Short-term outcomes of a multicentre randomized clinical trial comparing laparoscopic pylorus-preserving gastrectomy with laparoscopic distal gastrectomy for gastric cancer (the KLASS-04 trial).

BACKGROUND: There remain concerns about the safety and functional benefit of laparoscopic pylorus-preserving gastrectomy (LPPG) compared with laparoscopic distal gastrectomy (LDG). This study evaluated short-term outcomes of a randomized clinical trial (RCT) comparing LPPG with LDG for gastric cancer. METHODS: The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS)-04 trial was an investigator-initiated, open-label, parallel-assigned, superiority, multicentre RCT in Korea. Patients with cT1N0M0 cancer located in the middle third of the stomach at least 5 cm from the pylorus were randomized to undergo LPPG or LDG. Participants, care givers and those assessing the outcomes were not blinded to group assignment. Outcomes were 30-day postoperative morbidity rate and death at 90 days. RESULTS: Some 256 patients from nine institutions were randomized (LPPG 129 patients, LDG 127 patients) between July 2015 and July 2017 and outcomes for 253 patients were analysed. Postoperative complications within 30 days were seen in 19.3 and 15.5 per cent in the LPPG and LDG groups respectively (P = 0·419). Postoperative pyloric stenosis was observed in nine (7.2 per cent) and two (1·5 per cent) patients in the LPPG and LDG groups (P = 0·026) respectively. In multivariable analysis higher BMI was a risk factor for postoperative complications (odds ratio 1·17, 95 per cent c.i. 1·04 to 1·32; P = 0·011). Death at 90 days was zero in both groups. CONCLUSION: Postoperative complications and mortality was comparable in patients undergoing LPPG and LDG. Registration number: NCT02595086 (http://www.clinicaltrials.gov).

Underestimated caregiver burden by cancer patients and its association with quality of life, depression and anxiety among caregivers.

This study examined how patients with cancer estimate caregiver burden (CB) and the association between their underestimation of CB and their caregivers' self-ratings of their quality of life (CQOLC-K; Korean version of the Caregiver Quality of Life Index-Cancer), depression and anxiety (Korean version of the Hospital Anxiety and Depression Scale). Participants consisted of 990 patient-caregiver dyads recruited from a nationwide cross-sectional survey conducted in South Korea. Medical baseline data were retrieved from the hospital information systems of the participating centres. The patients with cancer who underestimated CB ranged from 18.62% (for physical CB) to 23.33% (for social CB). They had less advanced cancer, a lower income, were the caregiver's spouse, reported higher levels of family avoidance of communication about cancer, and had female caregivers. The patients' underestimation of CB was significantly related to lower CQoL and higher levels of caregiver depression and anxiety. The current study provides empirical evidence for the link between the underestimation of CB by patients with cancer and compromised caregiving experiences of cancer caregivers. Open family communication about cancer was discussed as one of several practical strategies for decreasing patients' underestimation of CB.

Reliability and validity of the Atopic Dermatitis Symptom Score (ADSS).

BACKGROUND: We have developed the Atopic Dermatitis Symptom Score (ADSS) by which patients or parents can easily assess and record AD symptoms on a daily basis in a smartphone application. The aim of this study was to evaluate the reliability and validity of the ADSS. METHODS: We enrolled 307 children and adolescents with AD. Parents or caregivers were asked to record daily symptoms of the patients (itching, sleep disturbance, erythema, dryness, oozing, and edema) using a scale of 0-4. Statistical analyses consisted of the test-retest reliability, concurrent validity, minimal clinically important difference (MCID), responsiveness, floor or ceiling effects, and screening accuracy. Receiver-operating characteristic analyses were conducted to evaluate the ADSS cutoff point for predicting severe AD (SCORing AD [SCORAD] ≥40). RESULTS: Test-retest reliability between daytime and night-time ADSS was good (intraclass correlation coefficient, 0.82 [95% CI: 0.70-0.90]). An increase in ADSS was significantly associated with an increase in SCORAD (r = 0.64, P < .0001) (concurrent validity). The MCID was 4.1 points for the ADSS. There was a significant association between changes in ADSS and SCORAD (r = 0.56, P < .0001), indicating good responsiveness. At the optimal ADSS cutoff value of 7.0, sensitivity, specificity, and positive and negative predictive values were 88.4%, 78.6%, 21.1%, and 99.1%, respectively (screening accuracy). CONCLUSIONS: The ADSS can be a useful tool for self-assessment of skin symptoms in children with AD.

Validation of two prognostic models for recurrence and survival after radical gastrectomy for gastric cancer.

BACKGROUND: Prognostic models from Korea and Italy have been developed that predict overall survival and cancer recurrence respectively after radical gastrectomy for gastric cancer. The aim of this study was to validate the two models in independent patient cohorts, and to evaluate which factors may explain differences in prognosis between Korean and Italian patients with gastric cancer. METHODS: Patients who underwent radical gastrectomy for gastric cancer between January 2000 and December 2004 at Seoul National University Hospital and at eight centres in Italy were included. Discrimination of the models was tested with receiver operating characteristic (ROC) curves and calculation of area under the curve (AUC). Calibration was evaluated by plotting actual survival probability against predicted survival probability for the Korean nomogram, and actual against predicted risk of recurrence for the Italian score. RESULTS: Some 2867 and 940 patients from Korea and Italy respectively were included. The Korean nomogram achieved good discrimination in the Italian cohort (AUC 0·80, 95 per cent c.i. 0·77 to 0·83), and the Italian model performed well in the Korean cohort (AUC 0·87, 0·85 to 0·89). The Korean nomogram also achieved good calibration, but this was not seen for the Italian model. Multivariable analyses confirmed that Italian ethnicity was an independent risk factor for cancer recurrence (odds ratio (OR) 1·72, 1·31 to 2·25; P < 0·001), but not for overall survival (OR 1·20, 0·95 to 1·53; P = 0·130). CONCLUSION: Both prognostic models performed fairly well in independent patient cohorts. Differences in recurrence rates of gastric cancer may be partially explained by ethnicity.

Who may benefit from robotic gastrectomy?: A subgroup analysis of multicenter prospective comparative study data on robotic versus laparoscopic gastrectomy.

AIMS: Robotic gastrectomy for gastric cancer has been proven to be a feasible and safe minimally invasive procedure. However, our previous multicenter prospective study indicated that robotic gastrectomy is not superior to laparoscopic gastrectomy. This study aimed to identify which subgroups of patients would benefit from robotic gastrectomy rather than from conventional laparoscopic gastrectomy. METHODS: A prospective multicenter comparative study comparing laparoscopic and robotic gastrectomy was previously conducted. We divided the patients into subgroups according to obesity, type of gastrectomy performed, and extent of lymph node dissection. Surgical outcomes were compared between the robotic and laparoscopic groups in each subgroup. RESULTS: A total of 434 patients were enrolled into the robotic (n = 223) and laparoscopic (n = 211) surgery groups. According to obesity and gastrectomy type, there was no difference in the estimated blood loss (EBL), number of retrieved lymph nodes, complication rate, open conversion rate, and the length of hospital stay between the robotic and laparoscopic groups. According to the extent of lymph node dissection, the robotic group showed a significantly lower EBL than did the laparoscopic group after D2 dissection (P = 0.021), while there was no difference in EBL in patients that did not undergo D2 dissection (P = 0.365). CONCLUSION: Patients with gastric cancer undergoing D2 lymph node dissection can benefit from less blood loss when a robotic surgery system is used.

Association between information provision and decisional conflict in cancer patients.

BACKGROUND: In this study, we aimed to identify demographic and clinical variables that correlate with perceived information provision among cancer patients and determine the association of information provision with decisional conflict (DC). PATIENTS AND METHODS: We enrolled a total of 625 patients with cancer from two Korean hospitals in 2012. We used the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire (QLQ-INFO26) to assess patients' perception of the information received from their doctors and the Decisional Conflict Scale (DCS) to assess DC. To identify predictive sociodemographic and clinical variables for adequate information provision, backward selective logistic regression analyses were conducted. In addition, adjusted multivariate logistic regression analyses were carried out to identify clinically meaningful differences of perceived level of information subscales associated with high DC. RESULTS: More than half of patients with cancer showed insufficient satisfaction with medical information about disease (56%), treatment (73%), other services (83%), and global score (80%). In multiple logistic regression analyses, lower income and education, female, unmarried status, type of cancer with good prognosis, and early stage of treatment process were associated with patients' perception of inadequate information provision. In addition, Information about the medical tests with high DCS values clarity [adjusted odds ratio (aOR), 0.54; 95% confidence interval (CI) 0.30-0.97] and support (aOR, 0.53; 95% CI 0.33-0.85) showed negative significance. For inadequate information perception about treatments and other services, all 5 DCS scales (uncertainty, informed, values clarity, support, and effective decision) were negatively related. Global score of inadequate information provision also showed negative association with high DCS effective decision (aOR, 0.43; 95% CI 0.26-0.71) and DCS uncertainty (aOR, 0.46; 95% CI 0.27-0.77). CONCLUSION: This study found that inadequate levels of perceived information correlated with several demographic and clinical characteristics. In addition, sufficient perceived information levels may be related to low levels of DC.

Effect of neoadjuvant chemotherapy on postoperative morbidity and mortality in patients with locally advanced gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy has been shown to improve the rate of complete (R0) resection and downstaging in patients with localized gastric cancer. There are few reports, however, regarding its impact on postoperative morbidity and mortality. The aims of this study were to analyse complication and mortality rates after neoadjuvant chemotherapy using a modified regimen of folinic acid, 5-fluorouracil and oxaliplatin (mFOLFOX6) for locally advanced gastric cancer (AGC), compared with rates in patients who underwent surgery without neoadjuvant chemotherapy. METHODS: Data were collected from patients with AGC enrolled in a phase II trial of four cycles of neoadjuvant mFOLFOX6 followed by surgery, between January 2005 and June 2008 at two of three institutions, and compared with those from a cohort of patients with AGC who underwent surgery alone at one of the institutions in 2006. RESULTS: Among 51 patients who received neoadjuvant chemotherapy, there were no deaths and a morbidity rate of 24 per cent after surgery. Comparison of 48 patients in one institution who received neoadjuvant chemotherapy with 92 patients who had surgery alone in the same institution showed no increase in postoperative morbidity (23 versus 29 per cent; P = 0·417). Combined resection was the only risk factor for postoperative morbidity after neoadjuvant chemotherapy. CONCLUSION: Neoadjuvant chemotherapy with mFOLFOX is a safe treatment for patients with localized AGC, and does not increase postoperative morbidity or mortality.

Low albumin-to-globulin ratio associated with cancer incidence and mortality in generally healthy adults.

BACKGROUND: Chronic inflammation is known to be one of the main steps in carcinogenesis. Identification of those with chronic inflammation may help identify subjects at risk of cancer. Previous studies have reported low albumin-to-globulin ratio (AGR) to be associated with increased cancer mortality in cancer patients, but there has been no study based on healthy populations. PATIENTS AND METHODS: Our retrospective cohort study involved 26 974 generally healthy adults aged 30 or older who visited Seoul National University Hospital Health Promotion Center for self-referred health checkup. National medical service claims data were used to determine cancer incidence, and Korean death registry data was used to determine mortality. Median follow-up time for survival was 5.9 years (interquartile range 4.1 years). RESULTS: Compared with subjects with AGR ≥ 1.5, subjects with 1.1 > AGR ≥ 1.0 and 1.0 > AGR showed adjusted hazard ratio (aHR) 2.69 (95% confidence interval, CI, 1.54-4.72) and aHR 6.71 (95% CI 3.56-12.66) for all-cause mortality, aHR 2.95 (95% CI 1.42-6.11) and aHR 4.38 (95% CI 1.57-12.25) for cancer mortality, and aHR 2.07 (95% CI 1.28-3.36) and aHR 3.99 (95% CI 2.10-7.58) for cancer incidence, respectively. When cancer incidence events after 2 years from baseline were separately analyzed, subjects with 1.1 > AGR ≥ 1.0 and 1.0 > AGR were associated with aHR 1.88 (95% CI 1.01-3.48) and aHR 2.55 (95% CI 1.03-7.11) for cancer incidence, respectively. Cancer events were increased in all types of cancer, but especially in liver and hematologic malignancies. CONCLUSIONS: Low AGR is a risk factor for cancer incidence and mortality, both short- and long terms, in a generally healthy screened population. The results of this study need to be replicated in larger studies, along with the determination of the sensitivity and other diagnostic values of low AGR.

Attitudinal concordance toward uptake and disclosure of genetic testing for cancer susceptibility in patient-family member dyads.

Decisions for cancer susceptibility genetic testing (CSGT) uptake and dissemination of results occur within the family context. A national survey was performed with 990 patient-family member dyads (participation rate:76.2%), with paired questionnaires examining attitudes toward CSGT uptake and disclosure of results in response to a hypothetical scenario in which a reliable CSGT was available for the specific cancer a patient was being treated. While most patients and family members responded they would uptake or recommend CSGT if available, concordance between the dyads was poor for both patient's testing (agreement rate 77.5%, weighted κ=0.09) and first-degree relatives' testing(agreement rate 78.0%, weighted κ=0.09). Most patients (93.2%) and family members (92.9%) indicated that patients should disclose positive CSGT results to family members, with dyadic agreement of 89.1% (κ=0.15). However, there were substantial disagreement regarding when disclosure should take place, who should make the disclosure (the patient or the health care professionals), and to whom the results should be disclosed. Patients and family members may hold different attitudes toward CSGT uptake of and disclosure of results within the family. Our findings reinforce the need for a family system approach to incorporate perspectives of patients as well as their family members.

PPP1R1B-STARD3 chimeric fusion transcript in human gastric cancer promotes tumorigenesis through activation of PI3K/AKT signaling.

Fusion genes act as potent oncogenes, resulting from chromosomal rearrangements or abnormal transcription in many human cancers. Although multiple gastric cancer genomes have been sequenced, the driving recurrent gene fusions have not been well characterized. Here, we used paired-end transcriptome sequencing to identify novel gene fusions in 18 human gastric cancer cell lines and 18 pairs of primary human gastric cancer tissues and their adjacent normal tissues. Multiple samples revealed expression of PPP1R1B-STARD3 fusion transcript. The presence of PPP1R1B-STARD3 correlated with elevated levels of PPP1R1B mRNA. PPP1R1B-STARD3 fusion transcript was detected in 21.3% of primary human gastric cancers but not in adjacent matched normal gastric tissues. Based on reverse transcription PCR analysis of DNA, unlike other fusions described in gastric cancer, the PPP1R1B-STARD3 appears to be generated by RNA processing without chromosomal rearrangement. Overexpression of PPP1R1B-STARD3 in MKN-28 significantly increased cell proliferation and colony formation. This increased proliferation was mediated by activation of phosphatidylinositol-3-kinase (PI3K)/AKT signaling. Furthermore, expression of PPP1R1B-STARD3 fusion transcript enhanced the tumor growth of MKN-28 cells in athymic nude mice. These findings show that PPP1R1B-STARD3 fusion transcript has a key role in subsets of gastric cancers through the activation of PI3K/AKT signaling.

Standard of practice on laparoscopic gastric cancer surgery in Korea and Japan: experts' survey.

INTRODUCTION: As the laparoscopic approach has become a popular gastric cancer treatment in Korea and Japan, the need for sharing current practices of surgeons who are experienced in laparoscopic gastric cancer surgery has increased. METHODS: We sent a questionnaire on laparoscopic instruments, image documentation, preoperative evaluation, surgical indication, operative methods, and postoperative management to laparoscopic experts in Korea and Japan, and 24 (14 from Korea and 10 from Japan) responded. RESULTS: Endoscopic ultrasound and preoperative endoscopy-guided clipping are routinely employed, respectively, by 14 (58%) and 20 (83%) of the surgeons. Surgeons perform laparoscopy-assisted distal gastrectomy (LADG) based on varying indications. Five surgeons (21%) performed LADG only for cases of stage T1 cancer, 15 (63%) performed LADG on patients with less than T2 lesions, and 4 (17%) performed LADG on patients with less than T3 lesions. With regard to postoperative anastomosis, 18 surgeons (75%) preferred extracorporeal anastomosis and 6 (25%) preferred intracorporeal anastomosis. The mean postoperative hospital stay was 6.5 days in Korea and 10.1 days in Japan (P < 0.001). CONCLUSION: This survey can help to inform the current practice of laparoscopic gastric cancer surgery in Korea and Japan, where laparoscopic surgery is frequently performed.

Stomach hanging technique using gauze during laparoscopic gastrectomy.

INTRODUCTION: Lifting the stomach using laparoscopic instruments during laparoscopic gastrectomy is difficult and increases the risk of crushing the tumor. In this study, we present a stomach hanging technique using gauze pieces that reduces the risk to the tumor. MATERIALS AND SURGICAL TECHNIQUE: After a partial omentectomy and the opening of the lesser sac, the antrum was wrapped with a 15-20-cm gauze piece. Next, a straight needle with 2-0 monofilament suture material pierced the abdominal cavity through the right subcostal area on the mid-clavicular line, and the gauze was then sutured twice in a figure of eight manner. The needle was removed percutaneously through the right middle quadrant of the abdomen. Another suture was applied to wrap the left side of the stomach. The stomach was easily lifted and positioned by pulling the four suture strings in different directions. After the suture materials were fastened to the abdominal wall using hemostat forceps, the surgical field was sufficiently exposed, facilitating lymph node dissection on the superior surface of the pancreas. This method freed the assistant from holding the stomach and enabled this individual to assist the operation in other ways. DISCUSSION: This stomach lifting technique using gauze is a good option for exposing the surgical field, enables the assistant to perform other tasks, and reduces the risk of crushing the tumor during laparoscopic gastrectomy.

MET in gastric carcinomas: comparison between protein expression and gene copy number and impact on clinical outcome.

BACKGROUND: The aim of this study was to compare gene copy number (GCN) and protein expression of MET and to evaluate their prognostic roles in gastric carcinomas. METHODS: MET protein expression and gene amplification (GA) status were determined by immunohistochemistry (IHC) and silver in-situ hybridisation (SISH), respectively, in a large series of gastric carcinoma. RESULTS: Protein overexpression was observed in 104 of 438 cases, with IHC 2+ in 94 and IHC 3+ in 10, and high polysomy of chromosome 7 and GA were found in 61 and 13 of 381, respectively. Direct comparison revealed a significant correlation between high level of protein expression and increased GCN. All cases with GA showed protein overexpression. Furthermore, all with IHC 3+ showed GA except 1, even which could be categorised as GA according to the ASCO/CAP guideline for human epidermal growth factor receptor 2 assessment. IHC 3+ and GA were significantly associated with poor prognosis. CONCLUSION: MET IHC reflects well on GA, and therefore, it could be a primary screening test for patient selection for anti-MET therapy if GA is a major determinant of drug responsiveness. Also, the prognostic role of MET indicates that anti-MET therapy is a very promising modality in adjuvant treatment for gastric cancer.

Serum biomarker panels for the diagnosis of gastric adenocarcinoma.

BACKGROUND: Currently, serum biomarkers, which are sufficiently sensitive and specific for early detection and risk classification of gastric adenocarcinoma do not exist. Therefore, this study identified a panel of serum biomarkers for the diagnosis of gastric adenocarcinoma. METHODS: A 29-plex array platform with 29 biomarkers, consisting of 11 proteins discovered through proteomics and 18 previously known to be cancer-associated, was constructed. A test/training set consisting of 120 gastric adenocarcinoma and 120 control samples were examined. After 13 proteins were selected as candidate biomarkers, multivariate classification analyses were used to identify algorithms for diagnostic biomarker combinations. These algorithms were independently validated using a set of 95 gastric adenocarcinoma and 51 control samples. RESULTS: Epidermal growth factor receptor (EGFR), pro-apolipoprotein A1 (proApoA1), apolipoprotein A1, transthyretin (TTR), regulated upon activation, normally T-expressed and presumably secreted (RANTES), D-dimer, vitronectin (VN), interleukin-6, α-2 macroglobulin, C-reactive protein and plasminogen activator inhibitor-1 were selected as classifiers in the two algorithms. These algorithms differentiated between the majority of gastric adenocarcinoma and control serum samples in the training/test set with high accuracy (>88%). These algorithms also accurately classified in the validation set (>85%). CONCLUSION: Two panels of combinatorial biomarkers, including EGFR, TTR, RANTES, and VN, are developed, which are less invasive method for the diagnosis of gastric adenocarcinoma. They could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy.

Validation of limited lymphadenectomy for lower-third gastric cancer based on depth of tumour invasion.

BACKGROUND: This study aimed to determine the appropriate extent of lymph node (LN) dissection in gastric cancer by analysing LN metastasis patterns from prospectively collected topographical data on nodal status at Seoul National University Hospital, Korea. METHODS: The metastasis rate for each LN station was analysed according to the depth of tumour invasion in patients with primary lower-third gastric cancer who underwent curative gastrectomy. The Maruyama Index of unresected disease (MI) was calculated using the WinEstimate(®) program with simulation of various extents of LN dissection. RESULTS: LN metastasis in mucosal cancer was rare; 2·6 per cent of patients had a MI of more than 5 with simulation of D1 plus station 7 dissection, whereas 0·9 per cent had a MI above 5 with D1 plus stations 7 and 8a. In submucosal cancer, 3·3 per cent of tumours metastasized to level 2 LN stations outside the range of D1 plus stations 7, 8a and 9. The proportion of patients with a MI above 5 was 9·0 per cent with D1 plus stations 7, 8a and 9 dissection. The nodal metastasis rate was higher at level 1 and 2 for muscularis propria or deeper cancers. CONCLUSION: D1 dissection plus stations 7 and 8a for mucosal cancer, and D2 dissection for cancers of the muscularis propria or deeper seems appropriate. For submucosal cancer, an expanded dissection to the D2 level should be considered to ensure complete removal of metastatic LNs.

Changes in clinicopathological features and survival after gastrectomy for gastric cancer over a 20-year period.

BACKGROUND: The pattern of gastric cancer in the Western world is changing, with an increased proportion of tumours in the upper stomach. The aim of this study was to investigate changes in clinicopathological features and survival of patients with resected gastric cancer at a single institution, in an area of high incidence in the Far East. METHODS: Clinical features and pathological findings were compared in patients with gastric cancer who underwent gastrectomy at Seoul National University Hospital during four consecutive periods (1986-1990, 1991-1995, 1996-2000 and 2001-2006). RESULTS: There were 12 026 patients. The mean age increased from 53·4 years in the first period to 57·4 years in the last (P < 0·001). The proportion of patients aged 70 years or older also increased, reaching 16·1 per cent in the final period. Upper-third cancer increased from 5·3 per cent in the first period to 14·0 per cent in the fourth (P < 0·001). Early gastric cancer (pathological T1) increased continuously over the four time intervals, from 24·8 to 48·9 per cent (P < 0·001). The overall 5-year survival rate increased from 64·0 per cent in the first period to 73·2 per cent at the end (P < 0·001), and this survival improvement was apparent in patients aged 40 years or more. CONCLUSION: The mean age of patients with gastric cancer has increased during the past 20 years. The proportion of early gastric cancer and overall survival have gradually increased, especially in patients aged over 40 years.

Safety of extended endoscopic mucosal resection and endoscopic submucosal dissection following the Japanese Gastric Cancer Association treatment guidelines.

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are widely performed. Indications for these procedures have been extended in Korea and Japan. The aim was to evaluate whether these extended indications are safe. METHODS: All patients who had surgery for early gastric cancer at Seoul National University Bundang Hospital between May 2003 and December 2007 were identified from a prospective database. Lymph node status was examined in patients who met extended indications for EMR and had undergone surgical resection. RESULTS: Of patients with mucosal cancers, 129 met extended indications for EMR or ESD and three (2.3 per cent) had lymph node metastasis. Of the 52 submucosal cancers meeting extended indications for EMR or ESD, two (4 per cent) had lymph node metastasis. Differentiated mucosal cancers without ulcer formation did not have lymph node metastasis, irrespective of size. CONCLUSION: Extending the indications for EMR and ESD according to the Japanese Gastric Cancer Association guidelines carries an increased risk of lymph node metastasis. For cancers meeting these criteria, treatment by gastric resection with lymph node dissection should still be considered. A well differentiated mucosal cancer of any size without ulceration may be considered as an extended indication for EMR or ESD.

Biomarker analysis in stage III-IV (M0) gastric cancer patients who received curative surgery followed by adjuvant 5-fluorouracil and cisplatin chemotherapy: epidermal growth factor receptor (EGFR) associated with favourable survival.

The aim of this study was to analyse the impact of epidermal growth factor receptor (EGFR), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), aurora kinase (ARK) A/B, and excision repair cross-complementing gene 1 (ERCC1) on the efficacy of adjuvant chemotherapy with 5-fluorouracil and cisplatin (FP) after curative gastric resection. Normal and cancer tissue were separately obtained from gastrectomy samples of 153 patients with AJCC stage III-IV (M0) who subsequently treated with adjuvant FP chemotherapy. TS, DPD, TP, ERCC1, and ARK proteins were measured by immunohistochemistry (IHC). EGFR expression was investigated using a standardized IHC with the EGFR PharmDx assay. Amplification of EGFR gene was analysed using fluorescent in situ hybridisation (FISH). In multivariate analysis, stage, ratio of positive to removed lymph nodes, and EGFR expression were significant prognostic factors for overall survival. Patients with higher EGFR expression had better overall survival than those with lower expression (relative risk: 0.475 (95% confidence interval, 0.282-0.791, P=0.005). Low EGFR expression might be a predictive marker for relapse in curative resected stage III-IV (M0) gastric cancer patients who received adjuvant FP chemotherapy.