigens in type 1 diabetes,whereas pancreastatin(PST)and catestatin have regulatory effects in carbohydrate metabolism.Furthermore,PST is related to gestational and type 2 diabetes.CgB has a crucial role in physiological insulin secretion.Secretogranins II and III have angiogenic activity in diabetic retinopathy(DR),and are novel targets in recent DR studies.Ongoing studies are beginning to investigate the potential use of granin derivatives as drugs to treat diabetes based on the divergent relationships between granins and different types of diabetes.

Longitudinal changes in personalized platelet count metrics are good indicators of initial 3-year outcome in colorectal cancer

BACKGROUND Platelet count or complete blood count(CBC)-based ratios including lymphocyteto-monocyte(LMR),neutrophil-to-lymphocyte(NLR),hemoglobin-to-platelet(HPR),red blood cell count distribution width-to-platelet(RPR),and platelet-tolymphocyte(PLR)ratio are good predictors of colorectal cancer(CRC)survival.Their change in time is not well documented,however.AIM To investigate the effect of longitudinal CBC ratio changes on CRC survival and their possible associations with clinicopathological properties,comorbidities,and anamnestic data.METHODS A retrospective longitudinal observational study was conducted with the inclusion of 835 CRC patients,who attended at Semmelweis University,Budapest.CBC ratios and two additional newly defined personalized platelet count metrics(pPLT_(D)and pPLT_(S),the platelet counts relative to the measurement at the time of CRC diagnosis and to the one 4-6 wk after tumor removal surgery,respectively)were recorded.RESULTS The 835 CRC patients had a total of 4608 measurements(5.52 visits/patient,in average).Longitudinal survival models revealed that the increases/decreases in LMR[hazard ratio(HR):0.4989,P<0.0001],NLR(HR:1.0819,P<0.0001),HPR(HR:0.0533,P=0.0038),pPLT_(D)(HR:4.9229,P<0.0001),and pPLT_(S)(HR:4.7568,P<0.0001)values were poor prognostic signs of disease-specific survival.The same was obtained for all-cause mortality.Most abnormal changes occurred within the first 3 years after the diagnosis of CRC.RPR and PLR had an only marginal effect on diseasespecific(P=0.0675)and all-cause mortality(Bayesian 95%credible interval:0.90–186.05),respectively.CONCLUSION LMR,NLR,and HPR are good metrics to follow the prognosis of the disease.pPLT_(D)and pPLT_(S)perform just as well as the former,while the use of RPR and PLR with the course of the disease is not recommended.Early detection of the abnormal changes in pPLT_(D),pPLT_(S),LMR,NLR,or HPR may alert the practicing oncologist for further therapy decisions in a timely manner.

Evidence based tools to improve efficiency of currently administered oncotherapies for tumors of the hepatopancreatobiliary system

Hepatopancreatobiliary tumors are challenging to treat,and the advanced or metastatic forms have a very low 5-year survival rate.Several drug combinations have been tested,and new therapeutic approaches have been introduced in the last decades,including radiofrequency and heat based methods.Hyperthermia is the artificial heating of tumors by various biophysical methods that may possess immunostimulant,tumoricidal,and chemoradiotherapy sensitizer effects.Both whole-body and regional hyperthermia studies have been conducted since the 1980s after the introduction of deep-seated tumor hyperthermia techniques.Results of the effects of hyperthermia in hepatocellular and pancreatic cancer are known from several studies.Hyperthermia in biliary cancers is a less investigated area.High local and overall responses to treatment,increased progression-free and overall survival,and improved laboratory and quality-of-life results are associated with hyperthermia in all three tumor types.With the evolution of chemotherapeutic agents and the introduction of newer techniques,the combination of adjuvant hyperthermia with those therapies is advantageous and has not been associated with an increase in alarming adverse effects.However,despite the many positive effects of hyperthermia,its use is still only known at the experimental level,and its concomitant utilization in routine cancer treatment is not certain because of the lack of thorough clinical studies.

New therapeutic approaches for type 1 diabetes:Disease-modifying therapies

It has been 100 years since the first successful clinical use of insulin, yet it remains the only treatment option for type 1 diabetes mellitus(T1DM) patients. Advances in diabetes care, such as insulin analogue therapies and new devices, including continuous glucose monitoring with continuous subcutaneous insulin infusion have improved the quality of life of patients but have no impact on the pathogenesis of the disease. They do not eliminate long-term complications and require several lifestyle sacrifices. A more ideal future therapy for T1DM, instead of supplementing the insufficient hormone production(a consequence of β-cell destruction), would also aim to stop or slow down the destructive autoimmune process. The discovery of the autoimmune nature of type 1 diabetes mellitus has presented several targets by which disease progression may be altered. The goal of disease-modifying therapies is to target autoimmune mechanisms and prevent β-cell destruction. T1DM patients with better β-cell function have better glycemic control, reduced incidence of long-term complications and hypoglycemic episodes. Unfortunately, at the time symptomatic T1DM is diagnosed, most of the insulin secreting β cells are usually lost. Therefore, to maximize the salvageable β-cell mass by disease-modifying therapies, detecting autoimmune markers in an early, optimally presymptomatic phase of T1DM is of great importance. Diseasemodifying therapies, such as immuno-and regenerative therapies are expected to take a relevant place in diabetology. The aim of this article was to provide a brief insight into the pathogenesis and course of T1DM and present the current state of disease-modifying therapeutic interventions that may impact future diabetes treatment.

High plasma CD40 ligand level is associated with more advanced stages and worse prognosis in colorectal cancer

BACKGROUND Colorectal cancer(CRC)is often associated with elevated platelet count(>400×10^(9)/L),known as thrombocytosis.The role of CD40 ligand(CD40L),a member of the tumor necrosis factor family,is controversial in CRC.Circulating CD40L is higher in CRC,but its relationship with disease staging and local and distant metastasis is not clear.Although most of the circulating CD40L is produced by platelets,no previous study investigated its relationship with CRC-related thrombocytosis.AIM To investigate the role of CD40L to predict the outcome of CRC and its relation to thrombocytosis.METHODS A total of 106 CRC patients and 50 age and sex-matched control subjects were enrolled for the study.Anamnestic data including comorbidities and histopathological data were collected.Laboratory measurements were performed at the time of CRC diagnosis and 1.5 mo and at least 6 mo after the surgical removal of the tumor.Plasma CD40L and thrombopoietin were measured via enzyme-linked immunosorbent assay,while plasma interleukin-6 was measured via electrochemiluminescence immunoassay.Patient follow-ups were terminated on January 31,2021.RESULTS Plasma CD40L of CRC patients was tendentiously higher,while platelet count(P=0.0479),interleukin-6(P=0.0002),and thrombopoietin(P=0.0024)levels were significantly higher as opposed to the control subjects.Twelve of the 106 CRC patients(11.3%)had thrombocytosis.Significantly higher CD40L was found in the presence of distant metastases(P=0.0055)and/or thrombocytosis(P=0.0294).A connection was found between CD40L and platelet count(P=0.0045),interleukin-6(P=0.0130),and thrombocytosis(P=0.0155).CD40L was constant with the course of CRC,and all baseline differences persisted throughout the whole study.Both pre-and postoperative elevated platelet count,CD40L,and interleukin-6 level were associated with poor overall and disease-specific survival of patients.The negative effect of CD40L and interleukin-6 on patient survival remained even after the stratification by thrombocytosis.CONCLUSION CD40L levels of CRC patients do not change with the course of the disease.The CD40L level is strongly correlated with platelet count,interleukin-6,thrombocytosis,and the presence of distant metastases.