Anti-miR-93-5p therapy prolongs sepsis survival by restoring the peripheral immune response.

Sepsis remains a leading cause of death for humans and currently has no pathogenesis-specific therapy. Hampered progress is partly due to a lack of insight into deep mechanistic processes. In the past decade, deciphering the functions of small noncoding miRNAs in sepsis pathogenesis became a dynamic research topic. To screen for new miRNA targets for sepsis therapeutics, we used samples for miRNA array analysis of PBMCs from patients with sepsis and control individuals, blood samples from 2 cohorts of patients with sepsis, and multiple animal models: mouse cecum ligation puncture-induced (CLP-induced) sepsis, mouse viral miRNA challenge, and baboon Gram+ and Gram- sepsis models. miR-93-5p met the criteria for a therapeutic target, as it was overexpressed in baboons that died early after induction of sepsis, was downregulated in patients who survived after sepsis, and correlated with negative clinical prognosticators for sepsis. Therapeutically, inhibition of miR-93-5p prolonged the overall survival of mice with CLP-induced sepsis, with a stronger effect in older mice. Mechanistically, anti-miR-93-5p therapy reduced inflammatory monocytes and increased circulating effector memory T cells, especially the CD4+ subset. AGO2 IP in miR-93-KO T cells identified important regulatory receptors, such as CD28, as direct miR-93-5p target genes. In conclusion, miR-93-5p is a potential therapeutic target in sepsis through the regulation of both innate and adaptive immunity, with possibly a greater benefit for elderly patients than for young patients.

Clinical Significance of Eligibility Criteria Determined by the SPIRITS Trial in Patients with Advanced Gastric Cancer.

INTRODUCTION: This study aimed to assess the clinical significance of eligibility criteria determined by phase 3 clinical trials in the clinical practice of patients with advanced gastric cancer who underwent chemotherapy. METHODS: Patients with stage IV gastric cancer who received chemotherapy between February 2002 and December 2021 were retrospectively enrolled and divided into two groups (the eligible vs. ineligible group) based on eligibility criteria determined by the SPIRITS (S-1 vs. S-1 plus cisplatin) trial. RESULTS: Among the 207 patients, 103 (49.8%) and 104 (50.2%) patients were classified into eligible and ineligible groups, respectively. Eligibility criteria were significantly correlated with age, the first-line regimen of chemotherapy, the presence or absence of conversion surgery, and tumor response to the first-line chemotherapy (all p < 0.01). The eligible group had a significantly higher induction of post-progression chemotherapy after first- and second-line chemotherapy than did the ineligible group (all p < 0.01). The ineligible group had significantly poorer prognoses than the eligible group (p < 0.0001). Multivariate analysis showed that peritoneal dissemination, tumor response, conversion surgery, and eligibility criteria were independent prognostic factors (all p < 0.05). CONCLUSION: Eligibility criteria determined by the SPIRITS trial may have clinical utility for predicting tumor response, the induction of conversion surgery, and prognosis in patients with advanced gastric cancer who underwent chemotherapy.

A prognostic scoring system for conversion surgery after trastuzumab-based chemotherapy for human epidermal growth factor receptor 2-positive advanced gastric cancer.

PURPOSE: To investigate the clinical indications and prognostic significance of surgical interventions after chemotherapy using trastuzumab-containing regimens for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). METHODS: A total of 146 patients with AGC who underwent chemotherapy were enrolled in this retrospective study. Tumors with an immunohistochemistry (IHC) score of 3 + or an IHC score of 2 + plus fluorescence in situ hybridization positivity were defined as HER2-positive AGC. We devised a scoring system for predicting prognosis associated with conversion surgery. RESULTS: Thirty-three patients received trastuzumab-based chemotherapy for HER2-positive tumors. Multivariate analyses identified advanced age, peritoneal dissemination, histologically undifferentiated tumors, and tumor response of progressive disease as independent prognostic factors for a worse prognosis. Twelve patients with HER2-positive AGC underwent conversion surgery. The conversion surgery group of patients with HER2-positive AGC had a better prognosis than the chemotherapy-alone group. A prognostic scoring system based on age, peritoneal dissemination, and histological type was significantly correlated with the presence or absence of conversion surgery and the prognosis of patients with HER2-positive AGC. CONCLUSIONS: Our scoring system has the clinical potential to predict prognosis associated with conversion surgery after trastuzumab-containing chemotherapy for patients with HER2-positive AGC.

Changes in Chemotherapeutic Strategies and Their Prognostic Impact in Patients With Advanced Gastric Cancer.

BACKGROUND/AIM: To investigate changes in post-progression chemotherapy (PPC) before and after nivolumab approval and determine their prognostic impact. PATIENTS AND METHODS: A total of 146 patients with unresectable gastric cancer who had at least progressive disease after first- and/or second-line chemotherapy were retrospectively enrolled. RESULTS: Among the 146 patients, 46 and 23 received ramucirumab and nivolumab, respectively. Moreover, 95 and 62 patients received PPC after first- and second-line chemotherapy, respectively. Group B (i.e., at least chemotherapy after nivolumab approval) had significantly higher proportions of patients receiving ramucirumab therapy, nivolumab therapy, and PPC after first- or second-line chemotherapy compared to group A (i.e., termination of chemotherapy before nivolumab approval). Group A had significantly poorer prognosis than group B. Multivariate analysis showed that age, number of distant metastatic sites, and ramucirumab therapy were independent prognostic factors. CONCLUSION: Changes in chemotherapeutic strategies, including PPC, might contribute to improved prognosis in patients with advanced gastric cancer.

The Clinical Significance of CA19-9 and Tumor Size Ratios for Predicting Prognosis After Conversion Surgery in Patients With Stage IV Gastric Cancer.

BACKGROUND/AIM: The clinical benefit of conversion surgery (CS) after chemotherapy remains unclear for stage IV gastric cancer (GC) patients. This study aimed to investigate the prognostic factors used to determine whether CS is a promising therapeutic strategy. PATIENTS AND METHODS: We retrospectively analyzed data from 156 patients diagnosed with unresectable stage IV GC who underwent chemotherapy as the initial treatment, including 40 patients who had R0 resection in CS. RESULTS: The median survival time of the CS patients was significant longer than that of patients who underwent chemotherapy alone. A multivariate analysis identified only pN3 as an independent prognostic factor in CS patients. Among the differentiated tumor type patients, carbohydrate antigen 19-9 (CA19-9) levels were significantly higher in pN3 patients than in pN0-2 patients before chemotherapy. Among undifferentiated tumor type patients, pN3 patients had a significantly lower tumor size ratio (before chemotherapy/before surgery) than pN0-2 patients. CONCLUSION: Although it is clinically difficult to diagnose lymph node metastasis using preoperative examinations, CA19-9 levels and tumor size ratios may be preoperative indicators for predicting pN3, which is associated with a poor prognosis in CS.

Prognostic Significance of HER2 Expression for Gastric Cancer With Clinically Para-aortic Lymph Node Metastasis.

BACKGROUND/AIM: To determine the prognostic utility of trastuzumab-based chemotherapy based on human epidermal growth factor receptor 2 (HER2) expression in patients with para-aortic lymph node (PAN) metastasis from gastric cancer. PATIENTS AND METHODS: A total of 41 patients with clinical PAN metastasis from gastric cancer who underwent chemotherapy were retrospectively enrolled. RESULTS: Eighteen (43.9%) patients had HER2-positive tumors and consequently, received trastuzumab-based chemotherapy. A total of 11 patients underwent surgery. HER2 status was significantly correlated with the number of distant metastatic sites, the presence or absence of trastuzumab-based chemotherapy, and the presence or absence of gastrectomy. HER2-positive patients had significantly better prognosis than HER2-negative patients. Multivariate analysis identified age and trastuzumab-based chemotherapy based on HER2 status as an independent prognostic factor. CONCLUSION: Assessing HER2 expression and subsequent trastuzumab-based chemotherapy can be an effective method for determining the prognosis of patients with PAN metastasis from gastric cancer.

Prognostic impact of surgery after chemotherapy for type 4 gastric cancer.

PURPOSE: To assess the clinical indications for, and prognostic impact of surgery after, chemotherapy for type 4 gastric cancer. METHODS: The subjects of this retrospective study were 67 patients who received chemotherapy for type 4 gastric cancer. The patients were grouped into those with progressive disease (PD group) and those without PD (non-PD group), according to the tumor response to chemotherapy. RESULTS: Distant metastases developed in 58 patients. With regard to tumor response, there were 16 patients in the PD group and 51 patients in the non-PD group. The prognosis of the PD group patients was significantly poorer than that of the non-PD group patients (p < 0.0001). R0 resection was performed for 21 of 23 patients who underwent surgery after chemotherapy. Multivariate analysis revealed tumor response and surgery as independent prognostic factors (p = 0.0001 and p = 0.0009, respectively). Moreover, multivariate analysis of the surgery group revealed that metastatic nodal status (N0-1 vs. N2-3) and residual tumor status (R0 vs. R1-2) were significant independent prognostic factors (p = 0.0258 and p = 0.0458, respectively). CONCLUSION: The findings of this study suggest that surgery after chemotherapy for type 4 gastric cancer may improve the prognosis of responders with N0-1 status, who undergo curative R0 resection.

Clinical Impact of the Prognostic Nutritional Index as a Predictor of Outcomes in Patients with Stage II/III Gastric Cancer: A Retrospective Cohort Study.

BACKGROUND: The Japanese Gastric Cancer Treatment Guidelines recommend S-1 and S-1 plus docetaxel as postoperative chemotherapy for pathological stage II and III gastric cancer (GC). There is currently no strategy for using chemotherapy to treat high-risk recurrent pathological stage II/III. Previous studies reported that the several nutritional, immunological, and inflammatory markers examined the association with clinical outcomes after surgery for GC. METHODS: Ninety patients with GC (stage II, n = 48; stage III, n = 42) for whom gastrectomy was performed at our institution between November 2009 and September 2018 were examined. Nutritional, immunological, and inflammatory markers were calculated from blood samples within 1 week before surgery. RESULTS: The prognostic nutritional index (PNI) status correlated with the pathological stage and disease recurrence after surgery (p = 0.015 and p < 0.0001, respectively). Thirty-three patients had disease recurrence after gastrectomy (stage II, n = 11; stage III, n = 22). The PNI was significantly lower in the recurrent group than in the non-recurrent group (p = 0.0003). The PNI correlated with overall survival and recurrence-free survival after gastrectomy (p = 0.0021 and p = 0.0001, respectively). A multivariate analysis identified the PNI as an independent prognostic factor (p = 0.006). CONCLUSION: The PNI may be useful for predicting the outcomes of patients with pathological stage II/III GC and may contribute to the selection of an appropriate adjuvant chemotherapy regimen.

Clinical significance of circulating tumor cells in the response to trastuzumab for HER2-negative metastatic gastric cancer.

PURPOSE: The prognosis of metastatic gastric cancer has improved due to trastuzumab in patients with HER2 positive. Circulating tumor cells (CTCs) have been examined as a prognostic predictor in gastric cancer. The clinical advantage of trastuzumab was examined in gastric cancer patients with HER2-negative tumor tissues and HER2-positive CTCs. METHODS: A total of 105 patients with metastatic or recurrence gastric cancer were enrolled. All patients were examined HER2 expression in CTC using the CellSearch system in blood specimens. RESULTS: CTCs were detected in 65 of 105 patients (61.9%) and 61 patients were divided into three groups: Group A (n = 27), histological HER2-positive; Group B (n = 17), histological HER2-negative and HER2-positive CTCs; and Group C (n = 17), HER2-negative on histology and CTCs. Patients received capecitabine plus cisplatin. Groups A and B were additionally treated by trastuzumab. There was no relationship between tumor tissues and CTCs in HER2 expression. Even if group B had no histological HER2 expression, group B showed a good prognosis as same as group A, and group C had a significantly worse overall survival than groups A and B. The multivariate analysis demonstrated that HER2-expression on CTCs was an independent prognostic factor for both overall and progression-free survival. CONCLUSION: The present results indicate the potential clinical utility of trastuzumab combined chemotherapy in patients with HER2-positive CTCs even if they are histologically HER2-negative.

Clinical Outcomes of Fully Covered Self-expanding Metallic Stent Placement for Palliation of Incurable Esophageal Cancer With or Without Radiotherapy.

BACKGROUND/AIM: A combination therapy of esophageal stent and chemoradiotherapy (CRT) is currently considered risky for severe complications. The aim of this study was to assess the safety and efficacy of a fully covered self-expandable metallic stent (FCSEMS) placement in palliating incurable esophageal cancer before and/or after CRT. PATIENTS AND METHODS: We retrospectively reviewed clinical outcomes of 64 incurable advanced esophageal cancer patients with FCSEMS placement. Forty-two of 64 patients had FCSEMS placement with RT. RESULTS: The rate of all of stent-related complications tended to be higher in patients who had RT, although no significant difference was observed. The stent-related deaths occurred in one patient due to hemorrhage after FCSEMS placement in the RT-negative group. CONCLUSION: Palliation of dysphagia or fistulas with FCSEMS in patients with incurable esophageal cancer before and/or after RT is not associated with an increased risk of life-threatening complications.

Clinical impact of creatine phosphokinase and c-reactive protein as predictors of postgastrectomy complications in patients with gastric cancer.

BACKGROUND: Postoperative complications have been linked to the morbidity and mortality of several cancers. However, predicting whether complications will occur in the early period after surgery or not is challenging. Hence, this study aimed to examine the diagnostic accuracy of serum creatine phosphokinase (CPK) and c-reactive protein (CRP) in predicting the development of postgastrectomy complications. METHODS: We retrospectively analyzed 188 patients with gastric cancer (GC) who underwent gastrectomy. The diagnostic accuracy of serum CPK and CRP was investigated using the areas under the curves (AUC). The CPK ratio was defined as the CPK on postoperative day (POD) 1 to the CPK on a preoperative day. RESULTS: Out of 188 patients, 48 (25.5%) developed postoperative complications. The complications group had a greater operative time (p = 0.037), higher CPK ratio on POD1 (p < 0.0001), and a higher serum CRP level on POD3 (p = 0.001). The AUC for the CPK ratio was 0.772, with an optimal cutoff value of 7.05, whereas that for CRP was 0.659, with an optimal cutoff value of 11.4 mg/L. The CPK ratio on POD1 (p < 0.0001) and the CRP on POD3 (p = 0.007) were independent factors for predicting the development of postgastrectomy complications. The CPK ratio on POD1 and the CRP on POD3 predicted postgastrectomy complications in 41 patients (85.4%). According to combined value of both CPK ratio and CRP level, the positive predictive value and the negative predictive value was 0.70 and 0.829. And sensitivity and specificity were 0.438 and 0.936. CONCLUSION: The CPK ratio on POD1 and the CRP on POD3 after gastrectomy for GC were predictive factors for complication development and may be employed to prevent the development of such complications and improve the prognosis of patients with GC.

Recurrent gastric cancer sustaining a partial response after the nivolumab discontinuation because of immune-related adverse events: a case report.

BACKGROUND: The prognosis of patients with recurrent gastric cancer is poor despite chemotherapy being clinically recommended as the first therapeutic strategy. Recent clinical trials have established the clinical utility of nivolumab in the third-line treatment of such patients. Immune-related adverse events (irAE) have been focused as a promising predictor for tumor response to nivolumab. This report aims to present a long-term survivor of recurrent gastric cancer who was followed up without any treatments after the nivolumab discontinuation because of irAE. CASE PRESENTATION: A 65-year-old male with stage III gastric cancer (cT4aN1M0) underwent surgery after neoadjuvant chemotherapy. Owing to the final pathological stage IIIB (ypT4bN1M0), the patient received adjuvant chemotherapy. Nevertheless, during adjuvant chemotherapy 1-year post-surgery, computed tomography (CT) revealed lymph node swelling in station no. 9. Thus, upon diagnosis with lymph node recurrence, the patient was treated with two courses of capecitabine + oxaliplatin and three courses of ramucirumab + paclitaxel as the first- and second-line regimens, respectively. Based on these regimens, the patient had a progressive disease to chemotherapy. Consequently, we administered nivolumab as the third-line regimen. After four courses of nivolumab, CT revealed a significant shrinkage of the metastatic lymph node, with a 45.6% reduction. We confirmed a partial response during 11 courses of nivolumab. Since the occurrence of grade 4 diabetes mellitus after 12 courses of nivolumab, the patient was followed up without any treatment after the nivolumab discontinuation. Currently, the patient remains a partial response for 15 months, since the nivolumab discontinuation and is alive for 31 months after disease recurrence. CONCLUSIONS: Acute irAE during nivolumab chemotherapy could be one of the crucial clinical factors to predict tumor suppression in patients with advanced gastric cancer.

The Diagnostic and Prognostic Value of a Liquid Biopsy for Esophageal Cancer: A Systematic Review and Meta-Analysis.

Esophageal cancer is among the most aggressive diseases, and circulating tumor cells (CTCs) have been recognized as novel biomarkers for various cancers over the past two decades, including esophageal cancer. CTCs might provide crucial clinical information for predicting cancer prognosis, monitoring therapeutic responses or recurrences, or elucidating the mechanism of metastasis. The isolation of CTCs is among the applications of a "liquid biopsy". There are various technologies for liquid biopsies, and they are classified into two main methods: cytometric or non-cytometric techniques. Here, we review a total of 57 eligible articles to summarize various technologies for the use of a liquid biopsy in esophageal cancer and perform a meta-analysis to assess the clinical utility of liquid biopsies as a prognostic and diagnostic biomarker technique. For prognostic evaluation, the pooled hazard ratio in the cytometric assay is relatively higher than that of the non-cytometric assay. On the other hand, a combination of multiple molecules, using a non-cytometric assay, might be a favorable biomarker technique for the early diagnosis of esophageal cancer. Although determining strong evidence for a biomarker by using a liquid biopsy is still challenging, our meta-analysis might be a milestone for the future development of liquid biopsies in use with esophageal cancer.

Clinical Significance of Conversion Surgery for Gastric Cancer with Peritoneal Dissemination: A Retrospective Study.

OBJECTIVE: Although chemotherapy has been clinically recommended as the initial treatment for patients with peritoneal dissemination of gastric cancer, poor prognosis has been noted among the same patients. However, the prognostic significance of conversion surgery after chemotherapy remains unclear. The present study therefore aimed to assess the clinical impact of conversion surgery among patients with peritoneal dissemination of gastric cancer. METHODS: A total of 93 patients with peritoneal dissemination of gastric cancer undergoing chemotherapy between February 2002 and October 2019 were retrospectively enrolled and subsequently divided into progressive disease (PD) and non-PD groups based on tumor response to chemotherapy. RESULTS: Among the included patients, 17 developed distant metastases at another site besides peritoneal dissemination. Based on tumor response, 24 and 69 patients were determined to have PD and non-PD, respectively, with the former having significantly poorer prognosis than the latter (p < 0.0001). A total of 19 patients underwent conversion surgery after chemotherapy, with the presence or absence of conversion surgery being significantly correlated with age, first-line chemotherapy regimen, and tumor response (p = 0.0134, p = 0.0337, and p = 0.0024, respectively). Patients in the non-PD group who underwent conversion surgery or chemotherapy alone had 3-year overall survival rates of 55.6 and 6.6%, respectively. Multivariate analysis identified conversion surgery alone as an independent prognostic factor in the non-PD group (p < 0.0001). CONCLUSION: Our retrospective study demonstrated that conversion surgery for gastric cancer with peritoneal dissemination might improve the prognosis of responders who developed no peritoneal dissemination after chemotherapy.

Conversion surgery for stage IV gastric cancer with a complete pathological response to nivolumab: a case report.

BACKGROUND: Patients with stage IV gastric cancer have a poor prognosis despite the recent development of multidisciplinary treatments that include chemotherapy. However, conversion surgery has emerged as a promising strategy to improve the prognosis in responders with unresectable gastric cancer after chemotherapy. Moreover, nivolumab is currently recommended as a third-line treatment in patients with unresectable advanced gastric cancer. However, there are few reports of conversion surgery after nivolumab in patients with stage IV gastric cancer. CASE PRESENTATION: A 68-year-old woman complaining of nausea was diagnosed with stage I gastric cancer (T2N0M0). Although we planned gastrectomy with lymphadenectomy, multiple liver metastases were detected during the surgery. After staging laparoscopy, we diagnosed this patient as having stage IV unresectable gastric cancer, and we administered chemotherapy and immunotherapy for 39 months (first-line regimen: 6 courses of S-1 plus oxaliplatin; second-line regimen: 6 courses of ramucirumab plus paclitaxel; and third-line regimen: 20 courses of nivolumab). Although the liver metastases completely disappeared after the second-line chemotherapy, lung metastases and a rapid enlargement of the primary tumor were confirmed. Consequently, the patient received nivolumab at a dose of 3 mg/kg intravenously every 2 weeks, then a dose of 240 mg/kg intravenously every 2 weeks from September 2018. After 20 courses of nivolumab, the primary tumor dramatically shrank and the lung metastases disappeared. The patient had a partial primary tumor response to nivolumab. Therefore, the patient underwent laparoscopic distal gastrectomy with D2 lymph node dissection. The macroscopic examination of the resected specimen showed an ulcer scar in the primary tumor site. The pathological examination demonstrated no residual tumors and no lymph node metastases, and the histological response of the primary tumor was categorized as grade 3. The postoperative course was uneventful, and the patient is receiving nivolumab to control potential liver and lung metastases. CONCLUSIONS: Conversion surgery might help control tumor progression in responders after chemotherapy and immunotherapy.

Response Rate and Prognostic Impact of Salvage Chemotherapy after Nivolumab in Patients with Advanced Gastric Cancer.

OBJECTIVE: Nivolumab is recommended as a third-line treatment in patients with unresectable advanced or recurrent gastric cancer. Although recent studies have demonstrated the prognostic impact of salvage chemotherapy after immune checkpoint inhibitors in several malignancies, its clinical significance remains unclear in patients with gastric cancer. This study aimed to investigate tumor response to subsequent chemotherapy after nivolumab in patients with advanced gastric cancer and assess the prognostic effect of salvage chemotherapy. METHODS: We retrospectively enrolled 31 patients with unresectable advanced or recurrent gastric cancer receiving nivolumab. RESULTS: Twenty-two and nine patients received nivolumab as third-line and fourth- to sixth-line treatments, respectively. The objective response rate (ORR) and disease control rate (DCR) to nivolumab were 20.0% (4/20) and 55.0% (11/20), respectively. Eleven patients received salvage chemotherapy after nivolumab. The ORR and DCR to salvage chemotherapy were 37.5% (3/8) and 75.0% (6/8), respectively. The median progression-free survival and overall survival following salvage chemotherapy were 285 and 360 days, respectively. CONCLUSION: Our preliminary study indicates that nivolumab exposure may enhance subsequent chemosensitivity in patients with advanced gastric cancer.

Regulation of aberrantly expressed SERPINH1 by antitumor miR-148a-5p inhibits cancer cell aggressiveness in gastric cancer.

RNA-sequencing-based microRNA (miRNA) expression signatures have revealed that miR-148a-5p (the passenger strand of the miR-148a-duplex) is downregulated in various kinds of cancer tissues. Analysis of The Cancer Genome Atlas (TCGA) database showed that low expression of miR-148a-5p was predictive of a lower survival rate (p = 0.041) in patients with gastric cancer (GC). Downregulation of miR-148a-5p was confirmed in GC clinical specimens, and its ectopic expression attenuated GC cell proliferation. Our search for miRNA target genes identified a total of 18 oncogenic targets of miR-148a-5p in GC cells. Among these targets, high expression levels of six genes (THBS2, P4HA3, SERPINH1, CDH11, BCAT1, and KCNG3) were closely associated with a poor prognosis (10-year survival rates) in GC patients (p < 0.05) according to TCGA database analyses. Furthermore, we focused on SERPINH1 as a chaperone protein involved in collagen folding in humans. Aberrant expression of SERPINH1 (mRNA and protein levels) was confirmed in GC clinical specimens. Knockdown assays of SERPINH1 using siRNAs resulted in inhibition of the aggressive phenotype of GC cells. Exploring the molecular networks controlled by miRNAs (including miRNA passenger strands) will broaden our understanding of the molecular pathogenesis of GC.

Evaluation of postoperative quality of life by PGSAS-45 following local gastrectomy based on the sentinel lymph node concept in early gastric cancer.

BACKGROUND: The usefulness of sentinel node navigation surgery (SNNS) for early gastric cancer has been demonstrated in a multicenter prospective study. However, quality of life (QOL) after local resection remains unclear. This present study investigated QOL after local resection and distal gastrectomy. METHODS: We examined 69 patients who underwent laparoscopic distal gastrectomy (LADG) (n = 44) and laparoscopic local resection (LLR) (n = 25) in our hospital between September 2011 and May 2018. We conducted a combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET) with SNNS as LLR. All patients had pStage I or II and none had received adjuvant chemotherapy. We evaluated QOL using the postgastrectomy syndrome assessment scale questionnaire (PGSAS-45) 1, 6, and 12 months after surgery. RESULTS: In PGSAS-45, no significant differences were observed between LLR and LADG at 1 and 6 months after surgery. At 12 months, the LLR group scored better for some of the subscales (SS). In the endoscopic evaluation, the LLR group showed significant improvements in residual gastritis at 6 months (P = 0.006) and esophageal reflux and residual gastritis at 12 months (P = 0.021 and P = 0.017). A significant difference was observed in the prognostic nutritional index, which was assessed using serum samples, between the two groups at 6 months (P = 0.028). The body weight ratio was better in the LLR group than in the LADG group at 6 and 12 months (P = 0.041 and P = 0.007, respectively). CONCLUSIONS: CLEAN-NET with SNNS preserved a better QOL and nutrition status than LADG in patients with early gastric cancer.

Indication and Prognostic Significance of Conversion Surgery in Patients with Liver Metastasis from Gastric Cancer.

OBJECTIVE: Chemotherapy is generally recommended as the first-line standard treatment in patients with liver metastasis from gastric cancer. However, the clinical impact of surgical treatment remains unclear in responders after chemotherapy. The present study aimed to investigate the tumor response and prognosis after chemotherapy and to assess the clinical indication of conversion surgery in responders. METHODS: The study retrospectively reviewed the clinical data of 44 patients with liver metastasis from gastric cancer who were treated with chemotherapy between February 2002 and January 2019. These patients were classified into progressive disease (PD) and non-PD groups according to tumor response. RESULTS: Among the 44 patients, 7 and 26 had peritoneal dissemination and ≥5 had metastatic liver nodules. Additionally, 15 and 29 patients had PD and non-PD, respectively. Surgical treatment was significantly correlated with tumor response (p < 0.0321). Prognostic differences between the PD and non-PD groups were significant (p < 0.0001). Moreover, gastrectomy and hepatectomy were significantly correlated with the number of liver metastases (≥5 vs. <5, respectively) in the non-PD group (p = 0.0025 and p = 0.0169, respectively). The 3-year survival rates among patients with non-PD undergoing both gastrectomy and hepatectomy (n = 6), gastrectomy alone (n = 7), and nonsurgical treatments (n = 16) were 100, 66.7, and 0%, respectively (p = 0.0026). Multivariate analysis identified peritoneal dissemination as an independent prognostic factor (p = 0.0225). CONCLUSION: Our preliminary results suggest that conversion surgery for gastric cancer with liver metastasis might be clinically indicated in chemotherapy responders with <5 metastatic liver nodules and without peritoneal dissemination.

A long-term survivor of recurrent esophagogastric junction adenocarcinoma treated with multidisciplinary therapy: a case report.

BACKGROUND: Patients with esophagogastric junction cancer are increasing in Western and Eastern countries. Conversely, the clinical significance of surgical resection remains controversial in these patients. We report a long-term survivor of recurrent esophagogastric junction adenocarcinoma who underwent constructive multimodal therapy, including surgical resection. CASE PRESENTATION: A 51-year-old man underwent total gastrectomy for esophagogastric junction adenocarcinoma in 2009. In June 2010, computed tomography (CT) indicated a lung nodule and we partially resected the right lower lung. It was pathologically diagnosed as distant metastasis from esophagogastric junction cancer. After lung resection, he received adjuvant chemotherapy with S-1 for 1 year. In September 2014, CT demonstrated a swelling of the upper mediastinal lymph node with abnormal uptake on fluorine-18 fluorodeoxyglucose positron emission tomography. We performed an ultrasonography-guided needle biopsy, and he was diagnosed with lymph nodal recurrence of esophagogastric junction adenocarcinoma by pathological examination and was subsequently treated with capecitabine plus cisplatin plus trastuzumab. Since CT showed a reduction in the metastatic upper mediastinal lymph node after chemotherapy, he underwent upper mediastinal lymphadenectomy in April 2015. Following surgery, we provided radiation therapy to the upper mediastinum and chemotherapy with S-1. At the last report, the patient was alive for 8 years and 3 months since the first surgery. CONCLUSIONS: This case report shows the clinical benefit of constructive multimodal therapy for recurrent esophagogastric junction adenocarcinoma.