Breast cancer (BC) is the most common malignancy to affect females. The first suggestions of BC and its treatment date back to Ancient Egypt, 1500-1600 B.C. Throughout history, the management of BC ...has evolved from extensive radical mastectomy towards less invasive treatments. Radical mastectomy was introduced by W.S. Halsted in 1894, involving the resection of the breast, regional lymph nodes, pectoralis major and minor. Despite its mutiloperative lymphatic mapping and the concept of sentinel lymph node (SLN) biopsy (SLNB) have been developed. SLNB has replaced axillary lymph node dissection (ALND) to be the standard procedure for axillary staging in patients with clinically node-negative BC. Many women have since been spared ALND, including those with negative SLNB or with SLNs involved with micrometastases (0.2-2 mm in size). In the last decade, evidence gathered from new clinical trials suggests that ALND may be safely omitted even in BC patients with 1 or 2 positive SLNs if adjuvant radiotherapy is delivered.ating effect, it had been the main surgical approach to BC patients until 1948, when Patey and Dyson proposed its modified form that conserved pectoralis major and minor and the level III of axillary lymph nodes. The latter was associated with less postoperative morbidity and improved quality of life. The idea of limited breast tissue resection was introduced in the 1970s by Umberto Veronesi and led to further minimizations of surgery in BC patients until breast conservation became the standard of care for early-stage disease. In the 1990s, intra
Karcinom dojke je najčešći maligni tumor u žena. Prvi zapisi o karcinomu dojke i njegovom liječenje datiraju iz drevnog Egipta 1500-1600 godina pr.n.e. Terapijski pristup bolesti mijenjao se kroz povijest te je nekadašnji invazivni, kao npr. radikalna mastektomija, s vremenom zamijenjen manje invazivnim kirurškim metodama. W.S. Halsted 1894. godine predstavlja metodu radikalne mastektomije. Ona uključuje potpunu resekciju dojke, regionalnih limfnih čvorova te velikog i malog pektoralnog mišića. Unatoč čestim postoperacijskim komplikacijama, zauzimala je glavno mjesto među kirurškim modalitetima liječenja karcinoma dojke sve do 1948. godine kada su Patey and Dyson predstavili modificiranu radikalnu mastektomiju kojom su se, za razliku od radikalne, sačuvali pektoralni mišići te pazušni limfni čvorovi lože III, te postoperacijske komplikacije smanjene, uz poboljšanje kvalitete života bolesnica. Ideju ograničene resekcije tkiva dojke predstavlja Veronesi 70-ih godina 20. stoljeća, nakon čega je i dalje nastavljeno smanjenje opsega i radikalnosti kiruških zahvata. Konačno, poštedna operacija dojke postaje standard u liječenju žena s ranim stadijem karcinoma dojke. Koncept biopsije limfnog čvora čuvara kod karcinoma dojke nailazi na svekoliku prihvaćenost, a njegovim usvajanjem mnoge su bolesnice pošteđene radikalnih disekcija aksilarnih limfnih čvorova, od onih čiji je nalaz biopsije limfnog čvora čuvara bio negativan, do onih s mikrometastazom u istome (malim tumorskim depozitom veličine 0.2-2 mm), dok zaključci novijih studija iz posljednjih deset godina, sugeriraju da i u žena kojima su biopsijom utvrđena metastaza u jednome do dva limfna čvora čuvara disekcija aksilarnih limfnih čvorova može se također izbjeći bez štetnih posljedica, uz primjenu adjuvantne radioterapije.
Purpose
Based on the risk of locoregional recurrence (LRR), postmastectomy radiotherapy (PMRT) is recommended in T1-T2pN1 breast carcinoma (BC). We aimed to elucidate our institutional strategies ...underlying selection of these patients for PMRT. In the no-PMRT subset, we compared various lymph node (LN) staging systems’ abilities to predict 5‑year overall and locoregional-free survival (OS/LRFS).
Methods
We retrospectively enrolled 548 women with T1-T2pN1 BC undergoing mastectomy and axillary LN dissection. Depending on PMRT delivery, the participants were divided into the PMRT and no-PMRT groups. Predictors of OS/LRFS were calculated for the no-PMRT group only. Based on Cox regression modelling, the number of positive LNs (PLN), negative LNs (NLN), LN ratio (LNR), log odds of PLN (LODDS), and modified LNR (mLNR) were modelled, each respectively, with OS model covariates (age, grade III, lymphovascular invasion LVI, tumor size, hormone receptor HR status) and LRFS model covariates (age, grade III, LVI). The C‑statistic, Akaike information criterion, and likelihood ratio χ
2
of the models were compared.
Results
Median follow-up was 60.5 (18–82), 61 (28–82), and 60 (18–80) months for the entire cohort, PMRT, and no-PMRT group, respectively. The PMRT and no-PMRT groups had comparable OS (
p
= 0.235). LRFS was better (
p
= 0.030) in the PMRT group comprising 105 subjects (19.16%) who were younger, more likely to have a higher-grade, HR−, HER2+ tumors, more PLNs, fewer NLNs, Ki-67 ≥ 20%, LVI, and extranodal extension (
p
≤
0.001). In the no-PMRT group, LNR-based OS/LRFS models exhibited superior prognostic performance.
Conclusion
In early-stage BC patients undergoing mastectomies, LN dissections and no PMRT, we propose LNR-based multivariable models to predict OS/LRFS with superior accuracy.
Amiodarone is a potent antiarrhythmic medication used to treat life-threatening ventricular arrhythmias; however, its well-established adverse effect is a thyroid disorder. Amiodarone-induced ...thyroiditis (AIT), a clinical entity involving two types with different etiopathology and treatment approaches, may occur at the beginning or even several years after amiodarone treatment discontinuation. The toxicity profile of amiodarone becomes especially important in young patients with lifelong cardiac disorders, which are often refractory to other antiarrhythmic drugs. Herein, we report the first case of non-sustained ventricular tachycardia (NSVT), an unusual presentation of type II AIT, in a young male patient who was previously diagnosed with left ventricular cardiomyopathy with excessive trabeculation.
A 36-year-old male non-athlete presented with tiredness during regular follow-up. Continuous electrocardiographic monitoring (cECG) revealed NSVT, whereas echocardiography and cardiac magnetic resonance imaging detected discrete structural and functional changes that could not fully explain the observed cECG report. Conversely, an unmeasurably low thyrotropin level on admission and previous exposure to amiodarone pointed the diagnostic pathway in the direction of the thyroid gland. Elevated free thyroxine and undetectable autoantibody titers with unremarkable sonographic findings raised clinical suspicion of type II AIT. Scintigraphic imaging with
Tc-2-methoxyisobutylisonitrile (sestamibi) revealed decreased thyroid uptake; hence, prednisone was introduced for treatment. Clear improvements in both biochemical and electrocardiographic parameters were observed after immunomodulatory treatment of type II AIT in this young patient with cardiomyopathy and excessive trabeculation.
Treatment of reversible causes of cardiac rhythm abnormalities such as type II AIT should be considered before choosing other treatment modalities, particularly in patients with structural cardiac disorders. The importance of a multidisciplinary approach in complex cases such as the one reported, thus, cannot be emphasized enough.
Glycoprotein 96 (gp96) is a member of the heat shock protein 90 family, which is an ubiquitous family of molecular chaperones that are involved in the regulation of protein folding and other ...essential cellular activities. Residing in the lumen of the endoplasmic reticulum, gp96 plays a key role in maintaining protein homeostasis, from assemblage to degradation. However, exposure to stressful conditions that disturb cellular homeostasis may translocate gp96 to the cell surface, which implies its additional functions, such as the regulation of intracellular signalling, proliferation, and apoptosis, as well as the modulation of the immune response. Besides its roles under physiological conditions, gp96 is also included in different stages of oncogenesis. In this review, we summarised available data on the structure, physiological, and pathophysiological roles of gp96, particularly in breast cancer oncogenesis.
Glikoprotein 96 (gp96) član je obitelji proteina toplinskog šoka 90 koja je inače sveprisutna obitelj molekularnih šaperona uključenih u regulaciju sinteze proteina, ali i drugih esencijalnih staničnih procesa. Gp96 je smješten u lumenu endoplazmatskog retikula stanice gdje igra ključnu ulogu u homeostazi proteina, od njihove sinteze do razlaganja. Međutim, uslijed izloženosti stresornim čimbenicima koji dovode do narušavanja stanične ravnoteže, može doći do premještanja gp96 na staničnu membranu pri čemu se aktiviraju njegove dodatne funkcije, kao što su regulacija unutarstanične signalizacije, proliferacije, apoptoze te modulacija imunološkog odgovora. Pored njegove uloge u fiziološkim uvjetima, gp96 također ima i aktivnu ulogu u različitim fazama onkogeneze. U ovom preglednom članku objedinili smo dostupna saznanja o strukturi, fiziološkim te patofiziološkim ulogama gp96, prvenstveno onima u onkogenezi kod karcinoma dojke.
Karcinom dojke najčešći je maligni tumor u žena. Prvi zapisi o karcinomu dojke i njegovu liječenje datiraju iz drevnog Egipta 1500 - 1600 godina pr. n. e. Terapijski pristup bolesti mijenjao se kroz ...povijest te je nekadašnji invazivni, kao npr. radikal-na mastektomija, s vremenom zamijenjen manje invazivnim kirurškim metodama. W. S. Halsted 1894. predstavlja metodu radikalne mastektomije koja uključuje potpunu resekciju dojke, regionalnih limfnih čvorova te velikog i malog pektoralnog mišića. Unatoč čestim postoperacijskim komplikacijama, zauzimala je glavno mjesto među kirurškim moda-litetima liječenja karcinoma dojke sve do 1948. kada su Patey and Dyson predstavili modifici-ranu radikalnu mastektomiju kojom su se, za razliku od radikalne, sačuvali pektoralni mišići te pazušni limfni čvorovi lože III, a postoperacijske su komplikacije smanjene, uz poboljšanje kvalitete života bolesnica. Ideju ograničene resekcije tkiva dojke predstavlja Veronesi 70-ih godina 20. stoljeća, nakon čega je i dalje nastavljeno smanjenje opsega i radikalnosti kiruških zahvata. Konačno, poštedna operacija dojke postaje standard u liječenju žena s ranim sta-dijem karcinoma dojke. Koncept biopsije limfnog čvora čuvara kod karcinoma dojke nailazi na svekoliku prihvaćenost, a njegovim usvajanjem mnoge su bolesnice pošteđene radikalnih disekcija aksilarnih limfnih čvorova, od onih čiji je nalaz biopsije limfnog čvora čuvara bio negativan do onih s mikrometastazom u istome (malim tumorskim depozitom veličine 0,2-2 mm), dok zaključci novijih studija iz posljednjih deset godina sugeriraju da se i u žena kojima je biopsijom utvrđena metastaza u jednome do dva limfna čvora čuvara disekcija aksilarnih limfnih čvorova može izbjeći bez štetnih posljedica, uz primjenu adjuvantne radioterapije.
Cilj: Cilj rada bio je procijeniti doprinos jednofotonske emisijske tomografije / kompjutorizirane tomografije somatostatinskih receptora (SR SPECT/CT) s 99mTc-EDDA/HYNIC-Tyr3-oktreotidom ...(99mTc-Tektrotyd) u dijagnostici i procjeni proširenosti bolesti kod pacijenata oboljelih od neuroendokrinih tumora (NET-ova). Ispitanici i metode: Retrospektivno je analizirano 120 SR SPECT/CT snimanja pacijenata s patohistološki dokazanim NET-om s obzirom na vizualizaciju primarnih lezija i metastaza. U 45 pacijenata učinjena je i pozitronska emisijska tomografija 18F-fluorodeoksiglukozom (18F-FDG PET/CT) te su nalazi uspoređeni s nalazima SR SPECT/CT-a i vrijednostima kromogranina A. Rezultati: Od 120 pacijenata 47 (39 %) je na SR SPECT/CT upućeno nakon odstranjenja primarne lezije. Od preostala 73 pacijenta (61 %), u 56 (77 %) primarni je tumor bio vidljiv SR SPECT/CT-om, a u 9 (12 %) poznata lezija nije akumulirala radiofarmak. U 8 (11 %) pacijenata s NET-om nepoznatog primarnog sijela nalaz je bio negativan. Od 68 (57 %) pacijenta s dokazanim metastazama, u njih 57 (84 %) bile su vidljive SR SPECT/CT-om, a u 11 (16 %) nisu akumulirale radiofarmak. Od 45 (38 %) pacijenata kojima je učinjen i 18F-FDG PET/CT, u 27 (60 %) detekcija primarnih lezija i metastaza bila je sukladna nalazu SR SPECT/CT-a. Osjetljivost SR SPECT/CT-a bila je 77 % za primarne lezije i 84 % za metastaze, a 18F-FDG PET/CT-a 75 % za primarne lezije i 76 % za metastaze. Vrijednosti kromogranina A nisu pokazale statistički signifikantnu korelaciju s nalazima slikovne dijagnostike. Zaključci: SR SPECT/CT ima visoku osjetljivost za detekciju NET-ova. Osim toga, potvrđena je komplementarnost s 18F-FDG PET/CT-om te kod pacijenata s negativnim nalazom SR SPECT/CT-a treba učiniti 18F-FDG PET/CT i obrnuto.
The aim: The aim of this study was to evaluate the significance of somatostatin receptor single-photon emission computed tomography/computed tomography (SR SPECT/CT) with 99mTc-EDDA/HYNIC-Tyr3-octreotide (99mTc-Tektrotyd) in diagnostics and staging of patients with neuroendocrine tumours. Patients and methods: We retrospectively enrolled 120 patients with histologically proven NET who underwent SR SPECT/CT between January 2013 and February 2017. The patients’ data and SR SPECT/CT findings regarding primary lesion and metastases were analysed. In 45 patients, 2-deoxy-2-18F-fluoroglucose positron emission computed tomography/computed tomography (18F-FDG PET/CT) was performed, and the findings were compared to SR SPECT/CT and chromogranin A values. Results: Out of 120 patients, 47 (39%) underwent SR SPECT/CT after surgical removal of the primary lesion. In 73 (61%) remaining patients, the primary lesion was detected on SR SPECT/CT in 56 (77%), in 9 (12%) lesion did not accumulate 99mTc-Tektrotyd. SR SPECT/CT was negative in the remaining 8 (11%) patients with unknown primary. Out of 68 patients (57%) with metastases, 57 (84%) were detected on SR SPECT/CT, while 11 did not accumulate 99mTc- Tektrotyd. 18F-FDG PET/CT was performed in 45 patients, and findings were concordant with SR SPECT/CT in 27 (60%). The the sensitivity of SR SPECT/CT was 77% for primary lesions and 84% for metastases, and sensitivity of 18F-FDG PET/CT was 75% 76%, respectively. In 70 (58%) patients with available chromogranin A no statistically significant correlation was found with imaging methods. Conclusion: In patients with NET and negative SR SPECT/CT findings, 18F-FDG PET/CT should be recommended and vice versa, because of the complementarity of these procedures.
Breast cancer (BC) is the most common malignancy to affect females. The first suggestions of BC and its treatment date back to Ancient Egypt, 1500-1600 B.C. Throughout history, the management of BC ...has evolved from extensive radical mastectomy towards less invasive treatments. Radical mastectomy was introduced by W.S. Halsted in 1894, involving the resection of the breast, regional lymph nodes, pectoralis major and minor. Despite its mutilating effect, it had been the main surgical approach to BC patients until 1948, when Patey and Dyson proposed its modified form that conserved pectoralis major and minor and the level III of axillary lymph nodes. The latter was associated with less postoperative morbidity and improved quality of life. The idea of limited breast tissue resection was introduced in the 1970s by Umberto Veronesi and led to further minimizations of surgery in BC patients until breast conservation became the standard of care for early-stage disease. In the 1990s, intraoperative lymphatic mapping and the concept of sentinel lymph node (SLN) biopsy (SLNB) have been developed. SLNB has replaced axillary lymph node dissection (ALND) to be the standard procedure for axillary staging in patients with clinically node-negative BC. Many women have since been spared ALND, including those with negative SLNB or with SLNs involved with micrometastases (0.2-2 mm in size). In the last decade, evidence gathered from new clinical trials suggests that ALND may be safely omitted even in BC patients with 1 or 2 positive SLNs if adjuvant radiotherapy is delivered.
IntroductionAmiodarone is a potent antiarrhythmic medication used to treat life-threatening ventricular arrhythmias; however, its well-established adverse effect is a thyroid disorder. ...Amiodarone-induced thyroiditis (AIT), a clinical entity involving two types with different etiopathology and treatment approaches, may occur at the beginning or even several years after amiodarone treatment discontinuation. The toxicity profile of amiodarone becomes especially important in young patients with lifelong cardiac disorders, which are often refractory to other antiarrhythmic drugs. Herein, we report the first case of non-sustained ventricular tachycardia (NSVT), an unusual presentation of type II AIT, in a young male patient who was previously diagnosed with left ventricular cardiomyopathy with excessive trabeculation. Case reportA 36-year-old male non-athlete presented with tiredness during regular follow-up. Continuous electrocardiographic monitoring (cECG) revealed NSVT, whereas echocardiography and cardiac magnetic resonance imaging detected discrete structural and functional changes that could not fully explain the observed cECG report. Conversely, an unmeasurably low thyrotropin level on admission and previous exposure to amiodarone pointed the diagnostic pathway in the direction of the thyroid gland. Elevated free thyroxine and undetectable autoantibody titers with unremarkable sonographic findings raised clinical suspicion of type II AIT. Scintigraphic imaging with 99mTc-2-methoxyisobutylisonitrile (sestamibi) revealed decreased thyroid uptake; hence, prednisone was introduced for treatment. Clear improvements in both biochemical and electrocardiographic parameters were observed after immunomodulatory treatment of type II AIT in this young patient with cardiomyopathy and excessive trabeculation. ConclusionTreatment of reversible causes of cardiac rhythm abnormalities such as type II AIT should be considered before choosing other treatment modalities, particularly in patients with structural cardiac disorders. The importance of a multidisciplinary approach in complex cases such as the one reported, thus, cannot be emphasized enough.
Cilj: Cilj rada bio je procijeniti doprinos jednofotonske emisijske tomografije / kompjutorizirane tomografije somatostatinskih receptora (SR SPECT/CT) s 99mTc-EDDA/HYNIC-Tyr3-oktreotidom ...(99mTc-Tektrotyd) u dijagnostici i procjeni proširenosti bolesti kod pacijenata oboljelih od neuroendokrinih tumora (NET-ova). Ispitanici i metode: Retrospektivno je analizirano 120 SR SPECT/CT snimanja pacijenata s patohistološki dokazanim NET-om s obzirom na vizualizaciju primarnih lezija i metastaza. U 45 pacijenata učinjena je i pozitronska emisijska tomografija 18F-fluorodeoksiglukozom (18F-FDG PET/CT) te su nalazi uspoređeni s nalazima SR SPECT/CT-a i vrijednostima kromogranina A. Rezultati: Od 120 pacijenata 47 (39 %) je na SR SPECT/CT upućeno nakon odstranjenja primarne lezije. Od preostala 73 pacijenta (61 %), u 56 (77 %) primarni je tumor bio vidljiv SR SPECT/CT-om, a u 9 (12 %) poznata lezija nije akumulirala radiofarmak. U 8 (11 %) pacijenata s NET-om nepoznatog primarnog sijela nalaz je bio negativan. Od 68 (57 %) pacijenta s dokazanim metastazama, u njih 57 (84 %) bile su vidljive SR SPECT/CT-om, a u 11 (16 %) nisu akumulirale radiofarmak. Od 45 (38 %) pacijenata kojima je učinjen i 18F-FDG PET/CT, u 27 (60 %) detekcija primarnih lezija i metastaza bila je sukladna nalazu SR SPECT/CT-a. Osjetljivost SR SPECT/CT-a bila je 77 % za primarne lezije i 84 % za metastaze, a 18F-FDG PET/CT-a 75 % za primarne lezije i 76 % za metastaze. Vrijednosti kromogranina A nisu pokazale statistički signifikantnu korelaciju s nalazima slikovne dijagnostike. Zaključci: SR SPECT/CT ima visoku osjetljivost za detekciju NET-ova. Osim toga, potvrđena je komplementarnost s 18F-FDG PET/CT-om te kod pacijenata s negativnim nalazom SR SPECT/CT-a treba učiniti 18F-FDG PET/CT i obrnuto.
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