Background We have already reported that, for patients undergoing elective colon cancer operations, perioperative infection can be prevented by a single intravenous dose of an antibiotic given ...immediately beforehand if mechanical bowel preparation and the administration of oral antibiotics are implemented. Synbiotics has been reported to reduce the rate of infection in patients after pancreatic cancer operations. The effectiveness of oral antibiotics and probiotics in preventing postoperative infection in elective colon cancer procedures was examined in a randomized controlled trial. Methods Three hundred ten patients with colon cancer randomly were assigned to one of three groups. All patients underwent mechanical bowel preparation and received a single intravenous dose of flomoxef immediately before operation. Probiotics were administered in Group A; oral antibiotics were administered in Group B; and neither probiotics nor oral antibiotics were administered in Group C. Stool samples were collected 9 and 2 days before and 7 and 14 days after the procedure. Clostridium difficile toxin and the number of bacteria in the intestine were determined. Results The rates of incisional surgical-site infection were 18.0%, 6.1%, and 17.9% in Groups A, B, and C, and the rates of leakage were 12.0%, 1.0%, and 7.4% in Groups A, B, and C, respectively, indicating that both rates were lesser in Group B than in Groups A and C ( P = .014 and P = .004, respectively). The detection rates of C. difficile toxin were not changed among the three groups. Conclusion We recommend oral antibiotics, rather than probiotics, as bowel preparation for elective colon cancer procedures to prevent surgical-site infections.
In addition to their major targets, clinically effective drugs may have unknown off-targets. By identifying such off-targets it may be possible to repurpose approved drugs for new indications. We are ...interested in the Golgi apparatus as a novel target for cancer therapy, but there is a paucity of candidate Golgi-disrupting drugs. Here, we aimed to identify Golgi-disrupting compounds from a panel of 34 approved anticancer drugs by using HBC-4 human breast cancer cells and immunofluorescence microscopy to visualize the Golgi apparatus. The screen identified five drugs having Golgi-disrupting activity. Four of them were vinca alkaloids (vinorelbine, vindesine, vincristine and vinblastine), and the fifth drug was eribulin. This is the first study to demonstrate that vinorelbine, vindesine and eribulin possess Golgi-disrupting activity. The 5 drugs are known to inhibit tubulin polymerization and to induce microtubule depolymerization. Interestingly, a microtubule-stabilizer paclitaxel did not induce Golgi-disruption, suggesting that the three-dimensionally preserved microtubules are partly responsible for maintaining the Golgi complex. Concerning eribulin, a noteworthy drug because of its high clinical efficacy against advanced breast cancer, we further confirmed its Golgi-disrupting activity in 3 different human breast cancer cell lines, BSY-1, MDA-MB-231 and MCF-7. Golgi-disruption may contribute to anticancer efficacy of eribulin. In conclusion, the present study revealed that 4 vinca alkaloids and eribulin possessed potential Golgi-disrupting activity among a panel of 34 approved anticancer drugs. Other drugs covering various molecular-targeted drugs and classical DNA-damaging drugs showed no Golgi-disrupting effect. These results suggest that tubulin polymerization-inhibitors might be promising candidate drugs with Golgi-disrupting activity.
Background
Seprafilm did not decrease small bowel obstruction (SBO), but significantly decreased reoperation in patients with inflammatory bowel disease. However, the preventive effect in colon ...cancer remains unclear.
Methods
We conducted a randomized controlled trial in patients with colon cancer. The study group comprised 345 patients with colon cancer. In the seprafilm group (n = 166), two sheets of seprafilm were inserted under a midline incision. Patients who were admitted and required decompression were considered to have SBO.
Results
The median follow‐up was 61.9 months. Patient characteristics were well balanced. There was no significant difference in the incidence of SBO between the seprafilm group (7.8%) and the control group (10.6%) (P = .46). In patients who underwent reoperation, SBO occurred in a midline incision in one patient and at other sites in four patients in the seprafilm group as compared with two patients and five patients, respectively, in the control group. Multivariate analysis showed that only a history of laparotomy was an independent risk factor for SBO.
Conclusions
Seprafilm did not decrease SBO or reoperation in colon cancer. The incidence of SBO caused by adhesion to the midline incision was relatively low as compared with that caused by adhesion to other sites.
Most previous reports to analyze risk factors for peritoneal recurrence in patients with colon cancer have been observational studies of a population-based cohort.
This study aimed to determine the ...risk factors for peritoneal recurrence in patients with stage II to III colon cancer who underwent curative resection.
This was a pooled analysis using a combined database obtained from 3 large phase III randomized trials (N = 3714).
Individual patient data were collected from the Japanese Foundation for Multidisciplinary Treatment of Cancer clinical trials 7, 15, and 33, which evaluated the benefits of postoperative 5-fluorouracil-based adjuvant therapies in patients with locally advanced colorectal cancer.
We included patients who had stage II to III colon cancer and underwent curative resection with over D2 lymph node dissection.
Main outcomes measured were risk factors for peritoneal recurrence without other organ metastasis after curative surgery.
Peritoneal recurrence occurred in 2.3% (86/3714) of all patients undergoing curative resection. Mean duration from operation to peritoneal recurrence was 17.0 ± 10.3 months. Of these patients with peritoneal recurrence, 29 patients (34%) had recurrence in ≥1 other organ. Multivariate analysis showed that age (≥60 y: HR = 0.531; p = 0.0182), pathological T4 (HR = 3.802; p < 0.0001), lymph node involvement (HR = 3.491; p = 0.0002), and lymphadenectomy (D2: HR = 1.801; p = 0.0356) were independent predictors of peritoneal recurrence. The overall survival was lower in patients who developed peritoneal recurrence than in those with other recurrence (HR = 1.594; p = 0.002).
The regimens of adjuvant chemotherapy were limited to oral 5-fluorouracil.
Our findings clarified the risk factors for peritoneal recurrence in patients who underwent curative resection for colon cancer. See Video Abstract at http://links.lww.com/DCR/A609.
Colon cancer (CC) incidence in young adults (age 20-49 years), termed early-onset CC (EO-CC), is increasing.
Individual patient data on 35 713 subjects with stage III colon cancer from 25 randomized ...studies in the Adjuvant Colon Cancer ENdpoint database were pooled. The distributions of demographics, clinicopathological features, biomarker status, and outcome data were summarized by age group. Overall survival, disease-free survival, time to recurrence, and survival after recurrence were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for sex, race, body mass index, performance status, disease stage, grade, risk group, number of lymph nodes examined, disease sidedness, and molecular markers. All statistical tests were 2-sided.
Using a 5% difference between age groups as the clinically meaningful cutoff, patients with stage III EO-CC had similar sex, race, performance status, risk group, tumor sidedness, and T stage compared with patients with late-onset CC (age 50 years and older). EO-CC patients were less likely to be overweight (30.2% vs 36.2%) and more commonly had 12 or more lymph nodes resected (69.5% vs 58.7%). EO-CC tumors were more frequently mismatch repair deficient (16.4% vs 11.5%) and less likely to have BRAFV600E (5.6% vs 14.0%), suggesting a higher rate of Lynch syndrome in EO-CC. Patients with EO-CC had statistically significantly better overall survival (hazard ratio HR = 0.81, 95% confidence interval CI = 0.74 to 0.89; P < .001), disease-free survival (HR = 0.91, 95% CI = 0.84 to 0.98; P = .01), and survival after recurrence (HR = 0.88, 95% CI = 0.80 to 0.97; P = .008) in the analysis without molecular markers; however, age at onset of CC lost its prognostic value when outcome was adjusted for molecular markers.
Tumor biology was found to be a more important prognostic factor than age of onset among stage III colon cancer patients in the Adjuvant Colon Cancer ENdpoint database.
Up to 6-months oxaliplatin-containing regimen is now widely accepted as a standard adjuvant chemotherapy for stage III colorectal cancer (CRC). However, oral fluoropyrimidine monotherapy is used for ...some part of patients, especially in Asian countries including Japan, and its optimal duration is yet to be fully investigated.
A total of 1306 patients with curatively-resected stage III CRC were randomly assigned to receive capecitabine (2500 mg/m
/day) for 14 out of 21 days for 6 (n = 654) or 12 (n = 650) months. The primary endpoint was disease-free survival (DFS), and the secondary endpoints were relapse-free survival (RFS), overall survival (OS), and adverse events.
The 3- and 5-year DFS were 70.0% and 65.3% in the 6M group and 75.3% and 68.7% in the 12M group, respectively (p = 0.0549, HR = 0.858, 90% CI: 0.732-1.004). The 5-year RFS was 69.3% and 74.1% in the 6M and 12M groups, respectively (p = 0.0143, HR = 0.796, 90% CI: 0.670-0.945). The 5-year OS was 83.2% and 87.6%, respectively (p = 0.0124, HR = 0.727, 90% CI: 0.575-0.919). The incidence of overall grade 3-4 adverse events was almost comparable in both groups.
Although 12-month adjuvant capecitabine did not demonstrate superior DFS to that of 6-month, the observed better RFS and OS in the 12-month treatment period could be of value in selected cases.
The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. We compared the effects of surgery with and without oral uracil and tegafur plus ...leucovorin (UFT/LV) in patients with high-risk stage II CC, adjusting for potential risk factors.
We enrolled patients with histologically confirmed stage II colon adenocarcinoma with at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes. Patients chose to be non-randomized or randomized to undergo surgery alone (NR-Group S or R-Group S) or surgery followed by 6 months of UFT/LV (NR-Group U or R-Group U). The primary endpoint was disease-free survival (DFS) after adjusting for previously reported risk factors using propensity score matching (1:2) and inverse probability of treatment weighting (IPTW) in the non-randomized arm.
Overall, 1,902 (98%) and 36 (2%) patients were enrolled in the non-randomized and randomized arms, respectively. There were too few patients in the randomized arm and these were therefore excluded from the analysis. Of the 1,902 patients, 402 in NR-Group S and 804 in NR-Group U were propensity score-matched. The 3-year DFS rate (95% confidence interval) was significantly higher in NR-Group U (80.9% 77.9%-83.4%) than in NR-Group S (74.0% 69.3%-78.0%) (hazard ratio, 0.64 0.50-0.83; P = 0.0006). The 3-year overall survival rate was not significantly different between NR-Group S and NR-Group U. Significantly higher 3-year DFS (P = 0.0013) and overall survival (P = 0.0315) rates were observed in NR-Group U compared with NR-Group S using IPTW.
Adjuvant chemotherapy with UFT/LV showed a significant survival benefit over surgery alone in patients with high-risk stage II CC characterized by at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes.
Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019) (UMIN Clinical Trials Registry: UMIN000007783 , date of registration: 18/04/2012).
Abstract
Introduction
Standard treatment strategy for low rectal cancer in Japan is different from Western countries. Total mesorectum excision (TME) + lateral lymph node dissection (LLND) is mainly ...carried out in Japan, whereas neoadjuvant chemoradiotherapy (nCRT) + TME is selected in Western countries. There is no clear definition of preoperative diagnosis of lateral lymph node metastasis. If we can predict lateral lymph node swelling that can be managed by nCRT from lateral lymph node swelling that require surgical resection, clinical benefit is significant. In the current study we assessed characteristics of the lateral lymph node recurrence (LLNR) and LLND that can be managed by nCRT.
Patients and Methods
Patients with low rectal cancer (n = 168) underwent nCRT between 2009 and 2016. We evaluated CEA, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lateral lymph node short axis pre and post nCRT, respectively, and also evaluated tumor shrinkage rate, tumor regression grade (TRG). We evaluated the relationship between each and LLNR.
Results
LLND was not carried out all patients. Factors associated with LLNR were PLR and lymph node short axis pre and post nCRT. (p = 0.0269, 0.0278, p < 0.0001, p < 0.0001, respectively). Positive recurrence cut-off values of lateral lymph node short-axis calculated were 11.6 mm pre nCRT and 5.5 mm post nCRT.
Conclusion
Results suggest that PLR before and after CRT was associated with control of LLNR, and LLND should be performed on lateral lymph nodes with short-axis of 5 mm and 11 mm pre and post nCRT.
Objectives: Carcinoembryonic antigen (CEA) is widely used for postoperative surveillance of colon cancer. Even if serum CEA is negative at initial surgery, it may turn positive at recurrence. We ...investigated the relation between serum CEA levels and the immunohistochemical staining status of CEA in the primary and resected metastatic tissues. Methods: Out of 224 patients with recurrent colon cancer between 1998 and 2012, we studied 46 patients in whom serum CEA levels were measured and immunohistochemical staining for CEA was possible in the primary and metastatic tissues. Results: The positive rate of serum CEA did not differ between initial surgery and recurrence, regardless of whether the cutoff value was set at 5 or 10 ng/ml (p = 0.829, p = 0.671). There was no relation between the CEA staining status and serum CEA level at initial surgery. However, the CEA staining status of metastatic tissue was significantly related to the serum CEA level at recurrence (p = 0.0046 and p = 0.0026). Conclusions: The immunohistochemical staining status of CEA in metastatic tissue is closely related to the serum CEA level. This finding suggests that serum CEA levels are influenced not only by the CEA production capacity of cancer cells but also by the ability of the surrounding tissue to release CEA into the blood.
Although colorectal cancer comprises several histological subtypes, the influences of histological subtypes on disease progression and treatment responses remain controversial.
We sought to evaluate ...the prognostic relevance of mucinous and poorly differentiated histological subtypes of colorectal cancer by the propensity score weighting analysis of prospectively collected data from multi-institute phase III trials.
Independent patient data analysis of a pooled database from 3 phase III trials was performed.
An integrated database of 3 multicenter prospective clinical trials (the Japanese Foundation for Multidisciplinary Treatment of Cancer 7, 15, and 33) was the source of study data.
Surgery alone or postoperative adjuvant chemotherapy was offered in patients with resectable colorectal cancer.
To balance essential variables more strictly for the comparison analyses, propensity score weighting was conducted with the use of a multinomial logistic regression model. We evaluated the clinical signatures of mucinous and poorly differentiated subtypes with regard to postoperative survival, recurrence, and chemosensitivity.
Of 5489 patients, 136 (2.5%) and 155 (2.8%) were pathologically diagnosed with poorly differentiated and mucinous subtypes. The poorly differentiated subtypes were associated with a poorer prognosis than the "others" group (HR, 1.69; 95% CI, 1.00-2.87; p = 0.051), particularly in the patient subgroup of adjuvant chemotherapy (HR, 2.16). Although the mucinous subtype had a marginal prognostic impact among patients with stage I to III colorectal cancer (HR, 1.33; 95% CI, 0.90-1.96), it was found to be an independent prognostic factor in the subpopulation of patients with stage II disease, being associated with a higher prevalence of peritoneal recurrence.
The treatment regimens of postoperative chemotherapy are now somewhat outdated.
Both mucinous and poorly differentiated subtypes have distinct clinical characteristics. Patients with the mucinous subtype require special attention during follow-up, even for stage II disease, because of the risk of peritoneal or local recurrence. See Video Abstract at http://links.lww.com/DCR/A531.
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