Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer: Updated Overall Survival Outcomes From Phase III PRODIGY.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The phase III PRODIGY study demonstrated that neoadjuvant chemotherapy with docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 chemotherapy (CSC) improved progression-free survival (PFS) compared with surgery followed by adjuvant S-1 (SC) for patients with resectable locally advanced gastric cancer (LAGC) with clinical T2-3N+ or T4Nany disease. The primary end point was PFS. Overall survival (OS) was the secondary end point. We herein report the long-term follow-up outcomes, including OS, from this trial. A total of 238 and 246 patients were randomly assigned to the CSC and SC arms, respectively, and were treated (full analysis set). As of the data cutoff (September 2022), the median follow-up duration of the surviving patients was 99.5 months. Compared with SC, CSC significantly increased the OS (adjusted hazard ratio [HR], 0.72; stratified log-rank P = .027) with an 8-year OS rate of 63.0% and 55.1% for the CSC and SC arms, respectively. CSC also significantly improved the PFS (HR, 0.70; stratified log-rank P = .016). In conclusion, neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, prolonged the OS of Asian patients with LAGC relative to patients treated with surgery and adjuvant S-1. It should be considered one of the standard treatment options for patients with LAGC in Asia.

Ethyl Formate Fumigation for Controlling Two Major Aphid Pests, Aphis spiraecola and Aphis gossypii, on Passion Fruit, from Cultivation to Post-Harvest Storage.

Tropical and subtropical crops are being increasingly cultivated in South Korea, leading to an increase in damage by exotic insect pests. Consequently, ethyl formate (EF) is currently being considered for quarantine and pre-shipment fumigation. In this study, we evaluated the effectiveness of EF fumigation for controlling Aphis spiraecola Patch and Aphis gossypii Glover, two representative quarantine pests on passion fruit ("Pink Bourbon") during greenhouse cultivation and post-harvest storage. The efficacy of EF against both aphids in terms of the lethal concentration causing 50% mortality (LCt50%) and LCt99% was 1.36-2.61 g h/m3 and 3.73-7.55 g h/m3 under greenhouse conditions (23 °C), and 1.37-2.02 g h/m3 and 3.80-14.59 g h/m3 post-harvest (5 °C), respectively. EF at 4 g/m3 for 4 h resulted in 100% mortality of A. spiraecola, which was more resistant to EF, without causing phytotoxic damage to the trees in a 340 m3 greenhouse. Post-harvest fruit fumigation at 10 g/m3 for 4 h in a mid-size (0.8 m3) fumigation chamber resulted in complete disinfection. Moreover, the EF level decreased below the EF threshold within 10 min after natural ventilation in the greenhouse. Therefore, our results suggest EF fumigation as an effective method for controlling A. spiraecola and A. gossypii.

Totally laparoscopic versus laparoscopy-assisted distal gastrectomy: the KLASS-07, a randomized controlled trial.

BACKGROUNDS: Strong evidence is lacking as no confirmatory randomized controlled trials (RCTs) have compared the efficacy of totally laparoscopic distal gastrectomy (TLDG) with laparoscopy-assisted distal gastrectomy (LADG). We performed an RCT to confirm if TLDG is different from LADG. METHODS: The KLASS-07 trial is a multicentre, open-label, parallel-group, phase III, RCT of 442 patients with clinical stage I gastric cancer. Patients were enrolled from 21 cancer care centers in South Korea between January 2018 and September 2020 and randomized to undergo TLDG or LADG using blocked randomization with a 1:1 allocation ratio, stratified by the participating investigators. Patients were treated through R0 resections by TLDG or LADG as the full analysis set of the KLASS-07 trial. The primary endpoint was morbidity within postoperative day 30, and the secondary endpoint was QoL for 1 year. This trial is registered at ClinicalTrials.gov (NCT NCT03393182). RESULTS: 442 patients were randomized (222 to TLDG, 220 to LADG), and 422 patients were included in the pure analysis (213 and 209, respectively). The overall complication rate did not differ between the two groups (TLDG vs. LADG: 12.2% vs. 17.2%). However, TLDG provided less postoperative ileus and pulmonary complications than LADG (0.9% vs. 5.7%, P= 0.006; and 0.5% vs. 4.3%, P= 0.035, respectively). The QoL was better after TLDG than after LADG regarding emotional functioning at 6 months, pain at 3 months, anxiety at 3 and 6 months, and body image at 3 and 6 months (all P< 0.05). However, these QoL differences were resolved at 1 year. CONCLUSIONS: The KLASS-07 trial confirmed that TLDG is not different from LADG in terms of postoperative complication but has advantages to reduce ileus and pulmonary complications. TLDG can be a good option to offer better QoL in terms of pain, body image, emotion, and anxiety at 3-6 months.

The Impact of Different Types of Complications on Long-Term Survival After Total Gastrectomy for Gastric Cancer.

PURPOSE: This study aimed to investigate the impact of different types of complications on long-term survival following total gastrectomy for gastric cancer. MATERIALS AND METHODS: A total of 926 patients who underwent total gastrectomy between 2008 and 2016 were included. Patients were divided into the morbidity and no-morbidity groups, and long-term survival was compared between the 2 groups. The prognostic impact of postoperative morbidity was assessed using a multivariate Cox proportional hazard model, which accounted for other prognostic factors. In the multivariate model, the effects of each complication on survival were analyzed. RESULTS: A total of 229 patients (24.7%) developed postoperative complications. Patients with postoperative morbidity showed significantly worse overall survival (OS) (5-year, 65.0% vs. 76.7%, P<0.001) and cancer-specific survival (CSS) (5-year, 74.2% vs. 83.1%, P=0.002) compared to those without morbidity. Multivariate analysis adjusting for other prognostic factors showed that postoperative morbidity remained an independent prognostic factor for OS (hazard ratio [HR], 1.442; 95% confidence interval [CI], 1.136-1.831) and CSS (HR, 1.463; 95% CI, 1.063-2.013). There was no significant difference in survival according to the severity of complications. The following complications showed a significant association with unfavorable long-term survival: ascites (HR, 1.868 for OS, HR, 2.052 for CSS), wound complications (HR, 2.653 for OS, HR, 2.847 for CSS), and pulmonary complications (HR, 2.031 for OS, HR, 1.915 for CSS). CONCLUSIONS: Postoperative morbidity adversely impacted survival following total gastrectomy for gastric cancer. Among the different types of complications, ascites, wound complications, and pulmonary complications exhibited significant associations with long-term survival.

Splenic hilar lymph node dissection enhances survival in Bormann type 4 gastric cancer.

Splenic hilar (no.10) lymph node dissection during total gastrectomy is no longer recommended for advanced proximal gastric cancer. However, the treatment efficacy of no.10 lymph node dissection in Borrmann type 4 tumors remains unclear. We enrolled 539 patients who underwent total gastrectomy for Borrmann type 4 tumors between 2006 and 2016 in four major institutions in Korea. We compared the long-term survival of the no.10 lymph node dissection (n = 309) and no-dissection groups (n = 230) using the propensity score (inverse probability of treatment weighting). The treatment effects of no.10 lymph node dissection were estimated in the weighted sample using the Cox proportional hazards regression model with a robust sandwich-type variance estimator. After inverse probability of treatment weighting, there were 540.4 patients in the no.10 lymph node dissection group and 532.7 in the no-dissection group. The two groups showed well-balanced baseline characteristics, including tumor node metastasis stage. The 5-year survival rates in the no.10 lymph node dissection and no-dissection groups were 45.7% and 38.6%, respectively (log-rank p = 0.036, hazard ratio 0.786, 95% confidence interval 0.630-0.982). Multivariate analysis revealed that no.10 lymph node dissection was an independent favorable prognostic factor (adjusted hazard ratio 0.747, 95% confidence interval 0.593-0.940) after adjusting for other prognostic factors. Sensitivity analyses in other inverse probability of treatment weighting models and the propensity score matching model showed similar results. Patients undergoing no.10 lymph node dissection showed improved survival compared to those without. No.10 lymph node dissection is recommended during total gastrectomy for patients with Borrmann type 4 gastric cancer.

Development of a Concurrent Treatment Technique of Ethyl Formate and Mixtures (Nitrogen, Phosphine) to Control Citrus Mealybug (Planococcus citri).

Currently, the fumigant ethyl formate (EF) is stored as a liquified gas in metal cylinders mixed with carbon dioxide (CO2), but this product type is expensive to manufacture, transport, and maintain in cylinders. To address these problems, we developed a new EF fumigation technique with a nitrogen (N2) carrier. In this report, the susceptibility of citrus mealybugs, one of the most resistant mealybugs to fumigants, to EF was assessed; the phytotoxicity of an EF + N2 concurrent treatment applied to banana fruit was examined to evaluate the efficacy compared to the current EF + CO2 product; and the increased efficacy with a phosphine (PH3) addition to EF + N2 was also assessed. Concurrent treatment of EF and N2 was performed at an LC50 concentration of EF. N2 was applied in seven doses from concentrations of 79% to 95%. The phytotoxicity of EF to bananas was assessed by applying EF at 35 mg/L with N2 at 79%, and the color, sugar content, and weight loss of bananas were measured for 14 days after treatment. The EF with N2 treatment resulted in more than 50% mortality at all growth stages of the mealybug, and there was no significant difference between the untreated and treated banana fruits. EF mixed with PH3 showed a higher efficacy than treatment with EF alone, but only a slight increase in efficacy was observed when the PH3 concentration increased. These results indicate that concurrent treatment with EF and N2 can be used to control mealybugs on banana fruits, and combined treatment with EF and PH3 can also enhance the efficacy against mealybugs.

Gene Regulatory Networks and Signaling Pathways in Palatogenesis and Cleft Palate: A Comprehensive Review.

Palatogenesis is a complex and intricate process involving the formation of the palate through various morphogenetic events highly dependent on the surrounding context. These events comprise outgrowth of palatal shelves from embryonic maxillary prominences, their elevation from a vertical to a horizontal position above the tongue, and their subsequent adhesion and fusion at the midline to separate oral and nasal cavities. Disruptions in any of these processes can result in cleft palate, a common congenital abnormality that significantly affects patient's quality of life, despite surgical intervention. Although many genes involved in palatogenesis have been identified through studies on genetically modified mice and human genetics, the precise roles of these genes and their products in signaling networks that regulate palatogenesis remain elusive. Recent investigations have revealed that palatal shelf growth, patterning, adhesion, and fusion are intricately regulated by numerous transcription factors and signaling pathways, including Sonic hedgehog (Shh), bone morphogenetic protein (Bmp), fibroblast growth factor (Fgf), transforming growth factor beta (Tgf-ß), Wnt signaling, and others. These studies have also identified a significant number of genes that are essential for palate development. Integrated information from these studies offers novel insights into gene regulatory networks and dynamic cellular processes underlying palatal shelf elevation, contact, and fusion, deepening our understanding of palatogenesis, and facilitating the development of more efficacious treatments for cleft palate.

Increased miR-200c levels disrupt palatal fusion by affecting apoptosis, cell proliferation, and cell migration.

The mammalian palate separates the oral and nasal cavities, facilitating proper feeding, respiration, and speech. Palatal shelves, composed of neural crest-derived mesenchyme and surrounding epithelium, are a pair of maxillary prominences contributing to this structure. Palatogenesis reaches completion upon the fusion of the midline epithelial seam (MES) following contact between medial edge epithelium (MEE) cells in the palatal shelves. This process entails numerous cellular and molecular occurrences, including apoptosis, cell proliferation, cell migration, and epithelial-mesenchymal transition (EMT). MicroRNAs (miRs) are small, endogenous, non-coding RNAs derived from double-stranded hairpin precursors that regulate gene expression by binding to target mRNA sequences. Although miR-200c is a positive regulator of E-cadherin, its role in palatogenesis remains unclear. This study aims to explore the role of miR-200c in palate development. Before contact with palatal shelves, mir-200c was expressed in the MEE along with E-cadherin. After palatal shelf contact, miR-200c was present in the palatal epithelial lining and epithelial islands surrounding the fusion region but absent in the mesenchyme. The function of miR-200c was investigated by utilizing a lentiviral vector to facilitate overexpression. Ectopic expression of miR-200c resulted in E-cadherin upregulation, impaired dissolution of the MES, and reduced cell migration for palatal fusion. The findings imply that miR-200c is essential in palatal fusion as it governs E-cadherin expression, cell death, and cell migration, acting as a non-coding RNA. This study may contribute to clarifying the underlying molecular mechanisms in palate formation and provides insights into potential gene therapies for cleft palate.

FOXA2 and STAT5A regulate oncogenic activity of KIF5B-RET fusion.

KIF5B-RET gene rearrangement occurs in ~1% of lung adenocarcinomas. Recently, targeted agents that inhibit RET phosphorylation have been evaluated in several clinical studies; however, little is known about the role of this gene fusion in driving lung cancer. Immunohistochemistry was used to evaluate the expression of the FOXA2 protein in tumor tissues of patients with lung adenocarcinoma. KIF5B-RET fusion cells proliferated in a cohesive form and grew tightly packed with variable-sized colonies. The expression of RET and its downstream signaling molecules, including p-BRAF, p-ERK, and p-AKT, increased. In KIF5B-RET fusion cells, the intracellular expression of p-ERK was higher in the cytoplasm than in the nucleus. Two transcription factors, STAT5A and FOXA2, exhibiting significantly different expressions at the mRNA level, were finally selected. p-STAT5A was highly expressed in the nucleus and cytoplasm, whereas the expression of the FOXA2 protein was lower; however, it was much higher in the nucleus than in the cytoplasm. Compared with the expression of FOXA2 in the RET rearrangement-wild NSCLC (45.0%), high expression (3+) were observed in most RET rearrangement NSCLCs (94.4%). Meanwhile, KIF5B-RET fusion cells began to increase belatedly from day 7 and only doubled on day 9 in 2D cell culture. However, tumors in mice injected with KIF5B-RET fusion cells began to rapidly increase from day 26. In cell cycle analyses, the KIF5B-RET fusion cells in G0/G1 were increased on day 4 (50.3 ± 2.6%) compared with the empty cells (39.3 ± 5.2%; P = 0.096). Cyclin D1 and E2 expressions were reduced, whereas CDK2 expression slightly increased. pRb and p21 expression was diminished compared with the empty cells, TGF-ß1 mRNA was highly expressed, and the proteins were accumulated mostly in the nucleus. Twist mRNA and protein expression was increased, whereas Snail mRNA and protein expression was decreased. Particularly, in KIF5B-RET fusion cells treated with FOXA2 siRNA, the expression of TGF-ß 1 mRNA was remarkably reduced but Twist1 and Snail mRNA were increased. Our data suggest that cell proliferation and invasiveness in KIF5B-RET fusion cells are regulated by the upregulation of STAT5A and FOXA2 through the continuous activation of multiple RET downstream signal cascades, including the ERK and AKT signaling pathways. We found that TGF-ß1 mRNA, where significant increments were observed in KIF5B-RET fusion cells, is regulated at the transcriptional level by FOXA2.

Supraclavicular cephalic vein draining into the internal jugular vein via the external jugular vein.

PURPOSE: The aim of this study is to report rare anatomical variations of the cephalic vein (CV) in a 77-year-old Korean male cadaver. CASE REPORT: On the right upper arm, the CV located lateral to the deltopectoral groove passed anterior to the clavicle at the lateral one-fourth of the clavicle without anastomosis to the axillary vein. It was connected to the transverse cervical and suprascapular veins by two communicating branches in the middle of its course at the neck, and opened into the external jugular vein at its junction with the internal jugular veins. The suprascapular and anterior jugular veins were flowed into the subclavian vein at the jugulo-subclavian venous confluence, and were connected by a short communicating branch. CONCLUSION: Detailed knowledge of the variations in the CV is expected to be helpful in decreasing unpredicted injuries and possible postoperative complications when invasive venous access is performed through the CV.

The impact of the 30-day postoperative complications on the quality of life following gastrectomy for gastric carcinoma: A prospective study.

BACKGROUND: The effect of postoperative complications on long-term quality of life (QoL) is controversial in abdominal surgery. This study aimed to investigate the impact of 30-day postoperative complications on long-term QoL after gastrectomy. METHOD: This is a longitudinal cohort study that enrolled 908 patients undergoing gastrectomy for gastric cancer between 2016 and 2017. QoL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) generic cancer (QLQ C-30) and gastric module (STO-22) preoperatively and at 1, 6, 12, and 24 months postoperatively. Patients were divided into the morbidity (30-day postoperative complications) and no-morbidity groups, and the postoperative QoL change was compared using a linear mixed model. RESULTS: The mean age was 62.5 ± 12.0 years. Subtotal and total gastrectomy was performed in 763 (84.0%) and 145 (16.0%) patients, respectively. There were 189 (20.8%) patients developing postoperative complications. The morbidity group showed worse scores in several functions and symptoms of QoL at the baseline. However, the two groups showed no significant difference in postoperative changes in most functions and symptoms of the QLQ C-30 and STO-22 (Pgroup × time > 0.05). The recovery of global health (Pgroup × time < 0.001) and anxiety (Pgroup × time = 0.008) was slightly better in the morbidity group. The subgroup analysis of patients developing major abdominal complications showed similar results. CONCLUSION: The morbidity group showed worse QoL in several functions and symptoms at the baseline. However, postoperative complications had little influence on QoL change following gastrectomy for gastric cancer.

Exploring ideal operative time for best outcomes in gastric cancer surgery: A multi-institutional study based on KLASS-07 database.

Objective: While a rushed operation can omit essential procedures, prolonged operative time results in higher morbidity. Nevertheless, the optimal operative time range remains uncertain. This study aimed to estimate the ideal operative time range and evaluate its applicability in laparoscopic cancer surgery. Methods: A prospectively collected multicenter database of 397 patients who underwent laparoscopic distal gastrectomy were retrospectively reviewed. The ideal operative time range was statistically calculated by separately analyzing the operative time of uneventful surgeries. Finally, intraoperative and postoperative outcomes were compared among the shorter, ideal, and longer operative time groups. Results: The statistically calculated ideal operative time was 135.4-165.4 min. The longer operative time (LOT) group had a lower rate of uneventful, perfect surgery than the ideal or shorter operative time (IOT/SOT) group (2.8% vs. 8.8% and 2.2% vs. 13.4%, all P<0.05). Longer operative time increased bleeding, postoperative morbidities, and delayed diet and discharge (all P<0.05). Particularly, an uneventful, perfect surgery could not be achieved when the operative time exceeded 240 min. Regardless of ideal time range, SOT group achieved the highest percentage of uneventful surgery (13.4%), which was possible by surgeon's ability to retrieve a higher number of lymph nodes and perform ≥150 gastrectomies annually. Conclusions: Operative time longer than the ideal time range (especially ≥240 min) should be avoided. If the essential operative procedure were faithfully conducted without compromising oncological safety, an operative time shorter than the ideal range leaded to a better prognosis. Efforts to minimize operative time should be attempted with sufficient surgical experience.

Differential RNA expression of immune-related genes and tumor cell proximity from intratumoral M1 macrophages in acral lentiginous melanomas treated with PD-1 blockade.

Immune checkpoint inhibitors (ICIs) offer improved survival for patients with advanced malignant melanomas. However, only a subset of these patients exhibit an objective response rate of 10-40 % with ICIs. We aimed to ascertain the effects of RNA signatures and the spatial distribution of immune cells on the treatment outcomes of patients with malignant melanomas undergoing ICI therapy. Clinical data were retrospectively collected from ICI-treated patients with malignant melanoma; RNA expression profiles were examined via next-generation sequencing, whereas the composition, density, and spatial distribution of immune cells were determined via multiplex immunohistochemistry. Patients with poor and good responses to ICIs showed significant differences in mRNA expression profiles. Different spatial distributions of T-cells, macrophages, and NK cells as well as RNA signatures of immune-related genes were found to be closely related to therapeutic outcomes in ICI-treated patients with malignant melanomas. The spatial distributions of PD-1+ T-cells and activated M1 macrophages showed a significant correlation with favorable responses to ICIs. Our findings highlight the clinical relevance of the spatial proximity of immune cell subsets in the treatment outcomes of metastatic malignant melanoma.

Synergistic Effect of Cold Treatment Combined with Ethyl Formate Fumigation against Drosophila suzukii (Diptera: Drosophilidae).

Drosophila suzukii is a quarantine pest that is rapidly spreading in berries. This study evaluated the synergistic effect of combination treatment with ethyl formate (EF) and cold temperature for D. suzukii control on imported grapes. A higher insecticidal effect was observed at 1 °C than at 5 °C at all developmental stages, and the pupal stage showed the strongest tolerance to cold temperature. After EF fumigation alone, eggs showed the highest tolerance at 216.67 mg·h/L (LCT99 value), and adults showed the highest susceptibility at <27.24 mg·h/L. Among the combination treatment methods, cold temperature after fumigation resulted in the best synergistic effect. The effect of this combination was significant, with 23.3% higher mortality for eggs, 22.4% for larvae, and 23.4% for pupae than observed with EF fumigation alone. Furthermore, the period of complete D. suzukii control in the 12 L desiccator was shorter in the combination treatment group at the LCT80 value than at the LCT50 value of the egg stage. EF showed a very high sorption rate (24%) after 4 h of exposure at a grape loading ratio of 15% in a 0.65 m3 fumigation chamber. As the grape loading ratio for combination treatment decreased, D. suzukii mortality increased, but when EF was administered at the LCT80 value, there was little difference in the mortalities of the eggs and larvae but not the pupae. All D. suzukii developmental stages were completely controlled within 7 days after combination treatment, and phytotoxicity was not observed in grapes. These results suggest that the combination of cold-temperature treatment and EF fumigation could be used for D. suzukii control.

Impact of the Deep Neuromuscular Block on Oncologic Quality of Laparoscopic Surgery in Obese Gastric Cancer Patients: A Randomized Clinical Trial.

BACKGROUND: Obesity can hinder laparoscopic procedures and impede oncological safety during laparoscopic cancer surgery. Deep neuromuscular block (NMB) reportedly improves laparoscopic surgical conditions, but its oncological benefits are unclear. We aimed to evaluate whether deep NMB improves the oncologic quality of laparoscopic cancer surgery in obese patients. STUDY DESIGN: We conducted a double-blinded, parallel-group, randomized, phase 3 trial at 9 institutions in Korea. Clinical stage I and II gastric cancer patients with a BMI at or above 25 kg m -2 were eligible and randomized 1:1 ratio to the deep or moderate NMB groups, with continuous infusion of rocuronium (0.5-1.0 and 0.1-0.5 mg kg -1 h -1, respectively). The primary endpoint was the number of retrieved lymph nodes (LNs). The secondary endpoints included the surgeon's surgical rating score (SRS) and interrupted events. RESULTS: Between August 2017 and July 2020, 196 patients were enrolled. Fifteen patients were excluded, and 181 patients were finally included in the study. There was no significant difference in the number of retrieved LNs between the deep (N = 88) and moderate NMB groups (N = 93; 44.6 ± 17.5 vs 41.5 ± 16.9, p = 0.239). However, deep NMB enabled retrieving more LNs in patients with a BMI at or above 28 kg/m2 than moderate NMB (49.2 ± 18.6 vs 39.2 ± 13.3, p = 0.026). Interrupted events during surgery were lower in the deep NMB group than in the moderate NMB group (21.6% vs 36.6%; p = 0.034). The SRS was not influenced by NMB depth. CONCLUSION: Deep NMB provides potential oncologic benefits by retrieving more LNs in patients with BMI at or above 28 kg/m2 during laparoscopic gastrectomy.

Radiological criteria for selecting candidates for neoadjuvant chemotherapy for gastric cancer: an exploratory analysis from the PRODIGY study.

BACKGROUND: In this exploratory analysis from the PRODIGY study, we aimed to define the radiological criteria to identify patients with gastric cancer who may derive maximal clinical benefit from neoadjuvant chemotherapy. PATIENTS AND METHODS: There were 246 patients allocated to receive surgery followed by adjuvant S-1 (SC group) and 238 allocated to receive neoadjuvant chemotherapy (CSC group). As the PRODIGY's radiological method of lymph node (LN) evaluation considers short diameter and morphology (the size and morphology method), a method considering only short diameter was also employed. In the SC group, the correlation between radiologic and pathologic findings was analyzed. The hazard ratio (HR) for the progression-free survival (PFS) of the CSC group was analyzed in subgroups with different cT/N stages. RESULTS: cT4 disease showed a sensitivity of 85.6% for detecting pT4 and had a low proportion of pathologic stage (pStage) I disease (4.5%). Among the criteria determined by different cT/N stages by each method of LN positivity, those involving cT4Nany or cT4N + by both methods had a minimal proportion of pStage I disease (≤ 5%), while cT4Nany by both methods and cT4N + by the size and morphology method exhibited ≥ 75.9% sensitivity for detecting pStage III disease. The relative risk reduction in PFS of the CSC group was greatest in patients meeting the cT4Nany criterion defined by both methods (HR 0.67, 95% confidence interval 0.48-0.93). CONCLUSIONS: The cT4Nany criterion, regardless of the radiological method used for LN evaluation, may help select patients with resectable gastric cancer for neoadjuvant chemotherapy.

Prospective multicentre randomised clinical trial comparing survival rates, quality of life and nutritional status between advanced gastric cancer patients with different follow-up intensities: study protocol for the STOFOLUP trial.

INTRODUCTION: Patients who underwent curative gastrectomy for gastric cancer are regularly followed-up for the early detection of recurrence and postoperative symptom management. However, there is a lack of evidence with regard to proper surveillance intervals and diagnostic tools. This study aims to evaluate whether frequent surveillance tests have a survival benefit or improve the quality of life in patients who underwent curative resection for advanced gastric cancer. METHODS AND ANALYSIS: The STOFOLUP trial is an investigator-initiated, parallel-assigned, multicentre randomised controlled trial involving 16 hospitals in the Republic of Korea. Patients (n=886) diagnosed with pathological stage II or III gastric adenocarcinoma will be randomised to either the 3-month or the 6-month group at a 1:1 ratio, stratified by trial site and tumour stage. Patients allocated to the 3-month group will undergo an abdominal CT scan every 3 months postoperatively and those allocated to the 6-month group will undergo CT every 6 months. The primary endpoint is 3-year overall survival and the secondary endpoints are quality of life, as assessed using KOrean QUality of life in Stomach cancer patients Study group-40, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and the stomach cancer-specific module (STO22), and nutritional outcomes. Other survival data including data concerning 3-year disease-free survival, recurrence-free survival, gastric cancer-specific survival and postrecurrence survival will also be estimated. The first patient was enrolled on July 2021 and active patient enrolment is currently underway. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of eight of the participating hospitals (NCC 2021-0085, KBSMC2021-01-059, SMC 2021-01-140, KC21OEDE0082, 4-2021-0281, AJIRB-MED-INT-20-608, 2021-0515 and H-2102-093-1198). This study will be disseminated through peer-reviewed publications, national or international conferences. TRIAL REGISTRATION NUMBER: NCT04740346.

Efficacy and Phytotoxicity Assessment of Successive Application of Methyl Bromide and Cold Treatment on Export Strawberry Fruits.

Recently, spotted wing Drosophila, Drosophila suzukii, is globally prevalent and causes agricultural losses to many fruits. To export Korean strawberry, methyl bromide fumigation is required to remove D. suzukii infestations, but Korean strawberry farmers are worried about fruit damage because methyl bromide can cause phytotoxicity on fresh commodities. In this report, we assessed the efficacy and phytotoxicity of single and successive application of methyl bromide and cold treatment on an export variety of strawberry to reduce fruit damage. The currently recommended dosage of methyl bromide, 40 g/m3 for 3 h at 18 °C, was enough to control all stages of D. suzukii without phytotoxicity. A dosage of 20 g/m3 of methyl bromide treatment for 3 h, followed by 1 d of cold (0 °C) treatment, showed 100% mortality in all growth stages of D. suzukii without fruit damage. Successive application of methyl bromide and cold treatment shows potential as a method of decreasing phytotoxicity and reducing the use of methyl bromide for environmental considerations.

Ethyl Formate as a Methyl Bromide Alternative for Fumigation of Citrus: Efficacy, Fruit Quality, and Workplace Safety.

Ethyl formate (EF) was evaluated as a potential alternative to methyl bromide (MB) for phytosanitary treatment of imported citrus fruit in the Republic of Korea. Planococcus citri (Risso) (Hemiptera: Pseudococcidae), a mealybug with known tolerance against EF and MB, was used as a representative pest to test efficacy of the two fumigants against eggs. In nine commercial-scale refrigerated container (67.5 m3) trials using imported orange, lemon and grapefruit, EF applied at the currently approved dose for citrus (70 g·m-3 at 5°C for 4 h, developed for Aspidiotus excisus Green (Hemiptera: Diaspididae), a species less EF tolerant than P. citri) resulted in 76.9-98.3% mortality of P. citri eggs. The EF treatment did not affect the sugar content or the color of peel and pulp of the treated fruit. When oranges were treated according to the current MB (64 g·m-3 at >5°C for 2 h) or EF treatment guidelines, the concentration of fumigant around the fruit fluctuated between 9.4 and 185.1 ppm for EF and 9.5-203.0 ppm for MB during the 72-h post-fumigation processes (venting [0-2 h], transportation to storage [2-24 h], and storage periods [24-72 h]) with both EF and MB maintained between 10 and 100 ppm during the storage period. Considering the efficacy of EF, its apparent lack of phytotoxicity, and its more manageable threshold limit value for humans (100 ppm EF compared to 1 ppm MB for an 8-h time weighted average exposure), our results suggest that EF may be a promising alternative to MB for the phytosanitary treatment of imported citrus in Korea.

Prognostic Value of the Anatomic Region of Metastatic Lymph Nodes in the Current TNM Staging of Gastric Cancer.

PURPOSE: The numeric N stage has replaced the topographic N stage in the current tumor node metastasis (TNM) staging in gastric carcinoma. However, the usefulness of the topographic N stage in the current TNM staging system is uncertain. We aimed to investigate the prognostic value of the topographic N stage in the current TNM staging system. MATERIALS AND METHODS: We reviewed the data of 3350 patients with gastric cancer who underwent curative gastrectomy. The anatomic regions of the metastatic lymph nodes (MLNs) were classified into 2 groups: perigastric and extra-perigastric. The prognostic value of the anatomic region was analyzed using a multivariate prognostic model with adjustments for the TNM stage. RESULTS: In patients with lymph node metastasis, extra-perigastric metastasis demonstrated significantly worse survival than perigastric metastasis alone (5-year survival rate, 39.6% vs. 73.1%, respectively, P<0.001). Extra-perigastric metastasis demonstrated significantly worse survival within the same pN stage; the multivariate analysis indicated that extra-perigastric metastasis was an independent poor prognostic factor (hazard ratio=1.33; 95% confidence interval=1.01-1.75). The anatomic region of the MLNs improved the goodness-of-fit (likelihood ratio statistics, 4.57; P=0.033) of the prognostic model using the TNM stage. CONCLUSIONS: The anatomic region of MLNs has an independent prognostic value in the numeric N stage in the current TNM staging of gastric carcinoma.