Yoshiaki Mihara

Differing deregulation of HER2 in primary gastric cancer and synchronous related metastatic lymph nodes

BackgroundThe aim of this study was to investigate how differences in expression of HER2 between primary gastric cancers (PGCs) and their corresponding metastatic lymph nodes (LMNs) might affect its potential as a prognostic indicator in treatments including anti-HER2 agents.MethodsThe analysis was conducted in 102 patients who underwent surgical resection for primary gastric cancers (PGCs; adenocarcinoma, intestinal type) with synchronous LNMs. HER2 gene status and protein expression were investigated by immunohistochemistry (IHC) in all patients; fluorescence in situ hybridization (FISH) was performed in 22 patients. The correlation between HER2 gene status in PGCs and their LNMs was evaluated.ResultsPositive HER2 expression as detected by IHC + FISH was observed in 27/102 PGC samples (26.5%) and 29/102 LNM samples (28.4%). HER2 amplification status in 102 paired PGC and LNM samples as evaluated by FISH + IHC was concordant in 92 patients (90.2%), 69 (67.6%) were unamplified and 23/102 (22.5%) were amplified at both sites, and discordant in 10 patients (9.8%), 4 (3.9%) were positive for PGC and negative for LNM, while 6 (5.9%) were positive for LNM and negative for PGC. The results of FISH + IHC showed very strong concordance in HER2 status between the PGC and LNM groups (k = 0.754).ConclusionThe high concordance between HER2 results for PGCs and their LNMs indicates that assessment of HER2 status in the primary cancer alone is a reliable basis for deciding treatment with anti-HER2 agents in patients with LNMs from gastric adenocarcinoma.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9365749431029643.

D2 gastrectomy with versus without bursectomy for gastric cancer.

Objectives:The purpose of this study was to determine the survival benefit of bursectomy by retrospectively comparing the prognosis in patients undergoing D2 lymphadenectomy and gastrectomy (D2 gastrectomy) with bursectomy for gastric cancer with that in patients undergoing D2 gastrectomy alone. Methods:A total of 254 consecutive stage IA to IIIC gastric cancer patients undergoing curative intent surgery between 2004 and 2009 were enrolled. The patients were divided into 2 groups: a bursectomy group, which included patients undergoing curative D2 gastrectomy with bursectomy by one surgeon, and a nonbursectomy group, which included those undergoing curative D2 gastrectomy alone by other surgeons. Results:No statistically significant difference was observed in the number of metastatic nodes or penetration of the serosa between the 2 groups. The overall incidence of surgery-related complications was 24.0% in the bursectomy group (29 of 121 patients) and 25.6% in the nonbursectomy group (34 of 133 patients). The 5-year overall survival rate was 85.8% in the bursectomy group and 80.8% in the nonbursectomy group (hazard ratio 0.82; 95% confidence interval, 0.37-1.74; P=0.60). Conclusions:The results of this retrospective study indicate no survival benefit for bursectomy plus D2 gastrectomy over D2 gastrectomy alone.

Dual primary gastric and colorectal cancer: is the prognosis better for synchronous or metachronous?

ObjectivesThe purpose of this study was to investigate the prognosis and clinicopathologic features of synchronous and metachronous dual primary gastric and colorectal cancer (DPGCC). MethodsWe reviewed clinical data of 96 patients with DPGCC, comprising 63 men and 33 women, from among 4523 patients with gastric or colorectal cancer who underwent surgical treatment or chemotherapy, but no endoscopic resection, for colorectal cancer between 1990 and 2009. The selected patients were classified into 2 groups according to the time of gastric or colorectal cancer detection as follows: synchronous group (n= 42) and metachronous group (n = 54). ResultsAmong 4523 patients treated for gastric and colorectal cancer, DPGCC was diagnosed in 96 (2.1%). In terms of clinicopathologic features, the proportion of early-stage gastric and colorectal cancer was higher in the metachronous DPGCC group, with P values of 0.02 and 0.01, respectively. Overall survival in the metachronous DPGCC group was significantly longer than in the synchronous DPGCC group (P = 0.02). Metachronous DPGCC was identified as an independent predictor of survival by both univariate and multivariate analyses, with a P value of 0.02 and 0.006, respectively. ConclusionMetachronous DPGCC had a better prognosis than synchronous DPGCC due to the tendency for metachronous DPGCC to occur in patients with early-stage cancer.

Phase II Study of Neoadjuvant Chemotherapy With S-1 and CDDP in Patients With Lymph Node Metastatic Stage II or III Gastric Cancer.

Objectives: We conducted a phase II trial to investigate the efficacy and safety of neoadjuvant chemotherapy (NAC) comprising S-1 and cisplatin (CDDP) followed by extensive resection in the management of resectable locally advanced gastric cancer with lymph node (LN) metastases. Methods: Patients with LN metastases from stage II or III gastric cancer received S-1 and CDDP, as NAC criteria for LN metastases were the involvement of ≥4 nodes <2 cm or ≥1 nodes ≥2 cm as confirmed by a total body computed tomography scan. All patients underwent extensive resection including D2 gastrectomy. The primary endpoint was complete resection rate and the secondary endpoints were 3-year relapse-free and overall survival. Results: Fifty patients were assessable for the analysis. The complete resection rate was 87.8%. Three-year relapse-free survival was 44.9% and 3-year overall survival rate was 48.0%. Conclusions: NAC with S-1 and CDDP is safe and may improve the complete resection rate in patients with metastatic LN gastric cancer. This suggests that LN metastases would provide good target lesions in future clinical trials of NAC.

Resection of Colorectal Cancer With Versus Without Preservation of Inferior Mesenteric Artery.

Objective: To assess the clinical significance of preservation of the inferior mesenteric artery (IMA) in comparison with IMA ligation in surgery for sigmoid colon or rectal (colorectal) cancer. Methods: Consecutive patients (n=862) with colorectal cancer who underwent intended surgical resection of the main tumor between 1986 and 2011 were retrospectively analyzed. The patients were divided into 2 groups: IMA preserved (n=745) and IMA ligated (n=117). Results: No significant difference was observed in incidence of advanced stage III or IV disease between the 2 groups (P=0.56 and 0.51, respectively), whereas a longer operation time (287 [95 to 700] vs. 215 [60 to 900] min, respectively; P<0.001) and greater amount of intraoperative bleeding (595 [15 to 4530] vs. 235 [1 to 11565] mL, respectively; P<0.001) were observed in the IMA-ligated group. The overall incidence of surgery-related complications was higher in the IMA-ligated group than in the IMA-preserved group (53.0% vs. 38.5%, respectively; P=0.003). Urinary dysfunction and abdominal abscess were significantly more frequent in the IMA-ligated group (11.1% vs. 4.0%, P=0.001; and 6.8% vs. 2.6%, P=0.01, respectively), and postoperative hospitalization was longer (11 to 140, median 28 vs. 5 to 153, median 19 d, respectively; P<0.001). No significant difference was found in overall survival rate between the 2 groups. Conclusions: For colorectal cancer resection, IMA preservation may be no change to IMA ligation as to patient’ survival, with small risk of operative morbidity.

Pharmacokinetics of oxaliplatin in gastrointestinal cancer patients with malignant ascites.

Abstract The pharmacokinetics of oxaliplatin in plasma and ascitic fluid was investigated in 5 gastrointestinal cancer patients with malignant ascites. Oxaliplatin was administered at 85 mg/m2 by 2-hour infusion in the FOLFOX4 regimen, and the concentrations of total and free platinum were measured. There was a trend of lower plasma Cmax values of total platinum in patients with a larger volume of ascetic fluid. The AUC0-t values of mean concentration curves of total plasma platinum, total ascites platinum, free plasma platinum, and free ascites platinum were 31.15, 7.96, 4.93 and 2.93 μg·h/ml, respectively. The concentrations of free ascites platinum were similar to those of free plasma platinum at the last sampling time of 26 h in each patient. The decrease or disappearance of ascitic fluid was observed in 4 patients. These results suggest that oxaliplatin exerted a beneficial effect in gastrointestinal cancer patients with malignant ascites, even when administered intravenously.

A complete response to S-1 plus cis-diamminedichloroplatinum in advanced-stage esophageal and gastric adenocarcinoma: a case report

BackgroundComplete remission from advanced-stage synchronous double primary (SDP) esophageal and gastric adenocarcinoma by chemotherapy alone is rare. We report a case of advanced-stage SDP esophageal and gastric adenocarcinoma in which a complete response to treatment was obtained with S-1 and cis-diamminedichloroplatinum (CDDP).Case presentationThe patient was a 74-year-old man referred to our hospital complaining of dysphagia. Gastrointestinal endoscopy was performed and advanced-stage SDP esophageal and gastric adenocarcinoma diagnosed. Computed tomography revealed multiple regional lymph node metastases in the mediastinum. Neoadjuvant chemotherapy with S-1 and CDDP for advanced esophageal and gastric cancer was planned. An endoscopy following two courses of chemotherapy revealed that the esophageal cancer had been replaced with a normal mucosal lesion and the gastric tumor with a scar lesion; the results of biopsies of both were negative for cancer. Computed tomography revealed that the multiple lymph node metastases had disappeared. We diagnosed a complete response to S-1 and CDDP in advanced-stage SDP esophageal and gastric cancer. The patient is still alive with no signs of recurrence 22 months after the disappearance of the original tumor and metastatic lesions without surgical treatment.ConclusionThese results suggest that complete remission from advanced-stage esophageal and gastric cancer can be obtained with chemotherapy with S-1 plus CDDP.