Koncept sentinel limfnog čvora i njegova uloga u liječenju bolesnika s melanomom

Melanoma is still one of the most life threatening tumors throughout the world. In the United States of America, its mortality rate has raised by 191% in men and 84% in women in the past forty years. It is mainly a cancer of light-pigmented persons like European populations. The incidence and mortality rates have increased substantially during the past decade, although there are extreme variations in the melanoma rates among different countries. Cutaneous melanoma can spread unpredictably and widely through the lymphatics. Identification of patients with occult melanoma metastases is important for accurate staging, treatment planning and prognosis. Based on the AJCC Melanoma Database, the most important prognostic factor in overall survival is melanoma thickness, however, the revised staging system recognizes the presence of metastases in regional lymph nodes as an independent powerful prognostic factor in the 5-year survival rate in stage II and III. Melanoma has a variable lymphatic drainage pathway, particularly those lesions located in the trunk, head and neck. In the past 15 years, a novel approach has been introduced in the management of skin melanoma. As the result of modern nuclear medicine techniques, identification of sentinel lymph node (SLN) by lymphoscintigraphy (LS) and sentinel lymph node biopsy (SLNB) using hand held gamma probe has become a standard procedure. In the early stage disease (AJCC I and II) and intermediate tumor thickness (1.2-3.5 mm), LS with SLNB is the method of choice for nodal staging and to define further surgical procedure, although in melanoma thinner than 1 mm surgical management of regional lymph nodes is still controversial. The overall conclusion from more than 1500 articles published during the last decade is that LS followed by SLNB with selective lymph node dissection in patients with cutaneous melanoma is still only of prognostic value, although it identifies patients with nodal metastases whose survival can be prolonged by immediate lymphadenectomy. Therefore, the AJCC staging system continues to consider micrometastases detected only by immunohistochemistry or polymerase chain reaction to be N0 disease. This article brings a review of current concepts and utility of LS and SLNB in cutaneous melanoma.Melanom je još uvijek jedan od najpogubnijih tumora u čitavom svijetu. U Sjedinjenim Američkim Državama se je stopa smrtnosti povećala u prošlih 40 godina za 191% kod muškaraca i 84% kod žena. To je većinom rak svijetlo pigmentiranih osoba poput europskih populacija. U prošlom desetljeću bitno su se povećale stope incidencije i smrtnosti, no postoje veoma velike razlike u stopi melanoma među različitim zemljama. Kožni melanom može se nepredvidivo i u velikoj mjeri širiti limfnim sustavom. Utvrđivanje bolesnika s okultnim metastazama melanoma važno je radi točnog određivanja stadija, planiranja liječenja te za prognozu. Prema podacima iz AJCC Melanoma Database, debljina melanoma najvažniji je prognostički čimbenik u sveukupnom preživljenju, ali je revidirani sustav određivanja stadija prepoznao i prisutnost metastaza u regionalnim limfnim čvorovima kao snažan neovisan prognostički čimbenik u 5-godišnjoj stopi preživljenja u stadiji I. i II. Melanom ima različite limfne puteve u limfnoj drenaži, poglavito melanomi smješteni na trupu, glavi i vratu. U proteklih 15 godina uveden je nov pristup u liječenju kožnog melanoma. Zahvaljujući suvremenim tehnikama nuklearne medicine, identificiranje sentinel limfnog čvora (SLN) limfoscintigrafijom (LS) i biopsija sentinel limfnog čvora (SLNB) pomoću ručne gama sonde postali su standardnim postupkom. U bolesti ranog stadija (AJCC I i II) i srednje debljine tumora (1,2-3,5 mm) LS uz SLNB čine metodu izbora za određivanje stadija čvora i odluku o daljnjem kirurškom zahvatu, iako je kod melanoma tanjih od 1 mm kirurško liječenje regionalnih limfnih čvorova još uvijek proturječno. Prema više od 1500 članaka objavljenih tijekom prošlog desetljeća, sveukupni zaključak je kako LS sa SLNB uz selektivnu disekciju limfnih čvorova u bolesnika s kožnim melanomom još uvijek ima tek prognostičku vrijednost, iako ukazuje na one bolesnike s metastazama u čvorovima čije se preživljenje može produžiti hitnom limfadenektomijom. Tako sustav određivanja stadija prema AJCC i dalje smatra mikrometastaze otkrivene samo pomoću imunohistokemijskih metoda ili lančanom reakcijom polimeraze kao bolest stadija N0. Ovaj članak donosi pregled današnjih spoznaja i primjene LS i SLNB kod kožnog melanoma

Koncept sentinel limfnog čvora i njegova uloga u liječenju bolesnika s melanomom

Melanoma is still one of the most life threatening tumors throughout the world. In the United States of America, its mortality rate has raised by 191% in men and 84% in women in the past forty years. It is mainly a cancer of light-pigmented persons like European populations. The incidence and mortality rates have increased substantially during the past decade, although there are extreme variations in the melanoma rates among different countries. Cutaneous melanoma can spread unpredictably and widely through the lymphatics. Identification of patients with occult melanoma metastases is important for accurate staging, treatment planning and prognosis. Based on the AJCC Melanoma Database, the most important prognostic factor in overall survival is melanoma thickness, however, the revised staging system recognizes the presence of metastases in regional lymph nodes as an independent powerful prognostic factor in the 5-year survival rate in stage II and III. Melanoma has a variable lymphatic drainage pathway, particularly those lesions located in the trunk, head and neck. In the past 15 years, a novel approach has been introduced in the management of skin melanoma. As the result of modern nuclear medicine techniques, identification of sentinel lymph node (SLN) by lymphoscintigraphy (LS) and sentinel lymph node biopsy (SLNB) using hand held gamma probe has become a standard procedure. In the early stage disease (AJCC I and II) and intermediate tumor thickness (1.2-3.5 mm), LS with SLNB is the method of choice for nodal staging and to define further surgical procedure, although in melanoma thinner than 1 mm surgical management of regional lymph nodes is still controversial. The overall conclusion from more than 1500 articles published during the last decade is that LS followed by SLNB with selective lymph node dissection in patients with cutaneous melanoma is still only of prognostic value, although it identifies patients with nodal metastases whose survival can be prolonged by immediate lymphadenectomy. Therefore, the AJCC staging system continues to consider micrometastases detected only by immunohistochemistry or polymerase chain reaction to be N0 disease. This article brings a review of current concepts and utility of LS and SLNB in cutaneous melanoma.Melanom je još uvijek jedan od najpogubnijih tumora u čitavom svijetu. U Sjedinjenim Američkim Državama se je stopa smrtnosti povećala u prošlih 40 godina za 191% kod muškaraca i 84% kod žena. To je većinom rak svijetlo pigmentiranih osoba poput europskih populacija. U prošlom desetljeću bitno su se povećale stope incidencije i smrtnosti, no postoje veoma velike razlike u stopi melanoma među različitim zemljama. Kožni melanom može se nepredvidivo i u velikoj mjeri širiti limfnim sustavom. Utvrđivanje bolesnika s okultnim metastazama melanoma važno je radi točnog određivanja stadija, planiranja liječenja te za prognozu. Prema podacima iz AJCC Melanoma Database, debljina melanoma najvažniji je prognostički čimbenik u sveukupnom preživljenju, ali je revidirani sustav određivanja stadija prepoznao i prisutnost metastaza u regionalnim limfnim čvorovima kao snažan neovisan prognostički čimbenik u 5-godišnjoj stopi preživljenja u stadiji I. i II. Melanom ima različite limfne puteve u limfnoj drenaži, poglavito melanomi smješteni na trupu, glavi i vratu. U proteklih 15 godina uveden je nov pristup u liječenju kožnog melanoma. Zahvaljujući suvremenim tehnikama nuklearne medicine, identificiranje sentinel limfnog čvora (SLN) limfoscintigrafijom (LS) i biopsija sentinel limfnog čvora (SLNB) pomoću ručne gama sonde postali su standardnim postupkom. U bolesti ranog stadija (AJCC I i II) i srednje debljine tumora (1,2-3,5 mm) LS uz SLNB čine metodu izbora za određivanje stadija čvora i odluku o daljnjem kirurškom zahvatu, iako je kod melanoma tanjih od 1 mm kirurško liječenje regionalnih limfnih čvorova još uvijek proturječno. Prema više od 1500 članaka objavljenih tijekom prošlog desetljeća, sveukupni zaključak je kako LS sa SLNB uz selektivnu disekciju limfnih čvorova u bolesnika s kožnim melanomom još uvijek ima tek prognostičku vrijednost, iako ukazuje na one bolesnike s metastazama u čvorovima čije se preživljenje može produžiti hitnom limfadenektomijom. Tako sustav određivanja stadija prema AJCC i dalje smatra mikrometastaze otkrivene samo pomoću imunohistokemijskih metoda ili lančanom reakcijom polimeraze kao bolest stadija N0. Ovaj članak donosi pregled današnjih spoznaja i primjene LS i SLNB kod kožnog melanoma

Vaskularna hibridna dvorana – operacijaska dvorana budućnosti

The last two decades have seen a paradigm shift in the treatment of vascular related diseases from once traditional open surgical repairs to the entire vascular tree being amenable to percutaneous interventions. Neither the classic operating room nor the conventional angiography suite is optimal for both open surgery and endovascular procedures. Important issues for the vascular hybrid operating room include quality of the imaging equipment, radiation burden, ease of use of the equipment, need for specially trained personnel, ergonomics, ability to perform both open and percutaneous procedures, sterile environments, as well as quality and efficiency of patient care. The most important feature of working in a dedicated hybrid vascular suite should be the ability to attain best treatment of vascular patients. Whether the interventional radiologist or the vascular surgeon uses the facilities is of less importance. Establishment of an endovascular operating room suite has the benefit of a sterile environment, and the possibility of performing hybrid procedures and conversions when necessary. Moreover, angiography immediately before treatment gives contemporary anatomical information, and after treatment provides quality control. Consequently, better quality and service can be provided to the individual patient. These changes in the treatment of vascular disease require that a new type of vascular specialist, named ‘vascular hybrid surgeon’, trained to perform both endovascular and open surgical procedures in this highly complex patient group.U posljednja dva desetljeća primjećuje se pomak u liječenju vaskularnih bolesti od tradicionalno otvorenih kirurških zahvata prema perkutanoj intervenciji cijelog vaskularnog stabla. Niti klasične operativne dvorane, a niti konvencionalne angio dvorane nisu optimalne za izvođenje otvorene operacije ili za endovaskularne zahvate. Glavne značajke vaskularne hibridne operativne dvorane obuhvaćaju kvalitetnu opremu za snimanje, radijacijski štit, opremu za jednostavnu upotrebu, potrebu za dobro izučenim kadrom, ergonomičnost, mogućnost odvijanja otvorenih i perkutanih zahvata, sterilnu okolinu, kao i kvalitetu i učinkovitost bolesničke skrbi. Najznačajnija značajka rada u hibridnoj vaskularnoj operacijskoj dvorani trebala bi biti mogućnost pružanja najbolje operacije bolesniku s krvožilnom bolešću. Manje je važno tko će opremu upotrebljavati, intervencijski radiolog ili vaskularni kirurg. Uspostava jedne endovaskularne operativne dvorane ima prednost sterilne okoline, mogućnost izvođenja hibridnih zahvata, te ako je potrebno i konverzije. Također, angiografija učinjena neposredno prije operativnog zahvata pruža točnije anatomske informacije, a nakon zahvata pruža bolju kontrolu kvalitete. Posljedično, bolja kvaliteta i usluga može se ponuditi svakom pojedinačnom bolesniku. Takve promjene u liječenju bolesnika s bolešću krvnih žila zahtijevaju i novi profil vaskularnog kirurga nazvan “vaskularni hibridni kirurg” koji mora biti osposobljen u izvođenju endovaskularnih, ali i otvorenih operativnih zahvata kod iznimno složene skupine bolesnika

Current Status of Iodine Intake in Croatia – The Results of 2009 Survey

In 1996, due to persistence of mild to moderate iodine deficiency, new law on obligatory salt iodination with 25 mg of potassium iodide (KI) per kg of salt was implemented in Croatia. Along with a new law, a new program formonitoring of iodine prophylaxis was implemented. Investigations of goiter and iodine intake performed in 2002, demonstrated sufficient iodine intake in Croatia with overall median of urinary iodine concentration (UIC) for schoolchildren in Croatia of 140 mg/L. In 2002, thyroid volumes (TV) measured by ultrasound in schoolchildren from all four geographic regions of Croatia were for the first time within the normal range according to ICCIDD reference values. Nowadays, Croatia is internationally recognized as iodine sufficient country. The aim of the present study was to assess current status of iodine intake in Croatia. The investigation was carried out in 2009. A total of 386 schoolchildren aged 7–10 years from all four major geographic regions of Croatia, 103 euthyroid pregnant women and 36 women of child-bearing age from Zagreb, the capital, were included in the survey. Urinary iodine concentration (UIC) was measured in all participants. Thyroid volumes were measured by ultrasound in schoolchildren from the capital of Zagreb (N=101) and the village of Rude (N=56). In the time period 2002–2009, the content of KI was analyzed in 384 salt samples from Croatian salt plants and samples of imported salt. An overall median UIC for schoolchildren in Croatia was 248 mg/L. Median UIC in pregnant women was 159 mg/L, with 50% of samples below and under 150 mg/L. Median UIC in women of child-bearing age was 136 mg/L. Thyroid volumes in schoolchildren were within the normal range according to the new reference values. Mean value of KI/kg of salt in samples from Croatian salt plants was 25.5 mg/kg and 24.9 mg/kg in samples of imported salt. A total of 72/384 (18.8%) of salt samples didn’t corresponded to the Croatian law on obligatory salt iodination. Presented data indicate sufficient iodine intake of the Croatian population. Current medians of UIC in schoolchildren in Croatia are significantly higher than medians measured in 2002. This indicates that other potential sources of iodine are present in Croatian diet that may contribute to overall iodine intake. Due to rising medians of UIC in schoolchildren in Croatia, it is important to conduct nutrition studies to identify potential sources of »silent prophylaxis« in order to avoid iodine excess

Current Status of Iodine Intake in Croatia – The Results of 2009 Survey

In 1996, due to persistence of mild to moderate iodine deficiency, new law on obligatory salt iodination with 25 mg of potassium iodide (KI) per kg of salt was implemented in Croatia. Along with a new law, a new program formonitoring of iodine prophylaxis was implemented. Investigations of goiter and iodine intake performed in 2002, demonstrated sufficient iodine intake in Croatia with overall median of urinary iodine concentration (UIC) for schoolchildren in Croatia of 140 mg/L. In 2002, thyroid volumes (TV) measured by ultrasound in schoolchildren from all four geographic regions of Croatia were for the first time within the normal range according to ICCIDD reference values. Nowadays, Croatia is internationally recognized as iodine sufficient country. The aim of the present study was to assess current status of iodine intake in Croatia. The investigation was carried out in 2009. A total of 386 schoolchildren aged 7–10 years from all four major geographic regions of Croatia, 103 euthyroid pregnant women and 36 women of child-bearing age from Zagreb, the capital, were included in the survey. Urinary iodine concentration (UIC) was measured in all participants. Thyroid volumes were measured by ultrasound in schoolchildren from the capital of Zagreb (N=101) and the village of Rude (N=56). In the time period 2002–2009, the content of KI was analyzed in 384 salt samples from Croatian salt plants and samples of imported salt. An overall median UIC for schoolchildren in Croatia was 248 mg/L. Median UIC in pregnant women was 159 mg/L, with 50% of samples below and under 150 mg/L. Median UIC in women of child-bearing age was 136 mg/L. Thyroid volumes in schoolchildren were within the normal range according to the new reference values. Mean value of KI/kg of salt in samples from Croatian salt plants was 25.5 mg/kg and 24.9 mg/kg in samples of imported salt. A total of 72/384 (18.8%) of salt samples didn’t corresponded to the Croatian law on obligatory salt iodination. Presented data indicate sufficient iodine intake of the Croatian population. Current medians of UIC in schoolchildren in Croatia are significantly higher than medians measured in 2002. This indicates that other potential sources of iodine are present in Croatian diet that may contribute to overall iodine intake. Due to rising medians of UIC in schoolchildren in Croatia, it is important to conduct nutrition studies to identify potential sources of »silent prophylaxis« in order to avoid iodine excess

The story of the Croatian village of Rude after fifty years of compulsory salt iodination in Croatia

The village of Rude is situated near Zagreb, the capital of Croatia in the last Alpine valley on Balkan. In the past, the village was well-known area of severe iodine deficiency disorders (IDD). In 1952', distinguished Croatian endocrinologist Professor Josip Matovinovic carried out detailed village survey. Goiter prevalence in school-age children was 85.0% (with 2.3% of cretins in the village). In 1953, the first regulation on compulsory salt iodination with 10 mg of KI/kg of salt was established in former Yugoslavia. Ten years later a dramatic decrease in goiter prevalence was recorded in all endangered areas of the country and no new cretins appeared. However, at the beginning of 1990' mild to moderate iodine deficiency still persisted in Croatia. In 1991, the village of Rude survey demonstrated goiter prevalence in school-age children of 35.0% and median of urinary iodine excretion (UIE) of 7.4 microg/dL. In 1996, the new obligatory regulation with 25 mg of KI/kg of salt was established in Croatia. The study aim was to monitor IDD status in the village after the new law on compulsory salt iodination. Measurements of UIE and thyroid volumes (Tvol) by ultrasound were performed in 7-11-y-old schoolchildren living in the village of Rude. Medians of UIE and body surface area (BSA)-adjusted Tvol in boys and girls were calculated. The study included 84 children in 1997, 132 in 2000, 72 in 2002, 85 in 2003 and 46 in 2004 for UIE measurement. Thyroid volumes were measured in 1999 (43 boys and 26 girls) and in 2005 (22 boys and 26 girls). Data were compared with the new WHO/ICCIDD reference values. Medians of UIE in schoolchildren from the village of Rude demonstrated rising values in microg/dL: 11.4 in 1997, 14.3 in 2000, 17.3 in 2002, 15.4 in 2003 and 19.0 in 2004. Significant decrease in BSA-adjusted Tvol was recorded from 1999-2005 in boys and girls from the village of Rude and in 2005 Tvol were within the normal range according to the new international reference values for Tvol in iodine-sufficient schoolchildren. As a result of increased iodine prophylaxis, IDD no longer exist in Croatia. Monitoring of IDD status in the village of Rude after new law on compulsory salt iodination in Croatia demonstrated rising medians of UIE together with significant reduction of Tvol. In 2005, Tvol in schoolchildren from the village of Rude were within the normal range according to the new international reference values for Tvol in iodine-sufficient schoolchildren

Current status of iodine intake in Croatia--the results of 2009 survey [Stanje unosa joda u Hrvatskoj - rezultati istraživanja provedenog 2009 godine]

In 1996, due to persistence of mild to moderate iodine deficiency, new law on obligatory salt iodination with 25 mg of potassium iodide (KI) per kg of salt was implemented in Croatia. Along with a new law, a new program for monitoring of iodine prophylaxis was implemented. Investigations of goiter and iodine intake performed in 2002, demonstrated sufficient iodine intake in Croatia with overall median of urinary iodine concentration (UIC) for schoolchildren in Croatia of 140 microg/L. In 2002, thyroid volumes (TV) measured by ultrasound in schoolchildren from all four geographic regions of Croatia were for the first time within the normal range according to ICCIDD reference values. Nowadays, Croatia is internationally recognized as iodine sufficient country. The aim of the present study was to assess current status of iodine intake in Croatia. The investigation was carried out in 2009. A total of 386 schoolchildren aged 7-10 years from all four major geographic regions of Croatia, 103 euthyroid pregnant women and 36 women of child-bearing age from Zagreb, the capital, were included in the survey. Urinary iodine concentration (UIC) was measured in all participants. Thyroid volumes were measured by ultrasound in schoolchildren from the capital of Zagreb (N = 101) and the village of Rude (N = 56). In the time period 2002-2009, the content of KI was analyzed in 384 salt samples from Croatian salt plants and samples of imported salt. An overall median UIC for schoolchildren in Croatia was 248 microg/L. Median UIC in pregnant women was 159 microg/L, with 50% of samples below and under 150 microg/L. Median UIC in women of child-bearing age was 136 microg/L. Thyroid volumes in schoolchildren were within the normal range according to the new reference values. Mean value of KI/kg of salt in samples from Croatian salt plants was 25.5 mg/kg and 24.9 mg/kg in samples of imported salt. A total of 72/384 (18.8%) of salt samples didn't corresponded to the Croatian law on obligatory salt iodination. Presented data indicate sufficient iodine intake of the Croatian population. Current medians of UIC in schoolchildren in Croatia are significantly higher than medians measured in 2002. This indicates that other potential sources of iodine are present in Croatian diet that may contribute to overall iodine intake. Due to rising medians of UIC in schoolchildren in Croatia, it is important to conduct nutrition studies to identify potential sources of "silent prophylaxis" in order to avoid iodine excess

The role of preoperative lymphoscintigraphy in surgery planning for sentinel lymph node biopsy in malignant melanoma

AIM: To evaluate four years of preoperative lymphoscintigraphy experience and the accuracy of sentinel lymph node biopsy in our institution in melanoma patients with various tumor thicknesses. An additional aim was to evaluate the recurrence rate related to pathohistological findings. - - - - - METHODS AND PATIENTS: During the period from February 2002 to November 2005, 201 patients underwent sentinel node biopsy. Lymphoscintigraphy for identification of sentinel nodes was performed four to six hours prior to operation of the patient. Sentinel lymph node biopsy using an intraoperative hand-held gamma probe was performed in all patients, together with wide local excision of biopsy wound or primary lesion (N=56). Immediate complete basin dissection was performed in patients with sentinel node metastases. In four patients delayed complete lymph node dissection was performed after definitive histopathologic examination of sentinel nodes. The accuracy of sentinel node biopsy was determined by comparing the intraoperative rates of sentinel node identification and the subsequent development of nodal metastases in regional nodal basins in patients with tumor-negative sentinel nodes and in those with tumorpositive sentinel nodes. - - - - - RESULTS: Using preoperative lymphoscintigraphy, we identified sentinel nodes in all but one of the 201 patients (99.0%), and in 248 nodal basins (1.2/patient) we observed 372 sentinel nodes (1.52 sentinels/basin; 1.8 sentinels/patient). The highest number of sentinel nodes was noticed in the groin of patients with melanoma on the lower extremities (1.5/patient), followed by the axilla (1.3/patient). Anomalous lymphatic drainage patterns were observed in 15.0% of all patients. The identification rate of sentinel nodes was 99.0% overall: 100% for the groin basins, and 98.0% for the axilla and head and neck basin. Forty-two patients (20.8%) had tumor-positive sentinel nodes. Ten patients (5.0%) had local or distant recurrences during a median follow-up of 23.1 months (range 2-46). The rate of false-negative lymphatic mapping and sentinel node biopsy as measured by nodal recurrence in patients with tumor-negative sentinel nodes was 1.3%. During the follow-up period, three of 201 patients died from other diseases and three patients died as the result of melanoma metastases, with a median follow-up of 13.5 months (range 12-22). - - - - - CONCLUSION: Preoperative lymphoscintigraphy is a sensitive, inexpensive and essential method for the identification of drainage basins, determination of the number and position of sentinel nodes and their location outside the usual nodal basins. Scintigraphic findings may lead to changes in surgical management due to the unpredictability of lymphatic drainage. The low incidence of regional disease recurrence in patients with tumor-negative sentinel nodes supports the use of preoperative lymphoscintigraphy and sentinel node biopsy as a safe and accurate procedure for staging the regional nodal basin in patients with malignant melanoma