Erratum: Korean Practice Guidelines for Gastric Cancer 2022: An Evidence-based, Multidisciplinary Approach.

This corrects the article on p. 3 in vol. 23, PMID: 36750993.

Korean Practice Guidelines for Gastric Cancer 2022: An Evidence-based, Multidisciplinary Approach.

Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.

Korean practice guidelines for gastric cancer 2022: an evidence-based, multidisciplinary approach

Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.

Prognostic roles of leptin-signaling proteins, PD-L1, and tumor-infiltrating lymphocytes in surgically-resected biliary tract cancers.

BACKGROUND: Biliary tract cancers are rare, with a poor patient prognosis. Leptin and programmed death-ligand 1 (PD-L1) influence CD8+ and forkhead box P3 (FOXP3)+ lymphocytes, and thus, cancer cell growth. We aimed to define the prognostic implications of these variables and the clinicopathological features of biliary tract cancers. METHODS: Immunohistochemistry for leptin signaling-related proteins (leptin, leptin receptor, pSTAT3, extracellular-regulated kinase, mammalian target of rapamycin), PD-L1, CD8, and FOXP3 and in situ hybridization for Epstein-Barr virus-encoded small RNAs were performed in 147 cases of surgically-resected biliary tract cancers. RESULTS: Immune cell PD-L1-positivity, tumor size < 3 cm, adjuvant chemotherapy, no recurrence, and early-stage tumors were correlated with better 5-year survival in the tumoral PD-L1(-) and leptin(-) subgroups, and extrahepatic cholangiocarcinoma through multivariate analysis (all p < 0.05). Immune cell PD-L1 and adjuvant chemotherapy lost its prognostic significance in the tumoral PD-L1+ and leptin+ subgroups. CONCLUSIONS: The prognostic implication of the variables may depend upon tumoral protein expression and the anatomical site. Immune cell PD-L1-positivity and the administration of adjuvant chemotherapy may indicate the favorable survival of patients with surgically-resected biliary tract cancers, specifically, in the tumoral PD-L1(-) or tumor leptin(-) subgroups and extrahepatic cholangiocarcinoma. PD-L1- or leptin-targeted therapy combined with conventional chemotherapy may benefit the tumoral PD-L1+ or leptin+ subgroups.

Closure of Petersen's Space Lowers the Incidence of Gastric Food Retention after Distal Gastrectomy with Gastrojejunostomy in Gastric Cancer Patients.

PURPOSE: Delayed gastric emptying usually manifests as gastric food retention. This study aimed to evaluate the incidence of gastric food retention after distal gastrectomy with gastrojejunostomy in gastric cancer patients and identify the risk factors for its development. MATERIALS AND METHODS: We retrospectively enrolled 245 patients who underwent distal gastrectomy with gastrojejunostomy for gastric cancer at Boramae Medical Center between March 2017 and December 2019. We analyzed the presence of gastric food residue via computed tomography (CT) scans at 3 and 12 months postoperatively and analyzed the risk factors that may influence the development of gastric food retention. RESULTS: CT scans were performed on 235 patients at 3 months and on 217 patients at 12 months postoperatively. In the group that received closure of Petersen's space, the incidence of gastric food retention was significantly low as per the 3- and 12-month postoperative follow-up CT scans (P=0.028 and 0.003, respectively). In addition, hypertension was related to gastric food retention as per the 12-month postoperative follow-up CT scans (P=0.011). No other factors were related to the development of gastric food retention. In the multivariate analysis, non-closure of Petersen's space (hazard ratio [HR], 2.54; 95% confidence interval [CI], 1.20-5.38; P=0.010) was the only significant risk factor for gastric food retention at 3 months postoperatively, while non-closure of Petersen's space (HR, 2.81; 95% CI, 1.40-5.64; P=0.004) and hypertension (HR, 2.30; 95% CI, 1.14-4.63; P=0.020) were both significant risk factors for gastric food retention at 12 months postoperatively. CONCLUSIONS: Closure of Petersen's space has an effect on decrease the incidence of gastric food retention after distal gastrectomy with gastrojejunostomy in gastric cancer patients.

Impact of the Interval between Previous Endoscopic Exam and Diagnosis on the Mortality and Treatment Modality of Undifferentiated-Type Gastric Cancer.

PURPOSE: The impact of the interval between previous endoscopy and diagnosis on the treatment modality or mortality of undifferentiated (UD)-type gastric cancer is unclear. This study aimed to investigate the effect of endoscopic screening interval on the stage, cancer-related mortality, and treatment methods of UD-type gastric cancer. MATERIALS AND METHODS: We reviewed the medical records of newly diagnosed patients with UD gastric cancer in 2013, in whom the interval between previous endoscopy and diagnosis could be determined. The patients were classified into different groups according to the period from the previous endoscopy to diagnosis (<12 months, 12-23 months, 24-35 months, ≥36 months, and no history of endoscopy), and the outcomes were compared between the groups. In addition, patients who underwent endoscopic and surgical treatment were reclassified based on the final treatment results. RESULTS: The number of enrolled patients was 440, with males representing 64.1% of the study population; 11.8% of the participants reported that they had undergone endoscopy for the first time in their cancer diagnosis. The percentage of stage I cancer at diagnosis significantly decreased as the interval from the previous endoscopy to diagnosis increased (65.4%, 63.2%, 64.2%, 45.9%, and 35.2% for intervals of <12 months, 12-23 months, 24-35 months, ≥36 months, and no previous endoscopy, respectively, P<0.01). Cancer-related mortality was significantly lower for a 3-year interval of endoscopy (P<0.001). CONCLUSIONS: A 3-year interval of endoscopic screening reduces gastric-cancer-related mortality, particularly in cases of UD histology.

Interleukin 10 level in the peritoneal cavity is a prognostic marker for peritoneal recurrence of T4 colorectal cancer.

Peritoneal recurrence (PR) is a major relapse pattern of colorectal cancer (CRC). We investigated whether peritoneal immune cytokines can predict PR. Cytokine concentrations of peritoneal fluid from CRC patients were measured. Patients were grouped according to peritoneal cancer burden (PCB): no tumor cells (≤ pT3), microscopic tumor cells (pT4), or gross tumors (M1c). Cytokine concentrations were compared among the three groups and the associations of those in pT4 patients with and without postoperative PR were assessed. Of the ten cytokines assayed, IL6, IL10, and TGFB1 increased with progression of PCB. Among these, IL10 was a marker of PR in pT4 (N = 61) patients based on ROC curve (p = 0.004). The IL10 cut-off value (14 pg/mL) divided patients into groups with a low (7%, 2 of 29 patients) or high (45%, 16 of 32 patients) 5-year PR (p < 0.001). Multivariable analysis identified high IL10 levels as the independent risk factor for PR. Separation of patients into training and test sets to evaluate the performance of IL10 cut-off model validated this cytokine as a risk factor for PR. Peritoneal IL10 is a prognostic marker of PR in pT4 CRC. Further research is necessary to identify immune response of intraperitoneal CRC growth.

Development and Validation of a Symptom-Focused Quality of Life Questionnaire (KOQUSS-40) for Gastric Cancer Patients after Gastrectomy.

PURPOSE: Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. MATERIALS AND METHODS: Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity. RESULTS: The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. CONCLUSION: The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.

Are the elderly patient's changes in the health-related quality of life one year after gastrectomy for stomach cancer different from those in young patients?

PURPOSE: Gastrectomy for elderly patients can significantly deteriorate the health-related quality of life (HRQoL). There was no report comparing HRQoL of elderly patients with young patients after gastrectomy for gastric cancer. This study assessed the differences in the changes of HRQoL at one year after gastrectomy according to age. METHODS: From May 2014 to Feb 2016, we prospectively enrolled patients undergoing gastrectomy for gastric cancer. They completed the European Organization for Research and Treatment of Cancer and gastric questionnaires preoperatively and at postoperative 1, 3, 6, 9, and 12 months. RESULTS: We included 57 elderly patients (≥70 years old) and 74 younger patients. The elderly had similar demographic, surgical, and pathological characteristics with young patients except that elderly had more comorbidity, laparoscopic gastrectomies, and lesser postoperative chemotherapy. One month after gastrectomy, the score of global health status/quality of life, physical, role, and social functioning were significantly impaired in elderly patients. Among them, physical and role functioning were more impaired than those of young patients. The scores of physical functioning, role functioning, cognitive functioning, and social functioning were not fully recovered till 1 year after surgery. There was a significant age group difference in the changes in physical function over the 1-year follow-up. CONCLUSION: Elderly patients' global health status/quality of life and social functioning significantly decreased at postoperative 1 month and recovered by 6 months after gastrectomy. There was a significant age-specific difference in physical functioning throughout the 1-year follow-up. Surgeons need to pay more attention to recovery of the elderly patients' HRQoL after gastrectomy.

Comparing the surgical outcomes of dual-port laparoscopic distal gastrectomy and three-port laparoscopic distal gastrectomy for gastric cancer.

PURPOSE: Many studies have demonstrated that single-incision or reduced-port laparoscopic distal gastrectomy is a feasible method compared to conventional laparoscopic distal gastrectomy. Using rigid-type laparoscope and right-side approach, we could perform dual-port laparoscopic distal gastrectomy (DPLDG) for gastric cancer. This study aimed to compare the surgical outcomes of DPLDG to those of 3-port laparoscopic distal gastrectomy (TPLDG). METHODS: From March 2017 to December 2019, this retrospective study included 218 patients with gastric cancer who underwent DPLDG (106 patients) or TPLDG (112 patients) at SMG-SNU Boramae Medical Center. Surgical outcomes were compared between 2 operation methods. RESULTS: Operation time was similar between DPLDG and TPLDG (158.9 ± 33.4 minutes vs. 154.0 ± 31.1 min, P = 0.787). The number of retrieved lymph nodes was similar between the 2 groups (35.3 ± 14.6 vs. 37.0 ± 13.5, P = 0.415). The complication rate in DPLDG and TPLDG groups was 10.4% and 8.9%, respectively (P = 0.894). The time to first flatus, time to first diet, and postoperative hospital stay were similar between the 2 groups. There were no reoperation or mortality cases. The cost of trocars was 359.9 US dollars (USD) in DPLDG and 291-391.4 USD in TPLDG. CONCLUSION: The surgical outcomes of DPLDG and TPLDG did not differ. Regarding fewer incisions, DPLDG can be an alternative option for TPLDG.

Comparison of surgical outcomes among different methods of esophagojejunostomy in laparoscopic total gastrectomy for clinical stage I proximal gastric cancer: results of a single-arm multicenter phase II clinical trial in Korea, KLASS 03.

BACKGROUND: Laparoscopic distal gastrectomy for early gastric cancer has been widely accepted, but laparoscopic total gastrectomy has still not gained popularity because of technical difficulty and unsolved safety issue. We conducted a single-arm multicenter phase II clinical trial to evaluate the safety and the feasibility of laparoscopic total gastrectomy for clinical stage I proximal gastric cancer in terms of postoperative morbidity and mortality in Korea. The secondary endpoint of this trial was comparison of surgical outcomes among the groups that received different methods of esophagojejunostomy (EJ). METHODS: The 160 patients of the full analysis set group were divided into three groups according to the method of EJ, the extracorporeal circular stapling group (EC; n = 45), the intracorporeal circular stapling group (IC; n = 64), and the intracorporeal linear stapling group (IL; n = 51). The clinicopathologic characteristics and the surgical outcomes were compared among these three groups. RESULTS: There were no significant differences in the early complication rates among the three groups (26.7% vs. 18.8% vs. 17.6%, EC vs. IC vs. IL; p = 0.516). The length of mini-laparotomy incision was significantly longer in the EC group than in the IC or IL group. The anastomosis time was significantly shorter in the EC group than in the IL group. The time to first flatus was significantly shorter in the IL group than in the EC group. The long-term complication rate was not significantly different among the three groups (4.4% vs. 12.7% vs. 7.8%; EC vs. IC vs. IL; p = 0.359), however, the long-term incidence of EJ stenosis in IC group (10.9%) was significantly higher than in EC (0%) and IL (2.0%) groups (p = 0.020). CONCLUSIONS: The extracorporeal circular stapling and the intracorporeal linear stapling were safe and feasible in laparoscopic total gastrectomy, however, intracorporeal circular stapling increased EJ stenosis.

Efficacy and Safety of Ursodeoxycholic Acid for the Prevention of Gallstone Formation After Gastrectomy in Patients With Gastric Cancer: The PEGASUS-D Randomized Clinical Trial.

Importance: The incidence of gallstones has been reported to increase after gastrectomy. However, few studies have been conducted on the prevention of gallstone formation in patients who have undergone gastrectomy. Objective: To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) in preventing gallstone formation after gastrectomy in patients with gastric cancer. Design, Setting, and Participants: The PEGASUS-D study (Efficacy and Safety of DWJ1319 in the Prevention of Gallstone Formation after Gastrectomy in Patient with Gastric Cancer: A Multicenter, Randomized, Double-blind, Placebo-controlled Study) was a randomized, double-blind, placebo-controlled clinical trial conducted at 12 institutions in the Republic of Korea. Adults (aged ≥19 years) with a diagnosis of gastric cancer who underwent total, distal, or proximal gastrectomy were enrolled between May 26, 2015, and January 9, 2017; follow-up ended January 8, 2018. Efficacy was evaluated by both the full analysis set, based on the intention-to-treat principle, and the per-protocol set; full analysis set findings were interpreted as the main results. Interventions: Eligible participants were randomly assigned to receive 300 mg of UDCA, 600 mg of UDCA, or placebo at a ratio of 1:1:1. Ursodeoxycholic acid and placebo were administered daily for 52 weeks. Main Outcomes and Measures: Gallstone formation was assessed with abdominal ultrasonography every 3 months for 12 months. Randomization and allocation to trial groups were carried out by an interactive web-response system. The primary end point was the proportion of patients developing gallstones within 12 months after gastrectomy. Results: A total of 521 patients (175 received 300 mg of UDCA, 178 received 600 mg of UDCA, and 168 received placebo) were randomized. The full analysis set included 465 patients (311 men; median age, 56.0 years [interquartile range, 48.0-64.0 years]), with 151 patients in the 300-mg group, 164 patients in the 600-mg group, and 150 patients in the placebo group. The proportion of patients developing gallstones within 12 months after gastrectomy was 8 of 151 (5.3%) in the 300-mg group, 7 of 164 (4.3%) in the 600-mg group, and 25 of 150 (16.7%) in the placebo group. Compared with the placebo group, odds ratios for gallstone formation were 0.27 (95% CI, 0.12-0.62; P = .002) in the 300-mg group and 0.20 (95% CI, 0.08-0.50; P < .001) in the 600-mg group. No significant adverse drug reactions were detected among the enrolled patients. Conclusions and Relevance: Administration of UDCA for 12 months significantly reduced the incidence of gallstones after gastrectomy for gastric cancer. These findings suggest that UDCA administration prevents gallstone formation after gastrectomy in patients with gastric cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02490111.

Prognostic perspectives of PD-L1 combined with tumor-infiltrating lymphocytes, Epstein-Barr virus, and microsatellite instability in gastric carcinomas.

BACKGROUND: The prognostic potential of PD-L1 is currently unclear in gastric carcinomas, although the immune checkpoint PD-1/PD-L1 inhibitors have produced promising results in clinical trials. METHODS: We explored the prognostic implications of programmed death ligand 1 (PD-L1) in 514 consecutive surgically-resected gastric carcinomas. Overall survival and recurrence-free survival were evaluated. Immunohistochemistry for PD-L1, CD8, FOXP3, and PD-1, and molecular grouping by in situ hybridization for Epstein-Barr virus (EBV)-encoded small RNAs and multiplex PCR for microsatellite instability (MSI) markers were performed. Additionally, to explore the function inherent to PD-L1, PD-L1-specific siRNA transfection, cell proliferation, invasion, migration and apoptosis assays were conducted in five gastric carcinoma cell lines. RESULTS: PD-L1(+) tumor and immune cells were observed in 101 (20%) and 244 patients (47%), respectively. "Tumoral PD-L1(+)/immune cell PD-L1(-)/CD8+/low tumor-infiltrating lymphocytes (TILs)," and more advanced-stage tumors were associated with unfavorable clinical outcomes in the entire cohort through multivariate analysis. Furthermore, tumoral PD-L1(+)/FOXP3+/low TILs were associated with worse clinical outcomes in EBV-positive and MSI-high carcinomas. Tumoral PD-L1(+) alone was an adverse prognostic factor in EBV-positive carcinomas, but not in MSI-high carcinomas, whereas PD-L1(+) immune cells or FOXP3+/high TILs alone were correlated with a favorable prognosis. PD-L1 knockdown in gastric carcinoma cells suppressed cell proliferation, invasion and migration, and increased apoptosis, which were all statistically significant in two EBV(+) cell lines, but not all in three EBV(-) cell lines. CONCLUSIONS: The prognostic impact of PD-L1 may depend on the tumor microenvironment, and statuses of EBV and MSI, although PD-L1 innately promotes cancer cell survival in cell-based assays. The combination of "tumoral PD-L1/immune cell PD-L1/CD8+ TILs" may serve as an independent prognostic factor. Tumoral PD-L1(+)/immune cell PD-L1(-)/CD8+/low TILs showing a worse prognosis may be beneficial for combinatorial therapies of anti-PD-L1/PD-1 and anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA4) that would promote effector T cells, thus attack the tumor.

Risk factors of elderly patients with postoperative delirium following major abdominal surgery for cancer.

Purpose: Postoperative delirium (POD) is a common complication in elderly patients after major abdominal surgery for cancer. Although POD is related with a poor outcome, there have not been many reports about POD after abdominal surgery in Korea. The aims of study were to analyze the characteristics and surgical outcomes of elderly patients with POD and to identify the risk factors of POD. Methods: From November 2016 to January 2019, we prospectively enrolled 63 patients who were aged ≥75 years and underwent major abdominal surgery for cancer. POD was daily assessed for up to 10 days postoperatively with the Confusion Assessment Method and a validated chart review. Results: POD occurred in eight patients (12.7%). Univariate analysis showed that the occurrence of POD was related to sodium <135 mEq/L (P=0.037), combined resection (P=0.023), longer surgery/anesthesia time (P=0.023 and P=0.037, respectively), increased blood loss (P=0.004), postoperative admission to intensive care unit (ICU) (P=0.023), and duration of Foley catheter (P=0.011), however, multivariate analysis identified no significant risk factors of POD. There was no difference in postoperative outcomes such as hospital stay, mortality, reoperation, and morbidity between patients with POD and without POD. Conclusion: Elderly patients with hyponatremia, combined resection, longer operation/anesthesia time and admission to ICU had tendencies to develop POD after major abdominal surgery. Surgeons should pay more attention to prevent POD, and a large-scale prospective study is needed to identify the risk factors of POD.

Bayesian analysis of longitudinal quality of life measures with informative missing data using a selection model.

Health-related quality of life consists of multi-dimensional measurements of physical and mental health domains. Health-related quality of life is often followed up to evaluate efficacy of treatments in clinical studies. During the follow-up period, a missing data problem inevitably arises. When missing data occur for reasons related to poor health-related quality of life, a complete-case only analysis can lead to invalid inferences. We propose a Bayesian approach to analyze longitudinal moderate to high-dimensional multivariate outcome data in the presence of non-ignorable missing data. To account for non-ignorable missing data, we employ a selection model for the joint likelihood factorization where we apply Bayesian spike and slab variable selection in the missing data mechanism to detect informative factors among multiple outcomes. We model the relationship between multiple outcomes and covariates using linear mixed effects models where multiple outcome correlations are captured by a hierarchical structure. We conduct simulation studies to evaluate the performance of the proposed method compared with the conventional last observation carried forward approach. We use a motivating example that originates from a longitudinal study of quality of life in gastric cancer patients who underwent distal gastrectomy. In this application, we demonstrate that our proposed method can offer efficiency gain in the marginal associations and provide the associations between outcomes and the absence of patients' information.

Natural History of Gastric Cancer: Observational Study of Gastric Cancer Patients Not Treated During Follow-Up.

BACKGROUND: Understanding the natural progression of untreated gastric cancer is critical for determining the disease prognosis as well as treatment options and timing. The aim of this study is to analyze the natural history of gastric cancer. PATIENTS AND METHODS: We included patients with gastric cancer who had not received any treatment and were staged using endoscopy/endoscopic ultrasonography and computed tomography on at least two follow-up visits during intervals of nontreatment. Tumor volumes were also measured in addition to the staging. Survival of each stage at diagnosis was also analyzed. RESULTS: A total of 101 patients were included. The mean follow-up period was 35.1 ± 34.4 months. The gastric cancer doubling time was 11.8 months for T1 and 6.2 months for T4. The progression time from early gastric cancer to advanced gastric cancer was 34 months. It decreased as the stages advanced: from 34 months between tumor-nodes-metastasis stage I and II to 1.8 months between stage III and IV. No variable was identified as a risk factor for cancer progression. The 5-year survival rates of untreated patients were 46.2% in stage I and 0% in stage II, stage III, and stage IV. CONCLUSIONS: The progression and doubling times of gastric cancer shorten as the stages advance. Objective data reported in this study can be a critical factor in determining treatment timing and screening interval.

A feasibility study of laparoscopic total gastrectomy for clinical stage I gastric cancer: a prospective multi-center phase II clinical trial, KLASS 03.

BACKGROUND: With improved short-term surgical outcomes, laparoscopic distal gastrectomy has rapidly gained popularity. However, the safety and feasibility of laparoscopic total gastrectomy (LTG) has not yet been proven due to the difficulty of the technique. This single-arm prospective multi-center study was conducted to evaluate the use of LTG for clinical stage I gastric cancer. METHODS: Between October 2012 and January 2014, 170 patients with pathologically proven, clinical stage I gastric adenocarcinoma located at the proximal stomach were enrolled. Twenty-two experienced surgeons from 19 institutions participated in this clinical trial. The primary end point was the incidence of postoperative morbidity and mortality at postoperative 30 days. The severity of postoperative complications was categorized according to Clavien-Dindo classification, and the incidence of postoperative morbidity and mortality was compared with that in a historical control. RESULTS: Of the enrolled patients, 160 met criteria for inclusion in the full analysis set. Postoperative morbidity and mortality rates reached 20.6% (33/160) and 0.6% (1/160), respectively. Fifteen patients (9.4%) had grade III or higher complications, and three reoperations (1.9%) were performed. The incidence of morbidity after LTG in this trial did not significantly differ from that reported in a previous study for open total gastrectomy (18%). CONCLUSIONS: LTG performed by experienced surgeons showed acceptable postoperative morbidity and mortality for patients with clinical stage I gastric cancer.

Effect of perioperative oral nutritional supplementation in malnourished patients who undergo gastrectomy: A prospective randomized trial.

BACKGROUND: The aim of this study was to examine the effect of a perioperative oral nutritional supplement in malnourished patients who undergo gastrectomy. METHODS: Patients who were determined as being moderately or severely malnourished according to a patient-generated subjective global assessment or who had a body mass index <18.5, were enrolled. The oral nutritional supplement group received 500 mL/d of standard oral nutritional supplement for 2 weeks before gastrectomy and for 4 weeks postoperatively. The primary endpoint was postoperative complications (Clavien-Dindo classification ≥II). The secondary endpoints included body weight changes, biochemical parameters, and quality of life survey results. RESULTS: A total of 127 patients (65 in the oral nutritional supplement group and 62 in the control group) were enrolled. The complication rates were not significantly different (29.2% versus 37.1%, P = .346). However, the incidences of overall complications, complications persisting until postoperative week 3 or 5, and severe complications (grade ≥IIIa) were significantly lower in the oral nutritional supplement group for patients with patient-generated subjective global assessment grade C. Total lymphocyte counts were significantly higher in the oral nutritional supplement group at postoperative weeks 3 and 5. For most patients, oral nutritional supplement was well tolerated preoperatively. However, only 26.2% and 50.8% of the patients in the oral nutritional supplement group could consume >250 mL/d of oral nutritional supplement postoperatively during the 2nd and 4th weeks, respectively. CONCLUSIONS: The routine application of perioperative oral nutritional supplement is not recommended for malnourished patients receiving gastrectomy. However, perioperative standard oral nutritional supplement administration may reduce the incidence, severity, and duration of complications after gastrectomy in severely malnourished patients (patient-generated subjective global assessment grade C).

The comprehensive complication index (CCI) is a more sensitive complication index than the conventional Clavien-Dindo classification in radical gastric cancer surgery.

BACKGROUND: The comprehensive complication index (CCI) integrates all complications of the Clavien-Dindo classification (CDC) and offers a metric approach to measure morbidity. The aim of this study was to evaluate the CCI at a high-volume center for gastric cancer surgery and to compare the CCI to the conventional CDC. METHODS: Clinical factors were collected from the prospective complication data of gastric cancer patients who underwent radical gastrectomy at Seoul National University Hospital from 2013 to 2014. CDC and CCI were calculated, and risk factors were investigated. Correlations and generalized linear models of hospital stay were compared between the CCI and CDC. The complication monitoring model with cumulative sum control-CCI (CUSUM-CCI) was displayed for individual surgeons, for comparisons between surgeons, and for the institution. RESULTS: From 1660 patients, 583 complications in 424 patients (25.5%) were identified. The rate of CDC grade IIIa or greater was 9.7%, and the overall CCI was 5.8 ± 11.7. Age, gender, Charlson score, combined resection, open method, and total gastrectomy were associated with increased CCI (p < 0.05). The CCI demonstrated a stronger relationship with hospital stay (ρ = 0.721, p < 0.001) than did the CDC (ρ = 0.634, p < 0.001). For prolonged hospital stays (≥30 days), only the CCI showed a moderate correlation (ρ = 0.544, p = 0.024), although the CDC did not. The CUSUM-CCI model displayed dynamic time-event differences in individual and comparison monitoring models. In the institution monitoring model, a gradual decrease in the CCI was observed. CONCLUSIONS: The CCI is more strongly correlated with postoperative hospital stay than is the conventional CDC. The CUSUM-CCI model can be used for the continuous monitoring of surgical quality.

Unexpected Appendiceal Pathologies and Their Changes With the Expanding Use of Preoperative Imaging Studies.

PURPOSE: The preoperative diagnosis of acute appendicitis is often challenging. Sometimes, pathologic results of the appendix embarrass or confuse surgeons. Therefore, more and more imaging studies are being performed to increase the accuracy of appendicitis diagnoses preoperatively. However, data on the effect of this increase in preoperative imaging studies on diagnostic accuracy are limited. We performed this study to explore unexpected appendiceal pathologies and to delineate the role of preoperative imaging studies in the diagnosis of acute appendicitis. METHODS: The medical records of 4,673 patients who underwent an appendectomy for assumed appendicitis between 1997 and 2012 were reviewed retrospectively. Pathological results and preoperative imaging studies were surveyed, and the frequencies of pathological results and preoperative imaging studies were investigated. RESULTS: The overall rate of pathology compatible with acute appendicitis was 84.4%. Unexpected pathological findings, such as normal histology, specific inflammations other than acute appendicitis, neoplastic lesions, and other pathologies, comprised 9.6%, 3.3%, 1.2%, and 1.5%, respectively. The rate of unexpected pathological results was significantly reduced because of the increase in preoperative imaging studies. The decrease in normal appendices contributed the most to the reduction while other unexpected pathologies did not change significantly despite the increased use of imaging studies. This decrease in normal appendices was significant in both male and female patients under the age of 60 years, but the differences in females were more prominent. CONCLUSION: Unexpected appendiceal pathologies comprised 15.6% of the cases. Preoperative imaging studies reduced them by decreasing the negative appendectomy rate of patients with normal appendices.