Background
Totally laparoscopic gastrectomy (TLG), which involves a complete intracorporeal gastric transection and the creation of an anastomosis, has been gradually adopted. However, a potential ...limitation of intracorporeal transection is the lack of tactile feedback, and whether this limitation influences oncological outcomes is unclear. The aim of this study is to evaluate the short- and long-term oncological safety of TLG using endoscopy-guided intracorporeal gastric transection for clinical stage (cStage) I gastric cancer.
Methods
A total of 1875 consecutive patients who underwent laparoscopic gastrectomy for cStage I gastric cancer between January 2007 and March 2015 were enrolled in this study. Marking clips were preoperatively placed and a transection line was determined by perceiving it tactually in laparoscopy-assisted gastrectomy (LAG) or endoscopically in TLG. After propensity score matching, 1366 patients (683 each for LAG and TLG groups) were selected to primarily test the non-inferiority of TLG to that of LAG for relapse-free survival (RFS).
Results
In the propensity-matched population, the 5-year RFS rates of the LAG and TLG groups were 94.3% (95% confidence interval (CI) 92.2–95.8%), and 95.6% (95% CI 93.8–96.9%), respectively. The hazard ratio (TLG/LAG) was 0.77 (95% CI 0.48–1.24,
P
for non-inferiority < 0.01). There were no significant differences in the recurrence profiles. The incidence of the remnant of marking clips or tumor tissue did not differ (LAG: 1.0% vs. TLG: 1.9%,
P
= 0.177).
Conclusions
TLG using preoperative markings and intraoperative endoscopic guidance provides cStage I gastric cancer patients with comparable oncological outcomes to the conventional method.
Background
The 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system provided a specific ‘ypTNM’ stage grouping for patients with esophageal cancer.
Objective
This study ...aimed to evaluate the clinical utility of the AJCC 8th edition ypTNM stage grouping for patients with esophageal squamous cell carcinoma (ESCC).
Methods
We enrolled 152 patients with ESCC who underwent surgery after neoadjuvant cisplatin plus 5-fluorouracil (CF) therapy between June 2005 and December 2011. ypStage was evaluated according to the AJCC 7th and 8th editions. Predictive performance for disease-specific survival (DSS) and overall survival (OS) was compared between both editions. The prognostic significance of ypTNM stage grouping was evaluated using univariate and multivariate analyses.
Results
Revision of the AJCC 7th edition to the 8th edition was associated with a change in ypStage in 96 patients (63.2%). The AJCC 8th edition revealed a better predictive performance than the 7th edition in terms of DSS (Akaike’s information criterion AIC 499 vs. 513; Bayesian information criterion BIC 505 versus 519; concordance index C-index 0.725 versus 0.679) and OS (AIC 662 vs. 674; BIC 669 vs. 681; C-index 0.662 vs. 0.622). On univariate and multivariate analyses, ypStage in the 8th edition was an independent prognostic factor for both DSS and OS.
Conclusions
ypTNM stage grouping in the AJCC 8th edition provided a better predictive performance for DSS and OS than that in the 7th edition. ypStage in the 8th edition was the most reliable prognostic factor for ESCC patients who underwent surgery after neoadjuvant CF therapy.
Background
Esophagojejunostomy is one of the most important surgical procedures in total gastrectomy. In the past, esophagojejunostomy was exclusively performed using a circular stapler in open total ...gastrectomy (OTG). With the increasing frequency of its use in laparoscopic gastrectomy, esophagojejunostomy using a linear stapler has been performed in OTG. However, it is still unclear whether the use of a linear stapler in esophagojejunostomy following OTG has any advantages compared with the conventional use of a circular stapler.
Methods
A total of 298 patients who underwent OTG for gastric cancer between 2014 and 2019 were enrolled in this study. Patients were categorized into circular and linear groups (group C and group L) according to the stapler type used for the esophagojejunostomy. After propensity score matching, 136 patients (68 each in groups C and L) were selected to compare the surgical outcomes including incidence of esophagojejunostomy-related complications and postoperative nutritional status.
Results
The median operation time was significantly longer in group L than in group C (261.5 min versus 325.5 min;
P
< 0.001). The incidence of esophagojejunostomy-related complications did not differ between the two groups (5.9% versus 2.9%;
P
= 0.68); however, no anastomotic stricture and bleeding occurred in group L. Bodyweight loss was significantly lower in group L than in group C at 6 months (15.9% versus 12.6%;
P
= 0.007) after surgery.
Conclusions
Esophagojejunostomy using a linear stapler following OTG is equally safe and possibly advantageous in anastomotic stricture, bleeding and nutritional status compared with the use of a circular stapler.
The combination of paclitaxel + ramucirumab is a standard second-line treatment in patients with advanced gastric cancer. This therapy has been associated with increased median overall survival and ...progression-free survival compared with those with paclitaxel monotherapy. We evaluated the cost-effectiveness of paclitaxel + ramucirumab combination therapy in patients with advanced gastric cancer, from the perspective of health care payers in Japan.
We constructed a Markov model to compare, over a time horizon of 3 years, the costs and effectiveness of the combination of paclitaxel + ramucirumab and paclitaxel alone as second-line therapies for advanced gastric cancer in Japan. Health outcomes were measured in life-years (LYs) and quality-adjusted (QA) LYs gained. Costs were calculated using year-2016 Japanese yen (¥1 = US $17.79) according to the social insurance reimbursement schedule and drug tariff of the fee-for-service system in Japan. Model robustness was addressed through 1-way and probabilistic sensitivity analyses. The costs and QALYs were discounted at a rate of 2% per year. The willingness-to-pay threshold was set at the World Health Organization's criterion of ¥12 million, because no consensus exists regarding the threshold for acceptable cost per QALY ratios in Japan's health policy.
Paclitaxel + ramucirumab combination therapy was estimated to provide an additional 0.09 QALYs (0.10 LYs) at a cost of ¥3,870,077, resulting in an incremental cost-effectiveness ratio of ¥43,010,248/QALY. The incremental cost-effectiveness ratio for the combination therapy was >¥12 million/QALY in all of the 1-way and probabilistic sensitivity analyses.
Adding ramucirumab to a regimen of paclitaxel in the second-line treatment of advanced gastric cancer is expected to provide a minimal incremental benefit at a high incremental cost per QALY. Based on our findings, adjustments in the price of ramucirumab, as well as improves in other clinical parameters such as survival time and adverse event in advanced gastric cancer therapy, are needed.
Background
The situation of positive resection margins (PRMs) varies notably between Western and Asian countries. In the West, PRMs are associated with advanced disease and R1, whereas in Asia, PRMs ...are also considered in early disease because stomach preservation was recently prioritized. Furthermore, PRMs are usually resected to obtain R0. However, the oncological impact of PRMs and additional resection remains unclear. The aim of this study is to evaluate the oncological impact of PRMs in laparoscopic gastrectomy (LG) for clinical stage (cStage) I gastric cancer.
Methods
A total of 2121 patients who underwent LG for cStage I gastric cancer between 2007 and 2015 were enrolled. Survival outcomes were compared between patients with PRMs (group P) and those without (group N). Furthermore, prognostic factors were analyzed using multivariate analysis.
Results
Twenty-seven patients (1.3%) had PRMs. Patients in group P had upper and more advanced disease, and the 5-year relapse-free survival (RFS) rate was worse in group P compared with group N (76.3% vs. 95.1%,
P
= 0.003). The 5-year RFS of patients with pT2 or deeper (pT2–4) disease in group P was significantly worse than that of patients in group N (66.7% vs. 89.5%,
P
= 0.030) although that of patients with pT1 was not. Likelihood ratio tests showed that there was a significant interaction between pT status and PRM (
P
= 0.005).
Conclusion
PRM in cStage I gastric cancer is associated with advanced upper disease. It remains an independent prognostic factor in pT2–4 disease even after an additional resection to obtain R0.
Comprehensive genomic sequencing (CGS) enables us to detect numerous genetic alterations in a single assay. We aimed to identify molecular markers for predicting prognosis and conversion surgery in ...Stage IV colorectal cancer (CRC) using CGS. One-hundred eleven patients with Stage IV CRC who underwent primary tumor resection were analyzed. We retrospectively investigated genetic alterations using CGS of a 415-gene panel. Clinicopathological variables and genetic alterations were analyzed to identify independent prognostic factors of overall survival (OS). Forty-five of 111 patients had R0 resection; of these, 11 patients underwent conversion surgery. Univariate and multivariate analyses identified histopathological grade 3, R0 resection, BRAF V600E mutation, and SRC mutation as independent prognostic factors for OS (P = 0.041, P = 0.013, P = 0.005, and P = 0.023, respectively). BRAF V600E and SRC mutations were mutually exclusive, and SRC mutation was significantly associated with left-sided tumor and liver metastasis compared to BRAF V600E mutation (P = 0.016 and P = 0.025, respectively). Eleven of the 74 initially unresectable patients underwent conversion surgery for R0 resection, yet none harbored BRAF V600E or SRC mutations. BRAF V600E and SRC mutations are important molecular markers which can predict prognosis and conversion surgery in Stage IV CRC.
Background Evaluation of human epidermal growth factor receptor 2 (HER2) overexpression caused by erb-b2 receptor tyrosine kinase 2 (ERBB2) amplification (AMP) by immunohistochemistry (IHC) and ...fluorescence in situ hybridization (FISH) is essential for treating unresectable metastatic gastric cancer (GC). A targeted tumour sequencing test enables comprehensive assessment of alterations in cancer-related genes, including ERBB2. This study aimed to evaluate the concordance between the targeted tumour sequencing test and IHC/FISH for detecting HER2-positive GC and to clarify the significance of ERBB2 AMP and concomitant genetic alterations in HER2 downstream pathways (DPs) in anti-HER2 therapy for unresectable metastatic GC patients. Methods ERBB2 copy number alteration (CNA) was examined via a targeted tumour sequencing test in 152 formalin-fixed paraffin-embedded (FFPE) GC tissues. ERBB2 CNA was compared to HER2 status evaluated by IHC/FISH in FFPE block sections, which were identical to those subjected to the targeted tumour sequencing test. Treatment outcomes of anti-HER2 therapy in 11 patients with unresectable metastatic GC was evaluated. Results ERBB2 AMP (greater than or equal to 2.5-fold change) was detected by the targeted tumour sequencing test in 15 patients (9.9%), and HER2 positivity (IHC 3 + or IHC 2+/FISH positive) was detected in 21 patients (13.8%). The overall percent agreement, positive percent agreement, negative percent agreement and Cohen's kappa between ERBB2 CNA and HER2 status were 94.7%, 66.7%, 99.2% and 0.75, respectively. Progression-free survival for trastuzumab therapy in patients with ERBB2 AMP was significantly longer than that in patients with no ERBB2 AMP detected by the targeted tumour sequencing test (median 14 months vs. 4 months, P = 0.007). Treatment response to trastuzumab therapy was reduced in patients with ERBB2 AMP and concomitant CNAs of genes in HER2 DPs. One patient with ERBB2 AMP and concomitant CNAs of genes in HER2 DPs achieved a durable response to trastuzumab deruxtecan as fourth-line therapy. Conclusions A targeted tumour sequencing test is a reliable modality for identifying HER2-positive GC. ERBB2 AMP and concomitant genetic alterations detected through the targeted tumour sequencing test are potential indicators of treatment response to trastuzumab therapy. The targeted tumour sequencing test has emerged as a plausible candidate for companion diagnostics to determine indications for anti-HER2 therapy in the era of precision medicine for GC. Keywords: Gastric cancer, HER2, ERBB2, Targeted tumour sequencing test, Trastuzumab
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lymphatic spread is the main mode of progression of esophageal squamous cell carcinoma (ESCC). Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid mediator, which produced by sphingosine ...kinase 1 (SphK1) activated by phosphorylation. The SphK1-S1P axis has a crucial role in lymphangiogenesis. However, the significance of phospho-SphK1 (pSphK1) in the progression of ESCC has not been fully investigated.
We evaluated pSphK1 expression in 92 surgically resected tumor tissues of ESCC by the immunohistochemistry. Fifty-nine (64%) patients with moderate or strong expression and 33 (36%) with negative or weak expression were classified in the pSphK1-high and pSphK1-low groups, respectively.
Higher pathological N category (pN) was more frequently observed in the pSphK1-high group (P < 0.01). The median number of lymph node metastasis (pSphK1-high: 2 versus pSphK1-low: 0; P < 0.01), the proportion of patients with lymphatic invasion (69% versus 18%; P < 0.01) and that with intramural metastasis (27% versus 3%; P < 0.01) were significantly higher in the pSphK1-high group. The presence of lymphatic invasion (odds ratio OR 5.63; P < 0.01) and pN1–3 (OR 3.26; P = 0.04) were independently associated with high pSphK1 expression. The 5-y overall survival rate of the pSphK1-high group was significantly lower than that of the pSphK1-low group (50.8% versus 67.3%; P = 0.01). High pSphK1 expression was not identified as a significant independent prognostic factor.
We provide the first evidence of the association between high expression of pSphK1 and both lymphatic spread and patient outcomes in ESCC.
Background A combination of assays for the presence of serum anti-Helicobacter pylori IgG antibody (HPA) and serum pepsinogen (PG) concentrations can be used to screen for gastric cancer risk. In ...Japan, this "ABC method" is considered an effective means of stratifying gastric cancer risk. This study aimed to ascertain its costeffectiveness for assessing gastric cancer risk. Methods A Markov model was constructed to compare the cost-effectiveness of two strategies for gastric cancer-risk screening over a 30-year period: the ABC method, which uses a combination of assessing the presence of and measuring serum PG concentrations and scheduling endoscopies accordingly, and annual endoscopic screening. Clinical and epidemiological data on variables in the model were obtained from published reports. Analyses were made from the perspective of the Japanese health care payer. Results According to base-case analysis, the ABC method cost less than annual endoscopie screening (64,489 vs. 64,074 USD) and saved more lives (18.16 vs. 18.30 quality-adjusted life years). One-way analyses confirmed the robustness of the cost-effectiveness results. The probability that the ABC method is cost-effective in Japanese individuals aged 50 years was 0.997. Conclusions A combination of HPA and serum PG assays, plus scheduling endoscopy accordingly, is a cost-effective method of screening for gastric cancer risk in Japan.
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