Survival landscape of different tumor regression grades and pathologic complete response in rectal cancer after neoadjuvant therapy based on reconstructed individual patient data.

BACKGROUND: Neoadjuvant therapy can lead to different tumor regression grades (TRG) in rectal cancer after neoadjuvant therapy. The purposes of this study are to investigate the relationships among TRG, pathologic complete response (pCR) and long-term survival, on the basis of reconstructed individual patient data (IPD). METHODS: The PubMed, Embase, Ovid and Cochrane CENTRAL databases were searched. The primary endpoint was to evaluate the survival landscape of different TRGs after neoadjuvant therapy and the secondary endpoint was to evaluate the associations between pCR and survival. IPD were reconstructed with Kaplan-Meier curves. RESULTS: The 10-year overall survival (OS) and 5-year disease-free survival (DFS) were clearly higher in the pCR group than in the non-pCR (npCR) group (80.5% vs. 48.3, 90.1% vs. 69.8%). Furthermore, the OS and DFS increased with improvement in tumor regression after neoadjuvant therapy. According to the IPD, the pCR group had longer OS (HR = 0.240, 95% CI = 0.177-0.325, p < 0.001) and DFS (HR = 0.274, 95% CI = 0.205-0.367, p < 0.001) than the npCR group. Better tumor regression was associated with better survival outcomes (p < 0.005). Direct calculation of published HR values yielded similar results. CONCLUSIONS: Our results indicate a positive relationship between better tumor regressions and improved survival benefits among the npCR group and patients with rectal cancer achieving pCR had much longer OS and DFS than patients achieving npCR, presenting a survival landscape of different TRGs and pCR in rectal cancer after neoadjuvant therapy.

Clinical evidence of prevention strategies for capecitabine-induced hand-foot syndrome.

Hand-foot syndrome (HFS) is the most common adverse effect of capecitabine-containing chemotherapy. The purpose of this study was to assess the efficacies of various prevention and treatment strategies for capecitabine-induced HFS. Searches of the PubMed and Embase databases were performed to identify relevant studies. The risk ratio (RR) with the corresponding 95% confidence interval (CI) was used as an effect measure to evaluate the efficacies of these prevention and treatment strategies. Publication bias was evaluated using Begg's and Egger's tests. Overall and subgroup analyses were conducted. All statistical analyses were conducted with Stata software version 12.0. Seventeen eligible studies were included. Our results indicated that celecoxib was significantly associated with a lower incidence of grade ≥2 capecitabine-induced HFS without heterogeneity (RR = 0.43, 95% CI = 0.23-0.81, I2  = 0.0%). However, pyridoxine and topical urea/lactic acid were not effective toward preventing capecitabine-induced grade 1, 2, 3, ≥1 or ≥2 HFS. Moreover, pyridoxine was not effective in treating capecitabine-induced HFS. Similar results were obtained by subgroup analysis. Our results indicate that celecoxib has potential prophylactic efficacy for capecitabine-induced HFS. However, pyridoxine and topical urea/lactic acid are not associated with a decrease in the incidence of capecitabine-induced HFS.

Impact of timing of adjuvant chemotherapy on survival in stage III colon cancer: a population-based study.

BACKGROUND: There is no consensus regarding the optimal time to initiate adjuvant chemotherapy after surgery for stage III colon cancer, and the relevant postoperative complications that cause delays in adjuvant chemotherapy are unknown. METHODS: Eligible patients aged ≥66 years who were diagnosed with stage III colon cancer from 1992 to 2008 were identified using the linked Surveillance, Epidemiology, and End Results-Medicare database. Kaplan-Meier analysis and a Cox proportional hazards model were utilized to evaluate the impact of the timing of adjuvant chemotherapy on overall survival (OS). RESULTS: A total of 18,491 patients were included. Delayed adjuvant chemotherapy was associated with worse OS (9-12 weeks: hazard ratio [HR] = 1.222, 95% confidence interval [CI] = 1.063-1.405; 13-16 weeks: HR = 1.252, 95% CI = 1.041-1.505; ≥ 17 weeks: HR = 1.969, 95% CI = 1.663-2.331). The efficacies of adjuvant chemotherapy within 5-8 weeks and ≤4 weeks were similar (HR = 1.045, 95% CI = 0.921-1.185). Compared with the non-chemotherapy group, chemotherapy initiated at ≥21 weeks did not significantly improve OS (HR = 0.882, 95% CI = 0.763-1.018). Patients with postoperative complications, particularly cardiac arrest, ostomy infection, shock, and septicemia, had a significantly higher risk of a 4- to 11-week delay in adjuvant chemotherapy (p < 0.05). CONCLUSIONS: Adjuvant chemotherapy initiated within 8 weeks was acceptable for patients with stage III colon cancer. Delayed adjuvant chemotherapy after 8 weeks was significantly associated with worse OS. However, adjuvant chemotherapy might still be useful even with a delay of approximately 5 months. Moreover, postoperative complications were significantly associated with delayed adjuvant chemotherapy.

Meta-analysis of the laparoscopic versus open colorectal surgery within fast track surgery.

BACKGROUND: Laparoscopic methods and fast-track surgery (FTS) can enhance recovery and reduce postoperative hospital stay. However, whether laparoscopic surgery can provide short-term benefits within FTS is controversial. Thus, we conducted a meta-analysis of published studies to evaluate the effect of laparoscopic colorectal surgery within FTS. METHODS: We searched PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies. Endpoints were duration of postoperative hospital stay, time to first bowel movement, total postoperative complication rate, readmission rate, mortality within 30 days after surgery, and conversation rate of laparoscopic surgery. RESULTS: Four randomized controlled trials and six clinical controlled trials (1510 patients) were eligible for analyses. Duration of postoperative hospital stay (weighted mean difference, -1.65 days; p < 0.001), time to first bowel movement (-1.13 days; p < 0.001), total postoperative complication rate (risk ratio [RR], 0.65; p < 0.001), readmission rate (0.46; p < 0.001), and mortality (0.45; p < 0.001) were significantly reduced in the laparoscopic surgery group. Overall conversion rate of laparoscopic surgery was 11.1%. Subgroup analyses based on each FT element demonstrated that studies without the element "prevention of hypothermia," "no bowel preparation," or "no routine use of drains" did not show significant differences between two groups with regard to duration of postoperative hospital stay or total prevalence of postoperative complications. CONCLUSION: Within FTS, laparoscopic methods can significantly shorten postoperative hospital stay, accelerate postoperative recovery, and enhance safety in colorectal surgery. The FT elements "prevention of hypothermia," "no bowel preparation," and "no routine use of drains" may play important parts in the combined effect of these two methods.

A dose-response meta-analysis reveals an association between vitamin B12 and colorectal cancer risk.

OBJECTIVE: The current meta-analysis evaluated the association between vitamin B12 intake and blood vitamin B12 level and colorectal cancer (CRC) risk. DESIGN: The PubMed and EMBASE databases were searched. A dose-response analysis was performed with generalized least squares regression, with the relative risk (RR) and 95 % CI as effect values. SETTING: The meta-analysis included seventeen studies. SUBJECTS: A total of 10 601 patients. RESULTS: The non-linear dose-response relationship between total vitamin B12 intake and CRC risk was insignificant (P=0·690), but the relationship between dietary vitamin B12 intake and CRC risk was significant (P<0·001). Every 4·5 µg/d increment in total and dietary vitamin B12 intake was inversely associated with CRC risk (total intake: RR=0·963; 95 % CI 0·928, 0·999; dietary intake: RR=0·914; 95 % CI 0·856, 0·977). The inverse association between vitamin B12 intake and CRC risk was also significant when vitamin B12 intake was over a dosage threshold, enhancing the non-linear relationship. The non-linear dose-response relationship between blood vitamin B12 level and CRC risk was insignificant (P=0·219). There was an insignificant association between every 150 pmol/l increment in blood vitamin B12 level and CRC risk (RR=1·023; 95 % CI 0·881, 1·187). CONCLUSIONS: Our meta-analysis indicates that evidence supports the use of vitamin B12 for cancer prevention, especially among populations with high-dose vitamin B12 intake, and that the association between CRC risk and total vitamin B12 intake is stronger than between CRC risk and dietary vitamin B12 intake only.

Aspirin and nonsteroidal anti-inflammatory drugs after but not before diagnosis are associated with improved breast cancer survival: a meta-analysis.

PURPOSE: The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer survival is still controversial. The aim of our meta-analysis was to assess the survival benefit of NSAIDs. METHODS: A literature search was conducted in PubMed and EMBASE (to September 2014). A meta-analysis was performed with hazard ratios (HRs) and 95% confidence intervals (CIs) as the effect measures. Subgroup analyses were based on time of NSAID use (before and after diagnosis), medication type (aspirin and other nonaspirin NSAIDs), and study design (cohort and case-control studies). RESULTS: There were 16 eligible studies. Use of NSAIDs after diagnosis was significantly inversely associated with relapse/metastasis (HR 0.69, 95% CI 0.59-0.80) and tended toward potentially protective effects on all-cause mortality, although significance was not reached (HR 0.79, 95% CI 0.61-1.02). In cohort studies, the association between post-diagnostic use of NSAIDs and breast cancer survival was stronger with reduced heterogeneity (breast-cancer-specific mortality: HR 0.65, 95% CI 0.48-0.89, I(2) = 65.3%; all-cause mortality: HR 0.73, 95% CI 0.57-0.92, I(2) = 83.2%; relapse/metastasis: HR 0.73, 95% CI 0.61-0.86, I(2) = 48.3%). Aspirin use after diagnosis was significantly associated with breast-cancer-specific mortality (HR 0.69, 95% CI 0.50-0.96) and relapse/metastasis (HR 0.75, 95% CI 0.56-1.00), and tended toward a protective effect on all-cause mortality, although significance was not reached (HR 0.79, 95% CI 0.60-1.03). Including cohort studies only, we obtained similar results and post-diagnostic use of aspirin was significantly associated with all-cause mortality (HR 0.72, 95% CI 0.56-0.93). CONCLUSIONS: NSAIDs and aspirin after but not before diagnosis were associated with improved breast cancer survival, including breast-cancer-specific mortality, all-cause mortality, and relapse/metastasis.

Laparoscopic resection with natural orifice specimen extraction versus conventional laparoscopy for colorectal disease: a meta-analysis.

PURPOSE: We wished to determine the effects of laparoscopic resection using natural orifice specimen extraction (NOSE) for patients with colorectal disease through a meta-analysis. METHODS: A study search was undertaken in PubMed, EMBASE, and Cochrane databases for eligible studies until December 2014. Duration of hospital stay, operation time, time to first flatus, pain score, cosmetic result, postoperative complications, and disease-free survival (DFS) were the main endpoints. The results were analyzed using RevMan v5.3. RESULTS: Nine clinical studies involving 837 patients were included for final analyses. Laparoscopic resection with NOSE had a shorter duration of hospital stay (weighted mean difference (WMD) = -0.62 days, 95 % confidence interval (CI) [-0.95, -0.28], p < 0.01) and time to first flatus (WMD = -0.59 days, 95 % CI [-0.78, -0.41], p < 0.01), less postoperative pain (WMD = -1.43, 95 % CI [-1.95, -0.90], p < 0.01), and postoperative complications (odds ratio (OR) = 0.51, 95 % CI [0.36, 0.74], p < 0.01) with better cosmetic result (WMD = 1.37, 95 % CI [0.59, 2.14], p < 0.01). However, the operation time was significantly longer in the NOSE group (WMD = 20.97 min, 95 % CI [4.33, 37.62], p = 0.01). No significant difference was observed in DFS (hazard ratio (HR) = 0.88, 95 % CI [0.49, 1.57], p = 0.67). CONCLUSION: Our meta-analysis supported the notion that laparoscopic resection with NOSE for colorectal disease can significantly reduce the duration of hospital stay, accelerate postoperative recovery with better cosmetic results, and in particular, result in less postoperative pain and fewer complications.

Fast-track surgery versus traditional perioperative care in laparoscopic colorectal cancer surgery: a meta-analysis.

BACKGROUND: Both laparoscopic and fast-track surgery (FTS) have shown some advantages in colorectal surgery. However, the effectiveness of using both methods together is unclear. We performed this meta-analysis to compare the effects of FTS with those of traditional perioperative care in laparoscopic colorectal cancer surgery. METHODS: We searched the PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies until April 2014. The main end points were the duration of the postoperative hospital stay, time to first flatus after surgery, time of first bowel movement, total postoperative complication rate, readmission rate, and mortality. RESULTS: Five randomized controlled trials and 5 clinical controlled trials with 1,317 patients were eligible for analysis. The duration of the postoperative hospital stay (weighted mean difference [WMD], -1.64 days; 95% confidence interval [CI], -2.25 to -1.03; p < 0.001), time to first flatus (WMD, -0.40 day; 95% CI, -0.77 to -0.04; p = 0.03), time of first bowel movement (WMD, -0.98 day; 95% CI, -1.45 to -0.52; p < 0.001), and total postoperative complication rate (risk ratio [RR], 0.67; 95% CI, 0.56-0.80; p < 0.001) were significantly reduced in the FTS group. No significant differences were noted in the readmission rate (RR, 0.64; 95% CI, 0.41-1.01; p = 0.06) or mortality (RR, 1.55; 95% CI, 0.42-5.71; p = 0.51). CONCLUSION: Among patients undergoing laparoscopic colorectal cancer surgery, FTS is associated with a significantly shorter postoperative hospital stay, more rapid postoperative recovery, and, notably, greater safety than is expected from traditional care.

Which is the best postoperative chemotherapy regimen in patients with rectal cancer after neoadjuvant therapy?

BACKGROUND: There is no general agreement about whether patients who have already received neoadjuvant chemoradiotherapy need further postoperative chemotherapy based on 5-fluorouracil(5-FU) or 5-FU plus oxaliplatin. METHODS: Medicare beneficiaries from 1992 to 2008 with Union for International Cancer Control ypStages I to III primary carcinoma of the rectum who underwent 5-FU-based neoadjuvant chemoradiotherapy and surgery for curative intent were identified through the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. A Cox proportional hazards model and propensity score-matched techniques were used to evaluate the effect of treatment on survival. RESULTS: For patients with resected rectal cancer who have already received 5-FU-based neoadjuvant chemoradiotherapy, postoperative 5-FU-based chemotherapy did not prolong cancer-specific survival (CSS) in ypStage I (P = 0.960) and ypStage II (P = 0.134); however, it significantly improved the CSS in ypStage III (hazard ratio = 1.547, 95% CI = 1.101-2.173, P = 0.012). No significant differences in survival between the 5-FU group and oxaliplatin group were observed. CONCLUSIONS: For patients with resected rectal cancer who have already received 5-FU-based neoadjuvant chemoradiotherapy, postoperative 5-FU-based chemotherapy prolongs the CSS of groups in ypStage III. Adding oxaliplatin to fluoropyrimidines in the postoperative chemotherapy did not improve the CSS for patients who received neoadjuvant chemoradiotherapy.

Gastric intestinal metaplasia: progress and remaining challenges.

Most gastric cancers arise in the setting of chronic inflammation which alters gland organization, such that acid-pumping parietal cells are lost, and remaining cells undergo metaplastic change in differentiation patterns. From a basic science perspective, recent progress has been made in understanding how atrophy and initial pyloric metaplasia occur. However, pathologists and cancer biologists have long been focused on the development of intestinal metaplasia patterns in this setting. Arguably, much less progress has been made in understanding the mechanisms that lead to the intestinalization seen in chronic atrophic gastritis and pyloric metaplasia. One plausible explanation for this disparity lies in the notable absence of reliable and reproducible small animal models within the field, which would facilitate the investigation of the mechanisms underlying the development of gastric intestinal metaplasia (GIM). This review offers an in-depth exploration of the current state of research in GIM, shedding light on its pivotal role in tumorigenesis. We delve into the histological subtypes of GIM and explore their respective associations with tumor formation. We present the current repertoire of biomarkers utilized to delineate the origins and progression of GIM and provide a comprehensive survey of the available, albeit limited, mouse lines employed for modeling GIM and engage in a discussion regarding potential cell lineages that serve as the origins of GIM. Finally, we expound upon the myriad signaling pathways recognized for their activity in GIM and posit on their potential overlap and interactions that contribute to the ultimate manifestation of the disease phenotype. Through our exhaustive review of the progression from gastric disease to GIM, we aim to establish the groundwork for future research endeavors dedicated to elucidating the etiology of GIM and developing strategies for its prevention and treatment, considering its potential precancerous nature.