Yoshikazu Uenosono

Sentinel Node Mapping for Gastric Cancer: A Prospective Multicenter Trial in Japan

PURPOSE Complicated gastric lymphatic drainage potentially undermines the utility of sentinel node (SN) biopsy in patients with gastric cancer. Encouraged by several favorable single-institution reports, we conducted a multicenter, single-arm, phase II study of SN mapping that used a standardized dual tracer endoscopic injection technique. PATIENTS AND METHODS Patients with previously untreated cT1 or cT2 gastric adenocarcinomas < 4 cm in gross diameter were eligible for inclusion in this study. SN mapping was performed by using a standardized dual tracer endoscopic injection technique. Following biopsy of the identified SNs, mandatory comprehensive D2 or modified D2 gastrectomy was performed according to current Japanese Gastric Cancer Association guidelines. RESULTS Among 433 patients who gave preoperative consent, 397 were deemed eligible on the basis of surgical findings. SN biopsy was performed in all patients, and the SN detection rate was 97.5% (387 of 397). Of 57 patients with lymph node metastasis by conventional hematoxylin and eosin staining, 93% (53 of 57) had positive SNs, and the accuracy of nodal evaluation for metastasis was 99% (383 of 387). Only four false-negative SN biopsies were observed, and pathologic analysis revealed that three of those biopsies were pT2 or tumors > 4 cm. We observed no serious adverse effects related to endoscopic tracer injection or the SN mapping procedure. CONCLUSION The endoscopic dual tracer method for SN biopsy was confirmed as safe and effective when applied to the superficial, relatively small gastric adenocarcinomas included in this study.

Evaluation of sentinel node concept in gastric cancer based on lymph node micrometastasis determined by reverse transcription-polymerase chain reaction.

Objective:To determine the adequacy of sentinel node (SN) concept based on micrometastasis using immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) in gastric cancer. Summary Background Data:The SN concept has recently been introduced in gastrointestinal tract cancers. The precise detection of lymph node metastasis including micrometastasis is important for SN navigation surgery. Methods:Sixty-one patients with gastric cancer who were preoperatively diagnosed with T1-T2 (cT1-T2) and N0 (cN0) were enrolled. They underwent standard radical gastrectomy with lymph node dissection. One day before surgery, 4 mCi of 99mTechnetium-tin colloid was endoscopically injected into the submucosa around the tumor. During surgery, radioisotope uptake in the lymph node was measured using Navigator GPS. All dissected lymph nodes were examined by RT-PCR in addition to hematoxylin and eosin staining and IHC. Results:Sentinel nodes were identified in all patients (100%). The incidences of metastasis determined by hematoxylin and eosin and IHC were 8.2% (5 of 61) and 13.1% (8 of 61), respectively. Micrometastases undetectable by IHC were identified in 14 patients (23.0%) by RT-PCR. Only 1 patient had micrometastasis detectable by RT-PCR in lymph nodes other than SN, but this patient had a cT2 tumor. In patients with cT1 and cN0 tumors, the false negative and accuracy rates were 0% and 100%, respectively. Conclusions:Although the incidence of micrometastasis detected by RT-PCR was quite high, SN navigation identified such metastasis in all patients except one. Thus, the SN concept was applicable to patients with cT1 and cN0 gastric cancer, even when micrometastasis was detectable by RT-PCR.

Lymphatic invasion using D2-40 monoclonal antibody and its relationship to lymph node micrometastasis in pN0 gastric cancer

The monoclonal antibody D2-40 is a specific lymphatic endothelial markers and D2-40 staining have been applicable to evaluate lymphatic invasion in various malignant neoplasms. In the present study, we investigated lymph node micrometastasis determined by immunohistochemistry (IHC) and reverse transcription–polymerase chain reaction (RT–PCR) in all dissected lymph nodes obtained from 80 patients with node-negative gastric cancer, and analysed the relationship between micrometastasis and clinicopathological findings including lymphatic invasion of the resected primary tumour using D2-40 immunohistochemical staining. The incidence of micrometastasis determined by IHC and RT–PCR was 11.3% (nine out of 80) and 31.3% (25 out of 80), respectively. Although haematoxylin–eosin (HE) staining revealed lymphatic invasion in 11.3% (nine out of 80) of patients, D2-40 staining uncovered new invasion in 23.8% (19 out of 80) of patients. In the diagnosis of HE and D2-40 staining, the incidence of micrometastasis was significantly higher in patients with lymphatic invasion than in those without lymphatic invasion (P=0.0150 and P<0.0001, respectively). Micrometastasis correlated more closely with D2-40 than with HE staining. We demonstrated a high incidence of micrometastasis and lymphatic invasion and a correlation between them even in pN0 gastric cancer. When planning less invasive treatment, the presence of such occult cancer cells should be considered.

Detection of sentinel nodes and micrometastases using radioisotope navigation and immunohistochemistry in patients with gastric cancer

Patients with early gastric cancer may be treated by minimally invasive surgery. This study investigated the value of sentinel node (SN) navigation surgery, including detection of micrometastases, in patients with clinical (c) T1 and T2 gastric cancer.

Evaluation of colloid size for sentinel nodes detection using radioisotope in early gastric cancer

The purpose of this study was to investigate the relationship between colloid size and the detection of sentinel nodes (SN) in early gastric cancer. Three size of 99mTechnetium-tin colloids (500, 100 and 50 nm) were preoperatively injected into the submucosa under endoscopic control. Lymph node metastasis and micrometastasis was examined. RI-uptake in the hottest nodes and the total RI-uptake in the hot nodes were highest in the size of 100 nm. At least one lymph node metastasis, including micrometastasis, was included in the hot nodes. RI-labeled colloid size was one of the important factors to detect SN in early gastric cancer.

Sentinel lymph node mapping with GI cancer

Precise evaluation of lymph node status is one of the most important factors in determining clinical outcome in treating gastro-intestinal (GI) cancer. Sentinel lymph node (SLN) mapping clearly has become highly feasible and accurate in staging GI cancer. The lunchtime symposium focused on the present status of SLN mapping for GI cancer. Dr. Kitigawa proposed a new strategy using sentinel node biopsy for esophageal cancer patients with clinically early stage disease. Dr. Uenosono reported on whether the SLN concept is applicable for gastric cancer through his analysis of more than 180 patients with cT1-2, N0 tumors. The detection rate was 95%, the false negative rate of lymph node metastasis including micro-metastasis was 4%, and accuracy was 99% in gastric cancer patients with cT1N0. Dr. Bilchik recommended the best technique for identifying SLNs in colorectal cancer: a combination of radiotracer and blue dye method, emphasizing that this technique will become increasingly popular because of the SLN concept, with improvement in staging accuracy. He stressed that this novel procedure offers the potential for significant upstaging of GI cancer. Dr. Saha emphasized that SLN mapping for colorectal cancer is highly successful and accurate in predicting the presence or absence of nodal disease with a relatively low incidence of skip metastases. It provided the “right nodes” to the pathologists for detailed analysis for appropriate staging and treatment with adjuvant chemotherapy. Although more evidence from large-scale multicenter clinical trials is required, SLN mapping may be very useful for individualizing multi-modal treatment for esophageal cancer and might be widely acceptable even for GI cancer.

B7‐H3 expression in gastric cancer: A novel molecular blood marker for detecting circulating tumor cells

The clinical significance of B7‐H3 expression in gastric cancer remains unclear, although the B7 ligand family plays a critical role in the T cell‐mediated immune response. We therefore investigated B7‐H3 expression as a blood marker of circulating tumor cells and determined correlations with tumor progression in patients with gastric cancer. B7‐H3 expression in gastric cell lines was initially evaluated by immunocytochemistry. Furthermore, we used quantitative RT‐PCR to assess B7‐H3 mRNA expression in four cell lines and in 95 blood specimens from patients with gastric cancer, as well as in 21 samples of peripheral blood lymphocytes from healthy volunteers. B7‐H3 expression in cell lines was identified by immunocytochemistry and quantitative RT‐PCR. Blood specimens from patients with gastric cancer contained significantly more copies of B7‐H3 mRNA than those from healthy volunteers without cancer (P < 0.0001). Levels of B7‐H3 expression significantly correlated with overall stage (P = 0.013). The 5‐year survival rate was significantly lower in patients with high B7‐H3 expression than with low expression (P = 0.02). Multivariate analysis demonstrated that B7‐H3 expression was an independent prognostic factor (P = 0.046). Our results indicate that B7‐H3 appears to be a useful blood marker for predicting tumor progression in gastric cancer. (Cancer Sci 2011; 102: 1019–1024)

Rapid immunohistochemical detection of lymph node micrometastasis during operation for upper gastrointestinal carcinoma

The intraoperative diagnosis of lymph node micrometastasis (LNM) may help guide the area of appropriate lymph node dissection. This study aimed to evaluate the rapid immunohistochemical detection of LNMs using frozen sections during operation for gastro‐oesophageal cancer.

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

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.

Characteristics and clinical relevance of postgastrectomy syndrome assessment scale (PGSAS)-45: newly developed integrated questionnaires for assessment of living status and quality of life in postgastrectomy patients.

BackgroundLack of a suitable instrument to comprehensively assess symptoms, living status, and quality of life in postgastrectomy patients prompted the authors to develop postgastrectomy syndrome assessment scale (PGSAS)-45.MethodsPGSAS-45 consists of 45 items in total: 8 items from SF-8, 15 items from GSRS, and an additional 22 items selected by 47 gastric surgeons. Using the PGSAS-45, a multi-institutional survey was conducted to determine the prevalence of postgastrectomy syndrome and its impact on everyday life among patients who underwent various types of gastrectomy. Eligible data were obtained from 2,368 patients operated and followed at 52 institutions in Japan. Of these, data from 1,777 patients were used in the current study in which symptom subscales of the PGSAS-45 were determined. We also considered the characteristics of the postgastrectomy syndrome and to what extent these symptoms influence patients’ living status and quality of life (QOL).ResultsBy factor analysis, 23 symptom-related items of PGSAS-45 were successfully clustered into seven symptom subscales that represent esophageal reflux, abdominal pain, meal-related distress, indigestion, diarrhea, constipation, and dumping. These seven symptom subscales and two other subscales measuring quality of ingestion and dissatisfaction for daily life, respectively, had good internal consistency in terms of Cronbach′s α (0.65–0.88).ConclusionPGSAS-45 provides a valid and reliable integrated index for evaluation of symptoms, living status, and QOL in gastrectomized patients.