High-risk Features for Recurrence in Patients With Stage III Colorectal Cancer: A Retrospective Cohort Study.

BACKGROUND/AIM: Risk classification for recurrence in stage III colorectal cancer (CRC) is not as well established as it is for stage II. This study aimed to identify high-risk factors for stage III colorectal cancer and to investigate their clinical significance. PATIENTS AND METHODS: We retrospectively analyzed data from 120 patients with stage III CRC who had undergone curative colectomy at our institution between 2014 and 2020. We used logistic regression analysis to identify risk factors for recurrence and subsequently explored their clinical significance. RESULTS: We identified three high-risk factors in stage III CRC: preoperative bowel obstruction [odds ratio (OR)=5.39; 95% confidence interval (CI)=1.61-18.03; p=0.007], N2 disease (OR=3.12; 95%CI=1.05-9.29; p=0.041), and having fewer than 17 examined lymph nodes (OR=3.17; 95%CI=1.11-8.99; p=0.031). The prognosis of patients was clearly stratified by the number of these risk factors, and furthermore, the effectiveness of adjuvant therapy depended on their number. CONCLUSION: Tumor obstruction, N-stage, and the number of lymph nodes examined are important high-risk features for recurrence. This study provides clinicians with valuable insights to predict and stratify patient outcomes in stage III CRC.

Phase II multi-institutional prospective trial of nab-paclitaxel as second-line chemotherapy for advanced gastric cancer refractory to fluoropyrimidine with modified dose reduction criteria (CCOG1303).

BACKGROUND: The aim of this study was to explore the efficacy and safety of nab-paclitaxel as second-line chemotherapy for advanced gastric cancer with modified dose reduction criteria by which the doses were manipulated earlier. METHODS: Gastric cancer patients who developed progression during the fluoropyrimidine-containing first-line chemotherapy were assigned to receive nab-paclitaxel (260 mg/m2) by triweekly administration. Dose reduction was regulated according to predefined toxicity criteria which included neutropenia less than 1000/mm3 and/or peripheral sensory neuropathy of grade 2 or more. The primary endpoint was progression-free survival. RESULTS: A total of 50 patients were enrolled, 47 of whom were eligible for efficacy analyses. The median number of treatment cycles and relative dose intensity given per patient was four (range 1-25), and 90% (range 60-100). Of total administration throughout the trial of 280 cycles, dose reduction was required in 50 cycles. The median progression-free survival was 3.5 months (95% confidence interval 2.5-4.4) that met the primary endpoint. The median overall survival was 9.0 months (95% confidence interval 6.8-11.8), overall response rate was 16% (95% confidence interval 2-30), and disease control rate was 72% (95% confidence interval 54-90). The median time to treatment failure was 3.5 months (95% confidence interval 2.5-4.4). Adverse events of grade 3 or worse included neutropenia in 49%, and peripheral sensory neuropathy in 11%. Febrile neutropenia occurred only in one patient (2%). CONCLUSION: The modified dose reduction criteria for triweekly administration of nab-paclitaxel resulted in decreased incidence of severe peripheral sensory neuropathy without decline in efficacy.

Effectiveness of plasma treatment on pancreatic cancer cells.

Non-equilibrium atmospheric pressure plasma (NEAPP) has attracted attention in cancer therapy. We explored the indirect effect of NEAPP through plasma-activated medium (PAM) on pancreatic cancer cells in vitro and in vivo. In this study, four pancreatic cancer cell lines were used and the antitumor effects of PAM treatment were evaluated using a cell proliferation assay. To explore functional mechanisms, morphological change and caspase-3/7 activation in cells were also assessed. Furthermore, reactive oxygen species (ROS) generation in cells was examined and N-acetyl cysteine (NAC), an intracellular ROS scavenger, was tested. Finally, the antitumor effect of local injection of PAM was investigated in a mouse xenograft model. We found that PAM treatment had lethal effect on pancreatic cancer cells. Typical morphological findings suggestive of apoptosis such as vacuolization of cell membranes, small and round cells and aggregation of cell nuclei, were observed in the PAM treated cells. Caspase-3/7 activation was detected in accordance with the observed morphological changes. Additionally, ROS uptake was observed in all cell lines tested, while the antitumor effects of PAM were completely inhibited with NAC. In the mouse xenograft model, the calculated tumor volume on day 28 in the PAM treatment group was significantly smaller compared with the control group [28 ± 22 vs. 89 ± 38 (mm(3) ± SD), p=0.0031]. These results show that PAM treatment of pancreatic cancer might be a promising therapeutic strategy.

Feeding duodenostomy decreases the incidence of mechanical obstruction after radical esophageal cancer surgery.

BACKGROUND: Nutritional support influences the outcome of gastroenterological surgery, and enteral nutrition effectively mitigates postoperative complications in highly invasive surgery such as resection of esophageal cancer. However, feeding via jejunostomy can cause complications including mechanical obstruction, which could be life threatening. From 2009, we began enteral feeding via duodenostomy to reduce the likelihood of complications. In this study, we compared duodenostomy with the conventional jejunostomy feeding, mainly looking at the catheter-related complications. METHODS: The database records of 378 patients with esophageal cancer who underwent radical esophagectomy with retrosternal or posterior mediastinal gastric tube reconstruction in our department from January 1998 to December 2012 were examined. Of the 378 patients, 111 underwent feeding via duodenostomy (FD) and 267 underwent feeding via jejunostomy (FJ), and their records were reviewed for the following catheter-related complications: site infection, dislodgement, peritonitis, and mechanical obstruction. RESULTS: Mechanical obstruction occurred in 12 patients in the FJ group but none in the FD group (4.5 % vs. 0 %, P = 0.023). Of the 12 cases, 7 (58.3 %) required surgery of which 2 had bowel resection due to strangulated mechanical obstruction. Catheter site infection was seen in 14 cases in the FJ group, of which 2 (14.2 %) had peritonitis following catheter dislocation, while only one case of site infection was seen in the FD group (5.2 % vs. 0.9 %, P = 0.078). CONCLUSIONS: Feeding via duodenectomy could be the procedure of choice since neither mechanical obstruction nor relaparotomy was seen during enteral feeding through this technique.

Effectiveness of plasma treatment on gastric cancer cells.

BACKGROUND: Treatment of peritoneal carcinomatosis arising from gastric cancer remains a considerable challenge. In recent years, the anticancer effect of nonequilibrium atmospheric pressure plasma (NEAPP) has been reported in several cancer cell lines. Use of NEAPP may develop into a new class of anticancer therapy that augments surgery, chemotherapy, and radiotherapy. METHOD: Gastric cancer cells were assessed for changes in cell morphology and rate of proliferation after treatment with NEAPP-exposed medium (PAM). To explore the functional mechanism, caspase 3/7, annexin V, and uptake of reactive oxygen species (ROS) were evaluated, along with the effect of the ROS scavenger N-acetylcysteine (NAC). RESULTS: PAM treatment for 24 h affected cell morphology, suggestive of induction of apoptosis. PAM cytotoxicity was influenced by the time of exposure to PAM, the type of cell line, and the number of cells seeded. Cells treated with PAM for 2 h demonstrated activated caspase 3/7 and an increased proportion of annexin V-positive cells compared with untreated cells. Additionally, ROS uptake was observed in PAM-treated cells, whereas NAC reduced the cytotoxicity induced by PAM presumably through reduction of ROS uptake. Furthermore, CD44 variant 9, which reportedly leads to glutathione synthesis and suppresses stress signaling of ROS, was overexpressed in PAM-resistant cells. CONCLUSIONS: PAM treatment induced apoptosis of gastric cancer cells through generation and uptake of ROS. Local administration of PAM could develop into an option to treat peritoneal carcinomatosis.