Survey of Information Acquisition and Satisfaction after Bariatric Surgery at a Tertiary Hospital in Korea.

Background: To determine how patients who underwent bariatric surgery at a tertiary hospital in Korea first considered and then decided to get the surgery and identify information gaps among patients and healthcare professionals. Methods: This study included 21 patients who underwent bariatric surgery to treat morbid obesity (body mass index [BMI] ≥35 or ≥30 kg/m2 together with obesity-related comorbidities) between August 2020 and February 2022. A telephone interview was conducted with the patients after at least 6 months had elapsed since the surgery. We asked how the patients decided to undergo bariatric surgery. We also inquired about their satisfaction with and concerns about the surgery. Results: Seventy-one percent of the patients were introduced to bariatric surgery following a recommendation from healthcare professionals, acquaintances, or social media. Most of the patients (52%) decided to undergo bariatric surgery based on recommendations from healthcare professionals in non-surgical departments. Satisfaction with the information provided differed among the patients. Post-surgical concerns were related to postoperative symptoms, weight regain, and psychological illness. Conclusion: Efforts are needed to raise awareness about bariatric surgery among healthcare professionals and the public. Tailored pre- and postoperative consultation may improve quality of life after bariatric surgery.

Comparison of Laparoscopic and Open Gastrectomy for Patients With Gastric Cancer Treated With Neoadjuvant Chemotherapy: A Multicenter Retrospective Study Based on the Korean Gastric Cancer Association Nationwide Survey.

PURPOSE: Despite scientific evidence regarding laparoscopic gastrectomy (LG) for advanced gastric cancer treatment, its application in patients receiving neoadjuvant chemotherapy remains uncertain. MATERIALS AND METHODS: We used the 2019 Korean Gastric Cancer Association nationwide survey database to extract data from 489 patients with primary gastric cancer who received neoadjuvant chemotherapy. After propensity score matching analysis, we compared the surgical outcomes of 97 patients who underwent LG and 97 patients who underwent open gastrectomy (OG). We investigated the risk factors for postoperative complications using multivariate analysis. RESULTS: The operative time was significantly shorter in the OG group. Patients in the LG group had significantly less blood loss than those in the OG group. Hospital stay and overall postoperative complications were similar between the two groups. The incidence of Clavien-Dindo grade ≥3 complications in the LG group was comparable with that in the OG group (1.03% vs. 4.12%, P=0.215). No statistically significant difference was observed in the number of harvested lymph nodes between the two groups (38.60 vs. 35.79, P=0.182). Multivariate analysis identified body mass index (odds ratio [OR], 1.824; 95% confidence interval [CI], 1.029-3.234; P=0.040) and extent of resection (OR, 3.154; 95% CI, 1.084-9.174; P=0.035) as independent risk factors for overall postoperative complications. CONCLUSIONS: Using a large nationwide multicenter survey database, we demonstrated that LG and OG had comparable short-term outcomes in patients with gastric cancer who received neoadjuvant chemotherapy.

Analysis of risk factors affecting long-term survival in elderly patients with advanced gastric cancer.

BACKGROUND: Factors predicting postoperative complications after gastrectomy for elderly patients with gastric cancer have been analyzed in several previous studies. However, there is limited research available on risk factors related to long-term survival. AIMS: This study aimed to analyze factors affecting long-term survival after curative gastrectomy in elderly patients with advanced gastric cancer. METHODS: This study included patients aged > 75 years with histologically confirmed advanced gastric cancer stage II or greater. Before analysis, risk factors were categorized into four groups: baseline characteristics, underlying diseases, surgical and pathologic factors, and nutritional factors. RESULTS: The mean follow-up duration was 71.0 months. The 5-year overall survival and disease-specific survival rates were 51.5% and 58.3%, respectively. Kaplan-Meier curves showed that patients who were female and overweight had significantly longer survival rates than those who were male and underweight. Elderly patients who underwent a total gastrectomy had poorer survival rates than those who underwent a distal gastrectomy. Multivariate analysis demonstrated that tumor stage, extent of gastrectomy, overweight status and overall complication were independent risk factors for overall survival. DISCUSSION: Our study show that the overweight patients, the extent of gastrectomy, tumor stage and overall complications are significant risk factors affecting long-term survival. CONCLUSIONS: Therefore, surgeons may be cautious in performing total gastrectomy in elderly gastric cancer patients. Additionally, it is important to focus on improving nutritional status and mitigating overall complications.

Long-term outcomes of a phase II study of neoadjuvant imatinib in large gastrointestinal stromal tumors of the stomach.

BACKGROUND: Neoadjuvant treatment is recommended for large GISTs due to their friability and risk of extensive operations; however, studies on the indications and long-term results of this approach are lacking. METHODS: Patients with large (≥ 10 cm) gastric GISTs were enrolled from multiple centers in Korea and Japan after a pathologic confirmation of c-KIT ( +) GISTs. Imatinib (400 mg/d) was given for 6-9 months preoperatively, and R0 resection was intended. Postoperative imatinib was given for at least 12 months and recommended for 3 years. RESULTS: A total of 56 patients were enrolled in this study, with 53 patients receiving imatinib treatment at least once and 48 patients undergoing R0 resection. The 5-year overall survival and progression-free survival rates were 94.3% and 61.6%, respectively. Even patients with stable disease by RECIST criteria responded well to preoperative imatinib treatment and could undergo R0 resection, with most being evaluated as partial response by CHOI criteria. The optimal reduction in tumor size was achieved with preoperative imatinib treatment for 24 weeks or more. No resumption of imatinib treatment was identified as an independent prognostic factor for recurrence after R0 resection. No additional size criteria for a higher risk of recurrence were identified in this cohort with a size of 10 cm or more. CONCLUSIONS: Neoadjuvant imatinib treatment is an effective treatment option for gastric GISTs 10 cm or larger. Postoperative imatinib treatment is recommended even after R0 resection to minimize recurrence.

Safety evaluation of curative gastrectomy for gastric cancer patients who underwent liver transplantation: a comparative study with conventional gastrectomy for gastric cancer patients.

BACKGROUND: We aimed to examine the technical and oncological safety of curative gastrectomy for gastric cancer patients who underwent liver transplantation. METHODS: In this study, we compared the surgical and oncological outcomes of two groups. The first group consisted of 32 consecutive patients who underwent curative gastrectomy for gastric cancer after liver transplantation (LT), while the other group consisted of 127 patients who underwent conventional gastrectomy (CG). In addition, a subgroup analysis was performed to evaluate the impact of the background differences and the surgical outcomes on the involvement of a specialized liver transplant surgery team. RESULTS: The mean operative time was significantly longer in the LT group (p < 0.05). Furthermore, there were more frequent cases of postoperative transfusion in the LT group compared to the CG group (p < 0.05). However, there were no significant differences in the overall complications between the groups (25.00 vs 23.62%, p = 0.874). The 5-year overall survival rates of the LT and CG groups were 76.7% and 90.1%, respectively (p < 0.05). The results of the subgroup analysis demonstrated no statistically significant difference in various early surgical outcomes, such as time to transfusion during surgery, first flatus, time to first soft diet, postoperative complications, hospital stay after surgery, and the number of harvested lymph nodes except for operation time. CONCLUSIONS: Despite one's medical history of undergoing LT, our study demonstrated that curative gastrectomy could be a surgically safe treatment for gastric cancer. However, further study should be conducted to identify the reason gastric cancer patients who underwent liver transplant surgery have lower overall survival rate.

Gastric Neuroendocrine Tumors According to the 2019 World Health Organization Grading System: A Single-Center, Retrospective Study.

Background/Aims: Although gastric neuroendocrine tumors (NETs) are uncommon neoplasms, their prevalence is increasing. The clinical importance of the World Health Organization (WHO) classification of gastric NETs, compared with NETs in other organs, has been underestimated. This study aimed to systematically evaluate the clinical and pathologic characteristics of gastric NETs based on the 2019 WHO classification and to assess the survival outcomes of patients from a single-center with a long-term follow-up. Methods: The medical records of 427 patients with gastric NETs who underwent endoscopic or surgical resection between January 2000 and March 2020 were retrospectively reviewed. All specimens were reclassified according to the 2019 WHO classification. The clinicopathologic characteristics, treatment, and oncologic outcomes of 139 gastric NETs were analyzed. Results: The patients' median age was 53.0 years (interquartile range [IQR], 46.0 to 63.0 years). The median follow-up period was 36.0 months (IQR, 15.0 to 63.0 months). Of the patients, 92, 44, and 3 had grades 1, 2, and 3 NETs, respectively. The mean tumor size significantly increased as the tumor grade increased (p=0.025). Patients with grades 2 and 3 gastric NETs more frequently had lymphovascular invasion (29.8% vs 10.9%, p=0.005) and deeper tissue invasion (8.5% vs 0%, p=0.012) than those with grade 1 tumors. The overall disease-specific survival rate was 100%. Two patients with grades 2-3 gastric NETs experienced extragastric recurrence. Conclusions: Although gastric NETs have an excellent prognosis, grade 2 or grade 3 gastric NETs are associated with a larger size, deeper invasion, and extragastric recurrence, which require active treatment.

Determinants of clinical outcomes of gastric cancer patients treated with neoadjuvant chemotherapy: a sub-analysis of the PRODIGY study.

BACKGROUND: In this post hoc analysis of the PRODIGY study, we aimed to investigate factors associated with survival outcomes and provide evidence for designing optimal perioperative treatment strategies for gastric cancer patients receiving neoadjuvant chemotherapy. PATIENTS AND METHODS: A total of 212 patients in the neoadjuvant chemotherapy group of the PRODIGY study were included as the study population. The prognostic impact of clinicopathologic factors, including the initial radiological clinical stage (cStage) and post-neoadjuvant chemotherapy pathological stage (ypStage), was analyzed. RESULTS: The median age was 58 years. The majority of patients (77.4%) had cStage III disease, and about 10% and 25% had ypStage 0 and I disease, respectively. According to the initial cStage, progression-free survival (PFS) and overall survival (OS) were significantly different (P < 0.01). PFS and OS were also different according to the ypStage (P < 0.01). In multivariate analyses, cStage IIIC disease (vs. cStage II) and ypStage II and III disease (vs. ypStage 0/I) were independent factors for poor survival outcomes. Based on the patterns of PFS and OS according to both cStage and ypStage, three patient groups were defined. These groups showed distinct PFS and OS (P < 0.01) with 5-year PFS rates of 95.7%, 77.9%, and 31.3% and 5-year OS rates of 95.7%, 82.4%, and 42.5%, respectively. CONCLUSIONS: Both initial cStage and ypStage were independent factors for survival outcomes of gastric cancer patients treated with neoadjuvant chemotherapy. Efforts should be made to develop optimal peri-operative treatment strategies for patients at different risks according to cStage and ypStage.

Reevaluation of the expanded indications in undifferentiated early gastric cancer for endoscopic submucosal dissection.

BACKGROUND: Although the criteria for the indication of endoscopic submucosal dissection (ESD) for undifferentiated early gastric cancer (UD-EGC) have been recently proposed, accumulating reports on the non-negligible rate of lymph node metastasis (LNM) after indicated ESD raise questions on the reliability of the current criteria. AIM: To investigate the prevalence and risk factors of LNM in UD-EGC cases meeting the expanded indication for ESD. METHODS: We retrospectively reviewed 4780 UD-EGC cases that underwent surgical resection between January 2008 and February 2019 at Asan Medical Center, a tertiary university hospital in Korea. To identify the risk factors of LNM of UD-EGC meeting the expanded criteria for ESD, we performed a case-control study by matching the cases with LNM to those without at a ratio of 1:4. We reviewed the clinical, endoscopic, and histologic features of the cases to identify features with a significant difference according to the presence of LNM. Univariate and multivariate logistic regression analyses were performed to estimate the odds ratios (ORs). RESULTS: Of the 4780 UD-EGC cases, 1240 (25.9%) were identified to meet the expanded indication for ESD. Of the 1240 cases, 14 (1.1%) cases had LNM. Among the various clinical, endoscopic, and histopathological features that were evaluated, mixed histology (tumors consisting of 10%-90% of signet ring cells) had a marginally significant association (P = 0.059) with the risk of LNM. Moreover, diffuse blurring of the muscularis mucosae (MM) underneath the tumorous epithelium, a previously unrecognized histologic feature, had a significant association with the absence of LNM (P = 0.028). Multivariate logistic regression analysis showed that the blurring of MM was the only explanatory variable significantly associated with a reduced risk of LNM (OR: 0.12, 95%CI: 0.02-0.95; P = 0.045). CONCLUSION: The risk of LNM is higher than expected when using the current expanded indication for UD-EGC. Histological evaluation could provide useful clues for reducing the risk of LNM.

Scoring Model Based on Nodal Metastasis Prediction Suggesting an Alternative Treatment to Total Gastrectomy in Proximal Early Gastric Cancer.

Purpose: Total gastrectomy (TG) with lymph node (LN) dissection is recommended for early gastric cancer (EGC) but is not indicated for endoscopic resection (ER). We aimed to identify patients who could avoid TG by establishing a scoring system for predicting lymph node metastasis (LNM) in proximal EGCs. Materials and Methods: Between January 2003 and December 2017, a total of 1,025 proximal EGC patients who underwent TG with LN dissection were enrolled. Patients who met the absolute ER criteria based on pathological examination were excluded. The pathological risk factors for LNM were determined using univariate and multivariate logistic regression analyses. A scoring system for predicting LNM was developed and applied to the validation group. Results: Of the 1,025 cases, 100 (9.8%) showed positive LNM. Multivariate analysis confirmed the following independent risk factors for LNM: tumor size >2 cm, submucosal invasion, lymphovascular invasion (LVI), and perineural invasion (PNI). A scoring system was created using the four aforementioned variables, and the areas under the receiver operating characteristic curves in both the training (0.85) and validation (0.84) groups indicated excellent discrimination. The probability of LNM in mucosal cancers without LVI or PNI, regardless of size, was <2.9%. Conclusions: Our scoring system involving four variables can predict the probability of LNM in proximal EGC and might be helpful in determining additional treatment plans after ER, functioning as a good indicator of the adequacy of treatments other than TG in high surgical risk patients.

Comparison of Standard D2 and Limited Lymph Node Dissection in Elderly Patients with Advanced Gastric Cancer.

BACKGROUND: Knowledge on the optimal extent of lymphadenectomy among elderly patients with advanced gastric cancer is limited. This study was designed to compare standard D2 and limited lymphadenectomy for evaluating the appropriate extent of lymphadenectomy. PATIENTS AND METHODS: We retrospectively reviewed patient's data based on a prospectively collected gastric cancer registry. The inclusion criteria were age above 75 years and histologically confirmed stage II or more advanced gastric cancer. In this study, 103 patients who underwent limited lymph node dissection and 134 patients who underwent standard D2 lymph node dissection were included to evaluate surgical and oncological outcomes using propensity score matching (PSM) analysis. RESULTS: The mean age after PSM was approximately 78 years in both groups. The Charlson Comorbidity Index was 5.81 ± 0.87 and 5.75 ± 0.76, respectively, and 12.5% of the patients in both groups had American Society of Anesthesiologists scores of more than 3. The limited lymphadenectomy group showed a shorter operation time and fewer retrieved lymph. However, other surgical outcomes and pathological data were not significantly different between the groups. No postoperative mortality within 30 days was observed. There were no significant differences in overall complications between the groups. The 3-year overall survival rates of the limited and standard lymphadenectomy groups were 58.3% and 73.6%, respectively. The 3-year recurrence-free survival rate of the limited lymphadenectomy group was lower than that of the standard lymphadenectomy group; however, the difference was not statistically significant. CONCLUSIONS: Standard D2 lymphadenectomy has better oncological outcomes in elderly patients with advanced gastric cancer.

Early experience of laparoscopic resection and comparison with open surgery for gastric gastrointestinal stromal tumor: a multicenter retrospective study.

The advantages of laparoscopic resection over open surgery in the treatment of gastric gastrointestinal stromal tumor (GIST) are not conclusive. This study aimed to evaluate the postoperative and oncologic outcome of laparoscopic resection for gastric GIST, compared to open surgery. We retrospectively reviewed the prospectively collected database of 1019 patients with gastric GIST after surgical resection at 13 Korean and 2 Japanese institutions. The surgical and oncologic outcomes were compared between laparoscopic and open group, through 1:1 propensity score matching (PSM). The laparoscopic group (N = 318) had a lower rate of overall complications (3.5% vs. 7.9%, P = 0.024) and wound complications (0.6% vs. 3.1%, P = 0.037), shorter hospitalization days (6.68 ± 4.99 vs. 8.79 ± 6.50, P < 0.001) than the open group (N = 318). The superiority of the laparoscopic approach was also demonstrated in patients with tumors larger than 5 cm, and at unfavorable locations. The recurrence-free survival was not different between the two groups, regardless of tumor size, locational favorableness, and risk classifications. Cox regression analysis revealed that tumor size larger than 5 cm, higher mitotic count, R1 resection, and tumor rupture during surgery were independent risk factors for recurrence. Laparoscopic surgery provides lower rates of complications and shorter hospitalizations for patients with gastric GIST than open surgery.

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.

PRODIGY: A Phase III Study of Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Versus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer.

PURPOSE: Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC. PATIENTS AND METHODS: Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 intravenously day 1, S-1 40 mg/m2 orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis. RESULTS: Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment. CONCLUSION: PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.

Totally laparoscopic total gastrectomy using the modified overlap method and conventional open total gastrectomy: A comparative study.

BACKGROUND: Although several methods of totally laparoscopic total gastrectomy (TLTG) have been reported. The best anastomosis technique for LTG has not been established. AIM: To investigate the effectiveness and surgical outcomes of TLTG using the modified overlap method compared with open total gastrectomy (OTG) using the circular stapled method. METHODS: We performed 151 and 131 surgeries using TLTG with the modified overlap method and OTG for gastric cancer between March 2012 and December 2018. Surgical and oncological outcomes were compared between groups using propensity score matching. In addition, we analyzed the risk factors associated with postoperative complications. RESULTS: Patients who underwent TLTG were discharged earlier than those who underwent OTG [TLTG (9.62 ± 5.32) vs OTG (13.51 ± 10.67), P < 0.05]. Time to first flatus and soft diet were significantly shorter in TLTG group. The pain scores at all postoperative periods and administration of opioids were significantly lower in the TLTG group than in the OTG group. No significant difference in early, late and esophagojejunostomy (EJ)-related complications or 5-year recurrence free and overall survival between groups. Multivariate analysis demonstrated that body mass index [odds ratio (OR), 1.824; 95% confidence interval (CI): 1.029-3.234, P = 0.040] and American Society of Anaesthesiologists (ASA) score (OR, 3.154; 95%CI: 1.084-9.174, P = 0.035) were independent risk factors of early complications. Additionally, age was associated with ≥ 3 Clavien-Dindo classification and EJ-related complications. CONCLUSION: Although TLTG with the modified overlap method showed similar complication rate and oncological outcome with OTG, it yields lower pain score, earlier bowel recovery, and discharge. Surgeons should perform total gastrectomy cautiously and delicately in patients with obesity, high ASA scores, and older ages.

Discovery and validation of an expression signature for recurrence prediction in high-risk diffuse-type gastric cancer.

BACKGROUND: Diffuse type gastric cancer (DGC), represented by low sensitivity to chemotherapy and poor prognosis, is a heterogenous malignancy in which patient subsets exhibit diverse oncological risk-profiles. This study aimed to develop molecular biomarkers for robust prognostic risk-stratification and improve survival outcomes in patients with diffuse type gastric cancer (DGC). METHODS: We undertook a systematic and comprehensive discovery and validation effort to identify recurrence prediction biomarkers by analyzing genome-wide transcriptomic profiling data from 157 patients with DGC, followed by their validation in 254 patients from 2 clinical cohorts. RESULTS: Genome-wide transcriptomic profiling identified a 7-gene panel for robust prediction of recurrence in DGC patients (AUC = 0.91), which was successfully validated in an independent dataset (AUC = 0.86). Examination of 180 specimens from a training cohort allowed us to establish a gene-based risk prediction model (AUC = 0.78; 95% CI 0.71-0.84), which was subsequently validated in an independent cohort of 74 GC patients (AUC = 0.83; 95% CI 0.72-0.90). The Kaplan-Meier analyses exhibited a consistently superior performance of our risk-prediction model in the identification of high- and low-risk patient subgroups, which was significantly improved when we combined our gene signature with the tumor stage in both clinical cohorts (AUC of 0.83 in the training cohort and 0.89 in the validation cohort). Finally, for an easier clinical translation, we established a nomogram that robustly predicted prognosis in patients with DGC. CONCLUSIONS: Our novel transcriptomic signature for risk-stratification and identification of high-risk patients with recurrence could serve as an important clinical decision-making tool in patients with DGC.

Transcriptomic Profiling Identifies a Risk Stratification Signature for Predicting Peritoneal Recurrence and Micrometastasis in Gastric Cancer.

PURPOSE: Gastric cancer peritoneal carcinomatosis is fatal. Delay in detection of peritoneal metastases contributes to high mortality, highlighting the need to develop biomarkers that can help identify patients at high risk for peritoneal recurrence or metastasis. EXPERIMENTAL DESIGN: We performed a systematic discovery and validation for the identification of peritoneal recurrence prediction and peritoneal metastasis detection biomarkers by analyzing expression profiling datasets from 249 patients with gastric cancer, followed by analysis of 426 patients from three cohorts for clinical validation. RESULTS: Genome-wide expression profiling identified a 12-gene panel for robust prediction of peritoneal recurrence in patients with gastric cancer (AUC = 0.95), which was successfully validated in a second dataset (AUC = 0.86). Examination of 216 specimens from a training cohort allowed us to establish a six gene-based risk-prediction model [AUC = 0.72; 95% confidence interval (CI): 0.66-0.78], which was subsequently validated in an independent cohort of 111 patients with gastric cancer (AUC = 0.76; 95% CI: 0.67-0.83). In both cohorts, combining tumor morphology and depth of invasion further improved the predictive accuracy of the prediction model (AUC = 0.84). Thereafter, we evaluated the performance of the identical six-gene panel for its ability to detect peritoneal metastasis by analyzing 210 gastric cancer specimens (prior 111 patients plus additional 99 cases), which discriminated patients with and without peritoneal metastasis (AUC = 0.72). Finally, our biomarker panel was also remarkably effective for identifying peritoneal micrometastasis (AUC = 0.72), and its diagnostic accuracy was significantly enhanced when depth of invasion was included in the model (AUC = 0.85). CONCLUSIONS: Our novel transcriptomic signature for risk stratification and identification of high-risk patients with peritoneal carcinomatosis might serve as an important clinical decision making in patients with gastric cancer.

Preoperative nutritional risk index and postoperative one-year skeletal muscle loss can predict the prognosis of patients with gastric adenocarcinoma: a registry-based study.

BACKGROUND: Patients with gastric cancer have an increased nutritional risk and experience a significant skeletal muscle loss after surgery. We aimed to determine whether muscle loss during the first postoperative year and preoperative nutritional status are indicators for predicting prognosis. METHODS: From a gastric cancer registry, a total of 958 patients who received curative gastrectomy followed by chemotherapy for stage 2 and 3 gastric cancer and survived longer than 1 year were investigated. Clinical and laboratory data were collected. Skeletal muscle index (SMI) was assessed based on the muscle area at the L3 level on abdominal computed tomography. RESULTS: Preoperative nutritional risk index (NRI) and postoperative decrement of SMI (dSMI) were significantly associated with overall survival (hazards ratio: 0.976 [95% CI: 0.962-0.991] and 1.060 [95% CI: 1.035-1.085], respectively) in a multivariate Cox regression analysis. Recurrence, tumor stage, comorbidity index were also significant prognostic indicators. Kaplan-Meier analyses exhibited that patients with higher NRI had a significantly longer survival than those with lower NRI (5-year overall survival: 75.8% vs. 63.0%, P <  0.001). In addition, a significantly better prognosis was observed in a patient group with less decrease of SMI (5-year overall survival: 75.7% vs. 66.2%, P = 0.009). A logistic regression analysis demonstrated that the performance of preoperative NRI and dSMI in mortality prediction was quite significant (AUC: 0.63, P <  0.001) and the combination of clinical factors enhanced the predictive accuracy to the AUC of 0.90 (P <  0.001). This prognostic relevance of NRI and dSMI was maintained in patients experiencing tumor recurrence and highlighted in those with stage 3 gastric adenocarcinoma. CONCLUSIONS: Preoperative NRI is a predictor of overall survival in stage 2 or 3 gastric cancer patients and skeletal muscle loss during the first postoperative year was significantly associated with the prognosis regardless of relapse in stage 3 tumors. These factors could be valuable adjuncts for accurate prediction of prognosis in gastric cancer patients.

Comparative Outcomes in Patients With Small- and Large-Cell Neuroendocrine Carcinoma (NEC) and Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm (MiNEN) of the Stomach.

BACKGROUND: Gastric neuroendocrine carcinomas (NECs), consisting of both large- and small-cell NECs, and mixed adenoneuroendocrine carcinomas (MANECs), including mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs), are a group of high-grade malignancies. Few studies to date have reported clinical outcomes, including prognosis, in patients with these tumors. This study therefore evaluated the clinicopathologic outcomes and prognosis in patients with NECs and MANECs. METHODS: This study included 36 patients diagnosed with gastric NECs, including 23 with large-cell and 13 with small-cell NECs, and 85 with MiNENs, including 70 with high-grade and 15 with intermediate-grade MiNENs. Clinical outcomes, including overall survival (OS) and disease-free survival (DFS), were assessed. RESULTS: DFS was significantly poorer in patients with NEC than in patients with intermediate-grade MiNEN (P < .05), whereas both OS and DFS were similar in patients with NEC and high-grade MiNEN (P > .05). Patients with large-cell NEC were more likely to undergo aggressive surgery than patients with high-grade MiNEN (P < .05). Lymphovascular invasion was more frequent and DFS poorer in patients with large-cell than small-cell NECs (P < .05 each). CONCLUSION: DFS is significantly poorer in patients with NEC than in patients with intermediate-grade MiNEN and significantly lower in patients with large-cell than small-cell NECs.

Advantages of ypTNM Staging in Post-surgical Prognosis for Initially Unresectable or Stage IV Gastric Cancers.

PURPOSE: For unresectable or initially metastatic gastric cancer, conversion surgery (CVS), after systemic chemotherapy, has received attention as a treatment strategy. This study evaluated the prognostic value of ypTNM stage and the oncologic outcomes in patients receiving CVS. MATERIALS AND METHODS: A retrospective review of clinicopathologic findings and oncologic outcomes of 116 patients who underwent CVS with curative intent, after combination chemotherapy, between January 2000 and December 2015, has been reported here. RESULTS: Twenty-six patients (22.4%) underwent combined resection of another organ and 12 patients received para-aortic lymphadenectomy (10.3%). Pathologic complete remission (CR) was confirmed in 11 cases (9.5%). The median overall survival (OS) and disease-free survival (DFS) times were 35.0 and 21.3 months, respectively. In multivariate analysis, ypTNM stage was the sole independent prognostic factor for DFS (P=0.042). Tumors invading an adjacent organ or involving distant lymph nodes showed better survival than those with peritoneal seeding or solid organ metastasis (P=0.084). Kaplan-Meier curves showed that the 3-year OS rate of patients with pathologic CR and those with CR of the primary tumor but residual node metastasis was 81.8% and 80.0%, respectively. OS was 65.8% for stage 1 patients, 49.8% for those at stage 2, and 36.3% for those at stage 3. CONCLUSIONS: The ypTNM staging is a significant prognostic factor in patients who underwent CVS for localized unresectable or stage IV gastric cancers. Patients with locally advanced but unresectable lesions or with tumors with distant nodal metastasis may be good candidates for CVS.

Comparative outcomes between totally laparoscopic total gastrectomy with the modified overlap method for early gastric cancer and advanced gastric cancer: review of 149 consecutive cases.

INTRODUCTION: Totally laparoscopic total gastrectomy (TLTG) for advanced gastric cancer (AGC) has not been conclusively substantiated. AIM: To evaluate TLTG treatment of AGC by comparing its effectiveness and surgical outcomes to those of TLTG treatment of early gastric cancer (EGC). MATERIAL AND METHODS: We performed TLTG with the (modified) overlap method for 149 gastric cancer cases between March 2012 and December 2018. We evaluated clinicopathologic characteristics, complications (including esophagojejunostomy site complications), and surgical outcomes. We also evaluated these variables in terms of their associations with EGC and AGC. RESULTS: Ninety-two males and 57 females, with a mean age of 60.7 years, were included. The mean operation time was 147.7 min. The mean number of harvested lymph nodes was 39.6. Thirteen (8.7%) patients experienced early complications, and 6 (4.0%) experienced late complications (Clavien-Dindo classification ≥ III). Eight (5.4%) patients underwent reoperation, and 8 (5.4%) were readmitted due to complications. There were no statistically significant differences in operation time, hospital stay, or surgical mortality between EGC and AGC. However, there were significant differences in early complications, late complications, rate of reoperation, and rate of readmission between EGC and AGC. CONCLUSIONS: Although it has some limitations, TLTG with the (modified) overlap method for AGC treatment is feasible, safe, and associated with favorable outcomes.