Theoretical Bases of Clinical Medicine Štěpán Tuček, M.D., Ph.D. IHOK FN Brno and MMCI Brno MUNI Faculty of Medicine Aim of TZKM? •„Taste“ of clinical medicine... • Cíle předmětu TZKM? •„Taste" of clinical medicine • •Breast Cancer •Intravenous access in oncology • Questions to start with? •What to do if the study load is too much? • •What is the most frequent malignancy in women in the Czech Republic? •What screening programme has just started in 2024? •Can a breathlessness (dyspnea) be a sign of breast cancer? •What is a central venous access? •How to treat a intravenous port (port-a-cath)? Recommended literature… •Mika Waltari: The Egyptian (1945) •Richard Gordon: Doctor in the house (1952), Doctor at Sea (1953) •Samuel Shem: The House of God (1978) Medical students congress in ancient India (700 B.C.) •Samudrah ivah gumbheeram •naivah shakyam czikitsitam •vaktum niravaasheshainah •Schlokhanam ayutaïr apih • Medical students congress in ancient India (700 B.C.) Breast cancer • 9 Incidence of the most frequent malignancies (CZE)? order males to 100k inhab. females to 100k inhab All to 100k inhab. 1 ? ? ? 2 3 4 5 10 Most common malignancies- incidence Health statistics Institute: Neoplasms 2018 order males to 100k inhab. females to 100k inhab All to 100k inhab. 1 Skin nonmelanoma 287 Skin nonmelanoma 250 Skin nonmelanoma 268 2 prostate 152 breast 133 colorectal 68 3 colorectal 83 colorectal 54 lung 61 4 lung 79 lung 43 kidney 29 5 kidney 38 Uterus (corp) 36 Incidence and mortality- Breast cancer CZE Obsah obrázku tabulka Popis se vygeneroval automaticky. image Source: cruk.org/cancerstats You are welcome to reuse this Cancer Research UK statistics content for your own work. Credit us as authors by referencing Cancer Research UK as the primary source. Suggested style: Cancer Research UK, full URL of the page, Accessed [month] [year]. image Breast Cancer (C50): 2011-2013 Average Number of New Cases Per Year and Age-Specific Incidence Rates per 100,000 Population, Females, UK Incidence BC age related Clinical signs What does a patient come with?? •Breast resistance – lump •Upper lateral quadrant most frequent •Edema of skin •Erythema of skin •Retraction of skin, ulceration •Inversion of mammila •Painless afections •General symptoms – fatigue, weight loss, dyspnea… • Clinical signs Lump • fyloides Advanced tumour Skin retraction + "mosquito bites" infiltrates • ca-pokroč Skin edema and erythema "peau d'orange" • C:\Users\grell\Desktop\One-Month-After-Redness.jpg Kůže pomeranče Inflamatorní karcinom prsu Mammila inversion • C:\Users\grell\Desktop\800px-Breast_cancer.jpg 63 Risk factors Can I do something not to have it in future? Risk factors •Family history: breast cancer of 1st degree relative (parents, siblings, children) •One - relative risk 1,5 - 2,0 •Two relatives 5,0 •Early period onset: before 12 yoa •Late menopause: after 55 yoa •Nullipara (no birth) + no breast feeding •Combined hormonal substitution •Smoking, low physical activity, night shifts? •Benign breast afections: Atypical ductal hyperplasia •Genetic factors, various – 5-10 % of breast tumours Genetic risk - example •BRCA1 a BRCA2 genes – DNA repair - homologeous recombination •Risk of ca breast in BRCA1 mutation = 80% (lifetime), ovarian ca 60%, BRCA2 mutation 70%, resp. 25% •Only prevention bilateral mastectomy + salphingo-oophorectomy • Screening – general principles •Cheap •Nonivasive •Highly sensitive (few patients "escape") •Effective (survival benefit...) • •Doesn't have to be specific Screening -oncology •Gynecologic •Cytology smears from cervix •From onset of regular gyno assessment •Mammar •Mammograph after 45yoa every 2 yrs •Colorectal •Occult stool bleeding after 50 yoa (hidden!! bleeding) or •Scr colonoscopy after 55 yoa •Lung ca - low dose CT in risky population (start 2022) • •2024 – prostate: PSA in selected patients •And referral to a specialist Obsah obrázku text, tiskárna Popis se vygeneroval automaticky. Obsah obrázku text Popis se vygeneroval automaticky. Diagnostics How do we find it?? 140924_MEDEX_SadDoctor ? ? Initial diagnostics •62-yo woman •New lump left breast (upper lateral quadrant) •Overall healthy and good shape • •What investigations??? •TNM staging... Mammography •Screening and diagnostic method for ca breast •Very sensitive and specific •Cheap and safe (low radiation) • •Size evaluation (in mm) •T stage •Diagnostics of regional lymph nodes •N stage • •Sometimes US better or MRI • C:\Users\grell\Desktop\mammogram-showing-tumor.jpg 31 MMG, US Staging Ca breast • T classification Size, characteristics T0 No evidence of primary tumour T1 Tumour ≤20 mm largest diameter T1a Tumour >1 mm but ≤5 mm largest diameter T1b Tumour >5 mm but ≤10 mm largest diameter T1c Tumour >10 mm but ≤20 mm largest diameter T2 Tumour >20 mm but ≤50 mm largest diameter T3 Tumour >50 mm v největším rozměru. T4 Tumour whatever size infiltrating chest wall and/or skin (ulceration, skin lesions) T4a Infiltrating chest wall (not only the muscle) T4b Ulceration and/or edema (including peau d'orange) of skin T4c either T4a or T4b. T4d Inflammatory carcinoma Distant metastases - staging •M stage •Assessment: •Chest: Xray, CT scan •Abdomen and pelvis: ultrasound, CT scan •Whole body – PET/CT or PET/MRI, wb CT •Bones – scintigraphy •Brain – MRI or CT (with contrast!!) Stage T N M I T1 N0 M0 IIA T0 N1 M0 T1 N1 M0 T2 N0 M0 IIB T2 N1 M0 T3 N0 M0 IIIA T1-3 N2 M0 T3 N1 M0 IIIB T4 Any N M0 IIIC whatever T N3 M0 IV whatever T whatever N M1 Stage 5-y OS I 95% IIA 85% IIB 80% IIIA 67% IIIB 41% IIIC 49% IV 15% Staging and survival – ca breast Histology what do we deal with?? Histology = cells and stroma •Morphology - "typing": •Ductal (85%), lobular, medullar, mixed •Grade of differentiation – "grading" •Grade 1 well diferentiated (good prognosis)- grade 4 undifferentiated (poor) •Morpho-biology: •Receptor expression: •Estrogene •Progesterone •HER2 receptor •Ki-67 – marker of proliferation (%) • Expression ER a PgR - immunohistochemistry • C:\Users\grell\Desktop\OL-09-03-1207-g00.jpg HER2 expression - immunohistochemistry • C:\Users\grell\Desktop\Herceptest0123.jpg •A+C : B+D: •No amplification HER2 amplification FISH HER2 positive BC •HER2 – transmembrane receptor •Active through homodimerization (HER2-HER2) or heterodimerization HER2-HER3 or HER2-EGFR • Triple negative breast cancer -TNBC • ER negat, PR negat, HER2 negat • ¯ •Only modality – chemotherapy •not hormones •not targeted (perhaps besides-VEGF therapy) • •Immunotherapy?? • • Subtypes breast cancer • Luminal A ER+, PgR+, HER2-, Ki67 low Triple negative ER-, PR-, HER2 negat Luminal B ER+, HER2+ or -, and another risk factor: PgR negative, Ki67 high HER2 overexpression (amplified) Subtypes breast cancer • • •Median overall survival • OS (months) site of metastases •luminal A 26,4 bones, liver •luminal B 19,2 bones, liver, lungs •luminal/HER2+ 15,6 bones, liver, brain •HER2+ 8,4 bones, liver, lungs, brain •Triple-negative 6,0 lungs, brain • (p < 0,001) • Kennecke H. et al, JCO 2010 Jul 10;3271-3277 Therapy how to cure? …if not cure, how to prolong life? Principles of therapy •Localized disease- attempt to cure •Resection of primary tumour – only possible curative approach •Neoadjuvant therapy in some cases – before the operation – chemotherapy or hormones •Aim is to shrink (downstage) the tumour and lessen the extent of surgery •Adjuvant therapy – after the operation •Aim to lower the risk for relapse •Toxicity (temporary) is not too relevant • •Metastatic disease – we can prolong life •Systemic treatment – chemotherapy, hormones, targeted treatment •Toxicity relevant! Quality of life! •Supportive care.. Operation remove it, if we can!!! Mastektomy •Total mastektomy – removal of breast in whole • •Breast saving operation – removing the tumour and small amount of surrounding tissue • •Aim to save natural shape and form of the breast Partial mastektomy •Axillar dissektion - ALND •Incision in axilla, removal of 10–40 lymph nodes of level I and II •All patients with lymf nodes involvement ("positive") •Real risk of long term lymfedema • •Sentinel node biopsy – SNB •Sentinel lymph nodes – first to be infiltrated (first to pass lympha from tissue surrounding the tumour •Removal of 1-3 lymph nodes in all patients with NO signs of LN involvement •I positive (infiltrated), ALND is pursued Operation in axilla Risks of nursing on an arm after ALND •infection (i.g. erysipelas) •cellulitis •Lymphedema or its progression • •The risk is relative •e.g. Hand surgery can be safe • •Recomm.: choose the other arm if possible for blood taking, BP measurement •Not aplicable for emergency!!! (risk/benefit) Adjuvant treatment prevent relapse!! cutcaster-photo-100140393-No-Return-Road-Sign Adjuvant treatment •After the operation •To minimize risk of relapse •Aim to kill residual microscopic disease •Multimodal treatment: •Chemotherapy – 4 months •Targeted treatment (HER2 posit.) – 1 year •Radiotherapy – 5 weeks •Hormones (ER/PgR posit.)– 5–10 years or more • Chemotherapy - whom for? •Selected patients with risky tumours: •Large tumour •Positive lymph nodes •Biologically aggressive disease – triple-negative, HER2 positive • Chemotherapy and breast cancer •Most used cytotoxic drugs: •Antracyclines - Doxorubicin, Epirubicin •Taxanes - Paclitaxel, Docetaxel •Cyclophosphamide, 5-Fluorouracil – only in combinations •Combinations in adjuvant setting: •AC – doxorubicin + cyclophosphamide •AC followed by paclitaxel •FAC – flurouracil + doxorubicin + cyclophosphamide •FEC – flurouracil + epirubicin + cyclophosphamide •TAC – docetaxel + doxorubicin + cyclophosphamide •CMF – cyclophosphamide + methotrexate + 5-fluorouracil •Metastatic setting: •Combination (more effective) or monotherapy (more gentle) – paclitaxel, epirubicin, vinorelbin, capecitabine • Targeted treatment •Used in HER2 positive breast cancers, approx. 15% pts •HER2 – transmembrane receptor, EGFR family (HER2=EGFR2) •Activated by homodimerization (HER2-HER2) or heterodimerization (HER2-HER3 nebo HER2-EGFR) • • HER2 positive breast cancer •anti-HER2 therapy – monoclonal antibodies against HER2 receptor •First used Trastuzumab (Herceptin™) •Later generations – pertuzumab, T-DM1 •Adding to chemo adds effectléčby • Hormonal therapy •Hormonal receptors expressed in 70 % BC (estrogene or progesterone receptor) = hormone sensitive tumour • •Usually low or moderate aggressive tumours (Luminal A a B) • •Sensitive to hormonal treatment: •Tamoxifen (Selective Estrogene Receptor Modulator - SERM) •Aromatase Inhibitors •Non-steroidal AI (anastrozole, letrozole) •Steroidal (exemestane) •Direct ER inhibitor (fulvestrant) • Hormonal therapy- mechanism of action (MOA) •1. competition – on estrogene receptor, modulation of ER – tamoxifen, direct ER inhibitor - fulvestrant • •2. inhibition – blockade of sythesis of estrogene (inhibition of aromatase enzyme in fatty tissue) – AI: anastrozole, letrozole, exemestan • •3. ablation – ovarian estrogene suppresion (farmacologic castration – LH-RH analogues – goserelin, buserelin, leuprorelin, triptorelin) • •4. adition - adding estrogenes, androgens or gestagenes – more in history Hormonal treatment •In adjuvant setting administered for 5-10 years •Very effective in Luminal A subtype of BC •Some patients can be saved from chemotherapy and use hormones only •Treatment with low/minimal toxicity (heat flushes, bones and joints pain, artificial menopause, endometrial carcinoma and tamoxifen) •After operaci a chemotherapy •Always follows partial mastectomy, sometimes total mastectomy (large tumour, positive LN) •5-6 weeks, dose 50-60 Gy •Reduces risk of local relapse and improves OS •Toxicity: dermatitis, skin deskvamation Radiotherapy Therapie of a disseminated incurable disease no cure, rather prolonging life and improving/keeping its quality Terms and Definition •Curative- aim to cure •Palliativní- (noncurative), cure not expected •Aim to prolong survival, quality of life •Invaziveness of the procedures according to life expectancy and pts' wish (years?? vs. days??) • •Causal treatment (anticancer) •Symptomatic treatment (symptoms) Therapy of metastatic disease •SR=ER/PgR positive + breast cancer (Luminal A/B subtypes) - •hormonotherapy very effective •Tamoxifen → AI → Fulvestrant • •If not effective or SR- chemotherapy • •HER2 positive tumours- combination with targeted treatment (trastuzumab, pertuzumab, T-DM1) Chemotherapie •Monotherapy better??? •If progression/toxicity, followed by further lines • Anti-HER2 therapy emtansine Disseminated hormone-dependent ca breast •Hormonotherapy •Preferred •Chemotherapy •If quick response and regression is needed • •Response anticipated within •Homones 2-3 months •chemotherapy – 2-3 weeks Specific and supportive care •Explain meaning •Why important? Specific and supportive care •Bone mets – bone-modifying agents (BMA) – bisphosphonates, denosumab •Painful bone mets – radiotherapy •Brain involvement – surgery, radiosurgery, radiotherapy •Pleural effusion – drainage, talcage • •Supportive care- anaemia, pain, nausea, neuropathy, nutrition, intravascular access management… •Psychologic, psychosocial and spiritual help Case: Patient – 62yo woman •1999- Carcinoma mammae l.dx- pT1 pN1 (1/12) M0 •Low differentiation carcinoma ER-, PR+, G3 •St.p. RAME, adjuvant CHT 6x FAC and 5 yrs adjuvant hormones Tamoxifen •9/2011- relapse- soft tissues, bone mets, liver, tumor marker elevation •Biopsy from liver lesions, phenotype: ER 80% PR 70%, Ki 67 25% • Case- continued • 1/2012 to 11/2012 paclitaxel 1x weekly - effect: minimal response • 11/2012 to 1/2013 capecitabine - effect of progression • 1/2013 XENA (capecitabine+vinorelbine) to 4/2013, effect- progression (OSS, HEP) •Still good shape, performance status (PS) 0 – no limitations, working, active Case continued, PET/CT 4/2013 (after chemo) Case continued • hormonotherapy fulvestrant • 500 mg every 4wks intra muscular Obsah obrázku text Popis se vygeneroval automaticky. Obsah obrázku diagram Popis se vygeneroval automaticky. Within 10mths effect of: overall improvement, all metastases regression (PET/CT - 3/2014) Case 2: Pt, 52 years old •2/2010- ca left breast pT1b pN0 MO •ER 80% PR 80%, low proliferation, HER 2 negative •Parcial mastektomy + SNB, radiotherapy, adjuvant Tamoxifen • •4/2014 dg liver lesions Case 2: continued Obsah obrázku text, kniha Popis se vygeneroval automaticky. Case 2: continued •5/2014 – biopsy liver lesions •Histology: lymfocytes infiltrating liver • •Radiologist: typical metastases – CT, US •7/2014- repeated biopsy liver- •Again- no cancer • Case 3: Female 29yo •2/2012 dg invasive ductal carcinoma •triple negative, high proliferation (Ki-67 90%)- rapid growth T2N1M0 •Neoadjuvant chemo- AC (doxorubicin +cyclophosphamide)- effect after 3 cycles- propo 3 cyklech – progrese •Změna na docetaxel- progrese after 2 cycles, carboplatin added- progression •Mastectomy + ALND •9/2012-brain metastases Case 3: Female 29yo image Kunzel.jpg Ca breast: Summary •Frequent malignancy in women •Not one dissease – various subtypes (biology, behaviour) • •Complex multimodal treatment- operation, radiotherapy, chemotherapy, hormones, targeted treatment • •Supportive care complex and important 80 Side effects of chemotherapy • •Blood cell production (bone marrow, hematotoxicity) •Germinal cells (spermias, eggs) •Mucose (GI tract et al.) •Nerves (feeling, movement, hearing) •Organs – heart, kidneys, liver, brain • •Often irreversible, long term 81 Příklady • 82 Side effects chemo •Alergies •Fatigue •Rash/other skin toxicity •Diarrhoea •Hypertension •Proteinuria •Further (bone marrow suppression, bleeding, anorexia, weight loss, flu like symptoms) • •Mostly reversible •Sometimes postponing/stopping of therapy necessary • •Irreversible possible also… •Organs (heart, lungs, inflammatory) 83 Pulmonary fibrosis lung2 lung 84 Skin symptoms – acne, blisters • rash4 rashthorax sunitinib 85 Treatment of rash effective rash3 rash 86 Hair + eye lashes • rash7 cheveux sunitinib2 Vascular /intravenous access in oncology •Complex •Dynamic evolution (material, methods) •evidence based • •Professional society •Society for ports and permanent catheters •www.sppk.eu • •World Congress of Vascular Access (WoCoVA.com) •guidelines • Obsah obrázku text, klipart Popis byl vytvořen automaticky Obsah obrázku text Popis byl vytvořen automaticky What is right (state of the art)? - 2023 •Choose a proper access, right indication •Right procedure (implantation) •Check the position of the tip of catheter •Complication- special and skilled personnel •Interdisciplinary team? • • •Right function, minimal burden for the patient Why interdisciplinary? •Indication (what for?).............. oncologist •Implantation.................surgeon, radiologist, oncologist •Nursing ..........registered nurse • •complications................. surgeon, hematologist, etc.? •state of the art? news? Legal aspects? • •Everybody knows his part... What is important to choose well? •For how long? •What for? (infusions, chemicals, nutrition, blood taking) •What will be administered? (pH, irritants, osmolality?) •Where will be administered (hospital, home setting) •Safety while inserting •Infectious and thrombotic risk management •Patient's preference (arm, chest) • •...economics? Cathegories •Location of the tip •periferal •central • •Lenght of use •Short term (up to 7 days) •Middle term (ap cca 4-6 týdnů) •Long term = permanent • (months even years) • Obsah obrázku diagram Popis se vygeneroval automaticky. Obsah obrázku doplňky, náhrdelník Popis se vygeneroval automaticky. Choice Guidelines 2019 • According to Italian guideline GAVeCeLT 2019 (Gli Accessi Venosi Centrali a Lungo Termine) DIVA = difficult intravenous acces CVC = central venous catheter • Purpose of tunnelization •Exit site of catheter different from insertion site • •Why? •Optimal fixation •Easier nursing •Smaller risk of complication (infection) Obsah obrázku interiér, osoba Popis se vygeneroval automaticky. ZIM = „Zone Insertion Method“ • •Robem Dawson - optimal choice of catheter exit site for PICC • • Bacterial skin colonization ZIM for central venous access • S laskavým svolením prim. Maňáska • S laskavým svolením prim. Maňáska IMG_0332.JPG ? S laskavým svolením prim. Maňáska ? IMG_0334.JPG S laskavým svolením prim. Maňáska ? IMG_0335.JPG S laskavým svolením prim. Maňáska What "central" means? http://ars.els-cdn.com/content/image/1-s2.0-S1051044307012638-gr3.jpg Distal tip of catheter • Steve Hill – Procedure Team Manager Christie Hospital NHS Foundation Trust, Manchester (UK) Peripheral or central access? IV therapy Osmolarity < 900 mOsm/l; and 5>pH<9; and Nonirritant and Short term use Osmolarity > 900 mOsm/l; or pH<5 or pH>9; or irritant or Mid-term use Peripheral access Central access Complication when inserting long term access • Port, Broviac, PICC •Failure to introduce •Pneumothorax (not in PICC) •Artery puncture •Hematoma •Nerve irritation •Primary malposition •Ductus thoracicus damaged (not in PICC) • • • • • • Complication prevention •Right indication of the type of venous access •Appropriate vein and site of access (entrance and exit site) •Ultrasound navigation •Correct placement of tip of catheter Xray check – necessary? •US guidance is safe •Experience of the performer •….not necessary?? • •Xray is a clear legal evidence of right position and absence of complications... Ultrasound guidance • • Ultrasound guidance C:\Documents and Settings\NTB-HP\Plocha\kniha\fotky vlastní\finální verze do knihy Viktor - kapitoly, obr., popisky\kapitola II-1 PICC\obr.10.PNG What is US good for? •Not for "hitting the right vein" •rather to avoid complications and risks and malfuction immediately and in time • •choice of optimal site = •Better side? left/right •Best vein (lumen, unexpected anatomical structures, valves etc.) •Optimal entrance/exit site position •Check of the entire vein course... • Tip position check? •Estimate (measure on surface) •Xray •Intravasal ECG monitoring •Magnetic guidance Obsah obrázku osoba, oblečení Popis byl vytvořen automaticky Stitchless fixation Obsah obrázku interiér Popis byl vytvořen automaticky Stitchless fixation Securacath Tissue glue (acrylic) G:\kadlečíková tuneliz.PICC\IMG-567ad3bad0c81c8349e22275df57ae3a-V.jpg Complications -infection + thrombosis •Peripheral cannula, CVC and midline • Always extract •(Pittiruti M, Hamilton H, Biffi R et al. ESPEN Guidelines on Parenteral Nutrition: central venous catheters (access, care, diagnosis and theraphy of complications) Clin Nutr 2009; 28:365-77) •PICC • Local infection - try to treat •Thrombosis- treat in situ, do not remove- full anticoagulation until the explantation •(Debourdeau P, Farge D, Beckers M et al. International clinical practice guidelines for the treatment and prophylaxis of thrombosis associated with central venous catheters in patients with cancer. J Thromb Haemost 2013; 11:71-80) •Broviac, port •Try to treat and save When to remove a Broviac or port •Severe sepsis •Tunnel infection (tunnelitis) •Septic thrombosis •Endocarditis •Osteomyelitis •Port chamber abscess •Infection mycotic, Staph. aureus •G- bacteria, Staph koag. Neg. Or Enterococcus –treat • •AB i.v. for 2 weeks, endocarditis 6 weeks, osteomyelitis 8 weeks • • Meemmel LA, Allon M, Bouza E et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Disease Society of America. Clin Infect Dis 2009; 49:1-45 • • Fernandez-Hidalgo N, Almirante B, Calleja R et al. Antibiotic-lock theraphy for long-term intravascular catheter-related bacteremia: reset of an open, non-comparative study. J Antimicrob Chemother 2006; 57: 1172-80 Taurolidin in prevention of biofilm formation and its destruction C:\Documents and Settings\NTB-HP\Plocha\main.jpg C:\Documents and Settings\NTB-HP\Plocha\index.jpg C:\Documents and Settings\NTB-HP\Plocha\index.jpg C:\Documents and Settings\NTB-HP\Plocha\images.jpg Complication prevention cont'd •Right indication •Home or frequent administration- tunneled cath. Or port or picc •Inpatients – PICC better than untunneled catheter • •Right flush technique •start/stop method – short bolus of saline repeated (2mls) producing turbulent flow •Saline or taurolidin stopper (no more heparin) PICC or port? •indikation (who decides)? •purpose •Estimated time of use • •Nursing (PICC weekly, port every 6weeks) •Swimming, sports, activities? •Risks evaluation •Availability (team, economics etc.) PICC or port – length of use •chemo 3-6 months (till a year)..... PICC •chemo longer than 4-6 months ............port, PICC port • Economics (czk- ZUM) • PICC port PICC port Cost 4884,- Cost 5900,- Cost 6400,- (incl. Securacath, glue, ECG lead) mikro 7700,- Implantation 1090 points Approx. 1000 pts. Approx. 1000 pts. Nursing cost complex (material, time...) PICC port Desinfection, gloves, gauze, flush, fixation, needleless connector 53,50Kč Desinfection, sterile and regular gloves, gauze, flush, fixation, needle 54,60Kč frequency 4x??? frequency 1x altogether 214,-Kč altogether 54,60Kč Winged Needle 117,50Kč Code PICC redressing 09237...45pts. Every week??? Blood sample taking- needle 30,-Kč Summary: what is right (state of the art) in venous access in 2023? •Appropriate access, indication •Right indroduction technique (US guided) •Check of the catheter tip position •Complication audit and multidisciplinary skilled and experienced team •"vascular team"? • • •Right funcion, minimal burden 131 Thank you for attention exhausted exhausted-little-boy 980586-exhausted-medical-student-or-nurse exhausted