Naoto Yamamoto

Learning curve for laparoscopy-assisted distal gastrectomy with regional lymph node dissection for early gastric cancer.

An assessment of the learning curve of laparoscopy-assisted distal gastrectomy (LADG) might encourage its worldwide spread among inexperienced surgeons. One hundred sixty-seven patients with early gastric cancer were enrolled in this study: 67 underwent conventional open distal gastrectomy and 100 underwent LADG after classification into 5 groups of 20 according to the surgeons level of experience. Patient characteristics and operative findings were compared between groups. Operation time was significantly longer, time to first flatus earlier, and blood loss reduced in the LADG groups compared with the open distal gastrectomy group. Surgeons with experience of 60 cases performed operations of similar times in both groups, and blood loss decreased with experience of 20 cases. There was no operative conversion, the frequency of nonsteroidal anti-inflammatory drugs administered were significantly less, and length of hospital stay were shorter by surgeons with experience of 60 cases. LADG is a technically feasible surgical procedure, depending on the surgeons technical proficiency. Experience of at least 60 cases of LADG seems to result in satisfactory patient outcomes.

Predictive factors for surgical complications of laparoscopy- assisted distal gastrectomy for gastric cancer

BackgroundSome studies have found high incidences of intraoperative and postoperative complications for patients with gastric cancer. To determine the predictive factors for the surgical complications of laparoscopic gastric surgery, surgical outcomes were evaluated.MethodsBetween April 2002 and December 2007, 152 patients with preoperatively diagnosed early gastric cancer who underwent laparoscopy-assisted distal gastrectomy (LADG) were enrolled. Visceral (VFA) and subcutaneous fat areas (SFA) were assessed by Fat Scan software. The predictive factors for surgical complications of LADG were evaluated by univariate and logistic regression analyses.ResultsOf 152 patients, conversion to open surgery due to uncontrollable bleeding was observed in nine male patients, and postoperative complications were detected in seven male and one female patient (four anastomotic leakage, two intraabdominal abscess, one pancreatic fistula, and one lymphorrhea). High body mass index (BMI) and high VFA independently predicted conversion to open surgery and postoperative complications. VFA was significantly higher, operation time was longer, blood loss was greater, and SFA was lower in male than in female patients, whereas no significant difference was observed in BMI between male and female patients.ConclusionsHigh BMI and high VFA can predict technical difficulties during laparoscopic gastric surgery and postoperative complications. Particularly, LADG should be performed cautiously to prevent surgical complications for male patients with high VFA. Predictive impact of VFA should be further determined in a larger set of patients.

The clinical significance of SWI/SNF complex in pancreatic cancer

Chromatin remodeling factors have been the subject of great interest in oncology. However, little is known about their role in pancreatic cancer. The objective of this study was to clarify the clinical significance of the SWItch/sucrose nonfermentable (SWI/SNF) complex in patients with pancreatic cancer. A total of 68 patients with pancreatic cancer who underwent R0, 1 resection were enrolled. Cancer tissues were processed to tissue microarray, then stained immunohistochemically by using antibody of SWI/SNF components; BRM, BRG1, BAF250a, BAF180 and BAF47. The correlation of expression levels and clinicopathological outcomes were analyzed, followed by the multivariate analysis of prognostic factors for overall survival. The expression levels of the SWI/SNF components were categorized as low or high according to the median value of Histoscore. Statistical analysis revealed that BRM expression was related to tumor size, T factor, M factor, lymphatic invasion and stage BRG1 expression to histology and stage BAF180 expression to tumor size and BAF47 expression to lymphatic invasion, respectively. Multivariate Cox proportional hazard analysis showed that high BRM and low BAF180 expression levels were independent predictors of worse survival in patients with pancreatic cancer. High BRM, and low BAF180 were also independent prognostic factors for poor survival in the subgroup with adjuvant gemcitabine. These results suggest that the specific cofactors of SWI/SNF chromatin remodeling complex certainly have roles in pancreatic cancer. High BRM, and low BAF180 are useful biomarkers for poor prognosis in pancreatic cancer.

Clinical significance of SPARC gene expression in patients with gastric cancer.

Secreted protein acidic and rich in cysteine (SPARC) is one of the first known matricellular proteins that modulates interactions between cells and extracellular matrix. Recent studies investigated the clinical significance of SPARC gene expression in the development, progression, and metastasis of cancer. The present study examined the relations of the relative expression of the SPARC gene to clinicopathological factors and overall survival in patients with gastric cancer.

The cellular level of histone H3 lysine 4 dimethylation correlates with response to adjuvant gemcitabine in Japanese pancreatic cancer patients treated with surgery

BACKGROUND To search for biomarkers identifying pancreatic cancer patients likely to benefit from adjuvant gemcitabine chemotherapy, we investigated the status of several histone modifications in pancreatic tumors and their relationship to clinicopathological features and outcomes. METHODS Sixty one pancreatic cancer patients, primarily treated by surgical removal of tumors, were involved in the study. Thirty patients completed postoperative adjuvant gemcitabine, and in 31 it was discontinued. Tumor specimens were examined using immunohistochemistry for di- and tri-methylation of histone H3 lysine 4 (H3K4me2 and H3K4me3), dimethylation and acetylation of histone H3 lysine 9 (H3K9me2 and H3K9ac), and acetylation of histone H3 lysine 18 (H3K18ac). Positive tumor staining for each histone modification was used to classify patients into low- and high-staining groups, which were examined for relationships to clinicopathological features and clinical outcomes. RESULTS High expression of H3K4me3 was related to the well and moderately differentiated tumor histological type (p = 0.012) and low expression of H3K4me2 was related to the presence of perineural invasion (p = 0.007). No cellular histone modifications were associated with overall or disease-free survival of patients as a whole. In the subgroup analyses, a low level of H3K4me2 was significantly associated with worse disease free survival in patients that completed adjuvant gemcitabine (p = 0.0239). Univariate and multivariate hazard models also indicated that a low level of H3K4me2 was a significant independent predictor of disease-free survival (p = 0.007). CONCLUSION H3K4me2 was found to be a predictor of response to adjuvant gemcitabine in Asian patients with pancreatic cancer.

Inflammation in background cirrhosis evokes malignant progression in HCC development from HCV-associated liver cirrhosis

Abstract Objective. It is accepted that inflammation promotes malignant progression in the development of cancers. Whether, this is true for hepatocellular carcinoma (HCC) remains as an open question. We examined the relationship between the inflammatory histology activity index (HAI) in the background liver cirrhosis (LC) and the histological grading of the HCC in the hepatectomized HCC patients with HCV-associated LC. Material and methods. Out of 264 HCC patients who underwent curative hepatic resection, 197 had HCV-associated LC. Among them, 52 patients with a small solitary HCC nodule (< 5 cm in diameter) were studied. Inflammation in the background LC was evaluated by modified Knodells HAI. To evaluate the inflammation, piece meal necrosis, intra lobular cellular degeneration and focal necrosis, portal cellular inflammation (0–4, each) were estimated. The average HAI was calculated. The grade of malignancy of HCC was determined by WHO classification. Results. The average HAI in the 15 patients with moderately differentiated HCC (4.3 ± 0.8, mean ± SD) was significantly larger than that in 11 patients with well differentiated HCC (3.5 ± 0.6, p = 0.036). The HAI in the 24 patients whose HCC nodules contained poorly differentiated HCC (5.2 ± 1.1) was significantly larger than that in patients with moderately differentiated HCC (p = 0.025). Thus, the HAI order was well differentiated group < moderately differentiated group < poorly differentiated group. Conclusions. Inflammation in the background non-cancerous cirrhotic portion would evoke malignant progression in HCC development from HCV-associated LC.

Clinical significance of platelet‑derived growth factor receptor‑β gene expression in stage II/III gastric cancer with S‑1 adjuvant chemotherapy

Overall survival remains unsatisfactory in stage II/III gastric cancer, even after curative surgery and adjuvant chemotherapy. Platelet-derived growth factor receptor-β (PDGFR-β) is associated with the proliferation of cancer cells. The present study therefore investigated the association of PDGFR-β gene expression with patient outcome in 134 stage II/III gastric cancer patients who received adjuvant chemotherapy with S-1. Relative PDGFR-β gene expression was measured in surgical cancer tissue and adjacent normal mucosa specimens by reverse transcription-quantitative polymerase chain reaction. The PDGFR-β gene expression levels were found to be significantly higher in the cancer tissues compared with the adjacent normal mucosa. A high level of PDGFR-β gene expression was associated with a significantly poorer 5-year overall survival rate compared with a low level of PDGFR-β expression. Upon multivariate analysis, PDGFR-β gene expression was found to be an independent predictor of survival. Overall, the study indicates that PDGFR-β overexpression in gastric cancer tissues is a useful independent predictor of outcome in patients with stage II/III gastric cancer who receive adjuvant chemotherapy with S-1.

Using NU-KNIT® for hemostasis around recurrent laryngeal nerve during transthoracic esophagectomy with lymphadenectomy for esophageal cancer

BackgroundWe thought that using electrocautery for hemostasis caused recurrent laryngeal nerve palsy. We reflected the prolonged use of electrocautery and employed NU-KNIT® to achieve hemostasis nearby the recurrent laryngeal nerve. We assessed that using NU-KNIT® hemostasis prevented or not postoperative recurrent laryngeal nerve palsy, retrospectively. The present study was evaluated to compare using electrocautery hemostasis with using NU-KNIT® hemostasis during lymphadenectomy along recurrent laryngeal nerve. The variables compared were morbidity rate of recurrent laryngeal nerve palsy, operation time, and blood loss.ResultsWe use NU-KNIT® to achieve hemostasis without strong compression. This group is named group N. On the other hand, we use electrocautery to achieve hemostasis. This group is named group E. Complication rate of recurrent laryngeal nerve palsy was higher in group E (55.6%) than group N (5.3%) (p = 0.007).ConclusionsEven hemostasis using NU-KNIT® was slightly more time-consuming than using electrocautery, we concluded that it would be useful to prevent recurrent laryngeal nerve palsy.

Clinicopathological significance and impact on outcomes of the gene expression levels of IGF‑1, IGF‑2 and IGF‑1R, IGFBP‑3 in patients with colorectal cancer: Overexpression of the IGFBP‑3 gene is an effective predictor of outcomes in patients with colorectal cancer

The insulin-like growth factors (IGF) system is involved in tumor proliferation, invasion and metastasis in cancer. The current study investigated the association of IGF-1, IGF-2 and IGF-1 receptor (IGF-1R), IGF binding proteins type 3 (IGFBP-3) mRNA expression levels with clinicopathological characteristics and outcomes of 202 patients with untreated colorectal cancer (CRC). IGF-1, IGF-2, IGF-1R and IGFBP-3 mRNA expression levels were analyzed in surgical specimens of cancer tissues and adjacent normal mucosa cells using reverse transcription-quantitative polymerase chain reaction. The IGF-1R gene expression level was significantly higher in cancer tissue compared with adjacent normal mucosa. By contrast, IGF-1 gene expression levels were reduced in cancer tissue compared with normal mucosa. IGF-2 and IGFBP-3 gene expression levels did not differ significantly between cancer tissue and adjacent normal mucosa. As for the association of gene expression and clinicopathological characteristics, IGFBP-3 gene expression was significantly associated with lymph node metastasis. High IGFBP-3 gene expression was associated with poor 5-year overall survival compared with patients with low IGFBP-3 expression. Furthermore, IGFBP-3 gene expression was identified as an independent prognostic factor using multivariate analysis. Overexpression of the IGFBP-3 gene is considered an effective independent predictor of outcomes in patients with CRC.

Clinical implications of dihydropyrimidine dehydrogenase expression in patients with pancreatic cancer who undergo curative resection with S-1 adjuvant chemotherapy

The predictive roles of dihydropyrimidine dehydrogenase (DPD) in patients who undergo curative resection and adjuvant chemotherapy with S-1, which is the oral 5-fluorouracil prodrug tegafur combined with oteracil and gimeracil, remain unclear. In the present study, the clinical data from 66 consecutive patients who underwent curative resection and received adjuvant chemotherapy with S-1 for the treatment of pancreatic cancer at Kanagawa Cancer Center (Yokohama City, Japan) from April 2005 to March 2014 were retrospectively analyzed. The association between the DPD status and the survival and clinicopathological features were investigated. Of the 66 patients, 34 patients exhibited positive DPD expression (51.5%). Although a significant increase in DPD expression in male patients was observed, no significant differences were identified for other clinicopathological parameters, including tumor factor or node factor, between the DPD-positive expression group and the DPD-negative expression group. The median follow-up period of the present study was 29.2 months. There was no significant difference in the 3-year overall survival (OS) rates following surgery, which were 12.6 and 14.5% in the DPD-positive and DPD-negative expression groups, respectively (P=0.352). However, in a subgroup analysis, a significant difference in the 3-year OS rates following surgery was noted, which were 58.9 and 14.5% in the DPD-high and DPD-low expression groups, respectively (P=0.019). The intratumoral DPD expression in curatively resected pancreatic cancer patients treated with S-1 adjuvant chemotherapy was identified to not be useful as a predictive marker, whereas the level of DPD expression is a potential predictive marker. The results of the present study require confirmation in another cohort or in a prospective multicenter study.