Imatinib response of gastrointestinal stromal tumor patients with germline mutation on KIT exon 13:A family report

Familial gastrointestinal stromal tumor(GIST) is a rare autosomal dominant disorder associated with mutations in the KIT gene in the majority of cases. Although, exon 11 appears to be the hot spot region for approximately 95% of germline mutations, pathogenic variations have also been identified in exon 8, 13 and 17. Exon 13 germline mutations are extremely rare amongst familial GISTs and seven families with a germline mutation have been reported to date. Moreover, the role of imatinib mesylate in this rare familiar settings is not completely known so far. We describe here clinical, imaging, pathological and genetic findings of a family with four affected members; grandmother, his son and two grand-sons having a germline gain-of-function mutation of KIT in exon 13 and discuss the imatinib mesylate treatment surveillance outcomes towards disease management.

Histopathological evaluation of long-term tenofovir disoproxil fumarate treatment in patients with hepatitis be antigen-negative chronic hepatitis B

BACKGROUND Hepatitis B virus is a universal health problem.There are approximately 250 million people living with hepatitis B worldwide,and approximately 600000 of these people die every year due to the virus.AIM To compare the pretreatment and post-treatment histopathological results of patients with hepatitis be antigen(HBeAg)-negative chronic hepatitis B(CHB)who had been receiving tenofovir disoproxil fumarate(TDF)treatment at our clinic for at least 5 years.METHODS Patients with HBeAg-negative CHB who were being treated with TDF(245 mg/d)were included in the study.Liver biopsies of patients before TDF treatment and liver biopsies after 5 years of TDF treatment were retrospectively compared.RESULTS A total of 50 HBeAg-negative CHB patients were included in the study(mean age:47.9±10.4 years,men:27.54%).Histological improvement was observed in 78%(39)of the patients after 5 years of treatment.After the 5 years of treatment,the mean Ishak score of the patients was 1.3±1.3,and the mean histologic activity index score was 4.1±2.8.A 1.53 point reduction in Ishak fibrosis score was detected after long-term TDF treatment.CONCLUSION Liver biopsies after 5 years of TDF treatment revealed a significant histological response and a regression of the necroinflammatory score compared to pretreatment liver biopsies.To better understand the effects of antiviral treatments on the improvement of liver histology,long-term studies involving larger numbers of patients are needed.

The predictors of long-COVID in the cohort of Turkish Thoracic Society-TURCOVID multicenter registry:One year follow-up results

Objective:To evaluate long-term effects of COVID-19,and to determine the risk factors in long-COVID in a cohort of the Turkish Thoracic Society(TTS)-TURCOVID multicenter registry.Methods:Thirteen centers participated with 831 patients;504 patients were enrolled after exclusions.The study was designed in three-steps:(1)Phone questionnaire;(2)retrospective evaluation of the medical records;(3)face-to-face visit.Results:In the first step,93.5%of the patients were hospitalized;61.7%had a history of pneumonia at the time of diagnosis.A total of 27.1%reported clinical symptoms at the end of the first year.Dyspnea(17.00%),fatigue(6.30%),and weakness(5.00%)were the most prevalent long-term symptoms.The incidence of long-term symptoms was increased by 2.91 fold(95%CI 1.04-8.13,P=0.041)in the presence of chronic obstructive pulmonary disease and by 1.84 fold(95%CI 1.10-3.10,P=0.021)in the presence of pneumonia at initial diagnosis,3.92 fold(95%CI 2.29-6.72,P=0.001)of dyspnea and 1.69 fold(95%CI 1.02-2.80,P=0.040)fatigue persists in the early-post-treatment period and 2.88 fold(95%CI 1.52-5.46,P=0.001)in the presence of emergency service admission in the post COVID period.In step 2,retrospective analysis of 231 patients revealed that 1.4%of the chest X-rays had not significantly improved at the end of the first year,while computed tomography(CT)scan detected fibrosis in 3.4%.In step 3,138(27.4%)patients admitted to face-to-face visit at the end of first year;at least one symptom persisted in 49.27%patients.The most common symptoms were dyspnea(27.60%),psychiatric symptoms(18.10%),and fatigue(17.40%).Thorax CT revealed fibrosis in 2.4%patients.Conclusions:COVID-19 symptoms can last for extended lengths of time,and severity of the disease as well as the presence of comorbidities might contribute to increased risk.Long-term clinical issues should be regularly evaluated after COVID-19.

Neoadjuvant intermediate-course versus long-course chemoradiotherapy in T3-4/N0+rectal cancer:Istanbul R-02 phase II randomized study

Radiation therapy(RT)is typically applied using one of two standard approaches for preoperative treatment of resectable locally advanced rectal cancer(LARC):short-course RT(SC-RT)alone or long-course RT(LC-RT)with concurrent fluorouracil(5-FU)chemotherapy.The Phase II single-arm KROG 11-02 study using intermediate-course(IC)(33 Gy(Gray)/10 fr(fraction)with concurrent capecitabine)preoperative chemoradiotherapy(CRT)demonstrated a pathologically complete response rate and a sphincter-sparing rate that were close to those of LC-CRT.The current trial aim to compare the pathological/oncological outcomes,toxicity,and quality of life results of LC-CRT and IC-CRT in cases of LARC.The prescribed dose was 33 Gy/10 fr for the IC-CRT group and 50.4 Gy/28 fr for the LC-CRT group.Concurrent chronomodulated capecitabine(Brunch regimen)1650 mg/m2/daily chemotherapy treatment was applied in both groups.The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer Module(EORTC QLQ-CR29)was administered at baseline and at three and six months after CRT.A total of 60 patients with LARC randomized to receive IC-CRT(n=30)or LC-CRT(n=30)were included in this phase II randomized trial.No significant difference was noted between groups in terms of pathological outcomes,including pathological response rates(ypT0N0-complete response:23.3%vs.16.7%,respectively,and ypT0-2N0-downstaging:50%for each;p=0.809)and Dworak score-based pathological tumor regression grade(Grade 4-complete response:23.3 vs.16.7%,p=0.839).The 5-year overall survival(73.3 vs.86.7%,p=0.173)rate was also similar.The acute radiation dermatitis(p<0.001)and any hematological toxicity(p=0.004)rates were significantly higher in the LC-CRT group,while no significant difference was noted between treatment groups in terms of baseline,third month,and sixth month EORTC QLQ-CR29 scores.

Evidence-based medical oncology and interventional radiology paradigms for liver-dominant colorectal cancer metastases

Colorectal cancer metastasizes predictably, with liver predominance in most cases. Because liver involvement has been shown to be a major determinant of survival in this population, liver-directed therapies are increasingly considered even in cases where there is(limited) extrahepatic disease. Unfortunately, these patients carry a known risk of recurrence in the liver regardless of initial therapy choice. Therefore, there is a demand for minimally invasive, non-surgical, personalized cancer treatments to preserve quality of life in the induction, consolidation, and maintenance phases of cancer therapy. This report aims to review evidence-based conceptual, pharmacological, and technological paradigm shifts in parenteral and percutaneous treatment strategies as well as forthcoming evidence regarding next-generation systemic, locoregional, and local treatment approaches for this patient population.

Blood rheology and aging

The flow properties of blood play significant roles in tissue perfusion by contributing to hydrodynamic resistance in blood vessels. These properties are influenced by pathophysiological processes, thereby increasing the clinical relevance of blood rheology information. There is well-established clinical evidence for impaired blood fluidity in humans of advanced age, including enhanced plasma and whole blood viscosity, impaired red blood cell (RBC) deformability and enhanced RBC aggregation. Increased plasma fibrinogen concentration is a common finding in many studies owing to the pro-inflammatory condition of aged individuals;this finding of increased fibrinogen concen-tration explains the higher plasma viscosity and RBC aggregation in elderly subjects. Enhanced oxidant stress in advanced age is also known to contribute to altered blood fluidity, with RBC deformability being an important determinant of blood viscosity. Several studies have shown that physical activity may improve the hemorheological picture in elderly subjects, yet well-designed observational and mechanistic studies are required to determine the specific effects of regular exercise on hemorheological parameters in healthy and older individuals.

Red Blood Cell Mechanical Stability

It has been well documented that shear forces effective above a certain magnitude under flow conditions causes damage in blood cells. This damage ranges from slight morphological alteration to the destruction of red blood cells (RBC). The hemolytic trauma to RBC can easily be detected by measuring free hemoglobin level in plasma, however there are no standardized protocols to quantitate subhemolytic trauma. Ektacytometry has been used to study the alterations in RBC mechanical properties induced by the application of shear stress at various levels. Additionally, a protocol for measuring the hemolytic threshold as an indicator of subhemolytic damage to RBC has been developed based on ektacytometry. These standardized protocols may find applications in the pre-clinical and clinical evaluation of artificial organs and biomedical devices contacting with blood.

An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease

Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD.However,to date,there is no appropriate guidance on CKD in individuals with MAFLD.Furthermore,there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.Methods and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.Conclusions:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.

Screening for hepatocellular carcinoma: summary of current guidelines up to 2018

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related to worldwide death with a great geographical variation. To be eligible for curative therapy at the time of diagnosis is important. However, the majority of cases are diagnosed at late stages. This can be achieved with applicable screening modalities. Until now, many organizations around the world have developed guidelines according to their own evidence-based data for screening of HCC. The purpose of this article is to review the screening modalities of HCC to assist gastroenterologists and providers involved in the management of HCC.