RESUMO
Background: The incidence of irinotecan-induced diarrhea varies between 60-90%, by which the incidence of severe diarrhea is 20-40%. The objective of this phase III trial was to determine the effectiveness of the probiotic mixture containing Bifidobacterium, BB-12® and Lactobacillus rhamnosus, LGG® in the prophylaxis of irinotecan-induced diarrhea in metastatic colorectal cancer patients due to a reduction in the activity of intestinal beta-D-glucuronidase. Methods: From March 2016 to May 2022, a total of 242 patients with colorectal cancer starting a new line of irinotecan-based therapy were registered to the study in 11 cancer centers in Slovakia. Patients were randomized in a ratio 1:1 to probiotic formula vs. placebo that was administered for 6 weeks. Each capsule of Probio-Tec® BG-Vcap-6.5 contained 2.7x109 colony-forming units (CFU) of 2 lyophilized probiotic strains Bifidobacterium, BB-12® (50%) and Lactobacillus rhamnosus GG, LGG® (50%). Results: Administration of probiotics compared to placebo was not associated with a significant reduction of grade 3/4 diarrhea (placebo arm 11.8% vs. probiotic arm 7.9%, p=0.38). Neither the overall incidence of diarrhea (46.2% vs. 41.2%, p=0.51) nor the incidence of enterocolitis (3.4% vs. 0.9%, p=0.37) was different in the placebo vs. probiotic arm. Subgroup analysis revealed that patients with colostomy had higher incidence of any diarrhea and grade 3/4 diarrhea in the placebo arm compared to the probiotic arm (48.5% vs. 22.2%, p=0.06 and 15.2% vs. 0%, p=0.06, respectively). Moreover, patients on probiotic arm had significantly better diarrhea-free survival (HR = 0.41, 95%CI 0.18 - 0.95, p=0.05) and needed less loperamide (p=0.01) compared to patients on placebo arm. We did not observe any infection caused by probiotic strains used in this study. Conclusion: This study failed to achieve its primary endpoint, and results suggest a lack of benefit of administered probiotic formula for the prevention of irinotecan-induced diarrhea. However, subgroup analysis suggests a possible benefit in patients with colostomy.
RESUMO
BACKGROUND: A laparoscopic approach for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) would have the potential to decrease morbidity and mortality rates,1 as similarly observed with laparoscopic liver surgery.2 METHODS: A 54-year-old woman with stage IV rectal cancer (cT3dN1M1) was indicated for the 'liver-first' approach. The patient presented with a massive bilobar metastatic liver involvement, including S4. Five lesions were localized in a small left liver lobe (future liver remnant < 25%). During the first stage of ALPPS, the liver parenchyma was transected with preservation of the central part of the middle hepatic vein, followed by a non-anatomical resection of S3 and a metastasectomy in S2. The procedure was completed by radiofrequency ablation of S2 lesions close to the S2 portobiliary triad, to spare venous drainage for S3. The second stage of ALPPS was performed 8 days later. RESULTS: Operative time was 300 min for the first stage of ALPPS and 200 min for the second stage. Peroperative blood loss did not exceed 50 mL per operation, and no postoperative complications were observed. The patient was discharged 7 days after the second surgery. One month later, a laparoscopic uncomplicated low anterior resection with tumor-free resection margins was performed. Five months after surgery, no disease progression was detected. CONCLUSION: A laparoscopic ALPPS procedure with preservation of one portobiliary triad in the left lobe would be feasible in selected patients. The laparoscopic approach would be very important for patients waiting for a final primary tumor surgery.
