CLINICAL TYPES, DIAGNOSTICS AND THERAPY OF MELANOMA

Melanom je zloćudni tumor kože i sluznica koji nastaje iz melanocita, a izrazito je sklon ranom limfogenom i hematogenom metastaziranju. Incidencija melanoma povećava se u cijelom svijetu, a veća je u muškaraca, u srednjoj životnoj dobi te u osoba svijetle puti, a najčešće anatomske lokalizacije ovog tumora su leđa u muškaraca i ekstremiteti u žena. Izlaganje ultraljubičastom zračenju jedan je od najvažnijih čimbenika u etiopatogenezi melanoma. Ostali čimbenici rizika su postojanje velikog broja nevusa, pozitivna obiteljska anamneza melanoma te jatrogena ili stečena imunosupresija. Najčešći tipovi melanoma su lentigo maligni melanom, površinsko šireći melanom, nodularni melanom i akrolentiginozni maligni melanom. U kliničkoj dijagnostici melanoma koristi se ABCDEFG pravilo. Dermatoskopija je neinvazivna dijagnostička metoda kojom se prvo procjenjuje je li lezija melanocitna ili nemelanocitna, a zatim radi li se o dobroćudnoj ili zloćudnoj leziji. Ekscizijska ili incizijska biopsija s patohistološkom analizom nužna je za postavljanje dijagnoze melanoma. Imunohistokemijske metode se koriste za potvrđivanje melanocitnog porijekla tumora. Biopsija limfnog čvora čuvara omogućava uvid u stanje limfnog čvora čuvara, te ukoliko je zahvaćen metastazama, provodi se disekcija svih regionalnih limfnih čvorova. Radiološka dijagnostika i PET/CT omogućuju određivanje proširenosti bolesti, praćenje bolesnika i otkrivanje metastatske bolesti. Sustav stupnjevanja melanoma prema prijedlogu Američke udruge za rak pomaže u planiranju odgovarajućeg liječenja i određivanju prognoze. Kirurška ekscizija je metoda izbora u bolesnika s melanomom, a u liječenju regionalnih i udaljenih metastaza primjenjuje se i radioterapija, standardna kemoterapija, ciljana terapija te imunoterapija. Praćenje oboljelih od melanoma preporučuje se provoditi doživotno.Melanoma is a malignant tumor of skin and mucous membranes that develops from melanocytes, and is highly susceptible for early lymphatic and hematogenic metastasis. The incidence of melanoma is increasing worldwide and it is higher in males, middle-aged and light-skinned people. The most common anatomical localizations of this tumor are the back in men and extremities in women. Exposure to ultraviolet radiation is one of the most important factors in etiopathogenesis of melanoma. The other risk factors are the existence of a large number of moles, a positive family history of melanoma and iatrogenic or acquired immunosuppression. The most common types of melanoma are lentigo maligna melanoma, superficial-spreading melanoma, nodular melanoma and acral lentiginous melanoma. ABCDEFG rule is an acronym used for the clinical detection of melanoma. Dermatoscopy is a non-invasive diagnostic method that determines whether the lesion is melanocytic or nonmelanocytic, and if it is a benign or malignant lesion. An excision or incision biopsy with pathohistological analysis is necessary for melanoma diagnosis. Immunohistological methods are used to confirm the melanocyte origin of the tumor. Sentinel lymph node biopsy is used for the identification and analysis of the sentinel lymph node, and if it is affected by metastases, a dissection of all regional lymph nodes is performed. Radiologic examinations, as well as PET/CT, are used for evaluating the spread of the disease, patient follow-up and identifying metastatic disease. The melanoma staging system according to the American Joint Committee on Cancer provides planning appropriate treatment and prognosis determination. Surgical excision is a method of choice in patients with melanoma. For regional and distant metastases radiotherapy, standard chemotherapy, targeted therapy and immunotherapy are also used. Follow-up for melanoma patients should be life-long

CLINICAL TYPES, DIAGNOSTICS AND THERAPY OF MELANOMA

Melanom je zloćudni tumor kože i sluznica koji nastaje iz melanocita, a izrazito je sklon ranom limfogenom i hematogenom metastaziranju. Incidencija melanoma povećava se u cijelom svijetu, a veća je u muškaraca, u srednjoj životnoj dobi te u osoba svijetle puti, a najčešće anatomske lokalizacije ovog tumora su leđa u muškaraca i ekstremiteti u žena. Izlaganje ultraljubičastom zračenju jedan je od najvažnijih čimbenika u etiopatogenezi melanoma. Ostali čimbenici rizika su postojanje velikog broja nevusa, pozitivna obiteljska anamneza melanoma te jatrogena ili stečena imunosupresija. Najčešći tipovi melanoma su lentigo maligni melanom, površinsko šireći melanom, nodularni melanom i akrolentiginozni maligni melanom. U kliničkoj dijagnostici melanoma koristi se ABCDEFG pravilo. Dermatoskopija je neinvazivna dijagnostička metoda kojom se prvo procjenjuje je li lezija melanocitna ili nemelanocitna, a zatim radi li se o dobroćudnoj ili zloćudnoj leziji. Ekscizijska ili incizijska biopsija s patohistološkom analizom nužna je za postavljanje dijagnoze melanoma. Imunohistokemijske metode se koriste za potvrđivanje melanocitnog porijekla tumora. Biopsija limfnog čvora čuvara omogućava uvid u stanje limfnog čvora čuvara, te ukoliko je zahvaćen metastazama, provodi se disekcija svih regionalnih limfnih čvorova. Radiološka dijagnostika i PET/CT omogućuju određivanje proširenosti bolesti, praćenje bolesnika i otkrivanje metastatske bolesti. Sustav stupnjevanja melanoma prema prijedlogu Američke udruge za rak pomaže u planiranju odgovarajućeg liječenja i određivanju prognoze. Kirurška ekscizija je metoda izbora u bolesnika s melanomom, a u liječenju regionalnih i udaljenih metastaza primjenjuje se i radioterapija, standardna kemoterapija, ciljana terapija te imunoterapija. Praćenje oboljelih od melanoma preporučuje se provoditi doživotno.Melanoma is a malignant tumor of skin and mucous membranes that develops from melanocytes, and is highly susceptible for early lymphatic and hematogenic metastasis. The incidence of melanoma is increasing worldwide and it is higher in males, middle-aged and light-skinned people. The most common anatomical localizations of this tumor are the back in men and extremities in women. Exposure to ultraviolet radiation is one of the most important factors in etiopathogenesis of melanoma. The other risk factors are the existence of a large number of moles, a positive family history of melanoma and iatrogenic or acquired immunosuppression. The most common types of melanoma are lentigo maligna melanoma, superficial-spreading melanoma, nodular melanoma and acral lentiginous melanoma. ABCDEFG rule is an acronym used for the clinical detection of melanoma. Dermatoscopy is a non-invasive diagnostic method that determines whether the lesion is melanocytic or nonmelanocytic, and if it is a benign or malignant lesion. An excision or incision biopsy with pathohistological analysis is necessary for melanoma diagnosis. Immunohistological methods are used to confirm the melanocyte origin of the tumor. Sentinel lymph node biopsy is used for the identification and analysis of the sentinel lymph node, and if it is affected by metastases, a dissection of all regional lymph nodes is performed. Radiologic examinations, as well as PET/CT, are used for evaluating the spread of the disease, patient follow-up and identifying metastatic disease. The melanoma staging system according to the American Joint Committee on Cancer provides planning appropriate treatment and prognosis determination. Surgical excision is a method of choice in patients with melanoma. For regional and distant metastases radiotherapy, standard chemotherapy, targeted therapy and immunotherapy are also used. Follow-up for melanoma patients should be life-long

The internal consistency and validity of the Vaccination Attitudes Examination Scale: A replication study

Background: Vaccinations are important preventative health behaviors. The recently developed Vaccination Attitudes Examination Scale (VAX) aims to measure the reasons behind refusal/hesitancy regarding vaccinations.  Purpose: The aim of this replication study is to conduct an independent test of the newly developed VAX scale in the U.K. We tested: (a) internal consistency (Cronbach’s alpha); (b) convergent validity by assessing its relationships with beliefs about medication, medical mistrust and perceived sensitivity to medicines; and (c) construct validity by testing how well the VAX scale discriminated between vaccinators and nonvaccinators.  Methods: A sample of 243 UK adults completed the VAX scale, the Beliefs about Medicines Questionnaire (BMQ), the Perceived Sensitivity to Medicines Scale (PSM) and the Medical Mistrust Index (MMI), in addition to demographics of age, gender, education levels and social deprivation. Participants were asked: (a) if they received an influenza vaccination in the past year; and (b) if they had a young child, had they vaccinated their young child against influenza in the past year.  Results: The VAX: (a) demonstrated high internal consistency (α=0.92); (b) was positively correlated with medical mistrust, beliefs about medicines and less strongly correlated with perceived sensitivity to medicines; and (c) successfully differentiated parental influenza vaccinators from non-vaccinators.  Conclusion: The VAX demonstrated good internal consistency, convergent and construct validity in an independent UK sample. It appears to be a useful measure to help us understand the health beliefs that promote or deter vaccination behavior

Thyroid hormones and antithyroid antibodies influence infertility treatment, reproductive outcome and indications for assisted reproduction

Cilj: Cilj istraživanja bio je utvrditi vrijednost rutinskog određivanja hormona štitnjače, autoprotutijela (antiperoksidazna – A-TPO, antitireoglobilinska A-Tg) u serumu te ultrazvučnog (UZ) pregleda štitnjače u procjeni ishoda liječenja neplodnih parova postupcima medicinski pomognute oplodnje. Ispitanice i metode: U istraživanje su uključene pacijentice (n = 222) s dijagnozom neplodnosti liječene u razdoblju od 2009. do 2015. godine postupcima medicinski pomognute oplodnje na Zavodu za humanu reprodukciju i Kliničkom zavodu za nuklearnu medicinu Kliničkog bolničkog centra u Rijeci. Pacijenticama je uzeta anamneza, učinjen je klinički i ultrazvučni pregled štitnjače, a određene su i koncentracije hormona i protutijela u serumu. Rezultati: Udio spontanih pobačaja bio je 29 % kod pacijentica s urednom funkcijom štitnjače, a 52 % kod pacijentica s autoimunom ili supkliničkom bolesti štitnjače. Zaključak: Povišene vrijednosti serumskih mikrosomalnih protutijela povezane su s češćim spontanim pobačajima nakon postupka medicinski pomognute oplodnje i u pacijentica koje imaju normalne serumske vrijednosti hormona štitnjače. Rutinsko određivanje hormona štitnjače i antitireoidnih antitijela u serumu te UZ pregled štitnjače može pomoći u utvrđivanju uzroka neplodnosti, probiru pacijentica s rizikom za spontani pobačaj te praćenju i liječenju neplodnosti.Aim: To estimate if the serum concentration of thyroid hormones, antithyroid antibodies and ultrasonographic examination of thyroid gland influence conception and reproductive outcome in infertile couples treated with methods of assisted reproduction Methods: Two hundred and twenty two (222) patients with infertility diagnosis have undergone a research during 2009 – 2015 in Department of human reproduction and Clinical department of nuclear medicine, University hospital Rijeka. The patients have undergone the anamnesis, clinical examination, ultrasound examination and we determined the levels of thyroid hormones and autoantibodies in serum. Results: The percent of patients with normal thyroid function who had spontaneous miscarriage was 29 %, whereas on patients with autoimune or subclinical thyroid gland disease was 52 %. Conclusion: Increased serum microsomal antibodies and increased incidence of miscarriage were observed also in infertile patients treated with methods of assisted reproduction with normal serum concentration of thyroid hormones. Routine determination of thyroid hormones, autoantibodies in serum and ultrasonographic examination of thyroid gland may be useful in infertility diagnosis, screening the patient with miscarriage risk, monitoring and treatment of infertility

CLINICAL TYPES, DIAGNOSTICS AND THERAPY OF MELANOMA

Melanom je zloćudni tumor kože i sluznica koji nastaje iz melanocita, a izrazito je sklon ranom limfogenom i hematogenom metastaziranju. Incidencija melanoma povećava se u cijelom svijetu, a veća je u muškaraca, u srednjoj životnoj dobi te u osoba svijetle puti, a najčešće anatomske lokalizacije ovog tumora su leđa u muškaraca i ekstremiteti u žena. Izlaganje ultraljubičastom zračenju jedan je od najvažnijih čimbenika u etiopatogenezi melanoma. Ostali čimbenici rizika su postojanje velikog broja nevusa, pozitivna obiteljska anamneza melanoma te jatrogena ili stečena imunosupresija. Najčešći tipovi melanoma su lentigo maligni melanom, površinsko šireći melanom, nodularni melanom i akrolentiginozni maligni melanom. U kliničkoj dijagnostici melanoma koristi se ABCDEFG pravilo. Dermatoskopija je neinvazivna dijagnostička metoda kojom se prvo procjenjuje je li lezija melanocitna ili nemelanocitna, a zatim radi li se o dobroćudnoj ili zloćudnoj leziji. Ekscizijska ili incizijska biopsija s patohistološkom analizom nužna je za postavljanje dijagnoze melanoma. Imunohistokemijske metode se koriste za potvrđivanje melanocitnog porijekla tumora. Biopsija limfnog čvora čuvara omogućava uvid u stanje limfnog čvora čuvara, te ukoliko je zahvaćen metastazama, provodi se disekcija svih regionalnih limfnih čvorova. Radiološka dijagnostika i PET/CT omogućuju određivanje proširenosti bolesti, praćenje bolesnika i otkrivanje metastatske bolesti. Sustav stupnjevanja melanoma prema prijedlogu Američke udruge za rak pomaže u planiranju odgovarajućeg liječenja i određivanju prognoze. Kirurška ekscizija je metoda izbora u bolesnika s melanomom, a u liječenju regionalnih i udaljenih metastaza primjenjuje se i radioterapija, standardna kemoterapija, ciljana terapija te imunoterapija. Praćenje oboljelih od melanoma preporučuje se provoditi doživotno.Melanoma is a malignant tumor of skin and mucous membranes that develops from melanocytes, and is highly susceptible for early lymphatic and hematogenic metastasis. The incidence of melanoma is increasing worldwide and it is higher in males, middle-aged and light-skinned people. The most common anatomical localizations of this tumor are the back in men and extremities in women. Exposure to ultraviolet radiation is one of the most important factors in etiopathogenesis of melanoma. The other risk factors are the existence of a large number of moles, a positive family history of melanoma and iatrogenic or acquired immunosuppression. The most common types of melanoma are lentigo maligna melanoma, superficial-spreading melanoma, nodular melanoma and acral lentiginous melanoma. ABCDEFG rule is an acronym used for the clinical detection of melanoma. Dermatoscopy is a non-invasive diagnostic method that determines whether the lesion is melanocytic or nonmelanocytic, and if it is a benign or malignant lesion. An excision or incision biopsy with pathohistological analysis is necessary for melanoma diagnosis. Immunohistological methods are used to confirm the melanocyte origin of the tumor. Sentinel lymph node biopsy is used for the identification and analysis of the sentinel lymph node, and if it is affected by metastases, a dissection of all regional lymph nodes is performed. Radiologic examinations, as well as PET/CT, are used for evaluating the spread of the disease, patient follow-up and identifying metastatic disease. The melanoma staging system according to the American Joint Committee on Cancer provides planning appropriate treatment and prognosis determination. Surgical excision is a method of choice in patients with melanoma. For regional and distant metastases radiotherapy, standard chemotherapy, targeted therapy and immunotherapy are also used. Follow-up for melanoma patients should be life-long

Dermoscopy in the diagnosis of different clinical types of melanoma

Melanom je zloćudni tumor kože i sluznica, izrazito sklon ranom limfogenom i hematogenom metastaziranju. Incidencija melanoma povećava se u cijelom svijetu, stoga je melanom sve značajniji javnozdravstveni problem. Dermatoskopija je neinvazivna dijagnostička metoda koja omogućuje vizualizaciju morfoloških struktura melanocitnih i nemelanocitnih kožnih promjena koje nisu vidljive golim okom te tako povezuje klinički pregled i patohistološku dijagnostiku. U analizi se koristi algoritam u dva koraka kojim se u prvom koraku procjenjuje je li promjena melanocitna ili nemelanocitna na temelju nazočnosti struktura kao što su pigmentna mreža, točke i globuli, homogena pigmentacija, radijalni tračci i paralelni uzorak. Ako je promjena melanocitna, u drugom koraku određujemo radi li se o dobroćudnoj ili zloćudnoj promjeni pomoću brojnih metoda kao što su analiza uzorka, lista sedam točaka, ABCD metoda te Menziesova metoda. Kod većine melanoma, neovisno o metodi koju koristimo, dermatoskopijom uočavamo neke od specifičnih kriterija za ovaj zloćudni tumor, a to su atipična pigmentna mreža, atipične točke i globuli, plavo-bijeli veo, nepravilni tračci, atipični vaskularni uzorak, asimetrična pigmentacija i regresijske strukture. No, pojedini klinički tipovi imaju i svoja specifična obilježja. Stoga, u ovom radu prikazujemo dermatoskopska obilježja vezana uz određeni tip melanoma, što dodatno omogućuje predviđanje patohistološke dijagnoze, prognoze i ishoda bolesti. Razvojem dermatoskopije došlo je do velikog napretka u ranoj dijagnostici melanoma, koja je preduvjet uspješnog liječenja.Melanoma is a malignant tumor of the skin and mucous membranes, highly prone to early lymphatic or hematogenous metastasis. The incidence of melanoma is increasing significantly worldwide, making melanoma a major public health problem. Dermoscopy is a non-invasive diagnostic method which enables visualization of melanocytic and non-melanocytic structures that are not visible to the naked eye, thus linking clinical examination and pathohistological diagnostics. In the analysis of pigmented skin lesions, a two-step algorithm is used to first assess whether the lesion is melanocytic or non-melanocytic, based on the presence of typical structures such as pigment network, dots and globules, homogeneous pigmentation, radial streaks, and a parallel pattern. If the lesion is melanocytic, the second step is to determine whether it is a benign or malignant lesion using a number of methods such as pattern analysis, 7-point checklist, ABCD method and the Menzies method. In most melanomas, regardless of the method we use, dermoscopy reveals some of the specific criteria for this malignant tumor, such as atypical pigment network, atypical dots and globules, blue-white veil, irregular streaks, atypical vascular pattern, asymmetric pigmentation and regression structures. However, some clinical types have their own specific characteristics. Therefore, in this paper, we present the dermatoscopic features associated with a specific type of melanoma, which further enables the prediction of pathohistological diagnosis, prognosis, and outcome of the disease. With the development of dermoscopy, great progress has been made in the early diagnosis of melanoma, which is necessary for a successful treatment

Subclinical Autoimmune Thyroid Dysfunction in Infertile Euthyroid Patients: The Risk of Spontaneous Abortion

OBJECTIVE: To investigate whether in vitro fertilization (IVF) procedures in patients with autoimmune thyroid disorder increase the likelihood of conception and delivery. STUDY DESIGN: The study included 125 patients (N=241 with male factor cases included) who were treated for infertility at the tertiary center between 2009 and 2015, either conservatively or by IVF. In all the participants, thyroid function was assessed by measuring serum concentrations of thyroid- stimulating hormone, free thyroxine, and free triiodothyronine, whereas thyroid autoimmunity was assessed by measuring thyroid peroxidase antibodies and thyroglobulin antibodies (TgAb) in the serum samples, and by thyroid ultrasound examinations. The reproductive outcomes were compared between the infertile patients with autoimmune thyroid disorder and patients with normal hormone levels, negative thyroid antibody tests, and normal ultrasound findings. RESULTS: In the group of patients with autoimmune thyroid disorder who were treated by IVF, significantly more women conceived. Also, significantly more women in this group had spontaneous abortions as compared to the women with euthyroid (p=0.039). The number of births per woman did not differ significantly between the groups. The percentage of births (birth per patient) was similar and without significant statistical difference. Similar results were observed in patients with autoimmune thyroid disorders and combined infertility (female- male). CONCLUSION: IVF procedures significantly increase the likelihood of conception in patients with subclinical autoimmune thyroid disorder, but not the likelihood of delivery. Despite the euthyroid status as a result of levothyroxine replacement, the risk of spontaneous abortion was increased in patients with autoimmune thyroid disorder, regardless of the type of infertility treatment (conservative or IVF)

Subclinical Autoimmune Thyroid Dysfunction in Infertile Euthyroid Patients: The Risk of Spontaneous Abortion

OBJECTIVE: To investigate whether in vitro fertilization (IVF) procedures in patients with autoimmune thyroid disorder increase the likelihood of conception and delivery. STUDY DESIGN: The study included 125 patients (N=241 with male factor cases included) who were treated for infertility at the tertiary center between 2009 and 2015, either conservatively or by IVF. In all the participants, thyroid function was assessed by measuring serum concentrations of thyroid- stimulating hormone, free thyroxine, and free triiodothyronine, whereas thyroid autoimmunity was assessed by measuring thyroid peroxidase antibodies and thyroglobulin antibodies (TgAb) in the serum samples, and by thyroid ultrasound examinations. The reproductive outcomes were compared between the infertile patients with autoimmune thyroid disorder and patients with normal hormone levels, negative thyroid antibody tests, and normal ultrasound findings. RESULTS: In the group of patients with autoimmune thyroid disorder who were treated by IVF, significantly more women conceived. Also, significantly more women in this group had spontaneous abortions as compared to the women with euthyroid (p=0.039). The number of births per woman did not differ significantly between the groups. The percentage of births (birth per patient) was similar and without significant statistical difference. Similar results were observed in patients with autoimmune thyroid disorders and combined infertility (female- male). CONCLUSION: IVF procedures significantly increase the likelihood of conception in patients with subclinical autoimmune thyroid disorder, but not the likelihood of delivery. Despite the euthyroid status as a result of levothyroxine replacement, the risk of spontaneous abortion was increased in patients with autoimmune thyroid disorder, regardless of the type of infertility treatment (conservative or IVF)

Could fecal microbial transplantation offer a new potential in the treatment of metastatic pancreatic ductal adenocarcinoma?

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers due to its aggressiveness and resistance to anti-cancer medications. Recent data suggest that solid tumors such as PDAC are infected with microbial agents, which can induce aggressive phenotype and metabolize chemotherapeutical agents. However, it was shown that gut microbiota can migrate to the pancreas and that fecal microbial transplantation (FMT) from longterm PDAC survivors can alter both gut and tumor microbiome, the immune response, and the growth of PDAC in a murine model. Although the effect of FMT on enhancing the immune response was exhibited in melanoma patients, there is no robust data to support the use of immunotherapy in the majority of PDAC patients, as chemotherapy remains the mainstay of treatment. Along with its direct cytotoxic effect, chemotherapy can also reduce ineffective cytokine sinks via lymphodepletion and increase translocation of the gut microbiota leading to stimulation of the immune response. However, chemotherapy requires a functional microbiota to exert those effects. We hypothesize that altering the microbiome with the FMT from the long-term PDAC survivors, combined with systemic treatment, can potentially enhance the relationship between chemotherapy, the immune system, and the microbiome. Albeit there is a lack of knowledge regarding the exact composition of the ideal donor microbiome and the optimal patient selection, due to the dismal prognosis of PDAC patients, such a trial could offer a low-risk, high-reward situation

Could fecal microbial transplantation offer a new potential in the treatment of metastatic pancreatic ductal adenocarcinoma?

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers due to its aggressiveness and resistance to anti-cancer medications. Recent data suggest that solid tumors such as PDAC are infected with microbial agents, which can induce aggressive phenotype and metabolize chemotherapeutical agents. However, it was shown that gut microbiota can migrate to the pancreas and that fecal microbial transplantation (FMT) from longterm PDAC survivors can alter both gut and tumor microbiome, the immune response, and the growth of PDAC in a murine model. Although the effect of FMT on enhancing the immune response was exhibited in melanoma patients, there is no robust data to support the use of immunotherapy in the majority of PDAC patients, as chemotherapy remains the mainstay of treatment. Along with its direct cytotoxic effect, chemotherapy can also reduce ineffective cytokine sinks via lymphodepletion and increase translocation of the gut microbiota leading to stimulation of the immune response. However, chemotherapy requires a functional microbiota to exert those effects. We hypothesize that altering the microbiome with the FMT from the long-term PDAC survivors, combined with systemic treatment, can potentially enhance the relationship between chemotherapy, the immune system, and the microbiome. Albeit there is a lack of knowledge regarding the exact composition of the ideal donor microbiome and the optimal patient selection, due to the dismal prognosis of PDAC patients, such a trial could offer a low-risk, high-reward situation