Management of elderly patients with early gastric cancer in Japan.

Management of elderly patients with early gastric cancer is an important issue in an aging society such as Japan. While endoscopic resection is recommended as the standard treatment for early gastric cancers with extremely low risk of lymph node metastasis (<1%), gastrectomy with lymphadenectomy is recommended for the other early gastric cancers as the standard treatment even in elderly patients. Endoscopic submucosal dissection is the most recommended endoscopic resection procedure because of its high ability for 'en bloc' resection. Endoscopic submucosal dissection can reportedly provide favorable short-term outcomes in elderly patients. In terms of patient prognosis, the importance of considering patients' physical and nutritional conditions before endoscopic submucosal dissection has recently attracted attention. With respect to gastrectomy, the nationwide data in Japan have demonstrated relatively low 5-year overall survival and non-negligible post-operative 90-day mortality in men aged ≥75 years and women aged ≥80 years compared with those in younger patients. Among these elderly patients, 20% or more reportedly died within 5 years after gastrectomy mostly due to other diseases. These facts suggested the necessity of a less invasive management option for the elderly patients. Efforts are being made to provide a non-invasive follow-up option without gastrectomy following endoscopic resection in elderly patients. To avoid the increase in gastric cancer-related deaths, the selection of patients with relatively low lymph node metastasis risk is essential, and several tools to estimate the lymph node metastasis risk from early gastric cancers have been developed. To avoid overtreatment with gastrectomy in more elderly early gastric cancer patients, new endoscopic submucosal dissection indications for them are also warranted.

A Pilot Study Analyzing the Clinical Utility of Comprehensive Genomic Profiling Using Plasma Cell-Free DNA for Solid Tumor Patients in Japan (PROFILE Study).

BACKGROUND: The clinical utility of plasma cell-free DNA in precision cancer medicine has not been established. A pilot study was conducted to investigate the clinical utility of comprehensive genomic profiling by liquid biopsy in a Japanese population. METHODS: In this PROFILE study, 102 patients with advanced solid tumors who showed progression with standard systemic therapy underwent liquid biopsy between August 2017 and February 2020. Liquid biopsy was performed using Guardant360. RESULTS: Of the 102 patients, 56 were women, and the median age was 65 years. Regarding the types of cancer, 31 were hepatobiliary and pancreatic cancer, 17 were gastrointestinal cancer, and 13 were breast cancer. Frequently altered genes were TP53 (53.9%, 46/102), KRAS (25.5%, 26/102), PIK3CA (19.6%, 20/102), and EGFR (17.6%, 18/102). At least one genetic aberration was detected in 92 patients (90.2%). Actionable mutation was discovered in 88 patients (86.3%), and 67 patients (65.7%) were clinical trial candidates. Of the 102 patients, 22 (21.6%) were able to receive biomarker-matched therapy. Their best responses were as follows: 1 complete response, 3 partial responses, 7 stable diseases, and 11 progressive diseases. Additionally, the treated patients were divided on the basis of matching scores (≥ 50% vs. < 50%). The patients were divided into high and low groups. The high group had a higher disease control rate (DCR) of 75% compared with 20% in the low group (P = 0.010). CONCLUSIONS: The results indicate that liquid biopsy is useful for identifying actionable mutations associated with the clinical response of selected patients.

Intraoperative blood loss as an independent prognostic factor for curative resection after neoadjuvant chemotherapy for gastric cancer: a single-center retrospective cohort study.

PURPOSE: Surgery-induced factors such as postoperative infectious complications (PICs) and intraoperative blood loss (IBL) have a negative impact on the survival of patients undergoing surgery for gastric cancer. A recent study showed that neoadjuvant chemotherapy (NAC) could reduce the negative impact of PICs; hence, we conducted the present study to investigate if NAC can also reduce the negative prognostic impact of IBL. METHODS: We reviewed 115 gastric cancer patients treated with NAC and radical gastrectomy. The cut-off for IBL predicting the long-term survival was assessed by a receiver operating characteristic curve. The Cox proportional hazard model was used to evaluate the association between patient characteristics including IBL, overall survival, and disease-free survival. RESULTS: The cut-off for IBL was set at 990 ml. Twenty-six patients had excessive IBL exceeding 990 ml (22.6%) and PICs developed in 33 patients (28.7%). The body mass index, IBL, ypT, and ypN were significant independent prognostic predictors, but PICs were not. CONCLUSION: NAC did not decrease the risk induced by excessive IBL. The prophylactic effect of NAC on surgery-induced risk was inconsistent.

Is surgery alone sufficient for treating T1 gastric cancer with extensive lymph node metastases?

BACKGROUND: Whether or not surgery alone is sufficient for treating patients with pathological stage T1N2M0 (Stage IIA), T1N3a/bM0 (Stage IIB/IIIB), and T3N0M0 (Stage IIA) gastric cancer who were not indicated for adjuvant treatment according to the Japanese gastric cancer treatment guideline remains unclear. METHODS: We retrospectively reviewed the clinical records of 236 patients who had been diagnosed with pT1N2-3b/pT3N0 gastric cancer and undergone R0 gastrectomy with lymph node dissection between January 2000 and December 2012 at the National Cancer Center Hospital, Japan. RESULTS: The 5-year recurrence-free survival (RFS) rates (95% confidence interval [CI]) of the patients with pathological (p) T1N2-3b and T3N0 cancer were 73.9% (63.1-84.7) and 89.5% (84.0-95.0), respectively. The only significant prognostic factors for the survival identified by a multivariate Cox regression analysis in patients with pT1N2-3 cancer were the pN stage (N3a/N2: hazard ratio [HR] 2.940, 95% CI 1.314-5.577; N3b/N2: HR 8.688, 95% CI 3.096-24.382) and tumor diameter (<30/ ≥ 30 mm) (HR 2.919; 95% CI 1.351-6.304). We divided the patients with pT1N2-3 gastric cancer into 3 risk categories (high, moderate, low) using these 2 significant prognostic factors and found that the 5-year RFS rates were significantly different among the 3 risk groups (low risk, 93.0%; moderate risk, 66.7%; high risk, 25.0%; P < 0.001). CONCLUSIONS: pT3N0 and large pT1N2 with a diameter ≥ 30 mm had an excellent prognosis, while pT1N2-3 with at least N3a/b or a tumor diameter < 30 mm showed a relatively poor prognosis. These patients may be candidates for adjuvant chemotherapy.

Different risks of nodal metastasis by tumor location in remnant gastric cancer after curative gastrectomy for gastric cancer.

BACKGROUND: Curative surgery for remnant gastric cancer (RGC) after gastrectomy for gastric cancer (GC) can be challenging. We examined the risk factors for lymph node metastasis in RGC, especially for tumors located at the greater curvature (G) or non-greater curvature (NG), to determine the appropriate indications of curative surgery. METHODS: Data from the two high-volume centers of Japan between 1998 and 2018 were retrospectively reviewed. Among the 137 patients enrolled in this study, 34 were classified as the G group and 103 as the NG group. The incidence of lymph node metastasis and its risk factors was evaluated. RESULTS: Lymph node metastasis was observed in 21.2% (29/137), including 38.2% (13/34) in the G group and 15.5% (16/103) in the NG group (p = 0.008). A logistic regression analysis showed that tumor location of G or NG (p = 0.042), tumor size (p = 0.002) and depth of invasion (p = 0.009) were significant independent risk factors for nodal metastasis. Risk classification using these factors showed that clinical T1-T2 with a maximum size < 35 mm located at the non-greater curvature had the lowest nodal metastatic risk (4.3%). CONCLUSIONS: Tumor location at the G or NG was a significant risk factor for nodal metastasis in RGC. When selecting curative surgery for RGC, physicians should consider the nodal metastatic risk calculated by the tumor location, size and depth of invasion.

Long-term outcomes of preoperative docetaxel with cisplatin plus S-1 therapy for gastric cancer with extensive nodal metastasis (JCOG1002).

BACKGROUND: Preoperative chemotherapy with cisplatin plus S-1 (CS) followed by gastrectomy with D2 plus para-aortic lymph node (PAN) dissection is regarded as a standard treatment in Japan for advanced gastric cancer with bulky lymph node (BN) and/or PAN metastasis. In the JCOG1002, we added docetaxel to CS (DCS) to further improve long-term outcomes. However, the primary endpoint, clinical response rate (RR), did not reach the expected level (Ito et al. in Gastric Cancer 20:322-31, 2017). Herein, we report our long-term survival results. METHODS: Patients with BN and/or PAN metastasis received 2 or 3 cycles of DCS therapy (docetaxel at 40 mg/m2 and cisplatin at 60 mg/m2 on day 1 and S-1 at 80 mg/m2 per day for 2 weeks, followed by a 2-week rest) followed by gastrectomy with D2 plus PAN dissection and postoperative S-1 for 1 year. RESULTS: Between July 2011 and May 2013, 53 patients were enrolled. Clinically, 17.0% had both PAN and BN metastasis, and the rest had either PAN (26.4%) or BN (56.6%) metastasis. Among all eligible patients, the 5-year overall survival was 54.9% (95% confidence interval 40.3-67.3%) at the last follow-up in May 2018. Among 44 eligible patients with R0 resection, the 5-year relapse-free survival was 47.7% (95% confidence interval 32.5-61.5%). CONCLUSIONS: Adding docetaxel to CS in preoperative chemotherapy for extensive nodal metastasis improved neither short-term outcomes nor long-term survival. Preoperative chemotherapy with CS followed by D2 + PAN dissection and postoperative S-1 remains the standard of care for patients with extensive nodal metastasis.

Predictive value of the surgical Apgar score on postoperative complications in advanced gastric cancer patients treated with neoadjuvant chemotherapy followed by radical gastrectomy: a single-center retrospective study.

BACKGROUND: The surgical Apgar score (SAS) or modified SAS (mSAS) has been reported as a simple and easy risk assessment system for predicting postoperative complications in primary surgery for gastric cancer. However, few studies have described the SAS's utility in gastric surgery after neoadjuvant chemotherapy (NAC). METHODS: One hundred and fifteen patients who received NAC and radical gastrectomy from 2008 and 2015 were included in this study. The SAS was determined by the estimated blood loss (EBL), lowest intraoperative mean arterial pressure, and lowest heart rate. The mSAS was determined by the EBL reassessed using the interquartile values. The predictive values of the SAS/mSAS for postoperative complications were assessed with univariate and multiple logistic regression analyses. RESULTS: Among the 115 patients, 41 (35.7%) developed postoperative complications. According to analyses with receiver operating characteristic curves of the SAS and mSAS for predicting postoperative complications, the cut-off value of the mSAS was set at 8. The rates of anastomotic leakage, pancreatic fistula, and arrhythmia in patients with high mSAS (> 8) values were higher than in those with low (0-3) and moderate [1-4] mSAS values. A multiple logistic regression analysis showed that the operation time, body mass index, and diabetes mellitus were independent risk factors for postoperative complications. The mSAS was not a significant predictor. CONCLUSION: The predictive value of SAS or mSAS for morbidity may be limited in patients who undergo gastric cancer surgery after NAC. Future prospective studies with a large sample size will be needed to confirm the present results.

Diagnostic Accuracy and Usefulness of Intraoperative Margin Assessment by Frozen Section in Gastric Cancer.

BACKGROUND: Intraoperative frozen examination is clinically important for negative margin confirmation in cancer surgery. We investigated the diagnostic accuracy of frozen-section assessment and risk factors for positive resection margins by studying gastric cancer specimens from 1115 patients treated at our hospital. METHODS: The results of gastric cancer patients who had undergone intraoperative margin assessment, employing frozen examination, with curative intent in our unit between 2000 and 2017 were retrospectively analyzed. Frozen section assessments were compared with the corresponding permanent section assessments to evaluate the accuracy, sensitivity, and specificity of the former. The causes of discordances between two assessments were examined. In addition, risk factors associated with positive margins were identified. RESULTS: In total, 1241 specimens were obtained from the 1115 patients. The accuracy, sensitivity, and specificity of frozen-section assessments were 99.4%, 99.5%, and 97.8%, respectively. There were eight discordant cases. Two false-negative cases required another gastrectomy after final pathological diagnosis because of missed neoplastic cells. Six false-positive cases underwent unnecessary additional resection due to false positive results. In our frozen series, 89 cases had a positive margin on permanent section. Multivariate regression analysis of patients with positive surgical margins revealed large diameter (≥ 50 mm) and T4 tumor to be independent risk factors. CONCLUSIONS: Intraoperative frozen examination is a highly accurate method that is useful for achieving negative margins. This procedure is especially recommended for patients with a tumor larger than 50 mm in maximum diameter or serosal invasion to confirm a negative margin.

The Therapeutic Survival Benefit of Splenic Hilar Nodal Dissection for Advanced Proximal Gastric Cancer Invading the Greater Curvature.

BACKGROUND: The Japan Clinical Oncology Group phase 3 study confirmed the survival non-inferiority of spleen-preserving surgery against splenectomy for advanced proximal gastric cancer not invading the greater curvature. However, the efficacy of #10 lymph node (LN) dissection for tumors that involve the greater curvature remains unclear. METHODS: Data from patients who underwent D2-total gastrectomy with splenectomy between January 2000 and December 2012 were retrospectively reviewed. The study included 593 patients. The patients were split into two groups, with 212 patients in the tumor invasion of the greater curvature (Gre) group and 381 patients in the non-Gre group. Survival curves and the state of LN metastasis and the index of estimated benefit from LN dissection of each station were evaluated. RESULTS: The incidence of #10 LN metastasis was 8.1% (48/593): 15.1% in the Gre group and 4.2% in the non-Gre group. The 5-year overall survival rates for the patients with and without #10 metastasis were respectively 46.9 and 50.2% (P = 0.829) in the Gre group and 49.6 and 62.3% (P = 0.074) in the non-Gre group. The indices for #10 LN dissection were 7.1 in the Gre group and 2.3 in the non-Gre group. In the Gre group, the node station with the highest index was #3, followed by #4d, #1, #4sb, #4sa, #7, #2, #10 (index > 7). CONCLUSION: The splenic hilar nodes should be prioritized as a component of D2 lymphadenectomy for advanced gastric cancer invading the greater curvature based on its high metastatic rate and index.

Correction to: Oncological safety of proximal gastrectomy for T2/T3 proximal gastric cancer.

The correct name of the corresponding author should be "Takaki Yoshikawa", and not "Takaki Yoshiaki" as given in the original publication of the article.

Does neoadjuvant chemotherapy cancel out the negative survival impact induced by surgical complications after gastrectomy?

BACKGROUND: Postoperative infectious complications (ICs) are associated with a poor prognosis following gastric cancer surgery. Neoadjuvant chemotherapy (NAC) targeting scirrhous-type or bulky nodal disease reportedly exerts a prophylactic effect on the negative impact of ICs. However, a recent study clearly showed that NAC for scirrhous-type disease had no survival benefit. We investigated this prophylactic effect and significant interactions among subgroups of histological response, macroscopic type, and bulky nodal disease. METHODS: We examined 115 patients who received NAC followed by radical gastrectomy between January 2008 and December 2015. The overall survival (OS) and disease-free survival (DFS) were compared between those with and without ICs. Our cohort included 62 with type 4/giant type 3, 44 with bulky nodal disease/para-aortic nodal disease, and 25 with other diseases. RESULTS: A histological response was observed in 80 patients (69.5%). Thirty three (28.7%) developed ICs. There was no significant difference in the OS [hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.47-1.99, p = 0.920] or DFS (HR 0.74; 95% CI 0.40-1.38, p = 0.342) by the presence of ICs. The HR was 1.00 in patients who had no response to NAC (grade 0/1a) and 0.95 in those who responded to NAC (grade 1b/2/3). No subgroups showed significant interactions for the OS. CONCLUSIONS: NAC may cancel out the negative impact of morbidity on the survival in advanced gastric cancer patients. The prophylactic effects by NAC do not depend on the tumor type or histological response.

Oncological safety of proximal gastrectomy for T2/T3 proximal gastric cancer.

BACKGROUND: It remains unclear whether total gastrectomy is necessary for patients with proximal T2/T3 gastric cancer. To explore the oncological safety of proximal gastrectomy for proximal T2/T3 gastric cancer, in this study, we evaluated the metastatic rates in and the therapeutic effect of dissection of key distal lymph node stations that are usually excluded in proximal gastrectomy. METHODS: In this study, we examined 202 patients seen between January 2000 and December 2012, who underwent total gastrectomy with lymph node dissection (D1/D1+/D2; 2/17/183) and was pathologically diagnosed as T2/T3 gastric cancer exclusively located in the upper third of the stomach. The theoretical therapeutic necessity of dissecting lymph nodes at each lymph node station was evaluated based on the therapeutic index calculated by multiplying the frequency of metastasis at each station and the 5-year survival rate of patients with metastasis to that station. RESULTS: The 5-year overall survival rate (95% confidence interval) was 72.9% (65.5-80.3). The metastatic rates at #4d and #12a were very low (0.99% and 0.006%, respectively), and those at #5 and #6 were zero, and therapeutic indices for #4d, #5, #6 and #12a were zero. On the other hand, the most frequent metastatic station was #3, followed by #1, #2 and #7 (overall metastatic rate > 12%), which was consistent with the order of the therapeutic indices. CONCLUSIONS: Considering the nodal stations that need to be dissected, proximal gastrectomy would be the choice and oncologically safe for patients with T2/T3 proximal gastric cancer.

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.

Feasibility of neoadjuvant S-1 and oxaliplatin followed by surgery for resectable advanced gastric adenocarcinoma.

PURPOSE: In Japan, the administration of S-1 following D2 gastrectomy is a standard treatment for stage II/III gastric cancer (GC). However, the survival of stage IIIB/IIIC GC remains unsatisfactory. To improve this, we conducted a multicenter phase II study to evaluate the safety and efficacy of a neoadjuvant S-1 and oxaliplatin regimen (SOX) followed by surgery targeted at stage III GC. METHODS: Oxaliplatin was administered intravenously (130 mg/m(2)) on day 1, and S-1 was administered orally (40 mg/m(2), twice a day) for 14 days followed by a seven-day rest period. After three cycles of therapy, D2 gastrectomy was performed. RESULTS: A total of 14 patients were enrolled and completed the protocol treatment. Grade 3/4 toxicities included thrombocytopenia (21.4 %), anorexia (14.3 %), and diarrhea (7.1 %). Seven patients (50 %) underwent total gastrectomy, and seven patients underwent distal gastrectomy. Grade 3/4 surgical complications included pancreatic fistula (21.4 %) and lung infection (7.1 %). The pathological response rate was 85.7 %. CONCLUSION: Although our data are limited and preliminary, neoadjuvant SOX followed by surgery can be performed safely with a high pathological response rate in patients with resectable advanced GC. Further investigation of this neoadjuvant approach is warranted.

Surgical treatment of non-early gastric remnant carcinoma developing after distal gastrectomy for gastric cancer.

BACKGROUND AND OBJECTIVES: The optimal surgical procedure for gastric remnant carcinoma (GRC) remains debatable. The aim of this study was to retrospectively evaluate the surgical treatments for T2-4 GRC developing after distal gastrectomy for gastric cancer. METHODS: Between 1970 and 2012, a total of 50 patients underwent R0 resection for T2-4 GRC. The clinicopathologic features, therapeutic methods, and follow-up data of these patients were reviewed. RESULTS: The tumor was located at a non-anastomotic site of the remnant stomach in 43 of the 50 patients. Total gastrectomy was performed in 48 patients and partial gastrectomy was in two patients. Lymph node metastasis was found in 19 patients. Major postoperative complications occurred in 16 patients. The overall 1-, 3-, and 5-year survival rates of the 50 patients were 90%, 66%, and 44%, respectively. Presence of small intestinal or esophageal infiltration and postoperative complications was independently associated with poorer survival. Dissection of the perigastric and splenic hilar/artery nodes was found to have potential therapeutic benefit. CONCLUSIONS: Surgical resection for T2-4 GRC developing after distal gastrectomy for gastric cancer can be invasive, but is feasible and effective. Total gastrectomy with splenectomy is one of the recommendable procedures for this disease.

Functional Advantages of Proximal Gastrectomy with Jejunal Interposition Over Total Gastrectomy with Roux-en-Y Esophagojejunostomy for Early Gastric Cancer.

BACKGROUND: The postoperative functional advantages of a proximal gastrectomy over a total gastrectomy remain debatable. The aim of this study was to evaluate the functional outcomes of a proximal gastrectomy with jejunal interposition (PG-JI), compared with those for a total gastrectomy with Roux-en-Y esophagojejunostomy (TG-RY), in patients with early gastric cancer. METHODS: Between 2007 and 2012, 65 patients underwent PG-JI and 117 underwent TG-RY for cT1 gastric cancer. Various parameters, including body weight, serum hemoglobin level, and interview-based symptoms, were prospectively evaluated in these patients. In patients who underwent PG-JI, the postoperative endoscopic findings were also assessed. RESULTS: All the surgeries were performed via a laparotomy alone. During a median postoperative follow-up of 42 months (range, 12-78 months), PG-JI offered significant reductions in body weight loss (12.5 ± 5.8 vs. 17.4 ± 6.4 %, P < 0.001), serum hemoglobin decline (7.0 ± 5.7 vs. 9.7 ± 5.4 %, P = 0.002), and dumping symptoms (11 % [7/65] vs. 30 % [35/117], P = 0.003), while being associated with similar incidences of anastomotic stricture (9 % [6/65] vs. 8 % [9/117], P = 0.781), small bowel obstruction (0 % [0/65] vs. 2 % [2/117], P = 0.538), stasis symptoms (51 % [33/65] vs. 44 % [51/117], P = 0.358), and reflux symptoms (34 % [22/65] vs. 23 % [27/117], P = 0.121), compared with TG-RY. Four cases of gastric remnant cancer and no cases of endoscopic reflux esophagitis were found after PG-JI. CONCLUSIONS: PG-JI has clear functional advantages over TG-RY, although it requires active surveillance for remnant gastric cancer.

HER2 expression in carcinomas of the true cardia (Siewert type II esophagogastric junction carcinoma).

OBJECTIVES: To evaluate the HER2 status in patients with Siewert type II esophagogastric junction carcinoma. BACKGROUND: Trastuzumab is now approved for use in the treatment of human epidermal growth factor receptor 2 (HER2)-positive unresectable metastatic gastric or esophagogastric junction (EGJ) carcinoma. Several studies have evaluated HER2 status in EGJ carcinoma, but none has addressed the implication of HER2 positivity in patients with Siewert type II EGJ carcinoma. METHODS: We retrospectively evaluated the frequency of HER2 positivity in a large single-center cohort of 208 patients with Siewert type II tumors. The relations between HER2 expression and the outcomes and other clinicopathologic features were examined. RESULTS: Overall, 18.2 % (38/208) of patients in our cohort had HER2-positive tumors. HER2 positivity was associated only with differentiated carcinomas. The 5-year overall survival (OS) rate was 58.7 %. The 5-year OS rates in the patient groups with HER2-negative and HER2-positive tumors were 61.2 and 48.5 %, respectively. There was no significant difference between the groups. Recurrence in the liver was observed in 23.7 % patients of the HER2-positive group and 7.6 % patients of the HER2-negative group. Multivariate analysis to identify the risk factors for liver recurrence revealed only HER2 positivity (p = 0.0155) as an independent predictive factor. CONCLUSIONS: HER2 positivity is a powerful predictor of liver recurrence in patients with Siewert type II EGJ carcinoma. Use of trastuzumab in combination with chemotherapy in an adjuvant setting can be a potentially useful therapeutic strategy to prevent hepatic recurrence in patients with resectable EGJ adenocarcinoma showing HER2 overexpression.