Cholangiocarcinoma (CCC) is an aggressive malignancy with poor therapeutic options and pronounced chemotherapy resistance. The bioactive broccoli substance, sulforaphane (SFN), is a promising new therapeutic option since it has been found to induce therapeutic effects in both experimental and epidemiological studies in various tumor entities. Thus, the present study was designed to assess the effect of SFN on cisplatin sensitivity in CCC. Human HuCCT-1 and TFK-1 cells, representing intrahepatic and extrahepatic CCC, respectively, were treated with cisplatin and SFN. Viability, the platinated DNA content, and apoptosis were assessed using both MTT assay and flow cytometry, while western blotting was used to analyze the expression of proteins involved in apoptosis and DNA damage. Whereas cisplatin was largely ineffective, SFN only therapy significantly decreased the viability of both CCC cell lines. The combination of SFN with cisplatin increased cisplatin cytotoxicity, which was particularly pronounced relatively early at 36 h after treatment. Apoptosis, which was reflected by the cleavage of caspase-3 and PARP, was significantly enhanced. Notably, only cisplatin was found to induce the expression of proteins involved in the DNA damage response; however, the presence of SFN appeared to enable otherwise cisplatin-resistant cells to undergo apoptosis. Due to the fact that SFN did not enhance the DNA platination levels upon cisplatin treatment, SFN may have exerted its activity via the inhibition of the anti-apoptotic proteins Bcl-2 and XIAP, as we observed. Data presented in the present study clearly demonstrated that SFN significantly decreased the drug resistance to cisplatin in human CCC. This highlights dietary co-treatment as a viable new treatment option for CCC.
Background: The novel surgical procedure transanal total mesorectal excision (taTME) has rapidly become an interest of research in order to overcome the shortcomings of laparoscopic surgery in the treatment of middle and low rectal cancer. taTME is a new natural orifice transluminal endoscopic surgery modality combining three rectal surgery techniques. Methods: A retrospective clinical study was conducted in a single centre for a period of 3 years, and herein we report on our first 25 taTME procedures in patients with middle and lower third rectal adenocarcinoma. Results: The main demographics were evaluated. The mean age of patients was 64 ± 12 years. There were predominantly males (72%) and 7 female patients (28%) with an average body mass index of 29 ± 4.8 kg/m2. High blood pressure, obesity, chronic heart insufficiency, chronic atrial fibrillation, and diabetes mellitus were commonly diagnosed in all patients. A circumferential resection margin >1 mm was achieved in 16% (n = 4), >2 mm in 40% (n = 10), and >3 mm in 44% (n = 11) of operated patients. The average CRM was 1.8 ± 0.9 cm. In 24% of cases, the distance of a tumour from the mesorectal fascia (MRF) was <1 mm; meanwhile, for 76% of patients, the tumour margin was >1 mm from the MRF. Recovery to flatus was 3 ± 1 days. The average length of hospital stay was 11 ± 3 days. The overall postoperative morbidity was 8%, i.e. one (4%) complication classified as Clavien-Dindo degree I and one (4%) major (IIIb) complication. Subsequently, all patients successfully recovered and were discharged from hospital. During the follow-up period no cancer recurrence was observed. Conclusion: Our results nicely demonstrate that taTME can be safely performed with acceptable perioperative complications in patients with middle or lower third rectal cancer. In addition, the perioperative morbidity is also acceptable. However, taTME remains a technically highly demanding operation but is feasible and safe after the appropriate experience is gained. Nevertheless, larger multi-centre prospective randomised studies are ongoing to confirm the safety and to verify oncological results when compared to laparoscopic rectal surgery.
Background. The aim of the study was to evaluate the safety and adequacy of high vascular ligation while performing surgery for left-sided colon cancer. We performed a retrospective analysis of prospectively collected data of patients operated laparoscopically for sigmoid or descending colon cancer in a single tertiary care institution over a period of 10 years. Patients and methods. Between January 2007 and December 2016 hand-assisted laparoscopic surgery (HALS) was performed on 228 patients due to invasive and histologically verified descending or sigmoid colon cancer with high ligation of inferior mesenteric artery and vein. Patients who had carcinoma in situ were excluded. The following variables were collected and prospectively studied: age, sex, cancer localization, cancer stage, type of surgery, operative time, lymph node harvest, intraoperative complications, conversions, duration of hospital and postoperative stay, postoperative complications occurring within 30 days. Complications were assessed by Clavien- Dindo classification. Results. Patient mean age was 64±10 years (range, 40 - 86). There were 112 females (49.1 %) and 116 males (50.9 %). A total of 149 (65.5 %) sigmoid colectomies and 79 (34.5 %) left hemicolectomies have been performed. There were total of 71 (31 %) patients with stage I disease, 67 (29.7 %) – stage II, 65 (28.4 %) stage III and 25 (10.9 %) stage IV. Aerage operative time was 105±39 minutes (range, 45-270). Average harvested lymph node count was 16.5±10 (range, 10 - 90). Length of postoperative stay was 6.3±3.2 days (range, 1-30). Eleven (4.82 %) patients had complications, three of them (1,3%) were reoperated. There was no anastomotic leakage detected in this group of patients. Conclusions. Our data support the opinion, that high vascular ligation while performing surgery for left sided colon cancer is safe. Recorded lymphnode harvest confirms oncological adequacy of such an approach.
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