Colorectal cancer: an update upon the diagnostic and therapeutic transdiciplinary approach

Scop: Prezentarea unor date actualizate referitoare la rolul ONCOTEAM în diagnosticul și terapia pacientului cu cancerului colorectal (CRC). Material și metode: În perioada 2018-2023, 147 de pacienți cu CRC au beneficiat de un abord individualizat. Evaluarea imagistică preoperatorie cu CT-scan/MRI cu difuzie a fost urmată de o descriere de tip ”hartă” a informațiilor pe baza cărora s-a efectuat intervenția chirurgicală și procesarea histopatologică conform metodologiei descrise anterior de echipa noastră în jurnalelel Diagnostics (DOI: 10.3390/diagnostics11020314) și Journal of the Belgian Society of Radiology (DOI: 10.5334/jbsr.3186). Examinările genetice au fost efectuate la indicațiile oncologului iar terapia post-operatorie a luat în considerare profilul molecular al celulelor tumorale. Rezultate: Utilizând acest protocol adaptat, am obținut un număr mediu de 15±2.23 limfonoduli prelevați per caz. Numărul depozitelor tumorale a fost, de asemenea, crescut și a dus la o supra-stadializare a 15% din cazuri. Utilizând o valoare a ”lymph node ratio” de 0.15, am obținut valori superioare celor obținute la abordarea clasică a 120 cazuri examinate anterior (p=0.002). Determinările genetice efectuate în timp au dus la o începere rapidă a terapiei oncologice individualizate și, deși profilul genei BRAF V600E este dificil a fi evaluat în țesuturi incluse în parafină, extracția ADN și determinările PCR au fost adecvate în toate cazurile examinate. Concluzii: Abordarea transdiciplinară a CRC poate fi efectuată doar dacă fiecare membru al echipei este implicat conștiincios în fiecare pas al diagnosticului sau terapiei. Costurile determinărilor au fost parțial acoperite în cadrul proiectelor PCCF 20/2018 și 10127/13/2021.Aim: To present an update regarding the role of the ONCOTEAM in the diagnosis and therapy of colorectal cancer (CRC). Materials and methods: During 2018-2023, 147 patients with CRC have benefited by an individualized approach. Preoperatively evaluation was done with CT-scan/diffusion-weighted MRI and a lymph node station map was typed. The next step consisted on surgical removal, based on the indications included in the map. Histopathological examination was based on the methods described by our team previously (DOI: 10.3390/diagnostics11020314; DOI: 10.5334/jbsr.3186). Genetic examinations were done based on the indications of the oncologist and the post-operative therapy was performed according to the molecular profile. Results: Based on the in-house adapted protocol, the median number of harvested lymph nodes per case was 15±2.23. The number of identified deposits was also significant and up-staged the tumors in 15% of the cases. The lymph node ratio value, using a cut-off of 0.15, was also superior to the classic approach of other 120 cases (p=0.002). The genetic examinations proved to be useful for an earlier start of post-operative therapy, without any cost for the patients. As regarding pre-analytical factors, although BRAF V600E gene profile is hard to be detected from paraffin-embedded tissues, the DNA extraction and PCR examinations were succesful in all of the cases. Conclusions: A proper transdiciplinary approach can be done only if any member of the team is attentively involved in each step of the diagnosis and therapy. The costs were partially supported by the projects PCCF 20/2018, and 10127/13/2021

The Utility of Magnetic Resonance Imaging in the Multidisciplinary Treatment of Patients with Rectal Cancer

Rectal cancer is one of the most common types of cancer in both men and women. In recent years, the importance of magnetic resonance imaging (MRI) has greatly increased in the multidisciplinary treatment of patients with rectal cancer. MRI has a particularly important role in the most accurate preoperative staging of these patients, both in terms of assessing the local invasion of the tumor and in terms of assessing the status of pelvic lymph nodes. Many patients with rectal cancer, especially those in the advanced stage of the disease, in the preoperative period undergo neoadjuvant radio chemotherapy. The evaluation of the clinical response of these patients to neoadjuvant therapy is of crucial importance both in terms of personalized treatment and in terms of their prognosis. In this regard, MRI has its clearly defined role at present in evaluating the efficacy of neoadjuvant therapy, as well as in postoperative follow-up

Synchronous Colorectal Cancer: Improving Accuracy of Detection and Analyzing Molecular Heterogeneity—The Main Keys for Optimal Approach

Background: In patients with synchronous colorectal cancer (SCRC), understanding the underlying molecular behavior of such cases is mandatory for designing individualized therapy. The aim of this paper is to highlight the importance of transdisciplinary evaluation of the pre- and post-operative assessment of patients with SCRCs, from imaging to molecular investigations. Methods: Six patients with SCRCs presented with two carcinomas each. In addition to the microsatellite status (MSS), the epithelial mesenchymal transition was checked in each tumor using the biomarkers β-catenin and E-cadherin, same as KRAS and BRAF mutations. Results: In two of the patients, the second tumor was missed at endoscopy, but diagnosed by a subsequent computed-tomography-scan (CT-scan). From the six patients, a total of 11 adenocarcinomas (ADKs) and one squamous cell carcinoma (SCC) were analyzed. All the examined carcinomas were BRAF-wildtype microsatellite stable tumors with an epithelial histological subtype. In two of the six cases, KRAS gene status showed discordance between the two synchronous tumors, with mutations in the index tumors and wildtype status in the companion ones. Conclusions: Preoperative CT-scans can be useful for detection of synchronous tumors which may be missed by colonoscopy. Where synchronous tumors are identified, therapy should be based on the molecular profile of the indexed tumors

Számítógépes tomográfia és hasűrinyomás-mérés alkalmazása az óriás medián hegsérvek kezelésében = Application of computed tomography and abdominal pressure measurement in the treatment of giant incisional hernias

Absztrakt: Bevezetés: Az óriás hasfali defektusok kezelése kihívást jelent a sebészek számára. CT-vizsgálattal meghatározható a sérvzsák és a hasüreg térfogata közötti arány, megállapítva a téraránytalanság mértékét, amely a műtét utáni hasűri nyomás mértékének kifejezője lehet. Célkitűzés: A posztoperatív óriás hasfali defektusok kivizsgálásában alkalmazott CT-vizsgálat jelentőségének alátámasztása, a rekonstrukciós módszer hatékonyságának elemzése a hasűrinyomás-méréssel. Módszer: Prospektív kutatást végzünk klinikánkon, vizsgálva az óriás hegsérvvel kezelt betegeinket, akiknél műtét előtt hasi CT-vizsgálat készül. A hasfal rekonstrukciója feszülésmentesen, retromuscularisan elhelyezett Prolene hálóval és sérvzsákból készített peritoneumlebenyekkel történik. Műtét alatt és műtét után hasűri nyomást mérünk, posztoperatívan 2, 4, 6 hónap után telefonon keresztül követjük betegeinket. Eredmények: Elért eredményeinket három eset kapcsán mutatjuk be. 1. eset: A 48 éves nőbetegnél óriás kiújult hegsérv, több társbetegség állt fenn. Testtömegindexe 43,6, a hasfali defektus átmérője 155 mm, a hegsérv térfogata 1536,63 cm3 volt. A műtét utáni 7. napon hazabocsátottuk. 2. eset: Az 51 éves férfi betegnél multilocularis óriás hegsérv keletkezett, testtömegindexe 26,85 volt. A két hasfali defektus átmérője 123 mm és 105 mm, térfogatuk együttes értéke 406,41 cm3 volt. A műtét utáni 5. napon a beteget elbocsátottuk. 3. eset: A 67 éves férfi beteg testtömegindexe 23,7, a hasfali defektus mérete 100 mm, térfogata 258,10 cm3 volt. A beteget a műtét utáni 4. napon elbocsátottuk. Következtetés: A preoperatív CT-vizsgálat adatai fontosak az alkalmazott műtéti technika megválasztásában. A sérvzsák és a háló együttes alkalmazása az óriás hegsérvek rekonstrukciójában olcsó és feszülésmentes műtéti technikát biztosít a fokozott rizikóval rendelkező betegek esetében. A technika rövid távú hatékonyságának elemzésére a húgyhólyagon keresztül mért hasűri nyomás a választandó módszer. Orv Hetil. 2020; 161(9): 347–353. | Abstract: Introduction: Giant abdominal wall defects represent a major challenge for surgeons. CT scan can determine the ratio between the volume of the hernia sac and the abdominal cavity, determining the extent of the disproportion, which is related to the postoperative abdominal pressure value. Aim: Confirmation of the significance of CT examination in postoperative giant abdominal wall defects, effectiveness analysis of the reconstruction method by abdominal pressure measurement. Method: A prospective study is conducted on patients with giant incisional hernias, with preoperatively performed abdominal CT scan. Tension-free abdominal wall reconstruction is realized with retromuscular Prolene mesh and hernial sac. Abdominal pressure is measured during and after surgery. Patients’ follow-up is performed through phone after 2–4–6 months. Results: We present our results through three cases. First case: 48-year-old woman presented a giant recurrent incisional hernia and multiple comorbidities. Maximum defect diameter was: 155 mm, hernia volume: 1536.63 cm3, BMI = 43.6. The patient was discharged after seven days. Second case: 51-year-old male patient presented with multilocular giant incisional hernia, BMI = 26,85. Maximum diameter of the two wall defects were 123 mm and 105 mm, their total volume: 406.41cm3. The patient was discharged after five days. Third case: A 67-year-old male patient presented with giant incisional hernia. The abdominal defect size was 100/100 mm (LL/CC), volume: 258.10 cm3, BMI = 23.7. The patient was discharged after four days. Conclusion: The proper surgical technique can be established based on the preoperative CT scan. Abdominal wall reconstruction with retromuscular Prolene mesh and hernial sac provides a cheap, reliable, tension-free technique. The technique’s short-term efficacy can be determined by abdominal pressure measuring through the bladder. Orv Hetil. 2020; 161(9): 347–353

Two-Year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson's disease

In a 6-month double-blind, placebo-controlled study of Parkinson's disease patients with motor fluctuations, safinamide 50 and 100 mg/d significantly increased ON-time without increasing dyskinesia. Further long-term safinamide use in these patients was evaluated over an additional 18 months. Patients continued on their randomized placebo, 50, or 100 mg/d safinamide. The primary endpoint was change in Dyskinesia Rating Scale total score during ON-time over 24 months. Other efficacy endpoints included change in ON-time without troublesome dyskinesia, changes in individual diary categories, depressive symptoms, and quality of life measures. Change in Dyskinesia Rating Scale was not significantly different in safinamide versus placebo groups, despite decreased mean total Dyskinesia Rating Scale with safinamide compared with an almost unchanged score in placebo. Ad hoc subgroup analysis of moderate to severe dyskinetic patients at baseline (36% of patients) showed a decrease with safinamide 100 mg/d compared with placebo (P50.0317). Improvements in motor function, activities of daily living, depressive symptoms, clinical status, and quality of life at 6 months remained significant at 24 months. Adverse events and discontinuation rates were similar with safinamide and placebo. This 2-year, controlled study of add-on safinamide in mid-to-late Parkinson's disease with motor fluctuations, although not demonstrating an overall difference in dyskinesias between patients and controls, showed improvement in dyskinesia in patients at least moderately dyskinetic at baseline. The study additionally demonstrated significant clinical benefits in ON-time (without troublesome dyskinesia), OFF-time, activities of daily living, motor symptoms, quality of life, and symptoms of depression

Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study

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