​Elektrokemoterapija posteriorne resekcijske površine pri raku trebušne slinavke zaradi zmanjšanja recidivov bolezni

Čebron, Žan (avtor), Trotovšek, Blaž (mentor), Serša, Gregor (komentor)

Uvod: Kljub številnim raziskavam v zadnjih desetletjih je rak trebušne slinavke še vedno med najbolj smrtonosnimi oblikami raka. 5-letno celokupno preživetje vseh bolnikov je 5─10 %. Tudi v primeru radikalne kirurške resekcije je prognoza bolezni še vedno slaba, saj je 5-letno preživetje le med 10 in 25 %. Lokalni recidivi predstavljajo približno 30 % vseh ponovitev bolezni. Z namenom zmanjšanja možnosti lokalne ponovitve bolezni ter izboljšanja preživetja smo zasnovali nov, hibridni pristop zdravljenja s kirurško resekcijo in intraoperativno elektrokemoterapijo posteriorne resekcijske površine. Bolniki in metode: V pilotno študijo smo vključili bolnike z resektabilnim duktalnim adenokarcinomom glave trebušne slinavke, ki so izpolnjevali vključitvene kriterije. Vključevanje bolnikov je potekalo med julijem 2020 in majem 2023. Po kirurški resekciji smo intraoperativno izvedli elektrokemoterapijo z bleomicinom. Električne pulze smo dovajali z uporabo ploščatih elektrod. Zajeli smo področje posteriorne resekcijske površine med zastavljenimi anatomskimi mejniki. Rezultati: Elektrokemoterapija posteriorne resekcijske površine je bila izvedljiva pri vseh 10 bolnikih. Povprečna starost bolnikov je bila 71 let (razpon 61─84 let). Pri 6/10 bolnikih je bila napravljena cefalična pankreatoduodenektomija po Whipplu, pri 4/10 bolnikih smo izvedli pankreatoduodenektomijo z ohranjenim pilorusom. Povprečni odmerek bleomicina je znašal 27,3 mg, povprečno število aplikacij električnih pulzov je bilo 33,8. Med izvajanjem elektrokemoterapije in prvih 24 ur po zdravljenju nismo opažali neželenih učinkov. Med hospitalizacijo smo opažali nasledenje zaplete: okužbo kirurške rane, paralitični ileus, globoko vensko trombozo, paroksizmalno atrijsko fibrilacijo, intraperitonealni hematom in dve postoperativni pankreatični fistuli (pri enem bolniku stopnje B, pri drugem le biokemično puščanje). Med vsemi zapleti sta bila le dva zapleta opredeljena kot stopnja 3a po Clavien-Dindo klasifikaciji, vsi ostali zapleti so bili stopnje 2 ali manj. Smrtnost v prvih 30 dnevih po zdravljenju je bila 0 %. 90-dnevna smrtnost vključenih bolnikov je bila 20 %. En bolnik je zaradi poznih pooperativnih zapletov umrl 36. dan po zdravljenju. Dodatno je zaradi hitrega progresa in zapletov povezanih s progresom bolezni drug bolnik umrl približno 2 meseca po zdravljenju. V okviru sledenja smo pri 4/9 bolnikih opažali trombozo portalnega žilja. Od vseh bolnikov so trije prejeli adjuvantno zdravljenje. 2-letno preživetje vključenih bolnikov je 30 %. Zaključek: Rak trebušne slinavke ostaja bolezen s slabo prognozo. Rezultati hibridnega pristopa zdravljenja, ki smo ga v sklopu pilotne študije izvedli na 10 bolnikih, kažejo, da je intraoperativna elektrokemoterapija posteriornega resekcijskega roba izvedljiva in varna. Za oceno učinkovitosti bi bile potrebne dodatne raziskave z daljšim sledenjem in večjim številom vključenih bolnikov. Hibridni pristop, ki združuje kirurško resekcijo in intraoperativno elektrokemoterapijo, bi morda lahko izboljšal onkološke rezultate.

• Jezik: Slovenski jezik
• Ključne besede: rak trebušne slinavke, intraoperativna kemoterapija, elektroporacija, pankreatikoduodenektomija, Whipplova resekcija, hibridno zdravljenje, bleomicin
• Vrsta gradiva: Doktorsko delo/naloga
• Organizacija: MF - Medicinska fakulteta
• Leto izida: 2026
• PID: 20.500.12556/RUL-181817
• Datum objave v RUL: 16.04.2026

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Electrochemotherapy of Posterior Resection Surface for Lowering Disease Recurrence Rate in Pancreatic Cancer

Izvleček

Introduction: Despite numerous studies in recent decades, pancreatic cancer remains one of the most lethal forms of cancer. The 5-year survival rate for all patients is 5-10%. Even in the case of radical surgical resection, the prognosis remains relatively poor, with 5-year survival ranging between 10% and 25%. Local recurrences account for approximately 30% of all disease relapses. To reduce the risk of local recurrence and improve survival, we designed a novel hybrid treatment approach combining surgical resection with intraoperative electrochemotherapy of the posterior resection margin. Patients and Methods: We included patients with resectable ductal adenocarcinoma of the pancreatic head who met the inclusion criteria in this pilot study. Patient enrollment took place between July 2020 and May 2023. Following surgical resection, intraoperative electrochemotherapy with bleomycin was performed. Electric pulses were delivered using plate electrodes, targeting the posterior resection surface between defined anatomical landmarks. Results: Electrochemotherapy of the posterior resection surface was feasible in all 10 patients. The average age of patients was 71 years (range 61–84 years). In 6 out of 10 patients, a classical Whipple pancreaticoduodenectomy was performed; in the remaining 4 patients, a pylorus-preserving pancreaticoduodenectomy was conducted. The average bleomycin dose was 27.3 mg and the average number of electric pulse applications was 33.8. No adverse effects were observed during electrochemotherapy or within the first 24 hours after treatment. During hospitalization, the following complications were noted: surgical wound infection, paralytic ileus, deep vein thrombosis, paroxysmal atrial fibrillation, intraperitoneal hematoma, and two postoperative pancreatic fistulas (one grade B, one only biochemical leak). Of all complications, only two were classified as grade 3a according to the Clavien-Dindo classification; all others were grade 2 or lower. The 30-day postoperative mortality rate was 0%. The 90-day mortality of the included patients was 20%. One patient died on day 36 after treatment due to late postoperative complications. Additionally, another patient died approximately two months after treatment because of rapid disease progression and progression-related complications. During follow-up, portal vein thrombosis was observed in 4 out of 9 patients. Of all patients, three received adjuvant therapy. The 2-year survival rate of the patients included was 30%. Conclusion: Pancreatic cancer remains a disease with poor prognosis. The results of the hybrid treatment approach conducted in this pilot study on 10 patients demonstrate that intraoperative electrochemotherapy of the posterior resection margin is feasible and safe. Further studies with longer follow-up and a larger patient cohort are needed to assess treatment efficacy. The hybrid approach combining surgical resection with intraoperative electrochemotherapy may contribute to improved oncological outcomes.

• Ključne besede: pancreatic cancer, intraoperative chemotherapy, electroporation, pancreaticoduodenectomy, Whipple resection, hybrid treatment, bleomycin