Hiromitsu Moriya

Clinical Experience of Laparoscopy-Assisted Proximal Gastrectomy with Toupet-Like Partial Fundoplication in Early Gastric Cancer for Preventing Reflux Esophagitis

BACKGROUND Laparoscopy-assisted proximal gastrectomy (LAPG) has become prevalent for early gastric cancer in the upper stomach, but standard esophagogastrostomy is sometimes complicated with reflux esophagitis. Clinical outcomes are described here in patients with reconstruction by esophagogastrostomy with Toupet-like partial fundoplication (TPF) in LAPG. STUDY DESIGN From November 2005 through December 2008, LAPG was performed in 36 patients with early gastric cancer, 26 (72.2%) of whom could have reconstruction with the TPF because the remnant stomach was sufficiently large. RESULTS In LAPG with TPF, mean operation time was 293 minutes, mean blood loss was 119 g, and the mean number of dissected lymph nodes was 25.1. Regarding postoperative complications, anastomotic leakage occurred in two patients. More than 1 year after operation, 3 (15.0%) of the 20 patients had heartburn and 6 (30.0%) had reflux esophagitis (Los Angeles classification grade A, n=2; grade B, n=4); proton pump inhibitors were effective in these patients. CONCLUSIONS Esophagogastrostomy with TPF could be a simple, safe, and useful technique for reconstruction after LAPG in patients with early gastric cancer, and its clinical usefulness is worthwhile for the prospective validation.

Technique of esophagojejunostomy using transoral placement of the pretilted anvil head after laparoscopic gastrectomy for gastric cancer

BACKGROUND During esophagojejunostomy using a circular stapler after laparoscopy-assisted gastrectomy, placement of the anvil head via the transabdominal approach proved difficult. The authors report on a method modified for laparoscopy-assisted, esophagojejunostomy performed by placing the pretilted anvil head via the transoral approach. METHODS Between November 2007 and December 2008, esophagojejunostomy was performed using the transoral, pretilted anvil head in 27 patients after laparoscopy-assisted gastrectomy. The anesthesiologist introduced the anvil while observing its passage through the pharynx. During the anastomosis, we kept the jejunum fixed in position with a silicone band Lig-A-Loops, thereby preventing the intestine from slipping off the shaft of the stapler. RESULTS Esophagojejunal anastomosis using the transoral anvil head was achieved successfully in 26 patients; for 1 patient, passage of the anvil head was difficult owing to esophageal stenosis. No other complications, such as hypopharyngeal perforation and/or esophageal mucosal injury, occurred during passage. No postoperative complications occurred, except for 1 patient who developed anastomotic stenosis, in whom mild relief was achieved using a bougie. CONCLUSION Esophagojejunostomy using the transoral pretilted anvil head is a simple and safe technique.

Intratumoral lymphangiogenesis of esophageal squamous cell carcinoma and relationship with regulatory factors and prognosis

The clinical and pathological significance of intratumoral lymphangiogenesis (ITL) with human esophageal squamous cell carcinomas (ESCC) remains unclear, as does the role of signaling molecules such as vascular endothelial growth factor (VEGF)‐A,C, platelet‐derived growth factor (PDGF)‐A, and p53, in the regulation of ITL. Lymphatic vessel density (LVD) was significantly increased in VEGF‐A and VEGF‐C immunohistochemical score 1 and 2–3 groups as compared to the score 0 group and also with high of VEGF‐A, VEGF‐C and PDGF‐A mRNA expression. Both LVD and blood vessel density (BVD) were significantly greater in the p53 gene mutant group than in the wild‐type group. Lymph node metastasis was significantly more frequent with than without ITL and Kaplan–Meier analysis indicated a significantly poorer prognosis. Multivariate analysis using Cox proportional hazard method showed that invasion depth, lymph node metastasis and ITL were independent prognostic factors.

Laparoscopy-assisted distal gastrectomy for early gastric cancer with complete situs inversus: report of a case.

We herein report our experience in performing a laparoscopy-assisted distal gastrectomy involving standard lymph node dissection for a patient with early gastric cancer and situs inversus. A superficial elevated lesion was found on the posterior wall of the antrum. The preoperative diagnosis was cStage IA (cT1, cN0, cH0, cP0, cM0). A laparoscopy-assisted distal gastrectomy with standard lymph node dissection (D1 + β) for early gastric cancer was successfully performed by shifting the monitor to the right and left, and by applying sufficient care and time. The course of blood vessels was not abnormal except for the right/left inversion. Billroth I reconstruction was performed through a delta-shaped anastomosis. The postoperative course was favorable and the patient was discharged on postoperative day 12. Based on a histopathological examination, a 5.0 × 5.0-cm, mucosal, poorly differentiated adenocarcinoma (pT1, pN0, sH0, sP0, sM0, Stage IA) was diagnosed.

Immunohistochemical analysis of RTKs expression identified HER3 as a prognostic indicator of gastric cancer

Standard treatment in Japan for the 13th Japanese Gastric Cancer Association stage II/III advanced gastric cancer is postoperative adjuvant S‐1 administration after curative surgery. High expression of receptor type tyrosine kinases (RTKs) has repeatedly represented poor prognosis for cancers. However it has not been demonstrated whether RTKs have prognostic relevance for stage II/III gastric cancer with standard treatment. Tumor tissues were obtained from 167 stage II/III advanced gastric cancer patients who underwent curative surgery and received postoperative S‐1 chemotherapy from 2000 to 2010. Expression of the RTKs including EGFR, HER2, HER3, IGF‐1R, and EphA2 was analyzed using immunohistochemistry (IHC). Analysis using a multivariate proportional hazard model identified the most significant RTKs that represented independent prognostic relevance. When tumor HER3 expression was classified into IHC 1+/2+ (n = 98) and IHC 0 (n = 69), the cumulative 5‐year Relapse Free Survival (5y‐RFS) was 56.5 and 82.9%, respectively (P = 0.0034). Significant prognostic relevance was similarly confirmed for IGF‐1R (P = 0.014), and EGFR (P = 0.030), but not for EphA2 or HER2 expression. Intriguingly, HER3 expression was closely correlated with IGF‐1R (P < 0.0001, R = 0.41), and EphA2 (P < 0.0001, R = 0.34) expression. Multivariate proportional hazard model analysis identified HER3 (IHC 1+/2+) (HR; 1.53, 95% CI, 1.11–2.16, P = 0.0078) as the sole RTK that was a poor prognostic factor independent of stage. Of the 53 patients who recurred, 40 patients (75.5%) were HER3‐positive. Thus, of the RTKs studied, HER3 was the only RTK identified as an independent prognostic indicator of stage II/III advanced gastric cancer with standard treatment.

Laparoscopic versus open distal gastrectomy for early gastric cancer in Japan: long-term clinical outcomes of a randomized clinical trial

PurposeWe report the long-term clinical outcomes of a randomized clinical trial comparing laparoscopy-assisted distal gastrectomy (LADG) with open DG (ODG).MethodsBetween 2005 and 2008, 63 patients with clinical T1 (cT1) gastric cancer were randomly assigned to undergo either LADG or ODG. Long-term clinical outcomes included prospective questionnaire-based symptoms and survival.ResultsBased on the responses to the prospective questionnaires, patients who underwent LADG reported greater satisfaction and were more likely to favor the procedure than those who underwent ODG. The most notable difference in symptoms was related to wound pain and diarrhea. After ODG, wound pain reduced in intensity but persisted throughout the follow-up. Surprisingly, diarrhea was more frequent after LADG than after ODG, possibly due to overeating, because symptoms elicited by overeating, such as vomiting after a meal or heartburn, were also more frequent after LADG. In terms of long-term survival, there were no cases of recurrence in either group.ConclusionsLADG was associated with less wound pain during long-term follow-up after surgery, whereas symptoms related to overeating were common. Based on our findings and the patients’ reported satisfaction, we recommend LADG for cT1 gastric cancer as an effective procedure with excellent long-term survival.

Conversion surgery after combination chemotherapy of docetaxel, cisplatin and S-1 (DCS) for far-advanced gastric cancer

PurposeA triplet regimen of docetaxel, cisplatin, and S-1(DCS) is highly effective against metastatic gastric cancer. We performed this study to clarify the safety and efficacy of surgical resection in patients with initially unresectable gastric cancer, after down-staging or disease control was achieved by DCS chemotherapy.MethodsThe subjects of this retrospective study were 31 consecutive patients with initially unresectable gastric cancer, who underwent surgical resection between October, 2006 and December, 2012, after down-staging or disease control was achieved by DCS chemotherapy. We evaluated the clinicopathological factors and clinical outcomes and assessed radiographic response based on the RECIST criteria, not by central review.ResultBefore DCS chemotherapy, 18 patients had extra-regional lymph node metastasis, 5 had liver metastasis, 8 had macroscopic peritoneal metastasis, and 8 had pancreatic head invasion. Twenty-three (74.2%) of the 31 patients underwent R0 resection. Postoperative morbidity and mortality rates were 16.1 and 0%. During chemotherapy, grade 3/4 toxicities included neutropenia (54.8%), leukopenia (32.3%), and anemia (16.1%). Median progression-free survival and median overall survival (OS) were 42.1 and 56.1 months, respectively. These results were similar for all patients, except those with locally advanced disease alone. In the multivariate analysis for OS, ypN remained an independent negative prognostic factor (p = 0.018).ConclusionSurgical resection after DCS chemotherapy for initially unresectable gastric cancer was safe and provided a reasonable R0 resection rate and good mid-term survival.

Neoadjuvant chemotherapy using concurrent Docetaxel/CDDP/ 5-FU (DCF) in esophageal squamous cell carcinoma and its short-term prognosis

Background Our aim in this study is to know whether clinical outcomes are improved by neoadjuvant chemotherapy (NAC) using Docetaxel/CDDP/5-FU (DCF) as compared to NAC using 5-FU/CDDP (FP).

The H19-PEG10/IGF2BP3 axis promotes gastric cancer progression in patients with high lymph node ratios

We previously demonstrated that the lymph node ratio (LNR) is a prognostic factor associated with EGFR expression, among first priority genes amplified or overexpressed in cancer. Here, we investigated the associations between high LNR and second, third, and fourth priority genes. We performed mRNA expression microarray analysis of tumor tissue from patients with stage III gastric cancer and high or low LNRs. Candidate high LNR-associated genes were further evaluated in 39 patients with stage III gastric cancer. The functional relevance of these genes was evaluated in gastric cancer cell lines. We focused on five genes: H19,PEG10, IGF2BP3, CD177, and PGA3. H19 and PEG10 were confirmed as high LNR-associated genes. H19, PEG10, and IGF2BP3 were found to promote each other’s expression. Knocking down H19 or PEG10 using RNAi decreased cell proliferation, invasion, anchorage-independent growth, and chemoresistance. These genes had a mutual relationship in MKN7 cells. H19 knockdown decreased expression of epithelial-mesenchymal transition-associated genes in MKN74 cells to suppress transformation. Thus, H19 promotes epithelial-mesenchymal transition in gastric cancer and is a potential therapeutic target.

The clinical significance of cysteine dioxygenase type 1 methylation in Barrett esophagus adenocarcinoma

Methylation of cysteine dioxygenase type 1 (CDO1) gene, a tumor suppressor gene, has been studied in various cancers; however, there is no information regarding Barrett esophagus cancer. In this study, the clinical significance of CDO1 methylation in Barrett esophagus adenocarcinoma (BEA) was clarified. CDO1 gene promoter methylation was analyzed for DNA from the patients specimens using quantitative methylation-specific polymerase chain reaction. Thirty-eight BEA patients who underwent resection were identified between 2000 and 2014. Hypermethylation of CDO1 gene was demonstrated to be frequently recognized even at early stage in BEA by quantitative methylation-specific polymerase chain reaction. In BEA, there is a robust prognostic difference between stage I and stage II/III/IV with regard to 5-year relapse-free survival (P = 0.0016) and 5-year overall survival (P = 0.0024), and the tumor size separated by 7 cm was also a prognostic factor. There was significant difference in CDO1 gene methylation according to the tumor size (P = 0.036). BEA patients with CDO1 gene methylation were shown marginally significantly poorer prognosis (P = 0.054) than otherwise patients. In conclusion, higher CDO1 gene methylation was seen in BEA at earlier stage than in squamous cell carcinoma, and it may account for aggressive phenotype of BEA.