Key nodal stations for predicting splenic hilar nodal metastasis in upper advanced gastric cancer without invasion of the greater curvature.

Background: Standard surgery for upper advanced gastric cancer without invasion of the greater curvature (UGC-GC) is spleen-preserving D2 total gastrectomy without dissection of the splenic-hilar nodes (#10). However, some patients with nodal metastasis to #10 survive more than 5 years due to nodal dissection of #10. If nodal metastasis to #10 is predictable based on the positivity of other nodes dissected by the current standard surgery without #10 nodal dissection, physicians may be able to consider #10 dissection. Methods: This study retrospectively reviewed data from the National Cancer Center Hospital in Japan between 2000 and 2012. We selected cases that met the following criteria: (1) D2 or more total gastrectomy with splenectomy, (2) UGC-GC, and (3) histological type is gastric adenocarcinoma. We performed univariate and multivariate analyses concerning lymph node stations associated with #10 metastasis. Results: A total of 366 patients were examined. A multivariate analysis revealed that #10 metastasis was associated with positivity of the nodes along the short gastric arteries (#4sa) and distal nodes along the splenic artery (#11d) (#4sa: p = 0.003, #11d: p = 0.016). When either key node was positive, the metastatic rate of #10 was 24.4%, and the therapeutic value index was 13.3. Conclusions: #4sa and #11d were key lymph nodes predicting #10 nodal metastasis in UGC-GC. When these key nodes are positive on computed tomography before surgery or according to a rapid pathological examination during surgery, dissection of #10 should be considered even if upper advanced tumors are not invading the greater curvature.

Impact of D2 Total Gastrectomy Including Splenectomy for Scirrhous Gastric Cancer in the Era of Effective Adjuvant Chemotherapy.

BACKGROUND: Total gastrectomy with D2 dissection including splenectomy (TGS) is usually selected for locally resectable scirrhous gastric cancer (SGC), which was established in the era of surgery alone. However, it remains unclear whether TGS for SGC is justified in the era of effective adjuvant chemotherapy. METHODS: This study included 112 SGC patients, consisting of 60 cases treated between January 2000 and December 2006 (Former group), and 52 cases treated between January 2007 and December 2016 (Latter group). We collected clinicopathological data and then examined the survival and the therapeutic value indexes. RESULTS: The background characteristics were well-balanced, except for sex and physical status. The Latter group might be characterized by frequent female (P = 0.037) and poorer physical status (P = 0.048). Adjuvant chemotherapy was administered to 86.5% of the Latter group and was 11.7% of the Former group (P < 0.001). The 5-year-overall survival rate of the Latter group was 58.7% (95% confidence interval: 43.5-71.1), seems better than that of the Former group (44.5%; 95% confidence interval 31.7-56.6) (hazard ratio = 0.758, P = 0.291). Improvement of the index from the Former group was observed in the Latter group at almost all stations. The ratio of the index between two groups was 1.42 at the D1 station and 1.67 at the D2 station. Index of splenic hilar node ranked similarly high in both groups. CONCLUSION: The therapeutic value index was improved in almost all nodal stations by S-1 adjuvant chemotherapy, especially in D2 nodes. TGS would be more important for locally resectable SGC in the era of effective adjuvant chemotherapy.

A discrimination model by machine learning to avoid gastrectomy for early gastric cancer.

Aim: Gastrectomy is recommended for patients with early gastric cancer (EGC) because the possibility of lymph node metastasis (LNM) cannot be completely denied. The aim of this study was to develop a discrimination model to select patients who do not require surgery using machine learning. Methods: Data from 382 patients who received gastrectomy for gastric cancer and who were diagnosed with pT1b were extracted for developing a discrimination model. For the validation of this discrimination model, data from 140 consecutive patients who underwent endoscopic resection followed by gastrectomy, with a diagnosis of pT1b EGC, were extracted. We applied XGBoost to develop a discrimination model for clinical and pathological variables. The performance of the discrimination model was evaluated based on the number of cases classified as true negatives for LNM, with no false negatives for LNM allowed. Results: Lymph node metastasis was observed in 95 patients (25%) in the development cohort and 11 patients (8%) in the validation cohort. The discrimination model was developed to identify 27 (7%) patients with no indications for additional surgery due to the prediction of an LNM-negative status with no false negatives. In the validation cohort, 13 (9%) patients were identified as having no indications for additional surgery and no patients with LNM were classified into this group. Conclusion: The discrimination model using XGBoost algorithms could select patients with no risk of LNM from patients with pT1b EGC. This discrimination model was considered promising for clinical decision-making in relation to patients with EGC.

Acceleration of sarcopenia in elderly patients who develop asymptomatic pneumonia shadow within one year after surgery for early gastric cancer.

BACKGROUND: Although early gastric cancer is curable with local treatment, the overall survival in elderly patients did not reach 80% at five years after surgery. The major cause of death in elderly patients with early gastric cancer is not cancer itself but is related to postoperative sarcopenia. Elderly patients frequently develop postoperative asymptomatic pneumonia shadow, which is associated with a poor prognosis. However, why asymptomatic pneumonia shadow worsens the prognosis remains unclear. We investigated whether sarcopenia is accelerated in patients who developed asymptomatic pneumonia shadow. METHODS: We retrospectively examined patients of > 75 years of age who underwent R0 gastrectomy for gastric cancer and were diagnosed with T1 disease at National Cancer Center Hospital between 2005 and 2012. The diagnosis of asymptomatic pneumonia shadow was defined by diagnostic findings of pneumonia (consolidation type, reticular type, and nodular type) which were newly observed on chest computed tomography performed one year after surgery in comparison to preoperative computed tomography. Postoperative muscle loss was assessed by a computed tomography-based analysis using the L3 skeletal muscle index before and two years after surgery and the rate of decrease was calculated. Patients were classified into two groups according to the rate of decrease (cut-off value: 10%). RESULTS: Of the 3412 patients who underwent gastrectomy in our hospital during the study period, 142 were included in this study. Asymptomatic pneumonia shadow was found in 26 patients (18%). Patients who developed asymptomatic pneumonia shadow showed a significantly greater loss of muscle volume in comparison to patients who did not develop asymptomatic pneumonia shadow. In the multivariate analysis, total gastrectomy and asymptomatic pneumonia shadow were the independent risk factors for severe muscle loss. However, there was no significant difference in prognosis between the two groups. CONCLUSIONS: Sarcopenia was accelerated in elderly patients who developed asymptomatic pneumonia shadow after surgery for early gastric cancer. However, the poor prognosis in these patients may not be related to accelerated sarcopenia.

Perioperative TAS-118 plus oxaliplatin in patients with locally advanced gastric cancer: APOLLO-11 study.

BACKGROUND: We investigated the feasibility of perioperative chemotherapy with S-1 and leucovorin (TAS-118) plus oxaliplatin in patients with locally advanced gastric cancer. METHODS: Patients with clinical T3-4N1-3M0 gastric cancer received four courses of TAS-118 (40-60 mg/body, orally, twice daily for seven days) plus oxaliplatin (85 mg/m2, intravenously, day one) every two weeks preoperatively followed by gastrectomy with D2 lymphadenectomy, followed by postoperative chemotherapy with either 12 courses of TAS-118 monotherapy (Step 1) or eight courses of TAS-118 plus oxaliplatin (Step 2). The primary endpoints were completion rates of preoperative chemotherapy with TAS-118 plus oxaliplatin and postoperative chemotherapy with TAS-118 monotherapy (Step 1) or TAS-118 plus oxaliplatin (Step 2). RESULTS: Among 45 patients enrolled, the preoperative chemotherapy completion rate was 88.9% (90% CI 78.0-95.5). Major grade ≥ 3 adverse events (AEs) were diarrhoea (17.8%) and neutropenia (8.9%). The R0 resection rate was 95.6% (90% CI 86.7-99.2). Complete pathological response was achieved in 6 patients (13.3%). Dose-limiting toxicity was not observed in 31 patients receiving postoperative chemotherapy (Step 1, n = 11; Step 2, n = 20), and completion rates were 90.9% (95% CI 63.6-99.5) for Step 1 and 80.0% (95% CI 59.9-92.9) for Step 2. No more than 10% of grade ≥ 3 AEs were observed in patients receiving Step 1. Hypokalaemia and neutropenia occurred in 3 and 2 patients, respectively, receiving Step 2. The 3-year recurrence-free and overall survival rates were 66.7% (95% CI 50.9-78.4) and 84.4% (95% CI 70.1-92.3), respectively. CONCLUSIONS: Perioperative chemotherapy with TAS-118 plus oxaliplatin with D2 gastrectomy is feasible.

Possible candidates for splenic hilar nodal dissection among patients with upper advanced gastric cancer without invasion of the greater curvature.

BACKGROUND: Spleen preserving D2 total gastrectomy without dissection of the splenic hilar nodes (#10) is a standard operation for upper advanced gastric cancer without invasion of the greater curvature (UGC-wGC). However, some patients with #10 metastasis have survived after splenectomy with dissection of #10. This study explored possible candidates for dissection of #10 among patients with UGC-wGC by examining the metastatic rate and the therapeutic index. METHODS: This study retrospectively reviewed data of patients treated in National Cancer Center Hospital (Japan) between 2000 and 2012. We applied the following inclusion criteria: (1) ≥ D2 total gastrectomy with splenectomy, (2) UGC-wGC, and (3) gastric adenocarcinoma histology. Univariate and multivariate analyses were performed to identify risk factors for #10 metastasis. RESULTS: A total of 366 patients were examined; #10 metastasis was observed in 4.4% (16/366). The multivariate analysis revealed that location (posterior vs. others, P = 0.025) and histology (undifferentiated vs. differentiated, P = 0.048) were significant factors for #10 metastasis among sex, age, tumor size, dominant circumferential location, macroscopic type, depth of invasion, and histology. The incidence of #10 metastasis was 14.9% (7/47) for tumors located on the posterior wall with undifferentiated type histology. The 5-year overall survival rate of these patients was 42.9%, and the therapeutic index was 6.38, which was the second highest value among the second-tier nodal stations. CONCLUSION: Even for upper advanced gastric cancer without invasion of the greater curvature, dissection of #10 could be justified for tumors located on the posterior wall with undifferentiated type histology.

Impact of D2 Gastrectomy for Locally Advanced Gastric Cancer in the Era of Effective Adjuvant Chemotherapy.

BACKGROUND: Gastrectomy with D2 dissection has been established as the standard procedure for locally advanced gastric cancer in the era of surgery alone. However, no consideration has been given to the efficacy of dissection in the era of effective adjuvant chemotherapy. METHODS: This study included 1298 advanced gastric cancer patients, consisting of 725 cases treated between January 2000 and December 2006 (Former group), and 573 cases treated between January 2007 and July 2015 (Latter group). Clinicopathological data were collected, survival and the therapeutic value index were determined. RESULTS: The background characteristics were well balanced, except for age, tumor location, and intraoperative blood loss. The Latter group showed the following characteristics: an older population (p < 0.001), a frequent upper location (p = 0.008), and less blood loss (p < 0.001). Adjuvant chemotherapy was administered to 75.2% of the Latter group and was 9.4% in the Former group. The 5-year overall survival rate of the Latter group was 75.7% (95% confidence interval: 71.7-79.1), significantly better than that of the Former group (70.0%, 95% confidence interval: 66.5-73.2) (p = 0.025). Improvement in the index from the Former group was observed in the Latter group at almost all stations. The ratio of the index between these two groups was 1.09 at the D1 station and 1.19 at the D2 station. CONCLUSION: The therapeutic value index was improved in all nodal stations by S-1 adjuvant chemotherapy, regardless of whether the D1 or D2 nodes were involved. D2 gastrectomy would be still important for locally advanced gastric cancer in the era of effective adjuvant chemotherapy.

Prediction of tissue-of-origin of early stage cancers using serum miRNomes.

BACKGROUND: Noninvasive detection of early stage cancers with accurate prediction of tumor tissue-of-origin could improve patient prognosis. Because miRNA profiles differ between organs, circulating miRNomics represent a promising method for early detection of cancers, but this has not been shown conclusively. METHODS: A serum miRNA profile (miRNomes)-based classifier was evaluated for its ability to discriminate cancer types using advanced machine learning. The training set comprised 7931 serum samples from patients with 13 types of solid cancers and 5013 noncancer samples. The validation set consisted of 1990 cancer and 1256 noncancer samples. The contribution of each miRNA to the cancer-type classification was evaluated, and those with a high contribution were identified. RESULTS: Cancer type was predicted with an accuracy of 0.88 (95% confidence interval [CI] = 0.87 to 0.90) in all stages and an accuracy of 0.90 (95% CI = 0.88 to 0.91) in resectable stages (stages 0-II). The F1 score for the discrimination of the 13 cancer types was 0.93. Optimal classification performance was achieved with at least 100 miRNAs that contributed the strongest to accurate prediction of cancer type. Assessment of tissue expression patterns of these miRNAs suggested that miRNAs secreted from the tumor environment could be used to establish cancer type-specific serum miRNomes. CONCLUSIONS: This study demonstrates that large-scale serum miRNomics in combination with machine learning could lead to the development of a blood-based cancer classification system. Further investigations of the regulating mechanisms of the miRNAs that contributed strongly to accurate prediction of cancer type could pave the way for the clinical use of circulating miRNA diagnostics.

[Gentle Method to Elevate Left Liver Lobe in Robot Assisted Gastrectomy].

Robot-assisted gastrectomy with the Davinci XiTM has been performed in our department since August 2019. This technique requires elevation of the left liver lobe. In order to prevent perioperative liver injury and expansion of postoperative subcutaneous emphysema, we use a silicone disc(HAKKO MEDICAL Co., Ltd.)and thread to elevate the liver. After docking the Davinci system, we move the needle as follows:(ⅰ). left side peritoneum near the left triangular ligament, (ⅱ). silicone rubber(, ⅲ). center of crus(, ⅳ). silicone rubber(, ⅴ). hepatic cirrus, and(ⅵ). right side peritoneum. Both ends of the thread are guided out of the abdominal cavity from both hepatic circumflex by end-close, forming a V-shape with the center of crus at the bottom, which provides a stable and effective view of the liver. Fifty-three cases were performed after introduction of this elevation technique. Median AST and ALT on postoperative day 1 were 37(14-1,556)IU/L and 30(10- 1,676)IU/L, respectively, although small subcutaneous emphysema confined to the anterior chest and upper abdominal wall was observed in 2 patients(3.8%). No cases of extensive subcutaneous emphysema involving the neck or extremities were observed. This elevation technique protects the liver and may reduce the incidence of postoperative subcutaneous emphysema.

Prognostic Impact of Long-term Postoperative Pneumonia in Elderly Patients with Early Gastric Cancer.

Background: Elderly patients with stage I gastric cancer, a disease that is curable by surgery, easily develop long-term postoperative pneumonia (LTPP) within two years after surgery despite showing no active symptoms. The present study assessed whether or not LTPP determines the later prognosis among elderly patients. Methods: We retrospectively examined patients >75 years old who underwent R0 gastrectomy for gastric cancer and were diagnosed with T1 disease at National Cancer Center Hospital between 2005 and 2012. LTPP was evaluated by chest computed tomography every year until two years after surgery. Results: Of the 3412 patients who underwent gastrectomy in our hospital during this period, 159 were included in this study. The elderly patients who developed LTPP had a worse prognosis than those who did not. Furthermore, their comorbidities and LTPP were significant independent risk factors for a poor prognosis. Patients who developed LTPP had a significantly higher risk of dying due to respiratory disease or cardiovascular disease than those without pneumonia. Conclusions: LTPP was significantly related to a poor survival and death from respiratory disease. To improve the prognosis, not only nutritional support but also exercise and rehabilitation program may be required for patients who develop LTPP within two years after surgery.

A retrospective 5-year survival analysis of surgically resected gastric cancer cases from the Japanese Gastric Cancer Association nationwide registry (2001-2013).

BACKGROUND: The nationwide registry of the Japanese Gastric Cancer Association collected data of surgically resected cases of gastric cancer between 2001 and 2013. These retrospective analyses aimed to delineate tumor characteristics, surgical history, and survival distribution. METHODS: Data from 254,706 patients with primary gastric cancer were included. The 5-year survival rates were calculated for various subsets of prognostic factors. RESULTS: The number of patients over 70 years old increased from 2001 to 2013. The frequency with which laparoscopic gastrectomy was opted for increased dramatically (from 3.5 to 40.8%) in 13 years. We focused on the patients registered between 2010 and 2013, for whom data collection was based on the 3rd edition of the Japanese classification and guidelines. Five-year overall survival (OS) rate among 92,305 patients with resected tumors was 70.6%. The 5-year OS rates of patients with pathological stage IA, IB, IIA, IIB, IIIA, IIIB, IIIC, and IV disease were 89.6%, 83.2%, 77.6%, 68.1%, 59.3%, 45.6%, 29.9%, and 14.0%, respectively. CONCLUSION: Our detailed analysis highlights the historical changes in outcomes of surgically treated gastric malignancies in Japan, and provides robust dataset for future analysis.

Long-term postoperative pneumonia in elderly patients with early gastric cancer.

BACKGROUND: Pneumonia is a major cause of death in the elderly population. Considering body weight loss, muscle loss, and reflux after gastrectomy, elderly patients are considered to be at very high risk for pneumonia, which could decrease overall survival because early gastric cancer is mostly curable only by surgery. We aimed to clarify the incidence of pneumonia in the long-term period after gastrectomy in elderly patients who were diagnosed with early gastric cancer and its risk factors. METHODS: We retrospectively examined patients of > 75 years of age who underwent R0 gastrectomy for gastric cancer and who were diagnosed with T1 disease at National Cancer Center Hospital between 2005 and 2012. Long-term postoperative pneumonia was diagnosed by chest computed tomography every year until 2 years after surgery. The presence of preoperative sarcopenia was assessed using preoperative L3 skeletal muscle index. RESULTS: 167 patients were included in this study. Long-term postoperative pneumonia was observed in 44 (26%) patients. Of the 44 people diagnosed with long-term postoperative pneumonia, 33 were diagnosed in the 1st year and 11 in the 2nd year. 117 patients (70%) were diagnosed with sarcopenia which was significantly frequently found in the patients who developed long-term postoperative pneumonia (91%) than those without (63%). Preoperative sarcopenia was the only independent risk factor in multivariate analysis. Type of gastrectomy was not a significant risk factor. CONCLUSIONS: Long-term postoperative pneumonia was frequently observed in the elderly patients. Preoperative sarcopenia was associated with long-term postoperative pneumonia in elderly patients who underwent curative surgery for gastric cancer. After gastrectomy, long-term special care would be required for elderly patients, especially with sarcopenia.

Optimal surgery and lymph node metastasis of duodenal bulbar neuroendocrine neoplasms.

BACKGROUND: There is no consensus on the extent of nodal dissection for duodenal bulbar NENs (neuroendocrine neoplasms). MATERIALS AND METHODS: We constructed and analyzed a combined dataset consisting of the patients who received surgery in our hospital and the patients from the literature based on a systematic review. The incidence, risk factors and location of nodal metastases were examined. RESULTS: Fifty-nine cases including 11 cases managed at our hospital and 48 cases identified from the literature search were examined. Nodal metastasis was observed in 24 patients (40.7%). The 5-year overall survival rate was 100%, regardless of nodal metastasis. Risk factors for lymph node metastasis were tumor size ≥15 mm and muscularis propria or deeper invasion. Stomach-related lymph node metastasis was found in >20% of patients who were positive for at least one risk factor and 15.4% when patients were negative for both risk factors, while pancreas-related lymph node metastasis was observed in 45.5% of patients who were positive for both risk factors, 7.7% who were only positive for one risk factor, and 0% who were negative for both risk factors. CONCLUSIONS: Tumor size and depth of invasion would determine whether the optimal surgery for duodenal bulbar NENs is distal gastrectomy or pancreatico-duodenectomy.

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.

PURPOSE: Gastric 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. METHODS: The 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. RESULTS: Thirty-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. CONCLUSIONS: A 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.

Radiofrequency therapy improves exercise capacity of mice with emphysema.

Emphysema is a common phenotype of chronic obstructive pulmonary disease (COPD). Although resection of emphysematous tissue can improve lung mechanics, it is invasive and fraught with adverse effects. Meanwhile, radiofrequency (RF) treatment is an extracorporeal method that leads to tissue destruction and remodeling, resulting in "volume reduction" and overall improvement in lung compliance of emphysematous lungs. Whether these changes lead to improved exercise tolerance is unknown. Here, we investigated the effectiveness of RF treatment to improve the exercise capacity of mice with emphysema. Fifty-two mice (7 weeks of age) were used in this experiment. A bilateral emphysema model was created by intratracheally instilling porcine pancreatic elastase (PPE) (1.5U/100 g body weight). RF treatment (0.5 W/ g body weight) was administered extracorporeally 14 days later and mice were sacrificed after another 21 days. The exercise capacity of mice was measured using a treadmill. Treadmill runs were performed just before PPE instillation (baseline), before RF treatment and before sacrifice. Following sacrifice, lung compliance and mean linear intercept (Lm) were measured and fibrosis was assessed using a modified Ashcroft score. There were 3 experimental groups: controls (instilled with saline, n = 12), emphysema (instilled with porcine pancreatic elastase, PPE, n = 11) and emphysema + treatment (instilled with PPE and given RF, n = 9). At endpoint, the maximum velocity of the emphysema + treatment group was significantly higher than that of the emphysema group, indicating improved exercise tolerance (86.29% of baseline vs 61.69% of baseline, p = 0.01). Histological analysis revealed a significant reduction in emphysema as denoted by Lm between the two groups (median 29.60 µm vs 35.68 µm, p = 0.03). The emphysema + treatment group also demonstrated a higher prevalence of lung fibrosis (≧Grade 3) compared with the emphysema group (11.7% vs 5.4%, p < 0.01). No severe adverse events from RF were observed. RF treatment improved the exercise capacity of mice with emphysema. These data highlight the therapeutic potential of RF treatment in improving the functional status of patients with COPD.

The prognostic impact of macroscopic serosal change on resectable advanced gastric cancer.

BACKGROUND: Advanced gastric cancer sometimes causes macroscopic serosal change (MSC) due to direct invasion or inflammation. However, the prognostic significance of MSC remains unclear. METHODS: A total of 1410 patients who had been diagnosed with deeper-than-pathological-T2 gastric cancer and undergone R0 gastrectomy with lymph node dissection at the National Cancer Center Hospital during January 2000 and December 2012 were restrospectively reviewed. RESULTS: MSC was not found in 108 of the 506 patients with pathological T4a (21.3%), whereas it was detected in 250 of the 904 patients with pathological T2-T3 (27.7%). The sensitivity, specificity and accuracy for diagnosing pathological serosa exposed (SE) by MSC were 78.7, 72.3 and 74.6%, respectively. The MSC-positive cases had a worse 5-year overall survival (OS) than the MSC-negative cases in pT3 (72.9% vs. 84.3%, p = 0.001), pT4a (56.2% vs. 73.4%, p = 0.001), pStageIIB (76.0% vs. 88.4%, p = 0.005), pStageIIIA (63.4% vs. 75.6%, p = 0.019), pStageIIIB (53.6% vs. 69.2%, p = 0.029) and pStage IIIC (27.6% vs. 50.0%, p = 0.062). A multivariate analysis showed that MSC was a significant independent predictor for the OS (hazard ratio [HR]: 1.587, 95%CI 1.209-2.083, p = 0.001) along with the tumor depth (HR: 7.742, 95%CI: 2.935-20.421, p < 0.001), nodal status (HR:5.783, 95% CI 3.985-8.391, p < 0.001) and age (HR:2.382, 95%CI: 1.918-2.957, p < 0.001). Peritoneal recurrence rates were higher in the MSC-positive cases than in the MSC-negative cases at each pT stage. CONCLUSIONS: In this study, the MSC was one of the independent prognostic factors in patients with resectable locally advanced gastric cancer.

Is lymph node dissection for neuroendocrine carcinoma of the stomach effective as it is for adenocarcinoma?

BACKGROUND: We evaluated the significance of lymph node dissection for gastric neuroendocrine carcinoma (NEC) by calculating the therapeutic value index for each station. METHODS: This study included 2164 advanced gastric cancer patients (common-type [Common-GC], n = 2125; and gastric NEC [NEC-GC], n = 39). Clinicopathological data were collected, and survival, type of recurrence, and the index for each type of gastrectomy were determined. RESULTS: NEC-GC was characterized by an older population (P = 0.009), upper tumor location (P = 0.021), frequent venous invasion (P < 0.001), and less neural invasion (P = 0.043). NEC-GC tended to be more frequent in men (P = 0.152), and to be associated with total gastrectomy (P = 0.177) and M1 cases (P = 0.167). The five-year overall survival rates of the Common-GC and NEC-GC groups were 73.8% (95% confidence interval: 71.8-75.6) and 54.7% (37.5-68.9), respectively (P = 0.016). Both groups showed similar index values in each station. Regarding the index of the peri-gastric nodal station (D1 station)/stations away from the stomach (D2 station), although the index of the D1 station was similar in the two groups (41.3 and 43.1), the index of the D2 station in the NEC-GC group was approximately half that of the Common-GC group (10.0 and 5.3). The total recurrence rates of the two groups were similar (P = 0.871). However, the rates of hematogenous and lymphatic recurrence tended to be higher in the NEC-GC group (P = 0.132 and P = 0.152). CONCLUSIONS: The therapeutic efficacy of the D1 station was similar in Common-GC and NEC-GC but that of the D2 station was worse in NEC-GC. Gastrectomy with D2 dissection would be less effective for NEC-GC.

Recurrence after ESD curative resection for early gastric cancer.

BACKGROUND: Endoscopic 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 PRESENTATION: A 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. CONCLUSION: This 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.

Laparoscopic resection of a primary diaphragmatic schwannoma: a case report and literature review.

BACKGROUND: Schwannomas are nerve sheath tumors that commonly originate from the stomach and small intestine. A primary schwannoma of the diaphragm is rare and does not show any symptoms until it grows to a certain size. Hence, it is extremely rare that it was found at a size that allowed resection under videoscopic surgery. CASE PRESENTATION: A 77-year-old woman was referred to our department for surgical treatment of a tumor located near the gastric fornix. She underwent a routine esophagogastroduodenoscopy 2 years and 7 months prior to the referral. It was suspected that she had a submucosal tumor measuring 10 mm, located in the fornix, and was then referred to her previous physician. During her follow-up, endoscopic ultrasonography (EUS) revealed that the cystic structure had continued to grow toward the gastric wall, and she was then referred to the endoscopy division of our hospital. She continued to be followed-up, and it was noted that the tumor was gradually increasing in size. Therefore, she requested surgical resection, and was finally referred to our division. Since the tumor was rather small, we planned a laparoscopic surgery. An initial examination during the operation revealed that the tumor was located on the left diaphragm. Since the tumor was relatively small and visibility was good, we decided to continue with the laparoscopic surgery. Partial diaphragmectomy with complete inclusion of the tumor was performed, and the defect of the diaphragm was directly closed by a running suture. Pathological examination revealed a benign schwannoma that had originated from the diaphragm. To support our findings, we also reviewed the scientific literature on diaphragmatic schwannoma cases reported up to April 2020. CONCLUSIONS: In this extremely rare case, we successfully resected the diaphragmatic schwannoma using laparoscopic surgery.

Extra-gastrointestinal stromal tumor arising in the lesser omentum with a platelet-derived growth factor receptor alpha (PDGFRA) mutation: a case report and literature review.

BACKGROUND: Gastrointestinal stromal tumors (GIST) arising from sites other than the gastrointestinal (GI) tract, termed extra-gastrointestinal stromal tumors (EGIST), are rare. Among EGIST, those with platelet-derived growth factor receptor alpha (PDGFRA) mutations are even rarer, with only a few cases reported. About 80% of GIST has KIT mutations, and 10% of GIST have PDGFRA mutations, which commonly affect the TK2 domain (exon 18). Among the exon 18 mutations, the D842V substitution is limited to gastric GIST. In EGIST, the degree of KIT and PDGFRA mutations varies on where the location of the tumor is, and it is suggested that omental EGIST is similar to gastric GIST. Adjuvant imatinib therapy is recommended for high-risk GIST; however, it is known that imatinib is less effective against GIST with a PDGFRA D842V mutation. CASE PRESENTATION: A 75-year-old man was referred to our hospital with an extrinsic tumor of the lesser curvature of the gastric body. Intraoperative findings showed a tumor located outside of the lesser omentum with no connection between the tumor and the gastric wall. The tumor was subsequently resected. Pathological examination indicated a GIST arising in the lesser omentum measuring 70 mm in its longer dimension. Because the tumor had a PDGFRA mutation (D842V substitution), imatinib was suspected to lack efficacy to the tumor. Thus, although the tumor was considered clinically to have a high risk of recurrence, adjuvant imatinib therapy was not indicated. The patient has been free of recurrence for 29 months since the surgery. CONCLUSION: We described a case of EGIST with a PDGFRA mutation arising in the lesser omentum. And we reviewed 57 cases of omental EGIST and showed that the clinicopathological characteristics and mutation status in omental EGIST were very similar to gastric GIST. In particular, PDGFAR D842V mutation rate in omental EGIST seemed as high as that in gastric GIST. These results suggested that omental EGIST is strongly related to gastric GIST, so the behavior of omental EGIST might be akin to gastric GIST. However, further studies are required to determine the prognosis and the necessity of adjuvant therapy for EGIST with a PDGFRA mutation.