Successful subtotal gastrectomy and hepatectomy for HER2-positive gastric cancer with liver metastasis after trastuzumab-based chemotherapy: a case report.

BACKGROUND: Conversion surgery (CS) after chemotherapy is weakly recommended as a promising tool for improving prognoses in patients with unresectable gastric cancer. Moreover, several investigators have demonstrated the clinical efficacy of subtotal gastrectomy (sTG) with a small remnant stomach for the nutritional status and surgical outcome compared with total gastrectomy. Here, we report a patient with liver metastasis from human epidermal growth factor receptor 2 (HER2)-positive gastric cancer who underwent sTG and hepatectomy after trastuzumab-based chemotherapy. CASE PRESENTATION: An 84-year-old male patient was diagnosed with HER2-positive gastric cancer with a single liver metastasis. He was treated with eight courses of trastuzumab in combination with S-1 and oxaliplatin as first-line chemotherapy. The primary tumor and liver metastasis shrank significantly. The metastatic liver lesion's reduction rate was 65%. According to the Response Evaluation Criteria in Solid Tumors, the patient had a partial response. Therefore, he underwent an sTG with D2 lymphadenectomy and partial hepatectomy of segment 2. Histopathological examination revealed a grade 3 histological response without lymph node metastases from the primary tumor. No viable cancer cells were observed in the resected liver specimens. The patient received adjuvant chemotherapy with S-1. The postoperative quality of life (QOL) evaluated using the Postgastrectomy Syndrome Assessment Scale-45 was maintained, and the patient was still alive 8 months after the CS without recurrence. CONCLUSIONS: An sTG with a small remnant stomach might be clinically useful for preventing a decline in QOL and improving prognoses in patients with stage IV gastric cancer after chemotherapy.

Clinical application and outcomes of sentinel node navigation surgery in patients with early gastric cancer.

Sentinel node navigation surgery (SNNS) has been recognized as a minimally invasive tool for individualized lymphadenectomy in patients with early gastric cancer (EGC). The aim of this study was to compare clinicopathological factors, adverse events, and clinical outcomes between sentinel node mapping (SNM) and SN dissection (SND) groups and assess the clinical utility of SNNS in patients with EGC. The clinical data of 157 patients with EGC, diagnosed as clinical T1N0M0 with tumors ≤ 40 mm, undergoing SNNS between March 2004 and April 2016 were retrospectively reviewed. Twenty-seven patients were excluded from the analysis. In the remaining 130 patients, 59 and 71 patients underwent standard lymphadenectomy for SNM and SND, respectively. The sentinel node detection rate in the SNM and SND groups was 98.3% (58/59) and 100% (71/71), respectively. Two (3.5%), 15 (25.9%), and 41 (70.7%) patients having sentinel nodes underwent total gastrectomy, proximal gastrectomy (PG), and distal gastrectomy (DG), respectively, in the SNM group. One (1.4%), 5 (7.0%), 10 (14.1%), 39 (54.9%), and 16 (22.5%) patients underwent PG, DG, segmental gastrectomy, local resection, and endoscopic submucosal dissection, respectively, in the SND group. There was no significant difference in postoperative complications between the SNM and SND groups (P = 0.781). Survival did not differ between the both groups (P = 0.856). The present results suggest that personalized surgery with SND provides technical safety and curability related with a favorable survival outcome in patients with EGC.

Sentinel node navigation surgery for gastroduodenal neuroendocrine tumors: Two case reports.

The percentage of gastroduodenal neuroendocrine tumors (NETs) among all gastroenteropancreatic (GEP) NETs has gradually increased worldwide. Sentinel node navigation surgery (SNNS) has been developed as a personalized approach in the surgical strategy for early gastrointestinal tract cancers. We herein report 2 cases of gastroduodenal NETs treated with SNNS. Technetium-tin colloid including indocyanine green was endoscopically injected into the submucosa around a tumor the day before surgery. Basin dissection including the sentinel nodes (SNs), which were identified by Navigator GPS and near-infrared fluorescence imaging, was performed during laparoscopic surgery. SNs were intraoperatively examined using hematoxylin-eosin (HE) staining.SNs were detected in 2 patients. Lymph node metastasis was intraoperatively identified in 1 of the 2 patients. Consequently, 1 patient with metastatic SNs underwent laparoscopic gastrectomy with lymphadenectomy. Pathological findings identified submucosal NET measuring 6.0 mm × 5.0 mm.Our results suggest that SNNS is a promising surgical tool for detecting subclinical lymph node metastasis in patients with gastroduodenal NETs.

The clinical usefulness of the intraoperative detection of sentinel lymph node metastases by a rapid RT-PCR system in patients with gastric cancer.

BACKGROUND: The incidence of pathological lymph node metastases in patients with gastric cancer is 5% to 10%, which means that approximately 90% of patients with gastric cancer may undergo unnecessary lymphadenectomy. The precise intraoperative diagnosis of sentinel lymph node (SN) metastases is essential. The purpose of the current study was to verify the usefulness of a rapid reverse transcriptase-polymerase chain reaction (RT-PCR) system compared with hematoxylin and eosin staining for such diagnoses. METHODS: A total of 113 patients with clinical T1-T2 (cT1-T2) gastric cancer, including 73 patients with cT1cN0 disease with a tumor diameter <4 cm, were enrolled in the current study. SNs were identified by a radioisotope method. Carcinoembryonic antigen and cytokeratin 19 were used as markers for RT-PCR and the cutoff values were set using 1701 lymph nodes harvested from 157 patients with gastric cancer. RESULTS: SNs were detected in all 113 patients. Sensitivity and accuracy for detection by paraffin section were both 100% in patients with cT1 disease and were 60% and 90%, respectively, in patients with cT2 disease. The sensitivity of RT-PCR for the detection of pathological SN metastases was 92.3%. Furthermore, 11 patients had SN metastases detected only by RT-PCR, and these patients had frequent lymphatic invasion. Hematoxylin and eosin staining detected SN metastases in 6 of 73 patients with cT1cN0 gastric cancer; RT-PCR and frozen section detected SN metastases in 6 and 4 of these patients, respectively. Accordingly, the sensitivity of RT-PCR and frozen section for the detection of those pathological SN metastases were 100% and 66.6%, respectively. CONCLUSIONS: The rapid RT-PCR system appears to have clinical usefulness for the intraoperative detection of SN metastases in patients with gastric cancer.

Clinical Significance of Circulating Tumor Cells in Peripheral Blood of Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma is an aggressive gastrointestinal tract cancer. To date, the presence of circulating tumor cells (CTC) has been reported as a prognostic factor in peripheral blood from patients with gastrointestinal cancers. METHODS: The CellSearch system was used to isolate and enumerate CTCs. A total of 90 patients with esophageal squamous cell carcinoma who received chemotherapy or chemoradiotherapy were enrolled. Peripheral blood specimens were collected before and after treatments. RESULTS: At baseline analysis, CTCs were detected in 25 patients (27.8 %). Overall survival was significantly shorter in patients with than without CTCs. Follow-up blood specimens were obtained from 71 patients. Partial response, stable disease, and progressive disease after treatment were seen in 32, 12, and 27 patients, respectively. CTC positivity after treatment in the progressive disease group (40.7 %) was significantly higher than that of the partial response group (6.3 %). Patients with a change in CTC status from positive to negative had a good prognosis as well as patients without baseline CTCs. CONCLUSIONS: Evaluation of CTCs may be a promising indicator for predicting tumor prognosis and the clinical efficacy of chemotherapy or chemoradiation therapy in patients with esophageal squamous cell carcinoma.

Clinical significance of stanniocalcin 2 expression as a predictor of tumor progression in gastric cancer.

Stanniocalcin 2 (STC2) is a glycoprotein hormone that plays an important role in calcium and phosphate homeostasis. Furthermore, recent studies have demonstrated that STC2 expression in the primary site is correlated with tumor progression in several types of malignancies. However, few reports have investigated the clinical significance of STC2 expression in the blood of patients with gastric cancer. Therefore, we examined STC2 expression as a molecular blood marker for detection of circulating tumor cells (CTCs) and assessed the relationship between STC2 expression and clinico-pathological features including prognosis in patients with gastric cancer. Quantitative PCR assay was used to assess STC2 mRNA expression in 4 gastric cancer cell lines and in blood specimens from 93 patients with gastric cancer and 22 healthy volunteers. The numbers of STC2 mRNA copies were significantly higher in the gastric cancer cell lines and in blood from patients with gastric cancer than in blood from healthy volunteers (P=0.0002 and P=0.01, respectively). STC2 expression was positive in 43 (46.2%) of the 93 patients with gastric cancer, and its expression was significantly correlated with age, depth of tumor invasion, lymph node metastasis, stage and venous invasion (P=0.023, P=0.045, P=0.035, P=0.007 and P=0.027, respectively). The 5-year survival rate was significantly lower in patients with STC2 expression compared to patients without STC2 expression (P=0.014). Our results indicate that STC2 could be a useful molecular blood marker for predicting tumor progression by monitoring CTCs in patients with gastric cancer.

Clinical significance of circulating tumor cells in peripheral blood from patients with gastric cancer.

BACKGROUND: The authors hypothesized that circulating tumor cells (CTCs) in patients with gastric cancer are associated with prognosis and disease recurrence. In this study, they evaluated CTCs in gastric cancer and clarified the clinical impact of CTCs. METHODS: In total, 265 consecutive patients with gastric cancer were enrolled. Fourteen patients were excluded from the analysis, including 12 patients who another cancer and 2 patients who refused the treatment. The remaining 251 patients were divided into 2 groups: 148 patients who underwent gastrectomy (the resection group) and 103 patients who did not undergo gastrectomy (the nonresectable group). Peripheral blood samples were collected before gastrectomy or chemotherapy. A proprietary test for capturing, identifying, and counting CTCs in blood was used for the isolation and enumeration of CTCs. RESULTS: CTCs were detected in 16 patients (10.8%) from the resection group and in 62 patients (60.2%) from the nonresectable group. The overall survival rate for the entire cohort was significantly lower in patients with CTCs than in those without CTCs (P < .0001). In the resection group, relapse-free and overall survival in patients with CTCs was significantly lower than in patients without CTCs (P < .0001). It was noteworthy that the expression of CTCs was an independent factor for determining the overall survival of patients with gastric cancer in multivariate analysis (P = .024). In the nonresectable group, the overall survival rate was significantly lower in patients with CTCs than in those without CTCs (P = .0044). CONCLUSIONS: The evaluation of CTCs in peripheral blood may be a useful tool for predicting tumor progression, prognosis, and the effect of chemotherapy in patients with gastric cancer.

Assessment of sentinel node concept in esophageal cancer based on lymph node micrometastasis.

PURPOSE: The clinical significance of lymph node micrometastasis remains unclear in patients with esophageal cancer. Therefore, accurate assessment of lymph node status including micrometastasis is important when performing sentinel node (SN) navigation surgery. The purpose of the present study was to investigate the adequacy of SN concept based on lymph node micrometastasis determined by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) in patients with esophageal cancer. METHODS: A total of 57 patients with esophageal cancer who were preoperatively diagnosed as having T1-T2 (cT1-T2) and N0 (cN0) were enrolled. They underwent standard esophagectomy with lymph node dissection. One day before surgery, a total of 3 mCi of 99mTechnetium-tin colloid was endoscopically injected into the submucosa around the tumor. During the operation, radioisotope uptake in the lymph nodes was measured using Navigator GPS. All dissected lymph nodes were investigated by RT-PCR using the double marker of CEA and SCC, hematoxylin-eosin (HE) staining, and IHC. RESULTS: Node-positive incidence identified by HE and IHC was 12.3% (7/57) and 19.3% (11/57), respectively. RT-PCR demonstrated micrometastasis in four of 46 patients without nodal metastasis determined by HE staining and IHC. No non-SN metastases were found in 42 patients without micrometastasis identified by IHC and RT-PCR of SN. Accuracy and false negative rates were 100% (57/57) and 0% (0/42), respectively. CONCLUSIONS: SN concept might be acceptable in patients with cT1-T2 and cN0 esophageal cancer, even in the presence of micrometastasis identified by IHC and RT-PCR.

Expression of stanniocalcin 1 as a potential biomarker of gastric cancer.

OBJECTIVE: We investigated stanniocalcin 1 (STC 1) expression to assess its clinical utility as a blood marker in patients with gastric cancer and evaluated its biological impact in terms of tumor aggressiveness. METHODS: Blood specimens from 93 patients with gastric cancer and 21 normal healthy volunteers were assessed by quantitative reverse transcription-polymerase chain reaction for STC 1 mRNA expression. RESULTS: The relative numbers of STC 1 mRNA copies were significantly higher in gastric cancer cell lines and in blood specimens from patients with gastric cancer than in blood specimens from healthy volunteers (p = 0.0001 and p = 0.003, respectively). The sensitivity and specificity of STC 1 mRNA expression for discriminating patients with gastric cancer from healthy volunteers were 69.9 and 71.4%, respectively. Furthermore, the sensitivity for STC 1 mRNA was higher than that for serum carcinoembryonic antigen and carbohydrate antigen 19-9. The presence of STC 1 expression was significantly correlated with depth of tumor invasion and tumor stage (p = 0.032 and p = 0.013, respectively). CONCLUSION: Our data strongly suggest that STC 1 is a potentially useful blood marker for predicting biological tumor aggressiveness in patients with gastric cancer.

Clinical significance of the B7-H4 coregulatory molecule as a novel prognostic marker in gastric cancer.

BACKGROUND: The B7-H4 coregulatory molecule is a member of the B7 family of molecules, which regulate the T-cell-mediated immune response through CD28 receptors. Recently, B7-H4 has been reported to be a negative regulator of the immune response in patients with several malignant diseases. However, few reports have investigated the clinical significance of B7-H4 expression in patients with gastric cancer. In the present study, we analyzed B7-H4 expression and the relationship between its expression and clinicopathological factors including prognosis in gastric cancer. METHODS: B7-H4 expression in gastric cancer cell lines and clinical gastric cancer specimens was initially assessed with the reverse transcription-polymerase chain reaction (RT-PCR). Moreover, B7-H4 and CD3 expression in 120 resected specimens from gastric cancer patients were evaluated by immunohistochemistry (IHC). RESULTS: B7-H4 expression was identified in the gastric cancer cell lines and clinical tumor tissues by RT-PCR. B7-H4 expression was high in 25.8% (31/120) of resected tumor specimens. B7-H4 expression significantly correlated with tumor stage (P = 0.04). The 5-year survival rate was significantly lower in patients with high B7-H4 expression than in those with low B7-H4 expression (P = 0.001). Multivariate analysis demonstrated that B7-H4 expression was an independent prognostic factor (P = 0.035). Immunohistochemical analysis of CD3 expression showed that B7-H4 expression was inversely correlated with the number of tumor infiltrating T lymphocytes (P < 0.001). CONCLUSIONS: The B7-H4 coregulatory molecule is a novel prognostic marker related to the T-cell-mediated immune response, and its pathway may be a molecular target for controlling tumor progression in patients with gastric cancer.

Expression of B7-H4 in blood of patients with gastric cancer predicts tumor progression and prognosis.

BACKGROUND AND OBJECTIVES: B7-H4 is a novel molecular B7 ligand that plays an important role as a negative regulator of the T cell-mediated immune response. However, the clinical significance of B7-H4 expression in gastric cancer remains uncertain. Here, we assessed B7-H4 expression in blood of patients with gastric cancer to determine whether or not it can predict tumor progression and prognosis. METHODS: We measured B7-H4 mRNA expression by quantitative RT-PCR in five gastric cell lines as well as in blood specimens from 94 patients with gastric cancer and from 22 healthy volunteers. RESULTS: Significantly more B7-H4 mRNA copies were found in gastric cell lines and in blood from patients with gastric cancer than in blood from healthy volunteers (P < 0.0001 and P < 0.0001, respectively). B7-H4 expressed in 71 (75.5%) of 94 patients with gastric cancer significantly correlated with depth of tumor invasion, lymph node metastasis, and overall stage (P = 0.006, P = 0.001, and P < 0.001, respectively). The 5-year survival rate was significantly lower in patients with than without B7-H4 expression (P = 0.04). CONCLUSIONS: The evaluation of B7-H4 expression in blood is a useful tool for predicting the progression of gastric cancer and prognosis.