Japanese Classification Of Gastric Carcinoma Research Articles

Late recurrent gastric carcinoma 12 years after surgery with attenuation of CD44 variant 9 expression

BackgroundLate recurrence of gastric cancer at 10 years post-gastrectomy is extremely rare, and the underlying mechanism remains unclear. We report a para-aortic lymph node metastasis case that recurred 12 years postoperatively.Case presentationA 44-year-old woman pathologically diagnosed with moderately to poorly differentiated adenocarcinoma with pT2(SS)pN2cM0pStageIIIA according to the Japanese Classification of Gastric Carcinoma (the 13th Edition) underwent laparoscopic distal gastrectomy with D1 + lymph node dissection. She received adjuvant chemotherapy with tegafur-uracil (400 mg/day) for 2 years. At postoperative year (POY) 5, a swollen lymph node was detected in the No.16b1lat lymph node station. However, positron emission tomography (PET) revealed normal uptake, and the levels of tumor markers were within normal limits; hence, the possibility of metastasis was considered low, and the patient was placed under observation. At POY 12, computed tomography revealed an enlargement of the No.16b1lat lymph node station, and PET showed abnormal uptake. Endoscopic ultrasound-guided fine-needle aspiration revealed a moderately differentiated adenocarcinoma. Hence, a diagnosis of recurrence of gastric cancer was made. The patient underwent para-aortic nodal dissection (PAND) of No.16b1lat & int stations. Immunochemical staining results also suggested the recurrence of gastric cancer. However, the expression of CD44 variant 9 (CD44v9), a cancer stem cell marker for gastric adenocarcinoma, was attenuated in the recurrent lesions compared with that in the primary lesions. Postoperatively, she received chemotherapy with tegafur–gimeracil–oteracil (80 mg/day) for 1 year. Bone metastasis was observed at POY 4 after PAND, and the IHC analysis showed a HER2 score of 3 + in a needle biopsy specimen of bone metastasis. The expression of CD44v9 was slightly positive. The patient is being treated with chemotherapy with FOLFOX + trastuzumab.ConclusionsA defense mechanism against reactive oxygen species has been reported as a mechanism causing recurrence of CD44v9-positive gastric cancer. Consequently, CD44v9-positive gastric cancer grows in metastatic organs, repeatedly self-renews, and proliferates to form recurrent lesions. In the present case, the degree of CD44v9 staining in recurrent lesions was suggested to be related to the recurrence time.

Prevalence, endoscopic and histopathological characteristics of early gastric cancer in Vietnamese patients

In Vietnam, gastric cancer (GC) ranks 4th in incidence and 3rd in mortality among all cancers. Most of the new GC cases in Vietnam were diagnosed at an advanced stage. Data on early gastric cancer (EGC) in Vietnam is very limited. This study aimed to evaluate the prevalence, endoscopic and histopathological characteristics of EGC among Vietnamese patients. This is a retrospective study conducted at the University Medical Center of Ho Chi Minh City, Vietnam from January 2014 to December 2019. Electronic medical records of patients with EGC were reviewed to collect data regarding age, gender, endoscopic findings of EGC lesions (including location, size, and their type according to the Japanese classification of gastric carcinoma), and histopathological characteristics of these lesions based on the resected gastric specimens. Among 1666 patients with GC, there were 67 EGC cases, accounting for 4.0%. All of the patients diagnosed with EGC were older than 40 years. The detection rate of EGCs gradually increased during the study period. The EGC lesions were mostly located in the antrum-incisura angularis (73.1%) with a median diameter of 1.0 cm. Regarding macroscopic types, a majority of these lesions were classified as type 0-IIc (31.3%) and type 0-IIa+0-IIc (29.9%). The most common histological type of EGC was adenocarcinoma (82.1%) and poorly differentiated type (40.3%). EGCs are mainly detected in individuals aged over 40 years. EGC lesions are commonly located in the antrum-incisura angularis and have characteristic features including the macroscopic and histological types.

Survival results by the prospectively determined clinical staging for locally advanced gastric cancer: An ancillary study of JCOG1302A (JCOG1302A2).

392 Background: Recently, neoadjuvant chemotherapy has been recognized as a promising strategy to improve the survival of patients with advanced gastric cancer. On the other hand, given the adverse events and treatment cost of chemotherapy, the candidate for NAC should be limited to patients who can benefit from NAC. In fact, as previously reported, the proportion of pathological stage I tumors was 50.4% in cT2N0, 38.7% in cT2N(+), 26.7% in cT3N0, 10.6% in cT3N(+), 9.0% in cT4aN0, and 3.0% in cT4aN(+). Therefore, clinical staging before initiation of treatment is increasingly important for determining therapeutic strategy. However, the long-term survival stratified by the prospectively-determined clinical stage has not been fully investigated. Methods: Between July 2013 and November 2014, the JCOG1302A examined 1260 patients with a clinical diagnosis of cT2/T3/T4, cN0/N1/N2/N3, M0, except for diffuse large tumors like linitis plastica and extensive bulky nodal diseases according to the Japanese Classification of Gastric Carcinoma (3rd English edition). The cT diagnosis was made by upper gastrointestinal endoscopy and comprehensive findings on upper abdominal contrast CT scan with 1 or 5 mm slice thickness. Lymph nodes with a shortest dimension greater than 8 mm or a longest dimension greater than 10 mm were defined as positive for metastasis. In this follow-up study, the survival data by stratifying the clinical staging were evaluated. Results: Among 1260 patients, survival data of 1177 were analyzed. With a median follow-up for 821 surviving patients of 6.0 years, the 5y-OS was 82.1% (95% CI, 77.3-85.9) in cT2 (n=319), 72.7% (68.2-76.6) in cT3 (n=450), 60.0% (54.9-64.7) in cT4a (n=401), and 40.0% (5.2-75.3) in cT4b (n=6), while that was 78.0% (74.2-81.2) in cN0 (n=560), 70.6% (65.4-75.2) in cN1 (n=350), 59.1% (52.5-65.1) in cN2 (n=241), and 28.4% (12.7-46.5) in cN3 (n=26), respectively. When combined with cT and cN, 5y-OS was 83.5% (77.8-87.8) in cT2N0 (n=226), 77.2% (71.0-82.2) in cT3N0 (n=232), 66.8% (56.3-75.2) in cT4aN0 (n=100), 100% in cT4bN0 (n=1), 78.7% (68.6-85.8) in cT2N(+)(n=93), 68.0% (61.1-73.8) in cT3N(+)(n=218), 57.7% (51.7-63.2) in cT4aN(+)(n=301), and 25.0% (0.9-66.5) in cT4bN(+)(n=5). Conclusions: Both the survival and the proportion of overdiagnosis of stage I patients in patients with cT4aN0, categorized as cstage IIB, was almost same as in those cT3N(+) categorized as cstage III. In considering the candidate for further treatment development of NAC with high toxic regime in future, cT3N(+) and cT4aN0 should be considered as equivalent category.

Dilemmas in definition and classification of adenocarcinoma of esophagogastric junction: from history to current status

In recent years, adenocarcinoma of esophagogastric junction (AEG) has received increased attention from the academic community. However, the esophagogastric junction (EGJ) straddles two anatomical regions: the thoracic cavity and the abdominal cavity. The histological features of the EGJ are different from those of the esophagus and stomach. There are general disagreements among the related disciplines regarding the definition and classification of AEG. By summarizing the views of different disciplines, including endoscopy, radiography, and pathology, a more comprehensive definition of the EGJ was formulated in the Japanese Classification of Gastric Carcinoma (the 15th edition), and the principle of endoscopic diagnostic priority was established. In recent years, with the development of physiological and anatomical studies, the EGJ has gradually expanded conceptually into a complex functional anatomical region covering the distal esophagus to the proximal stomach. The venous and lymphatic vessels in the EGJ are characterized by bidirectional flow, which is an important anatomical basis for the invasion and metastasis patterns of tumors in this region. The clinical practice of EGJ cancer has been promoted by the creation of Nishi and Siewert classification systems. With the support of a series of clinical studies for its scientificity and effectiveness, the Siewert classification is widely accepted by the international community, and successively introduced into major international practice guidelines. In general, the staging and management of Siewert Ⅰ and Ⅱ AEG are recommended as esophageal cancer, while Siewert Ⅲ AEG is recommended for gastric cancer. However, in the Japanese guidelines for the treatment of esophageal and gastric cancers, the Nishi classification is still used to define and classify EGJ cancer. Recent year, a Chinese consensus on the surgical treatment of AEG was formulated by multidisciplinary experts. The main controversies were summarized in the consensus, and proposals that incorporate the domestic situation were also presented. At present, only by returning to the basic anatomical and physiological perspectives, strengthening multidisciplinary communication and cooperation, and with the help of emerging bioinformatics, digital, and material technology, can it be possible to get out of the dilemma faced by traditional AEG classification and staging system.

Impact of Subclassification of Serosal Invasion on the Survival of Patients With T4a Gastric Cancer.

In the Japanese Classification of Gastric Carcinoma, T4a gastric cancer is defined as tumor invasion contiguous to the serosa or penetrating the serosa with exposure to the peritoneal cavity. The aim of this study was to assess the impact of T4a subclassification of gastric cancer on survival. A total of 326 patients with T4a cancer who had undergone gastrectomy were enrolled. The T4a tumors were classified into two groups: serosa-contiguous or serosa-exposed. The serosa-exposed group had a significantly worse prognosis, and multivariate analysis identified the T4a subclass as an independent prognostic factor. Analysis of the risk factors for recurrence identified the T4a subclass as a significant risk factor for peritoneal recurrence in patients undergoing curative gastrectomy. The serosa-contiguous and serosa-exposed subgroups of T4a gastric cancer showed different biological behaviors. These groups may need to be treated as separate.

Distal gastric tube resection with preservation of the right gastroepiploic artery for gastric tube cancer: a case report

BackgroundThe incidence of gastric tube cancer is increasing because of improved survival rates in patients with esophageal cancer treated by esophagectomy. Total resection of the gastric tube is expected to be highly curative, but it is associated with a higher risk of severe postoperative complications. Herein we report a case of early gastric tube cancer that was successfully treated by distal gastric tube resection with preservation of the right gastroepiploic artery (RGEA).Case presentationAn 82-year-old man was diagnosed as having gastric tube cancer, B-12-O, Type 0-IIc, T1b, N0, M0, cStage IA (Japanese Classification of Gastric Carcinoma). Upper gastrointestinal endoscopy showed a Type 0-IIc lesion measuring 30 mm in length in the lower part of the gastric tube, and histopathological examination of biopsy specimens revealed the features of poorly differentiated adenocarcinoma. The primary lesion could not be identified by computed tomography, and there was no obvious lymph node metastasis or distant metastasis. Considering that total resection of the gastric tube would have been highly invasive and that the gastric tube cancer was at a relatively early stage, we performed distal gastric tube resection with preservation of the RGEA. The postoperative course was uneventful, and the patient was discharged on postoperative day 12. There has been no recurrence during the 17 months of follow-up.ConclusionWe successfully treated a patient with gastric tube cancer by distal gastric tube resection with preservation of the RGEA. This treatment strategy may be acceptable for patients with early gastric tube cancer without lymph node metastasis, considering the balance between the surgical invasiveness and curability of the tumor.

History of the lymph node numbering system in the Japanese Classification of Gastric Carcinoma since 1962.

The Japanese Classification of Gastric Carcinoma was established by the Japanese Research Society for Gastric Cancer in 1962. The latest 15th edition was published in 2017. One of its main features is that lymph nodes are numbered as stations. The number of groups has increased from 16 to 36 in 55years. Seven groups (nos. 1, 2, 5, 7, 9, 10, and 15) were retained from the original classification. Nine groups (nos. 3, 4, 6, 8, 11, 12, 13, 14, and 16) were sub-divided into two or more groups. Furthermore, seven groups (nos. 17, 18, 19, 20, 110, 111, and 112) were added in the 6th, 11th, and 12th editions. This numbering system helps surgeons recognize the exact lymph nodes that need to be dissected. However, the numbering system has become extremely complicated. It is necessary to organize the historical background of each lymph node station and share the definitions clearly. This review focuses on nine anatomical zones around the stomach and summarizes the history of lymph node stations in the Japanese Classification of Gastric Carcinoma. Lymph node stations will continue to be modified in the future, and the historical background may be useful in future revisions.

Development and Validation of a Computed Tomography–Based Radiomics Signature to Predict Response to Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer

Neoadjuvant therapies have been shown to decrease tumor burden, increase resection rate, and improve the outcomes among patients with locally advanced gastric cancer (GC). However, not all patients are equally responsive; therefore, differentiating potential respondents from nonrespondents is clinically important. To use pretreatment computed tomography (CT)-pixelated feature-difference extraction techniques to identify diagnostically relevant features that could predict patients' response to neoadjuvant chemotherapy at diagnosis. This multicenter cohort study included patients with locally advanced GC who were treated from January 2010 to July 2017 at 2 hospitals in southern China (training cohort) and 1 hospital in northern China (external validation cohort). Their clinicopathological data, pretreatment CT images, and pathological reports were retrieved and analyzed. Data analysis was conducted from December 2017 to May 2021. All patients underwent 2 to 4 cycles of fluorouracil in combination with a platinum-based neoadjuvant chemotherapy regimen. All gastrectomies were performed according to the Japanese Classification of Gastric Carcinoma (14th edition) guidelines. Reliability of clinicopathological and radiomics-based features were assessed with area under receiver operating characteristic curve (AUC) and Mann-Whitney U test. A total of 323 patients (242 [74.9%] men; median [range] age, 58 [24-82] years) were included in the study, with 250 patients (77.4%) in the training cohort and 73 (22.6%) in the validation cohort. The baseline pretreatment characteristics of the training and validation cohorts were well-balanced. The number of respondents in the training and validation cohort was 122 (48.8%) and 40 (54.8%), respectively, and the number of nonrespondents was 128 (51.2%) and 33 (45.2%), respectively. No clinicopathological variables were significantly associated with treatment response. Using radiomics, 20 low-intercorrelated features from a total of 7477 features were used to construct a radiomics signature that demonstrated significant association with treatment response. Good discrimination performance of the radiomics signature for predicting treatment response in the training (AUC, 0.736; 95% CI, 0.675-0.798) and external validation (AUC, 0.679; 95% CI, 0.554-0.803) cohorts was observed. Decision curve analysis confirmed the clinical utility of the radiomics signature. In this study, the proposed radiomics signature showed potential as a clinical aid for predicting the response of patients with locally advanced GC before treatment, thereby allowing timely planning for effective treatments for potential nonrespondents.

Pathological complete response at the para-aortic nodes as a possible surrogate endpoint in gastric cancer surgery with para-aortic node dissection after neoadjuvant chemotherapy

PurposeGastric cancer with para-aortic node (PAN) metastasis has a chance to be cured with multidisciplinary treatment of D2 and PAN dissection (PAND) following neoadjuvant chemotherapy (NAC), but its prognosis remains unsatisfactory. To establish a better multidisciplinary treatment, a better surrogate endpoint is needed. The present study focused on a pathological complete response at the PANs alone as a new surrogate endpoint and evaluated its prognostic value. MethodsThe study examined patients who received radical gastrectomy with D2 and PAND after NAC for gastric cancer with PAN metastasis from 2004 to 2015. The study compared five methods of evaluating the response to NAC: RECIST, clinical disappearance of PANs (cPAN), histological response of the primary tumor defined by Japanese Classification of Gastric Carcinoma (JCGC histological criteria) and Becker's criteria, and pathological disappearance of PANs (pPAN). The efficacy of these methods was compared using the hazard ratio (HR) for death between responders and non-responders. ResultsThirty-two patients were analyzed. The respective HR and 5-year overall survival rates of responders and non-responders were 1.316 and 49.1% vs. 60.0% by RECIST, 1.106 and 52.9% vs. 52.5% by cPAN, 0.246 and 71.3% vs. 28.6% by JCGC histological criteria, 0.239 and 76.2% vs. 36.8% by Becker's criteria, and 0.074 and 81.0% vs. 0.0% by pPAN. ConclusionsA pathological complete response at the PANs had the lowest HR and clearly differentiated the survival, suggesting it might be a good surrogate endpoint for identifying future candidates for NAC in multidisciplinary treatment for gastric cancer with PAN metastasis.

Risk factors for recurrence in each pattern after curative gastrectomy for pStage II/III gastric cancer: An exploratory analysis of a randomized controlled trial (JCOG1001).

4052 Background: Peritoneal, lymph node, and hematogenous recurrence are frequently observed as patterns of recurrence after surgery for gastric cancer. However, the clinicopathological characteristics associated with each recurrence have rarely been comprehensively reported in a multicenter study. Understanding the risk factors for each pattern of recurrence would be helpful for the early detection of recurrence and the initiation of optimal treatment. This study investigated the risk factors for the first recurrence in each pattern after curative gastrectomy, using data from a multicenter randomized controlled trial (JCOG1001) that was designed to investigate the efficacy of bursectomy. Methods: Patients of 20-80 years of age, with cT3(SS)-T4a(SE) gastric carcinoma according to the 14th Japanese Classification of Gastric Carcinoma, with an ECOG PS of 0-1, and a body mass index of < 30 kg/m2, and without bulky lymph nodes, Borrmann type 4 or large type 3 carcinoma were eligible for inclusion in JCOG1001. Of the 1204 patients who were enrolled in JCOG1001, 932 pStage II/III patients with a common histological type were included in this study. Risk factors for hematogenous, lymph node, and peritoneal patterns of recurrence were estimated by a multivariable Fine and Grey model considering death or site of recurrence other than the first site of recurrence as competing risks. Results: The overall rate of recurrence was 27.1%. Hematogenous recurrence was the most frequent pattern (12.3%), followed by peritoneal (11.2%) and lymph node (7.5%) recurrence. Differentiated type (HR, 1.818; 1.237-2.674; p = 0.0024), pT4 (in comparison to pT1-3, HR, 1.511; 95% CI, 1.011-2.257; p = 0.0440), and pN3 (in comparison to pN0-2, HR, 2.431; 95% CI, 1.635-3.616; p < 0.0001) were associated with an increased incidence of hematogenous recurrence. Conversely, more than D2 lymphadenectomy reduced this pattern of recurrence (in comparison to D1+or D2 lymphadenectomy, HR, 0.575; 95% CI, 0.364-0.907; p = 0.0174). Peritoneal recurrence was significantly associated with large (≥5 cm) tumor (HR, 1.649; 95% CI, 1.034-2.629; p = 0.0356), pT4 (in comparison to pT1-3, HR, 3.222; 95% CI, 2.086-4.976; p < 0.0001), pN3 (in comparison to pN0-2, HR, 1.865; 95% CI, 1.275-2.727; p = 0.0013), and undifferentiated type (HR, 2.674; 95% CI, 1.628-4.394; p = 0.0001). Extended lymph node metastasis (pN3) was the only risk factor (in comparison to pN0-2, HR, 8.030; 95% CI, 4.605-14.002; p < 0.0001) for lymph node recurrence. Conclusions: The risk factors for recurrence differed according to the patterns of recurrence. Vigilant follow-up with an understanding of patterns of recurrence is required, especially for high-risk patients.

Advanced gastric cancer with abdominal wall invasion treated with curative resection after chemotherapy: a case report

IntroductionIn patients with gastric cancer, 6–27% of patients are diagnosed with T4b disease that invades adjacent organs, and curative resection can improve the prognosis of these patients.Case presentationA 70-year-old Japanese man presented with an abdominal tumor and was diagnosed with advanced gastric cancer (L-Circ type 3 T4b N2 M0 H0 stage IVA, based on the 15th edition of the Japanese Classification of Gastric Carcinoma) with extensive abdominal wall invasion. We performed open gastrojejunal bypass for gastric obstruction and initiated a chemotherapeutic regimen comprising S-1 (120 mg/day) and oxaliplatin (100 mg/m2). Upper gastrointestinal endoscopy performed after the administration of six courses of the S-1 and oxaliplatin regimen revealed a persistent primary lower gastric wall lesion; however, the diameter of the abdominal wall invasion and metastatic lymph nodes was significantly reduced, in addition to decreased serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels. Subsequently, the patient underwent distal gastrectomy with D2 lymphadenectomy combined with transverse colon and abdominal wall resection. We performed radical en bloc resection and achieved a tumor-free resection margin. Simple abdominal wall closure was performed without mesh or musculocutaneous flap placement. Histopathological examination of the resected tumor specimen showed direct invasion of the mesocolon and rectus abdominis muscle. The patient was postoperatively diagnosed with L Gre-Ant type5 T4b (SI: rectus abdominis muscle) N2 PM0 DM0 Stage IIIA R0 Grade 2a gastric cancer based on histopathological findings and received S-1 as adjuvant chemotherapy, 2 months postoperatively. No recurrence was detected 6 months postoperatively.ConclusionsWe report a case of advanced gastric cancer with extensive abdominal wall invasion that was successfully treated with gastrectomy combined with resection of adjacent organs showing tumor invasion after effective systemic chemotherapy. A therapeutic approach comprising curative surgery combined with perioperative chemotherapy is useful in patients with T4b gastric cancer.

Efficacy and safety of endoscopic submucosal dissection for gastric tube cancer: A multicenter retrospective study.

BACKGROUNDRecent improvements in the prognosis of patients with esophageal cancer have led to the increased occurrence of gastric tube cancer (GTC) in the reconstructed gastric tube. However, there are few reports on the treatment results of endoscopic submucosal dissection (ESD) for GTC.AIMTo evaluate the efficacy and safety of ESD for GTC after esophagectomy in a multicenter trial.METHODSWe retrospectively investigated 48 GTC lesions in 38 consecutive patients with GTC in the reconstructed gastric tube after esophagectomy who had undergone ESD between January 2005 and December 2019 at 8 institutions participating in the Okayama Gut Study group. The clinical indications of ESD for early gastric cancer were similarly applied for GTC after esophagectomy. ESD specimens were evaluated in 2-mm slices according to the Japanese Classification of Gastric Carcinoma with curability assessments divided into curative and non-curative resection based on the Gastric Cancer Treatment Guidelines. Patient characteristics, treatment results, clinical course, and treatment outcomes were analyzed.RESULTSThe median age of patients was 71.5 years (range, 57-84years), and there were 34 men and 4 women. The median observation period after ESD was 884 d (range, 8-4040 d). The median procedure time was 81 min (range, 29-334 min), the en bloc resection rate was 91.7% (44/48), and the curative resection rate was 79% (38/48). Complications during ESD were seen in 4% (2/48) of case, and those after ESD were seen in 10% (5/48) of case. The survival rate at 5 years was 59.5%. During the observation period after ESD, 10 patients died of other diseases. Although there were differences in the procedure time between institutions, a multivariate analysis showed that tumor size was the only factor associated with prolonged procedure time.CONCLUSIONESD for GTC after esophagectomy was shown to be safe and effective.

Final results of a phase III trial to evaluate bursectomy for patients with subserosal/serosal gastric cancer (JCOG1001).

206 Background: We previously reported that the superiority of bursectomy was not demonstrated for subserosal(SS)/serosal(SE) gastric cancer by the second interim analysis performed with 54% of the expected events observed. We report the final 5-year follow-up data. Methods: Eligibility criteria included histologically proven adenocarcinoma of the stomach, cT3(SS) or cT4a(SE). Patients were intraoperatively randomized to non-bursectomy arm or bursectomy arm. Primary endpoint was overall survival (OS), and secondary endpoint was relapse-free survival (RFS). A total of 1,200 patients were required to detect a hazard ratio of 0.77 with a one-sided alpha of 5% and 80% power. Results: A total of 1204 eligible patients with cT3 / cT4a gastric cancer were randomized (602 in non-bursectomy arm, 602 in bursectomy arm, respectively). Patients’ background and operative procedures were well balanced between the arms. The 5y-OS were 76.5% (95% CI, 72.8 to 79.7) in non-bursectomy arm and 74.9% (71.2 to 78.2) in bursectomy arm. Hazard ratio (HR) for bursectomy was 1.03 (0.83-1.27, one-sided p = 0.598). The 5y-RFS were 70.7% (66.9 to 74.2) in non-bursectomy arm and 66.8% (62.9 to 70.5) in bursectomy arm [HR: 1.131 (0.93-1.38)]. HR for death was almost similar in all sub-categories (0.73-1.29) except cN2 (13th edition of Japanese Classification of Gastric Carcinoma); HR classified by cN was 1.06 (95% CI: 0.75-1.49) for cN0 (n = 521), 1.25 (0.92-1.71) for cN1 (n = 525), and 0.59 (0.32-1.06) for cN2 (n = 158) (p = 0.048 for interaction). The most frequent site of recurrence was the peritoneum [74 (12.3%) in non-bursectomy arm, 73 (12.1%) in bursectomy arm], and bursectomy arm showed a trend of increasing liver metastasis (n = 45, 7.5%) as compared with non-bursectomy arm (n = 33, 5.5%). Six independent poor prognostic factors were identified by multivariable analysis for OS: age ≥ 66 (vs. ≤ 65) (HR, 1.30; 95% CI, 1.04-1.62), macroscopic type 3/5 (vs. type 0/1/2) (1.43; 1.15-1.79), total gastrectomy (vs. distal gastrectomy) (1.44; 1.03-2.02), pT3 (vs. pT1-2) (1.77; 1.17-2.676), pT4 (vs. pT1-2) (3.00; 1.99-4.53), pN1 (vs. pN0) (2.34; 1.52-3.59), pN2-3b (vs. pN0)(4.02; 2.82-5.74) and adjuvant chemotherapy (vs. without chemotherapy) (0.53; 0.42-0.67), but bursectomy was not significant (1.10 0.89-1.36). Conclusions: In the final analysis as well as in the interim analysis, bursectomy was not recommended as a standard treatment for cT3 or cT4 gastric cancer. Clinical trial information: UMIN000003688.

Recurrence after ESD curative resection for early gastric cancer

BackgroundEndoscopic submucosal dissection (ESD) is gaining ground as a minimally invasive treatment for early gastric cancer (EGC) that has a negligible risk of lymph node metastasis. According to the 5th edition of Japanese gastric cancer treatment guidelines, annual or biannual follow-up with endoscopy is recommended, but follow-up with abdominal ultrasonography or computed tomography (CT) for surveillance of metastases is not recommended after the eCuraA resection. However, we experienced a case of lymph node recurrence following ESD resulting in eCuraA.Case presentationA 76-year-old female received ESD for EGC in a previous hospital 4 years ago. Pathological findings were tub1, 30 mm, T1a (M), UL0, Ly0, V0, pHM-, pVM- (eCuraA) according to the 15th edition of Japanese Classification of Gastric Carcinoma. Follow-up esophagogastroduodenoscopy revealed submucosal tumor, which was suspected as a swollen lymph node by CT and endoscopic ultrasound fine-needle aspiration revealed the recurrence of gastric cancer. We performed total gastrectomy with D2 lymph node dissection. Postoperative pathological examination revealed no local recurrent tumor at the ESD site in the stomach. Swollen lymph node was diagnosed as metastasis and lymph node metastasis was limited near the cardia.ConclusionThis case provides valuable information about tumor with a minimum poorly differentiated adenocarcinoma component may develop lymph node metastasis even satisfying the guidelines criteria for curative resection.

An Intraoperative Model for Predicting Survival and Deciding Therapeutic Schedules: A Comprehensive Analysis of Peritoneal Metastasis in Patients With Advanced Gastric Cancer.

Background and Objective: No specialized prognostic model for patients with gastric cancer with peritoneal metastasis (GCPM) exists for intraoperative clinical decision making. This study aims to establish a new prognostic model to provide individual treatment decisions for patients with GCPM.Method: This retrospective analysis included 324 patients with GCPM diagnosed pathologically by laparoscopy from January 2007 to January 2018 who were randomly assigned to different sets (227 in the training set and 97 in the internal validation set). A nomogram was established from preoperative and intraoperative variables determined by a Cox model. The predictive ability and clinical applicability of the PM nomogram (PMN) were compared with the 15th Japanese Classification of Gastric Carcinoma (JCGC) Staging Guidelines for PM (P1abc). Additional external validation was performed using a dataset (n = 39) from the First Affiliated Hospital of University of Science and Technology of China.Results: The median survival time was 8 (range, 1–90) months. In the training set, each PMN substage had significantly different survival curves (P < 0.001), and the PMN was superior to the P1abc based on the results of time-dependent receiver operating characteristic curve, C-index, Akaike information criterion and likelihood ratio chi-square analyses. In the internal and external validation sets, the PMN was also better than the P1abc in terms of its predictive ability. Of the PMN1 patients, those undergoing palliative resection had better overall survival (OS) than those undergoing exploratory surgery (P < 0.05). Among the patients undergoing exploratory surgery, those who received chemotherapy exhibited better OS than those who did not (P < 0.05). Among the patients who received palliative resection, only PMN1 patients exhibited better OS following chemotherapy (P < 0.05).Conclusion: We developed and validated a simple, specific PM model for patients with GCPM that can predict prognosis well and guide treatment decisions.

Neoadjuvant chemotherapy with docetaxel plus oxaliplatin and S-1 for locally advanced, resectable gastric or gastro-esophageal junction adenocarcinoma: Short-term results from a phase II trial.

397 Background: In locally advanced, resectable gastric or gastro-oesophageal junction (EGJ) adenocarcinoma, perioperative the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin and docetaxel) is the standard chemotherapy in Europe. However, there is no evidence of neoadjuvant chemotherapy for resectable gastric cancer in Japan. Therefore, we conducted a phase II trial of neoadjuvant chemotherapy with docetaxel plus oxaliplatin, and S-1 (DOS) for locally advanced, resectable gastric or EGJ adenocarcinoma. Methods: Eligible patients had histologically confirmed gastric or EGJ adenocarcinoma of a clinical Stage III according to the 14th Edition of Japanese Classification of Gastric Carcinoma. DOS was administered for two or three preoperative cycles followed by eight postoperative cycles of S-1. Each 3-week cycle of DOS consisted of docetaxel 40 mg/m2 and oxaliplatin 100 mg/m2 on day 1 plus S-1 80-120 mg/body on days 1 to 14. Primary endpoint was 3-year progression-free survival rate, and secondary endpoints included overall survival, progression-free survival, response rate, histological response rate, R0 resection rate, and adverse events. Results: Of 50 enrolled patients, 48 (37 gastric and 11 EGJ) were eligible for the analysis. 42 (88%) patients completed two or three preoperative cycles of DOS. The most common grade 3-4 adverse events of DOS were neutropenia (69%), leukopenia (56%), diarrhea (19%), and febrile neutropenia (13%). Of 45 patients who underwent gastrectomy, postoperative morbidities (Clavien-Dindo ≥Grade II) occurred in 12 (27%) patients. R0 resection could be achieved in 43 (90%) patients. 12 (27%) and 30 (67%) of 45 patients achieved pathological response rate of Grade2-3 and Grade1b-3, respectively. There was no treatment-related death. Conclusions: Neoadjuvant DOS for locally advanced, resectable gastric or EGJ adenocarcinoma might be favorable. Long-term results will be published in two years. Clinical trial information: 000017652.

Feasibility and pathological response of TAS-118 + oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).

351 Background: TAS-118 is a novel oral agent, containing S-1 and leucovorin. In the SOLAR study (NCT02322593), TAS-118 + oxaliplatin (OHP) significantly improved overall survival compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC). We conducted this open-label study to assess feasibility of perioperative adjuvant chemotherapy with TAS-118 + OHP in pts with locally advanced resectable GC with lymph node metastasis. (Clinical trial information: UMIN000024688). Methods: Eligible pts who had histopathologically confirmed GC with clinical T3-4N1-3M0 on image findings (14th Japanese classification of gastric carcinoma), age 20 to 79 years, were enrolled in this study. The protocol treatment consisted of preoperative 4 courses of TAS-118 (80-120 mg/body, days 1-7) + OHP (85 mg/m2, day 1) every 2 weeks, and gastrectomy with D2 lymphadenectomy, followed by postoperative 12 courses of TAS-118 alone (step1) or 8 cycles of TAS-118 + OHP (step2). The primary endpoints were tolerability of preoperative chemotherapy, gastrectomy and postoperative chemotherapy with TAS-118 plus OHP. Here, we report the feasibility of preoperative chemotherapy and gastrectomy, and pathological response. Results: Between December 2016 and April 2018, 45 pts with a median age of 61 years were enrolled. The numbers of pts with T stage (cT3/4a) and those with N stage (cN1/2/3) were 13/32 and 25/17/3, respectively. The completion rate of preoperative chemotherapy and gastrectomy was 88.9% ( 95% CI 78.0-95.5) and 95.6% (95% CI 86.7-99.2). The relative dose intensity of TAS-118 and OHP was 86.0% and 90.6%. During the 4 cycles of preoperative TAS-118 + OHP, 2 pts discontinued the treatment due to adverse event (AE). Major grade 3-4 AEs were diarrhea (17.8%) and neutropenia (8.9%). R0 resection rate was as high as 95.6%. One pts experienced grade 4 postoperative bleeding, but no treatment-related death was reported. pCR was achieved in 6/45 pts (13.3%) and other 7 pts (28.9%) showed near complete regression (&lt;10 % residual tumor cells). Conclusions: Preoperative TAS-118 + OHP followed by D2 gastorectomy was well tolerated and showed promising efficacy. Clinical trial information: 000024688.

Implications for restaging in gastric cancer with peritoneal metastasis based on the 15th Japanese Classification of Gastric Carcinoma: An analysis from a comprehensive center

Backgroundand purpose: For gastric cancer patients with peritoneal metastasis (GCPM), there is no universally accepted prognostic staging system. This study aimed to validate the predictive ability of the 15th peritoneal metastasis staging system (P1abc) of the Japanese Classification of Gastric Carcinoma (JCGC). MethodsThe data of 309 GCPM patients from July 2007 to July 2017 were retrospectively analyzed. This study compared the prognosis prediction performances of P1abc, the previous JCGC PM staging (P123) and Gilly staging systems. ResultsThe survival curve revealed a significant difference in overall survival (OS) predicted by P1abc, P123 and Gilly staging (all P < 0.05), and the survival of the two adjacent substages were well distinguished by P1abc but not by P123 and Gilly staging. Both P123 and Gilly staging were substituted with P1abc staging in a 2-step multivariate analysis. The results showed that P1abc staging was superior to both P123 and Gilly staging in its discriminatory ability (C-index), predictive accuracy (AIC) and predictive homogeneity (likelihood ratio chi-square). A stratified analysis by different therapies indicated that for the P1a and P1b patients, OS following palliative resection combined with palliative chemotherapy (PRCPC) was better than that after palliative resection (PR) or palliative chemotherapy (PC) alone (P < 0.05). For the P1c patients, OS after receiving PC was significantly superior to that after receiving PRCPC or PR (P = 0.021). ConclusionP1abc staging is superior to P123 and Gilly staging in predicting the survival of GCPM patients. Surgeons can provide these patients with appropriate treatment options according to the corresponding substages within P1abc.

Practical membrane anatomy of en bloc mesogastrium excision in lymph node dissection of gastric cancer

Gastric cancer is a common malignant tumor of digestive system. D2 procedure is recognized as the standard operation for advanced gastric cancer at present. However, controversies still exist in the standardization and quality control of surgical procedures. Total mesorectal excision (TME) and complete mesocolic excision (CME) based on the membrane anatomy perfectly solve these problems in the treatment for colorectal cancer. However, the complexity of mesogastrium determines that TME and CME cannot be easily transplanted to the treatment of gastric cancer. The practical membrane anatomy in gastric cancer surgery is just emerging and its impact on the treatment of gastric cancer is immeasurable. By reviewing the evolution and embryonic development of digestive system, and combining with actual operation, this paper analyzes and redefines several key issues such as traditional Toldt space, Gerota fascia and complete mesenteric excision. On this basis, we propose a novel and feasible surgical procedure named regional en bloc mesogastrium excision (rEME) for distal gastric cancer. The concept of en bloc mesogastrium excision (EME) based on membrane anatomy may have some influences on the lymph node grouping from the 'Japanese Classification of Gastric Carcinoma'. Performance of EME may reduce the controversies about the group of lymph nodes and their borders. EME in the infra-pyloric region weakens the significance of subdivision of No.6 lymph nodes into No.6a, No.6v and No.6i. More studies are needed in the construction of a mature theoretical system for practical membrane anatomy in gastric surgery.

Prognostic significance of 14v-lymph node dissection to D2 dissection for lower-third gastric cancer.

BACKGROUNDRadical gastrectomy with D2 lymph node (LN) dissection is the standard surgical procedure for patients with resectable gastric cancer (GC). In the fifteenth edition of the Japanese Classification of Gastric Carcinoma, the 14v LN (LNs along the root of the superior mesenteric vein) was defined as the regional gastric LN. The efficacy of 14v LN dissection during radical distal gastrectomy for lower-third GC remains controversial.AIMTo analyze whether the addition of 14v LN dissection improved the survival of patients with lower-third GC.METHODSThe data from 65 patients who underwent 14v LN dissection and 65 patients treated without 14v LN dissection were selected using the propensity score-matched method from our institute database constructed between 2000 and 2012. Overall survival was compared between the groups.RESULTSOverall survival was similar between patients with 14v LN metastasis and those with distant metastasis (P = 0.521). Among patients with pathological stage IIIA disease, those who were treated with 14v LN dissection had a significantly higher overall survival than those treated without it (P = 0.020). Multivariate analysis showed that age < 65 years and pT2-3 stage were independent favorable prognostic factors for prolonged overall survival in patients with pathological stage IIIA disease. Patients with No. 1, No. 6, No. 8a, or No. 11p LN metastasis were at higher risk of having 14v LN metastasis.CONCLUSIONAdding 14v LN dissection to D2 dissection during radical distal gastrectomy may improve the overall survival of patients with pathological stage IIIA lower-third GC.