Puo-Hsien Le

Prognostic Value of the Preoperative Neutrophil to Lymphocyte Ratio in Resectable Gastric Cancer.

AbstractThis study aimed to investigate the prognostic value of the preoperative neutrophil to lymphocyte ratio (NLR) in resectable gastric cancer (GC).This was a retrospective review of 1030 patients with resectable GC managed between 2005 and 2011. Patients were stratified into 2 groups, those with a preoperative NLR >3.44 and those with a preoperative NLR ⩽3.44. Clinicopathological data affecting patient prognosis were collected prospectively and analyzed.The high NLR (>3.44) group had a higher proportion of a platelet to lymphocyte ratio >132, tumor size >4.8 cm, T4 lesions, metastatic tumors, a ratio of metastatic to examined lymph nodes >0.18, positive resection margins, and presence of vascular or lymphatic invasion than the low NLR (⩽3.44) group. Patients with a high preoperative NLR had significantly lower 3- and 5-year overall survival rates than those with a low preoperative NLR (55.1% vs 71.0% and 47.2% vs 64.1%, respectively; P < 0.001). Preoperative NLR was a prognostic factor for resectable GC in multivariate analysis.More aggressive tumor behavior was observed in patients with resectable GC with a high preoperative NLR than in those with a low preoperative NLR. High preoperative NLR was an independent unfavorable prognostic factor. Measurement of this ratio may serve as a clinically accessible and useful biomarker for patient outcomes.

Imatinib dose escalation versus sunitinib as a second-line treatment against advanced gastrointestinal stromal tumors: A nationwide population-based cohort study

BACKGROUND Although treatment with imatinib in advanced gastrointestinal stromal tumor (GIST) patients has led to significant clinical benefits, the disease will eventually progress due to imatinib resistance. Treatment options after failure of first-line imatinib include imatinib dose escalation or shifting to sunitinib. However, there is no large-scale study to compare the efficacy difference between these two treatment strategies or the role of surgery. RESULTS This study recruited 521 advanced GIST patients including 246, 125, and 150 placed in groups 1, 2, and 3, respectively. Groups 1 and 2 had significantly longer overall survival (OS) as compared with the group 3 (median 37.5 months versus 16.0 months; p < 0.0001). After adjusting for confounding variables, groups 1 and 2 had longer OS than group 3. A favorable survival trend was seen with surgery, although this benefit disappeared after adjusting for confounding factors. MATERIALS AND METHODS We conducted a nationwide population-based cohort study using data from the Taiwan National Health Insurance Research Database from July 2004 to December 2010. Advanced GIST patients who no longer responded to first-line imatinib were stratified into three groups: imatinib dose escalation (group 1); imatinib dose escalation and a shift to sunitinib (group 2); a direct shift to sunitinib (group 3). The therapeutic success of the three treatment regimens and the effect of surgery were evaluated by overall survival. CONCLUSIONS For advanced GIST patients who failed first-line imatinib treatment, imatinib dose escalation confers significantly longer OS compared to a direct switch to sunitinib. Surgery does not provide survival benefits.Background Although treatment with imatinib in advanced gastrointestinal stromal tumor (GIST) patients has led to significant clinical benefits, the disease will eventually progress due to imatinib resistance. Treatment options after failure of first-line imatinib include imatinib dose escalation or shifting to sunitinib. However, there is no large-scale study to compare the efficacy difference between these two treatment strategies or the role of surgery. Results This study recruited 521 advanced GIST patients including 246, 125, and 150 placed in groups 1, 2, and 3, respectively. Groups 1 and 2 had significantly longer overall survival (OS) as compared with the group 3 (median 37.5 months versus 16.0 months; p < 0.0001). After adjusting for confounding variables, groups 1 and 2 had longer OS than group 3. A favorable survival trend was seen with surgery, although this benefit disappeared after adjusting for confounding factors. Materials and Methods We conducted a nationwide population-based cohort study using data from the Taiwan National Health Insurance Research Database from July 2004 to December 2010. Advanced GIST patients who no longer responded to first-line imatinib were stratified into three groups: imatinib dose escalation (group 1); imatinib dose escalation and a shift to sunitinib (group 2); a direct shift to sunitinib (group 3). The therapeutic success of the three treatment regimens and the effect of surgery were evaluated by overall survival. Conclusions For advanced GIST patients who failed first-line imatinib treatment, imatinib dose escalation confers significantly longer OS compared to a direct switch to sunitinib. Surgery does not provide survival benefits.

Clinicopathological characteristics and outcomes in stage I–III mucinous gastric adenocarcinoma: a retrospective study at a single medical center

BackgroundThe clinicopathological characteristics and outcomes of mucinous gastric adenocarcinoma (GC) remain unclear. We report the clinicopathological features and prognosis of patients with mucinous histology who underwent radical-intent gastrectomy.MethodsWe reviewed the medical records of 1470 patients with pathologically proven undifferentiated GC undergoing radical-intent gastrectomy between 1995 and 2007. The patients were stratified into three groups according to their histological type: mucinous carcinoma (MC), signet ring cell carcinoma (SRCC), and poorly differentiated carcinoma (PDC). Clinicopathological factors affecting prognosis were collected prospectively and analyzed.ResultsIn stage III MC, the age and size were significantly greater and larger than in SRCC and PDC; a lower proportion of perineural invasion was identified in MC, and female predominance was noted in SRCC in comparison with MC and PDC. The cumulative overall survival rates of stage I–III GC patients with MC were significantly superior compared to those with PDC, but not SRCC. Stage III GC patients with MC had a better prognosis than those with SRCC or PDC; the difference in survival was not evident in stages I or II.ConclusionsThus, MC presents with different clinicopathological features and prognosis from SRCC and PDC. The patients with stage III gastric MC had favorable outcomes.

Mechanism of salutary effects of melatonin-mediated liver protection after trauma-hemorrhage: p38 MAPK-dependent iNOS/HIF-1α pathway

Although melatonin attenuates the increases in inflammatory mediators and reduces organ injury during trauma-hemorrhage, the mechanisms remain unclear. This study explored whether melatonin prevents liver injury after trauma-hemorrhage through the p38 mitogen-activated protein kinase (MAPK)-dependent, inducible nitrite oxide (iNOS)/hypoxia-inducible factor (HIF)-1α pathway. After a 5-cm midline laparotomy, male rats underwent hemorrhagic shock (mean blood pressure ~40 mmHg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, melatonin (2 mg/kg), melatonin plus p38 MAPK inhibitor SB203580 (2 mg/kg), or melatonin plus the melatonin receptor antagonist luzindole (2.5 mg/kg). At 2 h after trauma-hemorrhage, histopathology score of liver injury, liver tissue myeloperoxidase activity, malondialdehyde, adenosine triphosphate, serum alanine aminotransferase, and asparate aminotransferase levels were significantly increased compared with sham-operated control. Trauma-hemorrhage resulted in a significant decrease in the p38 MAPK activation compared with that in the sham-treated animals. Administration of melatonin after trauma-hemorrhage normalized liver p38 MAPK phosphorylation and iNOS and HIF-1α expression and attenuated cleaved caspase 3 and receptor interacting protein kinase-1 levels. Coadministration of SB203580 or luzindole abolished the melatonin-mediated attenuation of the trauma-hemorrhage-induced increase of iNOS/HIF-1α protein expression and liver injury markers. Taken together, our results suggest that melatonin prevents trauma-hemorrhage-induced liver injury in rats, at least in part, through melatonin receptor-related, p38 MAPK-dependent iNOS/HIF-1α pathway.NEW & NOTEWORTHY Trauma-hemorrhage resulted in a significant decrease in liver p38 MAPK activation and increase in nitrite oxide synthase (iNOS) and hypoxia-inducible factor (HIF)-1α expression. Administration of melatonin after trauma-hemorrhage normalized liver p38 MAPK phosphorylation and iNOS and HIF-1α expression, which was abolished by coadministration of SB203580 or luzindole. Melatonin prevents trauma-hemorrhage-induced liver injury in rats via the melatonin receptor-related, p38 MAPK-dependent iNOS/HIF-1α pathway.

Pancolitis associated with higher mortality risk of cytomegalovirus colitis in patients without inflammatory bowel disease

Background Cytomegalovirus (CMV) colitis typically presents in immunocompromised and inflammatory bowel disease (IBD) patients. Several studies have been conducted on the endoscopic characteristics of CMV colitis in IBD patients. Objectives The endoscopic findings of CMV colitis in non-IBD patients and their relationship with inhospital mortality are unclear. We aimed to describe the endoscopic presentation in these patients and to determine the endoscopic predictors of inhospital mortality. Patients and methods Patients with CMV colitis diagnosed using histology between April 2002 and December 2016 at the Linkou Chang Gung Memorial Hospital, Taiwan, were retrospectively enrolled. Patients diagnosed with IBD during follow-up were excluded. Patient data, including underlying diseases, endoscopic presentation, laboratory data, clinical course, complications, and clinical outcomes, were collected. The independent risk factors for inhospital mortality were analyzed with logistic regression. The difference of overall survival was compared using Kaplan–Meier survival curve and log rank test. All statistical calculations were performed using SPSS software, version 21. Results Sixty-nine patients were enrolled, and 8 IBD patients were excluded. Within the 61 non-IBD patients, 31 were diagnosed by colonoscopy and others by sigmoidoscopy. Ulceration (77%) was the most common endoscopic finding, followed by a cobblestone appearance (19.7%), colitis with/without erosions (9.8%), pseudomembrane (9.8%), and tumor/polyp-like lesions (8.2%). Among the patients who underwent full-length colonoscopy, 35.3% presented with right-sided colitis, 23.5% with left-sided colitis, and 32.4% with pancolitis. Pancolitis was identified as a negative predictor of inhospital mortality (odds ratio, 6.8; 95% confidence interval, 1.233–37.497; p=0.028) and overall survival (log rank p=0.018). Conclusion Colonoscopy is recommended for precise CMV colitis diagnosis and outcome prediction in non-IBD patients.

Prognostic Stratification of Advanced Gastric Signet Ring Cell Carcinoma by Clinicopathological Factors and GALNT14 Genotype

Background: Gastric signet ring cell carcinoma (SRCC) is a histologic variant characterized by abundant intracytoplasmic mucin. Although it has been recognized that gastric adenocarcinoma harboring this feature has poorer prognosis, prognostic stratification within gastric SRCCs themselves has not been clearly defined. N-acetylgalactosaminyltransferase14 (GALNT14) genotype has been associated to poorer treatment outcome in mucinous type colorectal cancer. Here we incorporated clinicopathological factors and GALNT14 genotype to stratify prognosis of advanced gastric SRCC. Methods: Totally 347 gastric SRCC patients were retrospectively enrolled for GALNT14 genotyping. Clinicopathological factors were included for prognosis stratification. Results: Of the 347 patients, 341 underwent radical-intent gastrectomy and 6 received palliative gastrectomy. Kaplan-Meier analysis for overall survival indicated that Tumor-Node-Metastasis staging could only stratify the patients into three prognosis-distinguishable groups: group-1 (stage IA); group-2 (stage IB/IIA) and group-3 (the remaining Tumor-Node-Metastasis stages combined). Multivariate Cox-proportional hazard models for group-3 patients revealed GALNT14 “TT” genotype (P = 0.0482). Tumor size (P = 0.0009), node status (P <0.0001), metastasis status (P = 0.0096), and perineural invasion (P = 0.037) independently associated with unfavorable OS. Exploratory subgroup analysis showed that GALNT14”TT” genotype was associated with unfavorable OS in SRCCs with more aggressive phenotypes: node status >0 (P = 0.0013), lymphatic invasion (P = 0.021), vascular invasion (P = 0.0076) and perineural invasion (P = 0.0161). Accordingly, a scoring system was established capable of stratifying advanced gastric SRCC patients into three distinguishable prognostic subgroups. Conclusions: Gastric SRCC could be stratified into different prognostic subgroups by combining clinicopathological factors and GALNT14 genotype.

Survival impact of the number of lymph node retrieved on patients with node-negative gastric cancer: more is better?

Adequate and proper lymphadenectomy has been widely accepted as a standard treatment for localized gastric cancer (GC) (1-3). The number of lymph node involvement is one of the parts of TNM classification based on American Joint Committee on Cancer (4). Accordingly, accuracy of nodal metastasis is important to predict patient’s survival precisely. In the issue of Annals of Surgical Oncology , Deng et al . investigated whether increasing the number of examined lymph node (NELN) will affect prognosis of node-negative GC patients after radical resection (5). Their results indicated that increasing the NELN improves the accuracy of cancer staging, especially in advanced stage disease. Furthermore, the authors also concluded that based on the discrepancy findings between China and Japan, inexperienced pathologists in China may potentially result in the low NELN, which led to incorrect cancer staging (5). Besides, they also observed that Chinese patients had more advanced diseases and less mean NELN as compared with Japanese patients. These are the principal causes explaining worse overall survival (OS) in Chinese patients than Japanese patients with regard to NELN.

Clinical characteristics of cytomegalovirus colitis: a 15-year experience from a tertiary reference center

Background Cytomegalovirus (CMV) colitis is considered rare in immunocompetent patients. Objective The predictors of mortality and the differences between immunocompetent and immunocompromised patients with this disease remain unknown. Thus, the aim of this retrospective cohort study was to clarify these issues. Patients and methods We enrolled all patients who were histologically diagnosed with CMV colitis between April 2002 and December 2016 in the Linkou Chang Gung Memorial Hospital. Patients were divided into two groups: immunocompetent and immunocompromised, and the differences between them were analyzed to develop in-hospital mortality predictors. Results A total of 69 patients (42, immunocompetent; 27, immunocompromised) were enrolled. The most common symptoms were melena in the immunocompetent group and diarrhea in the immunocompromised group. The in-hospital mortality rate showed no statistically significant difference between the two groups (26.2% vs 25.9%, P=0.981). Early diagnosis was the only significant independent predictor of in-hospital mortality (odds ratio [OR] 1.075, 95% CI 1.005–1.149, P=0.035). The cutoff of diagnostic timing was 9 days from admission, derived from the receiver operating characteristic curve using the Youden index. Conclusion CMV colitis in immunocompetent patients is markedly more common and fatal than has generally been acknowledged. Being alert to different ways in which this disease can present itself will enable early diagnosis and significantly reduce mortality.