Para-aortic lymph node dissection following neoadjuvant chemotherapy for type 4 or large type 3 gastric cancer with extensive lymph node metastasis.

BACKGROUND: D2 and para-aortic lymph node dissection (PAND) following neoadjuvant chemotherapy (NAC) are reportedly effective for gastric cancer (GC) with extensive lymph node metastasis (ELM), such as para-aortic nodal metastasis or bulky nodal metastasis, around the major perigastric arteries. However, type 4 and large type 3 tumors were excluded from previous studies, as they are considered special subtypes that easily spread to the peritoneum. Whether or not PAND contributes to the survival of type 4 or large type 3GC with ELM is thus unclear. METHODS: This study examined patients who underwent radical gastrectomy with D2 resection and PAND following NAC between 2002 and 2019. Patients were classified into the normal-type group and the type 4 or large type 3 group. The overall survival (OS) and prognostic factors were investigated. RESULTS: Forty-nine patients were examined and classified into the normal-type group (34 patients) and type 4 or large type 3 group (15 patients). The 5-year OS rates of the normal-type and type 4 or large type 3 groups were 55.5% and 26.7%, respectively. Type 4 or large type 3 tumors were an independent risk factor for a poor prognosis in the multivariate analysis (hazard ratio: 2.506, 95% confidence interval: 1.111-5.650, and p = 0.027). CONCLUSIONS: The prognosis of type 4 or large type 3 GC with ELM treated with radical gastrectomy with D2 and PAND after NAC was poor. Type 4 or large type 3 GC with ELM should be treated using a different strategy than the normal type with ELM.

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.

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.

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.

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.

[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.

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.

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.

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.

A nodal diagnosis by computed tomography is unreliable for patients who need additional gastrectomy after endoscopic submucosal dissection.

PURPOSE: T1 gastric cancer is treated by endoscopic submucosal dissection (ESD) or surgery, considering the risk of lymph node metastasis. Additional gastrectomy is necessary when the pathological specimens after ESD show some risk of lymph node metastasis. Preoperative computed tomography (CT) after ESD sometimes reveals enlarged lymph nodes, which should prompt surgeons to select D2 over D1/D1+. However, whether or not CT after ESD is reliable remains unclear. METHODS: Patients who underwent radical gastrectomy for clinical T1 between April 2015 and June 2019 were enrolled. The patients were classified into those who underwent CT after ESD (group A) and those who underwent CT before primary surgery or ESD (group B). The accuracy of the nodal diagnosis was compared between groups. RESULTS: A total of 650 patients (group A; 81, group B; 569) were examined. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value (group A vs. group B) were 77.8% vs. 84.2%, 0.0% vs. 15.9%, 84.0% vs. 95.7%, 0.0% vs. 38.2%, and 91.3% vs. 87.1%, respectively. The false-positive rate was 100% in group A and 61.8% in group B (p = 0.011). CONCLUSIONS: A nodal diagnosis by CT is unreliable for patients who need additional gastrectomy after ESD.

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.

Incidence of and risk factors for preoperative deep venous thrombosis in patients undergoing gastric cancer surgery.

BACKGROUND: Pulmonary thromboembolism (PE) is one of the life-threatening complications of gastric cancer surgery. D-dimer assay is a safe and rapid tool to exclude the presence of deep venous thrombosis (DVT). In July 2012, we started preoperative DVT screening of patients scheduled for gastric cancer surgery using a combination of D-dimer measurements and lower extremity venous ultrasonography to prevent PE. METHODS: Between July 2012 and August 2015, 976 consecutive patients underwent gastric cancer surgery with preoperative D-dimer screening. Lower extremity venous ultrasonography was performed in patients with a positive D-dimer assay result (greater than 1.0 µg/ml). The incidence of and risk factors for preoperative DVT and the incidence of PE were examined in patients undergoing gastric cancer surgery. RESULTS: Of the 976 patients, 176 (18.0%) showed positive D-dimer assay results, and in 13 (1.3%) DVT was diagnosed by lower extremity ultrasonography. Our analysis identified neoadjuvant chemotherapy as a risk factor for preoperative detection of DVT in patients undergoing gastric cancer surgery (P = 0.021). The incidence of PE was 0.1% (1/976). CONCLUSION: Preoperative gastric cancer patients receiving neoadjuvant chemotherapy seem to be at higher risk for the development of DVT.

Evaluation of 64-Channel Contrast-Enhanced Multi-detector Row Computed Tomography for Preoperative N Staging in cT2-4 Gastric Carcinoma.

BACKGROUND: Preoperative N staging is essential for the best treatment planning in patients with gastric carcinoma. The aim of this study was to evaluate the accuracy of preoperative N staging using contrast-enhanced multi-detector row computed tomography (CE-MDCT) in patients with resectable cT2-4 gastric carcinoma. METHODS: A total of 218 patients who underwent a gastrectomy with D2 lymphadenectomy for previously untreated cT2-4 primary gastric carcinoma were studied. Preoperative N staging was performed according to the 7th (UICC) TNM Staging System using pre-specified criteria on a 64-channel CE-MDCT and was compared with postoperative pathologic N staging. RESULTS: In all 218 patients, a distal or total gastrectomy was performed. The overall accuracy of the preoperative N staging was 46.3% (101/218), with the proportion of over- and under-staging being 26.6% (58/218) and 27.1% (59/218), respectively. The sensitivity, specificity, and accuracy for lymph node metastasis (≥pN1) were 79.1% (106/134), 50.0% (42/84), and 67.9% (148/218), respectively. The sensitivity, specificity, and accuracy for multiple lymph node metastases (≥pN2) were 80.2% (73/91), 68.5% (87/127), and 73.4% (160/218), respectively. Multivariate analyses showed that macroscopic type 2 and ≥6 cm-sized tumors were associated with preoperative over-N staging, while macroscopic type 1/3 tumors were associated with under-N staging. CONCLUSION: Preoperative N staging with pinpoint accuracy is difficult. However, CE-MDCT offers a reasonably high sensitivity and specificity for ≥pN2 and may be useful for selecting candidates for neoadjuvant therapies. The macroscopic type and size of the primary tumor may affect the accuracy of preoperative N staging.

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.

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.

Characteristics of Metachronous Remnant Gastric Cancer After Proximal Gastrectomy: A Retrospective Analysis.

PURPOSE: Despite annual endoscopy, patients with metachronous remnant gastric cancer (MRGC) following proximal gastrectomy (PG) are at times ineligible for endoscopic resection (ER). This study aimed to clarify the clinical risk factors for ER inapplicability. MATERIALS AND METHODS: We reviewed the records of 203 patients who underwent PG for cT1 gastric cancer between 2006 and 2015. The remnant stomach was categorized as a pseudofornix, corpus, or antrum. RESULTS: Thirty-two MRGCs were identified in the 29 patients. Twenty MRGCs were classified as ER (ER group, 62.5%), whereas 12 were not (non-ER group, 37.5%). MRGCs were located in the pseudo-fornix in 1, corpus in 5, and antrum in 14 in the ER group, and in the pseudo-fornix in 6, corpus in 4, and antrum in 2 in the non-ER group (P=0.019). Multivariate analysis revealed that the pseudo-fornix was an independent risk factor for non-ER (P=0.014). In the non-ER group, MRGCs at the pseudo-fornix (n=6) had more frequent undifferentiated-type histology (4/6 vs. 0/6), deeper (≥pT1b2; 6/6 vs. 2/6) and nodal metastasis (3/6 vs. 0/6) than non-pseudo-fornix lesions (n=6). We examined the visibility of the region developing MRGC on an annual follow-up endoscopy one year before MRGC detection. In seven lesions at the pseudofornix, visibility was only secured in two (28.6%) because of food residues. Of the 25 lesions in the non-pseudo-fornix, visibility was secured in 21 lesions (84%; P=0.010). CONCLUSIONS: Endoscopic visibility increases the chances of ER applicability. Special preparation is required to ensure the complete clearance of food residues in the pseudo-fornix.

Functional role of CD44v-xCT system in the development of spasmolytic polypeptide-expressing metaplasia.

Cancer development is often preceded by the appearance of preneoplastic lesions. In gastric carcinogenesis, chronic inflammation and histopathologic progression of the stomach epithelium lead to the development of metaplasia and eventually adenocarcinoma. The cell surface protein CD44, especially its variant isoforms (CD44v), has been implicated in metaplasia-carcinoma sequence progression in the stomach. We recently found that CD44v interacts with and stabilizes xCT, a subunit of the cystine transporter system xc(-), in cancer cells and thereby increases cystine uptake and confers resistance to various types of cellular stress in vivo. The functional relevance of CD44v and xCT in the development of preneoplastic lesions, however, has remained unknown. We have now examined the role of the CD44v-xCT system in the development of spasmolytic polypeptide-expressing metaplasia (SPEM) in mouse models of gastric carcinogenesis. CD44v was found to be expressed de novo in SPEM, and CD44v(+) metaplastic cells manifested upregulation of xCT expression compared with CD44v(-) cells. Genetic ablation of CD44 or treatment with sulfasalazine, an inhibitor of xCT-dependent cystine transport, suppressed the development of SPEM and subsequent gastric tumor growth. Therapy targeted to CD44v-xCT could thus prove effective for prevention or attenuation of the CD44v-dependent development of preneoplastic lesions and cancer.

Intraoperative fluorescence lymphography using indocyanine green in a patient with chylothorax after esophagectomy: report of a case.

We report a case of chylothorax treated successfully by a new diagnostic tool: indocyanine green (ICG) fluorescence lymphography. The patient, a 65-year-old man with adenocarcinoma of the esophagogastric junction, underwent radical esophagectomy, which was followed by the development of chylothorax. On postoperative day 10, we performed transabdominal ligation of the thoracic duct. During the re-operation, we injected ICG into the mesentery of the small bowel. We then performed mass ligation of the tissue right and dorsal of the aorta, including the thoracic duct, after which a near-infrared camera system revealed a fluorescent stripe on the caudal part of the ligation. The remnant thoracic duct appeared to be dilated as a result of lymphatic stasis. The patient was discharged 35 days after his initial surgery. We report this case to demonstrate the usefulness of intraoperative ICG lymphography as a tool to identify and confirm ligation of the thoracic duct transabdominally.