Yoshio Gunji

Prospective randomized study of open versus laparoscopy-assisted distal gastrectomy with extraperigastric lymph node dissection for early gastric cancer

BackgroundLaparoscopy-assisted surgery with extraperigastric lymph node dissection for gastric cancers has been described, but the clinical benefits of these surgeries still are unclear. Short-term clinical outcomes were compared between laparoscopy-assisted distal gastrectomy (LADG) and conventional open distal gastrectomy (ODG) for early gastric cancer in a prospective randomized fashion.MethodsFor this study, 28 patients with early gastric cancers in the lower half of the stomach were randomly assigned to either LADG (n = 4) or ODG (n = 14). Postoperative pain, levels of acute inflammatory responses, and pathologic evaluation of the operative specimens were compared.ResultsThe LADG group required a significantly shorter period of postoperative epidural anesthesia, showed significantly lower levels of serum interleukin-6 and C-reactive protein, and had no major postsurgery complications. Pathologic examinations showed that surgery was equally radical in the two groups.ConclusionThe findings show that LADG with extraperigastric lymph node dissection is a safe and less invasive alternative to the open procedure.

Sentinel lymph node mapping for gastric cancer using a dual procedure with dye- and gamma probe-guided techniques

BACKGROUND Increasing evidence supports the sentinel lymph node (SN) concept for melanoma and breast cancers. SN biopsy may replace routine lymph node dissection in the treatment of these cancers. But there are little data evaluating this concept in patients with gastric cancer. The objective of this study was to test the feasibility of SN mapping in gastric cancers by using the dual-mapping procedure with dye and radioactive colloid. STUDY DESIGN Thirty-one consecutive patients preoperatively diagnosed as T1-2 and N0 underwent SN biopsy using the dual-mapping procedure. Distributions of SNs identified by the dye-guided technique (blue nodes; BNs) were compared with those identified by the gamma probe guided technique (hot nodes; HNs). RESULTS Among the 31 patients, 7 were found to have lymph node metastases. All positive nodes were detected by SN biopsy using the dual method. So, an accuracy rate of 100% was achieved in predicting the status of regional lymph nodes. Both BNs and HNs were identified in 28 of 31 patients (90%), but significant discrepancy of distribution was noted between BNs and HNs. Among the 28 patients with identified BNs, there was one metastasis in a non-BN. So the accuracy rate was 96% for the dye-guided technique. In contrast, among the 28 patients with identified HNs, 2 patients had metastasis in non-HNs, making the accuracy rate 93% for the gamma probe-guided technique. CONCLUSIONS SN mapping is feasible in gastric cancer, but the dye-guided and gamma probe-guided techniques are complementary. So we recommend the dual-mapping procedure.

Studies of the effects of FK506 on renal allografting in the beagle dog

The immunosuppressive activities of a newly discovered macrolide extracted from Streptomyces tsukubaensis, FK506, were examined using 38 renal allografts in the beagle dog. The median survival time was 15.5 days in dogs without treatment, 61 days with a dose of 0.08 mg/kg/day and 176 days with a dose of 0.16 mg/kg/day of intramuscularly administered FK506. Prolongation of survival was statistically significant when compared with controls (P = 0.02, 0.0044, respectively). None of 6 recipient dogs receiving the agent at a dose of 0.16 mg/kg/day encountered rejection during the treatment course. Three of them survived over 200 days. Oral administration of FK506 at a dose of 0.32 mg/kg/day did not prolong the median survival time (20.5 days) compared with the placebo treated control (16.5 days), but oral treatment with 1.0 mg/kg/day resulted in all of the recipient dogs surviving over 130 days. Histological studies of 7 kidney graft biopsy specimens of the dogs surviving over 3 months revealed no cell infiltration or only some degree of reversible interstitial cell infiltration, but vascular and glomerular changes were not observed in any of the specimens. Irregularity of nuclear shape and cytoplasmic vacuolation of the pars recta of the proximal tubules were observed in one dog each. Liver biopsy specimens showed no consistent evidence of hepatocellular damage. Three dogs died of intussusception 2–3 weeks posttransplant. The dogs treated intramuscularly with 0.32 mg/kg/day suffered from anorexia. Two dogs receiving oral treatment at a dose of 1.0 mg/kg developed papilloma of the skin around day 60, but the tumors disappeared by day 120. We conclude that FK506 is a powerful immunosuppressant in the dog with tolerable side effects.

Clinical significance of serum vascular endothelial growth factor in esophageal squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis in malignant tumors. An increased in the serum VEGF concentration (S‐VEGF) has been found in patients with various solid tumors and appears to be correlated with tumor burden. The objective of the current study was to determine the correlation between pretreatment S‐VEGF and clinicopathologic features in patients with esophageal squamous cell carcinoma.

Serum p53 antibody is a useful tumor marker in superficial esophageal squamous cell carcinoma

Patients with superficial (mucosal or submucosal) esophageal carcinoma (SEC) have significantly better survival rates than patients with advanced carcinoma. Some patients with advanced esophageal carcinoma have been reported to test positive for serum p53 antibodies (Abs). Because very few patients with superficial carcinoma have been examined, the aim of this study was to evaluate the clinical significance of serum p53‐Abs in patients with superficial esophageal squamous cell carcinoma (SESCC).

EFFECTS OF COMBINATION TREATMENT WITH FK506 AND CYCLOSPORINE ON SURVIVAL TIME AND VASCULAR CHANGES IN RENAL-ALLOGRAFT-RECIPIENT DOGS

In our previous experiments studying the effects of FK506 on renal allografting in the dog, we encountered two major problems. One problem was anorexia and the other problem was vascular changes mainly in the recipient heart. Anorexia was generally dose dependent, but the vascular changes were seen to be more prominent at lower doses rather than at higher immunosuppressive doses. The present study was undertaken to study these two problems. A nonanorexic, vascular change-related, nonimmunosuppressive dose of FK506 was combined with a low dose of cyclosporine or prednisolone in beagle dogs after renal allografting. Treatment with either FK506 alone at a dose of 0.32 mg/kg or cyclosporine alone at 2.5 mg/kg was not effective in prolonging renal recipient survival. The recipient dogs died of rejection, and a variety of vascular changes were observed in the hearts of both groups. Combined treatment with FK506 and cyclosporine at these same doses resulted in statistically significant prolongation of the survival time of the renal recipient (P less than 0.01), and histologic studies showed that the frequency and severity of the vascular changes were suppressed in the recipient receiving the combined treatment. The combination of FK506 and prednisolone at 0.5 mg/kg was not effective in prolonging survival. Furthermore, the extent of vascular changes was similar to those found in recipients receiving FK506 alone. The data suggest that combined treatment with low doses of both FK506 and cyclosporine acted synergistically in prolonging canine renal allografts and that the vascular changes frequently seen at low doses of FK506 were reduced by additional immunosuppression with a low dose of cyclosporine.

High Frequency of Cancer Patients with Abnormal Assembly of the T Cell Receptor‐CD3 Complex in Peripheral Blood T Lymphocytes

Structural abnormality of T cell receptor (TCR)‐CD3 complex on the cell surface was investigated in peripheral blood lymphocytes (PBL) from 55 cancer patients. In 24 of the 68 tests done on these patients, the CD3C chain was not detected by immunoprecipitation with anti‐CD3ζ monoclonal antibody (mAb), but was observed with anti‐CD3ζ mAb, suggesting that a high frequency of cancer patients possesses abnormal T cell receptor (TCR) complex in PBL. On the other hand, the total ζ chain was missing in several advanced cases. During follow‐up of several patients, the ζ chain became undetectable after two or three months of cancer progression. It appears that immunosuppressive status can be monitored by analyzing the TCR‐CD3 complex on the cell surface of PBL.

A prospective randomized trial of hand-sutured versus mechanically stapled anastomoses for gastroduodenostomy after distal gastrectomy

BackgroundAlthough mechanical stapling is now an established alternative to conventional hand suturing for the construction of gastrointestinal anastomoses, its role in gastroduodenostomy remains to be defined. We compared the clinical outcome after mechanical stapling with that after hand suturing in patients who underwent gastroduodenostomy after distal gastrectomy.MethodsFrom April 2000 through August 2001, a total of 187 patients with gastric cancer who received distal gastrectomy were randomly assigned to reconstruction by mechanically stapled or by hand-sutured gastroduodenal anastomoses.ResultsThe baseline clinical characteristics were similar in the patients with mechanically stapled and those with hand-sutured anastomoses. There was no in-hospital mortality in either group. One patient (1.1%) in the mechanically stapled group (n = 92) and 2 (2.1%) in the hand-sutured group (n = 95) had anastomotic leakage. Anastomotic stenosis developed in 4 patients (4.3%) who underwent mechanical stapling, as compared with 6 (6.3%) who underwent hand suturing. Anastomotic bleeding occurred in 1 patient (1.1%) who under-went mechanical stapling and 1 patient in the hand-sutured group (1.1%). Mechanical stapling of the anastomoses was significantly quicker than hand-suturing of the anastomoses (median time, 14 vs 25 min; p = 0.02). The two groups were comparable with respect to other outcome measures, including incidence of general complications, recovery of gastrointestinal function, duration of postoperative hospital stay, and radiological diameter of the anastomosis.ConclusionIn patients with gastric cancer who undergo gastroduodenostomy after distal gastrectomy, mechanical stapling is quicker than hand suturing. These procedures are similar with respect to anastomotic complications and other outcome measures.

Prognostic Significance of the Number of Metastatic Lymph Nodes in Early Gastric Cancer

Background: The prognostic value of the number of metastatic lymph nodes in early gastric cancer has not been evaluated much, although the significance of metastatic lymph nodes is defined by the location of positive nodes, according to the JRSGC for gastric cancer. Methods: The postoperative courses of 305 early gastric cancer patients who had undergone D2-extended lymphadenectomy were followed up for a median of 108 months to evaluate the significance of the number of metastatic lymph nodes on recurrence of the disease. Results: Recurrence of gastric cancer was more frequently observed in submucosal cancer than in mucosal cancer. All patients but one who revealed recurrence had nodal metastasis at the time of surgery. In cases with 1–3 metastatic lymph nodes, no patient had revealed any sign of recurrence; however, in cases with 4 or more metastatic lymph nodes, 6 of 7 patients died of recurrent disease. There were 3 cases of bone metastases, 2 of peritoneal dissemination, and 1 each of both recurrent diseases. Conclusions: These data suggest that in n-positive cases, in which there are 4 or more metastatic lymph nodes, there is a high probability of recurrence of early gastric cancer, and especially of hematogenic metastasis.

Preclinical Study of Adenoviral p53 Gene Therapy for Esophageal Cancer

Abstract An alteration of the p53 gene function is a major factor in the development of esophageal cancer. Recently, p53 gene therapy has been applied for clinical studies in lung cancer and head and neck cancer. However, no preclinical studies have yet demonstrated an anticancer effect of adenoviral-mediated wild-type p53 gene therapy on esophageal cancer. We herein evaluated the effect of p53 adenoviral gene therapy on human esophageal squamous cell carcinoma to test the ability of clinical application. A normal esophageal epithelial cell line (EN53F) and two human esophageal cancer cell lines (ECGI-10 and T.Tn) with a p53 alteration were used. The transduction efficiency, p53 protein expression, p21 protein expression, the induction of apoptosis, and growth suppression were assessed by using the recombinant adenoviral vector Ad5CMV-p53. The transduction efficiency was 60%–80% at 100 plaque-forming units (PFU)/cell and 80%–100% at 300 PFU/cell. A significant growth suppression following an Ad5CMV-p53 infection was observed in both cancer cell lines. A Western blot analysis confirmed the presence of both exogenous p53 protein expression and p21 protein induction. Apoptotic cell death was observed with TUNEL staining. T.Tn xenografts in nude mice transduced with Ad5CMV-p53 demonstrated significant growth suppression. These data suggest that Ad5CMV-p53 may thus be a potentially effective therapeutic agent for locally advanced esophageal cancer.