Analiza intraoperativne procene statusa resekcione margine jetrenih metastaza kolorektalnog adenokarcinoma u odnosu na patohistološki nalaz

Abstract

Više od 50,0% bolesnika sa kolorektalnim karcinomom (CRC) u nekoj od faza osnovne bolesti razvije jetrene metastaze (CRLM). Hirurška resekcija jetre jedina je potencijalno kurativna metoda njihovog lečenja. Cilj hirurškog lečenja je: postizanje negativne resekcione margine (RM–) od 1 mm, a na taj način i obezbeđivanje najbolje prognoze za bolesnike. RM mogu procenjivati patolog na resekatima jetre (RLS) i hirurg, intraoperativno. Cilj ovog rada je da se utvrdi stepen slaganja intraoperativne procene RM koju je izvršio hirurg i procene RM od strane patologa na definitivnom patohistološkom preparatu. Istraživanje je sprovedeno kao dvostruko slepo, prospektivno i nerandomizovano. Hirurg je procenjivao RM za svaki RLS intraoperativno, odmah nakon resekcije. Resekcije jetre izvedene su od strane tri hirurga. NJihova procena RM komparirana je sa procenom RM koju su izveli patolozi, kao „zlatnim standardom”. RM od 1 mm i više je ocenjena kao negativna. Izračunata je senzitivnost, specifičnost, pozitivna i negativna prediktivna vrednost, te ukupna tačnost hirurške procene RM u odnosu na procenu RM od strane patologa. Takođe, analiziran je klinički značaj hirurške procene RM, praćenjem vremena preživljavanja bez bolesti (DFS) u odnosu na postignutu RM. U periodu od 1. januara 2018. do 31. avgusta 2019. godine 69 bolesnika operisanih zbog CRLM uključeno je u istraživanje. Resecirano je ukupno 154 RLS sa 176 CRLM. Hirurzi su registrovali RM+ na 30 (19,5%) RLS. Patolozi su se složili sa hirurzima u 24 (80,0%) slučaja, dok su u šest (20,0%) slučajeva smatrali drugačije. Patolozi su registrovali RM+ na 43 (27,9%) resekata jetre. Hirurzi su bili saglasni u 24 (55,8%) slučaja, dok su kod 19 (44,2%) resekata jetre smatrali drugačije. Uzimajući rezultat patohistološkog pregleda preparata kao „zlatni standard” utvrđeno je da je RM bila istinski pozitivna u 24 (15,6%) slučaja, dok je u šest (3,9%) slučajeva rezultat bio lažno pozitivan. Istinski negativna RM postignuta je u 105 (68,2%) slučajeva, dok je lažno negativnih rezultata bilo na 19 (12,3%) RLS. Dobijena je senzitivnost hirurške procene RM+ od 55,8%, specifičnost od 94,6%, pozitivna prediktivna vrednost od 80,0%, negativna prediktivna vrednost od 84,7%, te ukupna tačnost od 83,8%. Rezultati Maknemarovog (Mc Nemar) (x² = 6,76; p = 0,009) i Koenovog (Cohen) kappa testa (0,55) ukazuju na srednji stepen slaganja i na statistički značajnu razliku u distribuciji nalaza. Prosečan DFS za bolesnike sa RM– i RM+ kada je RM procenjivao hirurg iznosio je 6,5 ± 4,84 i 5,5 ± 4,30 meseci (p = 0,005). Kada je RM procenjivao patolog, prosečan DFS bolesnika sa RM– iznosio je 6,7 ± 4,96 meseci naspram 5,0 ± 4,15 meseci kod bolesnika sa RM+ (p = 0,016). Postoji srednji stepen slaganja u proceni RM između hirurga i patologa, a statistički značajna razlika u distribuciji nalaza, tako da patolog registruje više RM+. Hirurg uspešno procenjuje RM kada je ona negativna. RM+ ima negativan uticaj na DFS bolesnika, kako u slučaju kada RM procenjuje patolog, tako i u slučaju procene RM od strane hirurga.

More than 50.0% of patients with colorectal cancer (CRC) develop liver metastases (CRLM) at some stage of the primary disease. Surgical resection of the liver is the only potentially curative method of their treatment. The goal of surgical treatment is to achieve a negative resection margin (RM–) of 1 mm, and thus provide the best prognosis for patients. The resection margin (RM) can be assessed by a pathologist on the resected liver specimen (RLS) and by a surgeon intraoperatively. The aim of this study was to determine the degree of agreement between the intraoperative assessment of RM performed by the surgeon and the assessment of RM by the pathologist. The study was conducted as double-blind, prospective, and nonrandomized. The surgeon assessed the RM for each RLS intraoperatively, immediately after resection. Liver resections were performed by three surgeons. Their assessment of RM was compared with the assessment of RM performed by pathologists as the „gold standard”. RM of 1 mm and more was rated as negative. Sensitivity, specificity, positive and negative predictive value, and the overall accuracy of the surgical assessment of RM in relation to the assessment of RM by pathologists were calculated. The clinical significance of surgical assessment of RM was also analyzed, by monitoring disease free survival (DFS) in relation to achieved RM. In the period from January 1, 2018 to August 31, 2019, 69 patients operated on for CRLM were included in the study. A total of 154 RLS with 176 CRLMs were removed. Surgeons registered RM+ on 30 (19.5%) RLS. Pathologists agreed with surgeons in 24 (80.0%) cases, while in 6 (20.0%) cases they considered otherwise. Pathologists registered RM+ on 43 (27.9%) resected liver specimen. Surgeons agreed in 24 (55.8%) cases, while in 19 (44,2%) cases they considered otherwise. Taking the results of the histopathological assessment as the „gold standard” it was determined that RM was true positive in 24 (15.6%) cases, while in 6 (3.9%) cases the result was false positive. True negative RM was achieved in 105 (68.2%) cases, while false negative results were achieved in 19 (12.3%) RLS. The sensitivity of the surgical assessment of RM + of 55.8%, specificity of 94.6%, positive predictive value of 80.0%, negative predictive value of 84.7%, and overall accuracy of 83.8% were obtained. The results of Mc Nemar (x² = 6.76; p = 0.009) and Cohen kappa test (0.55), indicate a medium degree of agreement and a statistically significant difference in the distribution of findings. Median DFS for surgeon assessed RM– and RM+ were 6,5 ± 4,84 and 5,5 ± 4,30 months (p = 0,005). When RM was assessed by a pathologist, the median DFS of patients with RM– was 6.7 ± 4.96 months versus 5.0 ± 4.15 months in patients with RM + (p = 0.016). There is a medium degree of agreement in the assessment of RM between surgeons and pathologists, and a statistically significant difference in the distribution of findings so that the pathologist registers more RM+. The surgeon successfully evaluates the RM when it is negative. RM + has a negative impact on DFS patients, both in the case when RM is assessed by a pathologist, and in the case of assessment of RM by a surgeon.