Kazuhito Nabeshima

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.

Functional outcomes by reconstruction technique following laparoscopic proximal gastrectomy for gastric cancer: double tract versus jejunal interposition

BackgroundFor early gastric cancer located in the upper third of the stomach, we have adopted laparoscopic 1/2-proximal gastrectomy (PG) with two types of reconstruction: double tract reconstruction (L-DT) and jejunal interposition reconstruction with crimping of the jejunum on the anal side of the jejunogastrostomy with a knifeless linear stapler (L-JIP).MethodsFunctional outcomes were prospectively compared between these two types of reconstruction following laparoscopic PG. Resection and reconstruction were performed using L-DT (n = 10) and L-JIP (n = 10) alternately. Quality of life was evaluated through a questionnaire and endoscopic examination of the ten patients in each group, and functional evaluations were carried out in five patients of each group.ResultsThe postoperative/preoperative body weight ratio was significantly higher in the L-JIP group than in the L-DT group. While the incidence of reflux esophagitis was 10% in both groups, the endoscope could reach the remnant stomach in all patients. In the L-DT group, the plasma acetaminophen concentration at 15 minutes and the insulin level at 30 minutes were markedly increased after oral administration, while the increases in the blood sugar level at 30 and 60 minutes were more gradual than in the L-JIP group.ConclusionsWhile L-JIP may be thought of as the ideal method for function-preserving gastrectomy, L-DT may be suitable for gastric cancer patients with impaired glucose tolerance. These results raise the possibility of individualized selection of reconstruction for gastric cancer patients with various kinds of preoperative complications.

Focus on the Conditions of Resection and Reconstruction in Gastric Cancer

To assess the roles of the extent of gastric resection and duodenal food passage reconstruction in gastric cancer, we examined a consecutive series of 1,061 patients who underwent total or partial (proximal and distal) gastrectomies with or without duodenal food passage reconstruction between August of 1974 and January of 2002, and received gastrectomies with D2–3 lymph node dissection. Patients who underwent distal or proximal gastrectomy were found to have significantly better survival rates than those who underwent total gastrectomy in stages 1A (10-year survival: 86.6 and 78.9 vs. 61.6%), 2 (56.5 and 65.6 vs. 34.4%), 3A (45.9 and 33.3 vs. 15.2%), and 4 (5-year survival rates: 23.7 and 50.0 vs. 7.1%). Additionally, patients with duodenal food passage reconstruction or double tract reconstruction also showed significantly better survival rates than those without duodenal food reconstruction in stages 1A (10-year survival: 86.4 and 82.5 vs. 61.7%), 1B (69.9 and 90.6 vs. 54.1%), 2 (60.5 and 63.3 vs. 16.5%), and 3A (39.9 and 47.4 vs. 23.1%). In multivariate analysis, the independent prognostic factors were age at operation, depth of tumor, duodenal food passage reconstruction, and lymph node metastasis. Our results indicate that both the extent of gastric resection and duodenal food passage reconstruction were important factors in the outcome of gastric cancer patients, and that surgeons should perform minimal gastric resection with preservation of the duodenal food passage when the gastric stump is tumor-free.

Phase II study of neoadjuvant imatinib in large gastrointestinal stromal tumours of the stomach

Background:Gastrointestinal stromal tumours (GISTs) with high-risk features have poor prognosis even if adjuvant treatment is given. Neoadjuvant imatinib may increase the cure rate by shrinking large GISTs and preserve organ function.Methods:We conducted an Asian multinational phase II study for patients with gastric GISTs ≥10 cm. Patients received neoadjuvant imatinib (400 mg/day) for 6–9 months. The primary end point was R0 resection rate.Results:A total of 56 patients were enroled in this study. In the full analysis set of 53 patients, neoadjuvant imatinib for ≥6 months was completed in 46 patients. Grade 3–4 neutropenia and rash occurred in 8% and 9%, respectively, but there were no treatment-related deaths. The response rate by RECIST was 62% (95% CI, 48–75%). The R0 resection rate was 91% (48/53) (95% CI, 79–97%). Preservation of at least half of the stomach was achieved in 42 of 48 patients with R0 resection. At the median follow-up time of 32 months, 2-year overall and progression-free survival rates were 98% and 89%, respectively.Conclusions:Neoadjuvant imatinib treatment for 6–9 months is a promising treatment for large gastric GISTs, allowing a high R0 resection rate with acceptable toxicity.

A phase II study of doxifluridine and docetaxel combination chemotherapy for advanced or recurrent gastric cancer

BackgroundThe aim of this study was to establish the efficacy and safety of doxifluridine and docetaxel for patients with advanced or recurrent gastric cancer.MethodsThe regimen consisted of oral administration of doxifluridine 533 mg/m2 per day on days 1–14 and an intravenous infusion of docetaxel 50 mg/m2 on day 8. The primary endpoint was the overall response rate. The secondary endpoints were overall survival, progression-free survival, and toxicities.ResultsBetween June 2004 and December 2006, a total of 40 eligible patients were enrolled in this study. Seven of them showed a partial response, with an overall response rate of 17.5%. The response rate was 18.8% in 32 patients with refractory tumors. The median progression-free survival time and the median overall survival time were 2.6 months and 12.7 months, respectively, in all 40 patients; and 2.6 months and 14.0 months, respectively, in the 32 patients with refractory tumors. Grade 3/4 hematological toxicity included neutropenia in 52.5%, leukocytopenia in 17.5%, and febrile neutropenia in 7.5%. Grade 3 or more nonhematological toxicities were infrequent.ConclusionThe combination chemotherapy of doxifluridine and docetaxel was well tolerated and relatively effective when used as a second-line chemotherapy for advanced or recurrent gastric cancer.

Endoscopy‐assisted anastomosis: a modified technique for laparoscopic side‐to‐side esophagojejunostomy following a total gastrectomy

Introduction: Esophagojejunostomy with a circular stapling device is sometimes difficult to perform in a laparoscopic setting. On the other hand, a side‐to‐side anastomosis with a linear stapling device is technically challenging.

Prognostic significance of morphological distribution of metastatic foci in lymph nodes with gastric cancer.

Background/Aims: The morphological distribution of tumor cells in metastatic lymph nodes has been investigated in positive sentinel lymph nodes in several solid cancers. The aim of this study was to clarify the effect of the distribution of metastatic foci in lymph nodes on the prognosis in gastric cancer. Methods: The distribution of metastatic foci in the 100 node-positive patients who had undergone curative gastrectomy were classified into two groups: (1) massive type, in which the tumor occupied the entire lymph node, and (2) non-massive type, in which the tumor did not occupy the entire lymph node. Results: There were 38 patients in the massive type group and 62 patients in the non-massive type group. The 10-year survival rate was significantly poorer in the massive type group (p = 0.001). Multivariate analysis showed that distributional type and nodal status were independent prognostic factors. UICC N stage was subcategorized by distributional type, and survival was shown to be significantly worse in the massive type in the N1 group (p = 0.035). Conclusion: It seems necessary to take the morphological distribution of metastatic foci into consideration when dealing with node-positive patients who had received curative resection for gastric cancer.

A Case of Helicobacter pylori-negative Advanced Gastric Cancer with Massive Eosinophilia

The incidence of Helicobacter pylori-negative gastric cancer is very low. A 60-year-old man was referred to Tokai University Hospital from a local clinic because of eosinophilia. The laboratory data revealed prominent eosinophilia, with a white blood cell count of 7,900 /μL and increased eosinophil granulocyte level of 1,659 /μL. After an examination for secondary eosinophilia, esophagogastroduodenoscopy showed an enlarged gastric fold in the corpus, suggesting type 4 gastric cancer. Repeated esophagogastroduodenoscopy (EGD) and a re-biopsy demonstrated poorly differentiated adenocarcinoma and signet ring cell carcinoma. The patient was negative for Helicobacter pylori infection according to the serum anti-Helicobacter pylori antibody, culture and histopathological findings.

A prospective observational study on changes in physical activity, quality of life, and self-efficacy in perioperative patients with gastric cancer

Background: Patients undergoing major surgery often experience “post-operative dysfunction”, which may affect their physical strength and mental activity for a significant period post-operatively. We aimed to clarify the post-operative changes in physical activity, quality of life, and self-efficacy in patients with gastric cancer. Methods: Physical activity, health-related quality of life, and self-efficacy were assessed in subjects using self-administered questionnaires before surgery, at discharge, and 1, 3, and 6 months after discharge. Post-operative parameters were compared to baseline data using the Friedman test with Bonferroni correction, as well as the Wilcoxon two-sample test. Results: Seventeen subjects were included. Dietary intake and number of steps walked significantly decreased for up to 1 month after discharge, whereas physical activity of ≥3 metabolic equivalents of task and exercise-expended energy were lowest at discharge. These differences were all statistically significant. Importantly, the patients did subsequently improve. Body mass index did not differ significantly at discharge, but showed a gradual, significant decrease at 1 and 3 months after discharge. With respect to health-related quality of life, the physical, role, and social functions decreased significantly for a month after surgery, whereas symptoms of fatigue, anorexia, and diarrhea were significantly severe during the first month after discharge. Self-efficacy in terms of symptoms, activities of daily living, and disease status significantly decreased at discharge, but subsequently improved. Conclusions: Patients with gastric cancer showed lower dietary intake and body mass index up to 1 and 3 months after discharge, respectively. Physical activity and self-efficacy were lowest at discharge but improved subsequently. It is necessary, both preoperatively and in the first month following discharge, to provide patients with support that encourages self-management of physical changes and symptoms, and a return to normal levels of physical activity.

An Intra-Abdominal Desmoid Tumor, Embedded in the Pancreas, Preoperatively Diagnosed as an Extragastric Growing Gastrointestinal Stromal Tumor

A 45-year-old woman was found to have a pancreatic tumor by abdominal ultrasound performed for a medical check-up. Abdominal contrast-enhanced computed tomography showed a hypovascular tumor measuring 30 mm in diameter in the pancreatic tail. Endoscopic ultrasound-guided fine needle aspiration was performed. An extragastric growing gastrointestinal stromal tumor was thereby diagnosed preoperatively, and surgical resection was planned. Laparoscopic surgery was attempted but conversion to open surgery was necessitated by extensive adhesions, and distal pancreatectomy, splenectomy, and partial gastrectomy were performed. The histological diagnosis was an intra-abdominal desmoid tumor. A desmoid tumor is a fibrous soft tissue tumor arising in the fascia and musculoaponeurotic tissues. It usually occurs in the extremities and abdominal wall, and only rarely in the abdominal cavity. We experienced a case with an intra-abdominal desmoid tumor that was histologically diagnosed after laparotomy, which had been preoperatively diagnosed as an extragastric growing gastrointestinal stromal tumor. Although rare, desmoid tumors should be considered in the differential diagnosis of intra-abdominal tumors. Herein, we report this case with a literature review.