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

Challenges and controversies in open pancreatoduodenectomies

Duodenopancreatectomia cefalopancreatica este o procedura intricata, ce necesita o inalta precizie datorita proximitatii structurilor vitale, sustinuta prin expertiza. O data cu evolutia chirurgiei si aparitia de instrumente inovatoare, mortalitatea a scazut sub 5%, dar morbiditatea a ramas la 30%, in special datorita fistulelor de anastomoza si a evenimentelor hemoragice. In acest sens, chirurgia deschisa confera rezultate mai bune, cu o curba de invatare rezonabila. Cu atat mai mult, cu cat efectuarea de trialuri clinice este dificila in acest domeniu, atat in chirurgia deschisa, cat si minim invaziva, pentru a obtine evidente valoroase, astfel subiectul ramane unul de dezbatere.Whipple procedure is intricate and demands high precision due to the proximity of critical structures, which requires an achieved expertise. With the innovative instruments and evolution of surgery, the perioperative morbidity still stands at 30% with a mortality lower than 5%, primary because of anastomotic leaks and haemorrhagic events. Therefore open surgery provides better outcomes with a decent learning curve. Furthermore, it is challenging to conduct clinical trials in the field of pancreatic surgery both open or minimally-invasive to obtain high-level evidence, remaining a subject open to debate

Emergency Treatment of Transverse Colon Cancer

This chapter deals with the emergency treatment of transverse colon cancer. The main complications that classify transverse colon cancer in an emergency setting are obstruction, perforation accompanied by localized or generalized peritonitis, and hemorrhage which may be occult or cataclysmic with hemorrhagic shock. We present the technical principles of radical surgical resection using embryological, anatomical, and oncological concepts. In this chapter we also discuss the principles of lymphadenectomy associated with complete excision of the mesocolon with high vascular ligation, in particular with T3 or T4 cancers requiring D2/D3 lymphadenectomy. The use of infrapyloric, gastro-epiploic, and prepancreatic lymphadenectomy is recommended due to the frequent metastases in these regional lymph nodes

Analysis of microRNA signatures using size-coded ligation-mediated PCR

The expression pattern and regulatory functions of microRNAs (miRNAs) are intensively investigated in various tissues, cell types and disorders. Differential miRNA expression signatures have been revealed in healthy and unhealthy tissues using high-throughput profiling methods. For further analyses of miRNA signatures in biological samples, we describe here a simple and efficient method to detect multiple miRNAs simultaneously in total RNA. The size-coded ligation-mediated polymerase chain reaction (SL-PCR) method is based on size-coded DNA probe hybridization in solution, followed-by ligation, PCR amplification and gel fractionation. The new method shows quantitative and specific detection of miRNAs. We profiled miRNAs of the let-7 family in a number of organisms, tissues and cell types and the results correspond with their incidence in the genome and reported expression levels. Finally, SL-PCR detected let-7 expression changes in human embryonic stem cells as they differentiate to neuron and also in young and aged mice brain and bone marrow. We conclude that the method can efficiently reveal miRNA signatures in a range of biological samples

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Sternochondroplasty with metal blade retainers located retrosternal efficacy in patients with pectus excavatum

State Medical and Pharmaceutical University Targu Mures, Romania, The 6th International Medical Congress for Students and Young Doctors, May 12-14, 2016Introduction: Pectus Excavatum (PE) is a deformity of the anterior chest wall, in which the sternum and rib cartilage presents an abnormal development. In these cases, the anterior thoracic wall presents a concave shape depression. Surgical treatment of this condition is a great need for patients, because symptoms are often severe and affect the quality of life of these patients. Objective: Present study aims to objectify early and late postoperative complications after it was performed sternochondroplasty with metal blade retainers located retrosternal. Material and methods: We conducted a retrospective observational study over a period of 20 years (1.10.1995-1.10.2015). In this regard I used casuistry of Surgical Clinic no. 1 of SCJU Mures. We introduced in the study 68 patients (41 male, 27 female) diagnosed with PE, on whom we practiced sternochondroplasty with metal blade retainers located retrosternal. Results: Mean age of the patients in the study was 17.4 years, with a range between 8 and 20 years. Most common symptoms on this patients were recorded: palpitations (n=23), exertional dyspnea (n=15), cough (n=15), chest pain (n=22) and dysphagia (n=2). Also 29 patients at clinical examination presented deformations of the spine (12 patients – kyphosis; 17 patients- scoliosis). The degree of deformation was evaluated by measuring the angle formed by the body of the sternum and the manubrium towards the spine. Thereby, we obtained the following results: 42 patients had an angle of 10 to 15 degrees; 20 patients had an angle of 15 to 20 degrees and 11 patients with an angle greater than 20 degrees. Of the total number of operated patients, 11 had immediate postoperative complications, as follows: 3 hematoma patients, 4 patients with bilateral pneumothorax, 3 with unilateral pneumotorax and one patient experienced hemorrhage at cartilage section. Late complications were represented by 2 cases of thoracic deformity recurrence and 4 cases of patients with keloid scars. In the study group we observed that early complication rate was 16%, while the late complications rate was 9%. Conclusions: Surgery is the only treatment able to lead to improvements of symptoms in patients with PE. Sternochondroplasty with metal blade disposed retrosternal represents a viable surgical method of treatment of these parietal chest defects

Gastrointestinal Carcinoma with Plasmacytoid Morphology: Positivity for c-MET, Arylsulfatase, and Markers of Epithelial-Mesenchymal Transition, as Indicators of Aggressivity

Background. Plasmacytoid urothelial carcinoma is a rare and aggressive histologic variant of high-grade carcinoma of the urinary bladder. Few than 250 cases have been reported in the urinary bladder till January 2019. In this paper, a case series of unusual gastrointestinal carcinomas with plasmacytoid morphology was included. Only one similar case of the stomach was previously published and no such cases were found in colon. Methods. We present the complex immunoprofile, using a panel of 39 biomarkers, of the largest group of primary gastrointestinal carcinomas with plasmacytoid morphology reported in literature (one from upper rectum and six from stomach). Results. All of the seven cases showed lymph node metastases and only one survived over 25 weeks after surgical excision. The indicators of aggressivity were age (over 60), advanced stage (from IIIA to IV), E-cadherin negativity, and vimentin positivity. The immunoprofile indicated unfavorable prognosis for mesenchymal-type carcinomas (negativity for E-cadherin and positivity for vimentin, with membrane to nuclear translocation or negativity of β-catenin). The survivor showed an “epithelial-type adenocarcinoma with plasmacytoid dedifferentiation”, with membrane positivity for E-cadherin and β-catenin and vimentin negativity. All of the cases expressed c-MET and were negative for HER-2. Conclusions. Primary carcinoma with plasmacytoid morphology is a dedifferentiated variant of adenocarcinoma or poorly cohesive carcinomas. Vimentin positive dedifferentiated-poorly cohesive carcinomas should be considered as mesenchymal-type highly malignant carcinomas. This rare histologic variant of gastrointestinal cancer might respond to anti-c-MET tyrosine kinases