Pomen dihalnega testa C13 pri ocenjevanju eksokrine funkcije trebušne slinavke po resekciji želodca

Siuka, Darko (author), Janša, Rado (mentor)

Izhodišče in namen. 13C mešani trigliceridni dihalni test (13C MTGT) je neinvaziven test, ki posredno oceni aktivost pankreatične lipaze in morebitno pankreatično eksokrino insuficienco (PEI). 13C MTGT je nepraktičen, saj traja vsaj 5 ur. Ker je za bolnike in za zdravstveno osebje časovno obremenjujoč, potrebujemo teste, ki bodo krajši in bolnikom bolj prijazni. Različne raziskave so obravnavale bolnike s sumom na PEI pri katerih so opravili dolg šesturni ali modificiran, skrajšan 13C MTGT dihalni test, nobena pa ni z modificiranim dihalnim testom obravnavala skupine bolnikov po subtotalni in totalni resekciji želodca. Namen naše doktorske naloge je bil ugotoviti dodatno izboljšano diagnostično moč 13C mešanega trigliceridnega dihalnega testa (13C MTGT) v primerjavi s standardnim testom s fekalno elastazo (FE-1) in fekalnim kimotripsinom za dokaz pankreatične eksokrine insuficience (PEI) pri bolnikih po subtotalni in totalni resekciji želodca. Ugotoviti smo želeli primerljivosti občutljivosti skrajšanega 4-urnega in dolgega 5-urnega 13C MTGT dihalnega testa pri dokazovanju PEI pri bolnikih po subtotalni in totalni resekciji želodca. Prav tako smo želeli ugotoviti optimalnost časa skrajšanega 13C MTGT dihalnega testa z ohranjeno občutljivostjo določanja PEI pri bolnikih po subtotalni in totalni resekciji želodca. Metode. V našo presečno opazovalno raziskavo, ki je potekala prospektivno smo vključili bolnike po totalni in subtotalni resekciji želodca in zdrave prostovoljce. Po podpisani privolitvi in vključitvi v raziskavo smo pridobili demografske in klinične podatke o bolnikih. Vsem preiskovancem smo zjutraj po 12-urnem postu odvzeli periferno kri in urin za laboratorijsko analizo. Oddali so blato za določitev fekalne elastaze (FE-1) in fekalnega kimotripsina. Koncentracijo smo merili z encimsko metodo (ELISA), detektirali pa fotometrično. Vsem preiskovancem smo opravili 5-urni 13C MTGT dihalni test z izdihi zraka na 30 minut, vseh testnih epruvet je bilo 11. Koncentracijo 13C v izdihanem zraku smo z masnim spektrometrom razmerja izotopov (IRMS) določili relativno vsebnost 13C v izdihanem CO2. Podatke smo statistično analizirali. PEI smo potrdili, če so imeli bolniki kumulativno stopnjo izdihanega 13C pod 26,8 % po 5-ih urah. Bolnikom z dokazano PEI, smo uvedli pankreatično encimsko nadomestno terapijo (PERT), jim podrobno svetovali glede prehrane, odmerkov PERT in svetovali sodelovanje z dietetikom ter redne kontrole v dispanzerju za bolezni prebavil pri gastroenterologu, ob že rednih kirurških kontrolah. Rezultati. V analizo smo vključili podatke 65-ih udeležencev (22 bolnikov po totalni resekciji želodca, 23 po subtotalni resekciji želodca in 20 zdravih prostovoljcev). Pri 22-ih bolnikih smo dokazali PEI (11 po totalni in 11 po subtotalni resekciji želodca). 13C MTGT dihalni test je pokazal statistično pomembno razliko v deležu izdihanega 13C že po 60-ih minutah (p=0,034). Analiza krivulje karakteristike delovanja sprejemnika (ROC) je pokazala 'cut-off' vrednost 13,74 % po 150-ih minutah z ohranjeno diagnostično močjo v primerjavi s standardnim 5-urnim testom z občutljivostjo in specifičnostjo nad 90 %. Število dokazanih bolnikov s PEI je bilo zaradi uporabe 13C MTGT dihalnega testa pri bolnikih po totalni in subtotalni resekciji želodca večje kot v primeru dokazovanja le s fekalno elastazo in kimotripsinom (33,3 % vs. 48,9 %, p=0,00001). Prekrivanje FE-1 in kimotripsina z dihalnim testom je bilo dokaj slabo, saj smo pri hudi obliki PEI (dokazani z znižano FE-1) le-to s 13C MTGT dihalnim testom dokazali le pri enem bolniku, pri zmerni tudi samo pri enem, pri blagi pa pri 5-ih bolnikih. Dodatnih 15 bolnikov, ki je imelo sicer normalne vrednosti pankreatične elastaze, je imelo PEI dokazano s 13C MTGT dihalnim testom. Statistična povezava med metodama tako ni bila statistično značilna (p=0,123). Pri primerjavi dihalnega testa s fekalnim kimotripsinom prav tako nismo dokazali statistične značilnosti (p=0,088). PEI je bila s pomočjo fekalnega kimotripsina dokazana pri 13-ih bolnikih, od teh jih je imelo le 7 dokazano PEI z dihalnim testom. Hitrost pasaže skozi zgornja prebavila, glede na tip resekcije želodca, ni vplival na potreben čas dihalnega testa, saj v naši raziskavi med bolniki po subtotalni in totalni resekciji želodca ni bilo statistično signifikantne razlike v senzitivnosti 13C MTGT dihalnega testa. Zaključki. V naši raziskavi smo dokazali, da je za detekcijo PEI v skupini bolnikov po subtotalni in totalni resekciji želodca varno uporabljati skrajšan 13C MTGT dihalni test, optimalen čas trajanja pa je tako skrajšan na 2,5 ure, z visoko občutljivostjo in specifičnostjo (95 in 90,9 %). S to raziskavo smo preiskavo naredili časovno bolj sprejemljivo in udobno, tako za bolnike kot za zdravstveno osebje. Pričakujemo, da bo raziskava doprinesla novost v obravnavi bolnikov s PEI po resekciji želodca in izboljšala njihovo kakovost življenja, prav tako pa olajšala diagnostični postopek teh bolnikov tako v Sloveniji kot po svetu.

• Language: Slovenian
• Keywords: pankreatična eksokrina insuficienca, resekcija želodca, dihalni test 13C
• Work type: Doctoral dissertation
• Organization: MF - Faculty of Medicine
• Year: 2024
• PID: 20.500.12556/RUL-164801
• Publication date in RUL: 13.11.2024

Secondary language

• Language: English
• Title: The importance of the C13 breath test for the determination of the exocrine function of the pancreas after gastrectomy

Abstract

Background and aim. The 13C mixed triglyceride breath test (13C MTGT) is a non-invasive test for indirect detection of pancreatic exocrine insufficiency (PEI) but it requires breath sampling in a long five-hour procedure. This long procedure is time consuming for patients and also stressful for medical staff, so we need tests that are shorter and more patient friendly. Various studies studied patients with suspected PEI who underwent a long six-hour or a modified, abbreviated 13C MTGT breath test, but none have studied groups of patients after subtotal and total gastrectomy with a modified breath test. The purpose of our doctoral thesis was to determine the additional diagnostic power of the 13C mixed triglyceride breath test (13C MTGT) in addition to the standard test with fecal elastase (FE-1) and fecal chymotrypsin for detecting of pancreatic exocrine insufficiency (PEI) in patients after subtotal and total gastrectomy. We aimed to determine the equivalence of the sensitivity of the abbreviated 4-hour and long 5-hour 13C MTGT breath test in detecting PEI in patients after subtotal and total gastrectomy. We also aimed to determine the optimal timing of the 13C MTGT breath test with preserved sensitivity of PEI detection in patients after subtotal and total gastrectomy. Methods. This cross-sectional observational study included 3 groups of subjects; healthy controls, patients with subtotal and patients with total gastrectomy. After signed informed consent demographic and clinical data of patients were collected. Peripheral blood and urine were taken from all subjects in the morning after a 12-hour fast for laboratory analysis. Stool samples to determine faecal elastase (FE-1) and chymotrypsin were collected and measured by ELISA. All subjects performed 5-hour 13C-MTGT breath test. The concentration and relative content of 13C in exhaled air was measured by isotope ratio mass spectrometer (IRMS). PEI was confirmed as values of 13C-exhalation < 26.8% after 5 hours. To the patients with detected PEI, pancreatic enzyme replacement therapy (PERT) was introduced. They received detailed advice on diet, PERT doses, and advised cooperation with a dietitian and regular check-ups in the Outpatient clinic for gastrointestinal diseases in addition to regular surgical check-ups. Results. We included the data of 65 participants in the analysis (22 patients after total gastrectomy, 23 after subtotal gastrectomy and 20 healthy volunteers), in 22 we demonstrated PEI (11 after total and 11 after subtotal gastrectomy). The 13C MTGT breath test showed a statistically significant difference in the proportion of exhaled 13C already after 60 minutes (p=0.034). Receiver operating characteristic (ROC) curve analysis showed a cut-off value of 13.74% after 150 minutes with preserved diagnostic power compared to the standard 5-hour test with sensitivity and specificity above 90%. Due to the use of the 13C MTGT breath test in patients after total and subtotal gastrectomy, the number of proven patients with PEI was higher than in the case of evidence only with fecal elastase and chymotrypsin (33.3% vs 48.9%, p=0.00001). The overlap of FE-1 and chymotrypsin with the breath test was rather poor, since in severe PEI, demonstrated by reduced FE-1, this was demonstrated by the 13C MTGT breath test in only one patient, in moderate PEI also in only one, and in mild in 5 patients. An additional 15 patients, who had otherwise normal pancreatic elastase values, had PEI demonstrated by the 13C MTGT breath test. The statistical correlation between the two methods was thus not statistically significant (p=0.123). When comparing the breath test with fecal chymotrypsin, we also did not demonstrate any statistical significance (p=0.088). PEI was demonstrated by faecal chymotrypsin in 13 patients, of which only 7 had proven PEI by breath test. The speed of passage through the upper gastrointestinal tract, depending on the type of gastrectomy, did not affect the required time of the breath test, since in our study there was no statistically significant difference in the sensitivity of the 13C MTGT breath test between patients after subtotal and total gastrectomy. Conclusions. In our research abbreviated 13C MTGT test could be abbreviated from 5 to 2.5 hours without decrease in its diagnostic accuracy for detection of PEI in patients with subtotal or total gastrectomy performed for gastric cancer. This allows significant time savings in the diagnostics of PEI in this subgroup of patients.

• Keywords: pancreatic exocrine insufficiency, gastric resection, breath test 13C