Subjective and functional results after total gastrectomy: prospective study for longterm comparison of reconstruction procedures

Background: Many reconstruction procedures have been developed in efforts to resolve patients' complaints after total gastrectomy. However, there have been few reports of longterm comparisons between reconstruction procedures, especially with regard to the prevention of duodenal food passage. This study was undertaken to compare the longterm subjective and functional results among Roux-en-Y esophagojejunostomy (R-Y), R-Y with pouch (P-Y), and jejunal interposition with pouch (P-I) after total gastrectomy. Methods: Consecutive patients requiring curative total gastrectomy were enrolled in this prospective study by the envelope method. Results: Hospital stay was longer following a P-I than an R-Y or a P-Y. Over 50% of R-Y patients complained of heartburn, and 20% of R-Y patients showed dumping syndrome throughout the postoperative period, with this rate being significantly different from rates in the other two groups. P-Y patients complained of early satiety in the late postoperative period, while P-I patients complained of early satiety in the early postoperative period. The nutritional index in P-I patients was higher than those in patients with the other two procedures. Gastrointestinal and hepatobiliary dual scintigraphy (GHDS) showed that the rate of bile reflux with an R-Y was relatively high after surgery. Food reflux with a P-Y was increased (9.4% to 11.1%), but with a P-I food reflux was decreased at 3 years after surgery (13.3% to 9.9%). Patients with a P-Y had a faster recovery of body, weight in the early postoperative period; however, at 5 years after operation, body weight recovery with a P-I was greatest. Conclusion: Reconstruction should be performed with pouch formation after total gastrectomy with curative intent. Received: March 7, 2002 / Accepted: September 26, 2002 Acknowledgments This study was partly supported by the University of Tsukuba Research Project. Offprint requests to: S. Adachi     

Seasonal changes in calcium homeostasis affect the incidence of postoperative tetany in patients with Graves' disease

BACKGROUND: We have found that postoperative tetany occurs in patients with Graves' disease who have secondary hyperparathyroidism caused by a deficiency in calcium and vitamin D concomitant with transient hypoparathyroidism after surgery. There are seasonal variations in serum 25-hydroxyvitamin D (25[OH]D) concentrations. The purpose of this study was to investigate the effects of seasonal changes in calcium homeostasis on the incidence of postoperative tetany in patients with Graves' disease who undergo subtotal thyroidectomy. PATIENTS AND METHODS: A prospective study was carried out to investigate sequential changes in serum levels of intact parathyroid hormone (iPTH), calcium and other electrolytes, 25(OH)D, and 1,25-dihydroxyvitamin D (1,25[OH]2D) in female patients with Graves' disease who underwent subtotal thyroidectomy during the summer (n = 89) and during the winter (n = 89). RESULTS: The serum levels of calcium, magnesium, and 25(OH)D were significantly higher, but iPTH levels and 1,25(OH)2D levels were lower in summer than in winter. The percentage of vitamin D deficiency (25(OH)D < 25 nmol/L) was 23% in summer and 62% in winter (P < .001). iPTH was below the detection limit on the first postoperative day in 15 patients (13.8%) in summer and in 13 patients (11.4%) in winter. In summery, tetany developed in only 4 of 15 patients and in one patient whose iPTH level was below normal (incidence of tetany, 5.6%). In winter, however, tetany developed in 6 of 13 patients and in 4 patients whose iPTH level was below normal (incidence of tetany, 11.2%). CONCLUSIONS: Patients with Graves' disease are more susceptible to calcium and vitamin D deficiency during the winter than during the summer, resulting in the tendency toward a higher incidence of postoperative tetany in winter.     

The significance of arytenoid edema following radiotherapy of laryngeal carcinoma with respect to residual and recurrent tumour

We sometimes experience patients with persistent or progressive arytenoid edema, among which residual or recurrent cancer is often accompanied. Because it is difficult to distinguish tumour rest or recurrence from normal tissue sequelae in the early period after irradiation, it is important to know both the contributing factors for arytenoid edema, and the incidence of residual or recurrent tumours in patients with postirradiation laryngeal edema. We therefore reviewed the charts of 67 patients with early laryngeal carcinoma who had received a curative dose of irradiation in the last 5 years. Fourteen patients (20.9%) had moderate or severe laryngeal edema persisting for or developing at more than 3 months after completion of a course of definitive radiotherapy. The incidence was highest in supraglottic T₂ disease, followed by glottic T₂ tumour. Of the 14 patients with edema, six (42.9%) had persistent or recurrent disease. The primary disease was uncontrolled in 18 patients, 17 of whom received successful salvage surgery. In patients without residual tumours, the edema was usually moderate and resolved within a year, although four patients had chronic edema lasting more than a year after treatment. All four had supraglottic T₂ lesions and received 70 Gy of X-ray. We also reviewed, for sake of comparison, the records of 38 patients treated with radiotherapy at doses of more than 40 Gy between l975 and 1980, when endoscopic microsurgery for laryngeal cancer was introduced as a primary part of treatment. The incidence of persistent or late developed edema over the period, though not significant, was 36.8%: nearly twice that of the last 5 years. Microscopic endolaryngeal surgical procedures seem to have been a causal factor for edema in this period.     

Sequence Analysis of Genes Encoding Rodent Homologues of the Human Tumor-rejection Antigen SART-1

Human SART-1 ( hSART-1 ) gene encodes a 125 kD protein with a leucine-zipper motif expressed in the nucleus of all proliferating cells, and a 43 kD protein expressed in the cytosol of most epithelial cancers. In this study, two rodent genes ( rSART-1 and mSART-1 ) homologous to hSART-1 were cloned from cDNA libraries of murine brain and a rat tumor cell line, respectively. mSART-1 and rSART-1 were highly homologous to hSART-1 with 86% and 84% identity at the nucleotide level, and 95% and 91% at the protein level, respectively. The leucine zipper domain and two basic amino acid portions that bind DNA, as well as peptide sequences recognized by human cyto-toxic T lymphocytes (CTLs), were all conserved in these rodent genes. Nuclear protein homologous to the 125 kD hSART-1₈₀₀ protein, but not to the 43 kD cytosol SART-1₂₅₉ protein, was detectable with specific antibody in the nuclear fractions of rodent tumor cell lines, and normal rodent fetal liver and testis. These rodent genes should be a novel tool for studies on the biological roles of the SART-1 gene, and also in the construction of animal models of specific immuno-therapy using SART-1 gene products.     

Longitudinal elongation of primary afferent axons in the dorsal funiculus of the chick embryo spinal cord

The longitudinal elongation of primary afferent axons (PAAs) in the dorsal funiculus of chick embryo spinal cord was examined using a lipophilic tracer, DiI and immunohistochemistry. The earliest developing PAAs in the brachial segments invaded the spinal cord around embryonic day (E) 3.5. Thereafter, they elongated both rostrally and caudally in the presumptive dorsal funiculus, with frequent contacts between pre-existing axons and later arriving growth cones. By E4, the PAAs had elongated 3 segments both rostrally and caudally. In the course of their longitudinal elongation, the PAAs shifted their trajectory dorsally within the dorsal funiculus. By E6-6.5, the PAAs had extended as far as 10 segments rostrally and 6 segments caudally in the dorsal funiculus, and collaterals began to enter the dorsal horn. By E9, the PAAs extended up to 13 segments rostrally and 7 segments caudally, and collaterals reached the ventral spinal cord. During their longitudinal course, the PAAs shifted their trajectory medially within the dorsal funiculus.     

Radical resection of hilar bile duct carcinoma and predictors of survival

BACKGROUND: Patients with carcinoma of the main hepatic duct have a poor prognosis. This study attempted to identify clinicopathological predictors of survival after resection. METHODS: A retrospective review was performed of 114 patients who presented with hepatic ductal carcinoma between 1976 and 1998. Of the 114 patients, 98 had a radical resection, three underwent palliative resection and 13 were not treated surgically. Forty-six patients with stage IVA disease had microscopic tumour residue after resection. Of these, 28 patients were treated with radiotherapy and the remaining 18 had resection alone. RESULTS: The overall operative morbidity and mortality rates were 14 and 4 per cent respectively. The overall 5-year survival rate after resection was 28 per cent. Nineteen patients survived for more than 5 years, including ten with stage IVA disease. The main prognostic factors were performance status; jaundice; tumour location; gross appearance; histological grade; T, N and M categories in tumour node metastasis (TNM) classification; TNM stage; and residual tumour. Adjuvant radiotherapy, tumour extension into the hepatic ducts, histological grade, N and residual tumour were independent predictive factors by multivariate Cox analysis. CONCLUSION: This study suggests that radical resection provides the best survival rate for patients with hilar bile duct carcinoma. For patients with stage IVA disease, following complete gross resection radiotherapy improved treatment outcome.     

Vaccination of dendritic cells loaded with interleukin-12-secreting cancer cells augments in vivo antitumor immunity: characteristics of syngeneic and allogeneic antigen-presenting cell cancer hybrid cells.

Cancer immunotherapy by fusion of antigen-presenting cells and tumor cells has been shown to induce potent antitumor immunity. In this study, we characterized syngeneic and allogeneic, murine macrophage/dendritic cell (DC)-cancer fusion cells for the antitumor effects. The results showed the superiority of allogeneic cells as fusion partners in both types of antigen-presenting cells in an in vivo immunotherapy model. A potent induction of tumor-specific CTLs was observed in these immunized conditions. In addition, the immunization with DC-cancer fusion cells was better than that with macrophage-cancer fusion cells. Both syngeneic and allogeneic DC-cancer fusion cells induced higher levels of IFN-gamma production than macrophage-cancer fusion cells. Interestingly, allogeneic DC-cancer fusion cells were superior in that they efficiently induced Th1-type cytokines but not the Th2-type cytokines interleukin (IL)-10 and IL-4, whereas syngeneic DC-cancer fusion cells were powerful inducers of both Th1 and Th2 cytokines. These results suggest that allogeneic DCs are suitable as fusion cells in cancer immunotherapy. To further enhance the antitumor immunity in the clinical setting, we prepared DCs fused with IL-12 gene-transferred cancer cells and thus generated IL-12-secreting DC-cancer fusion cells. Immunization with these gene-modified DC-cancer fusion cells was able to elicit a markedly enhanced antitumor effect in the in vivo therapeutic model. This novel IL-12-producing fusion cell vaccine might be one promising intervention for future cancer immunotherapy.     

Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas.

PURPOSE: Squamous cell carcinoma (SCC) and adenocarcinoma of the lung are currently subject to similar treatment regimens despite distinct differences in histology and epidemiology. The aim of this study is to identify a molecular target with diagnostic and therapeutic values for SCC. EXPERIMENTAL DESIGN: Genes specifically up-regulated in SCC were explored through microarray analysis of 5 SCCs, 5 adenocarcinomas, 10 small cell lung carcinomas, 27 normal tissues, and 40 cancer cell lines. Clinical usefulness of these genes was subsequently examined mainly by immunohistochemical analysis. RESULTS: Seven genes, including aldo-keto reductase family 1, member B10 (AKR1B10), were identified as SCC-specific genes. AKR1B10 was further examined by immunohistochemical analysis of 101 non-small cell lung carcinomas (NSCLC) and its overexpression was observed in 27 of 32 (84.4%) SCCs and 19 of 65 (29.2%) adenocarcinomas. Multiple regression analysis showed that smoking was an independent variable responsible for AKR1B10 overexpression in NSCLCs (P < 0.01) and adenocarcinomas (P < 0.01). AKR1B10 staining was occasionally observed even in squamous metaplasia, a precancerous lesion of SCC. CONCLUSION: AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and many adenocarcinoma cases of smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.     

MUC 1 core protein as a marker of gallbladder malignancy.

AIM: The significance of MUC 1 expression in the gallbladder tissues in relation to cancer and non-cancer disease is not well understood. The aim of this study was to clarify the significance of MUC 1 expression. MATERIALS AND METHODS: A monoclonal antibody (CA 15--3; DF 3) was applied to stain MUC 1 core protein in surgical specimens. RESULTS: MUC 1 expression is significantly higher (p<0.0001) in gallbladder cancer (69/88) compare to non-cancerous tissue, while, very trace in normal and inflammatory tissues. The expression rate was significantly lower (p<0.0001) when the cancer did not penetrate the mucosal layer than when cancers did penetrate this layer. The MUC 1 expression rate was (4/14) in T1 tumours, (11/14) in T4, (40/45) in T3, and (14/15) in T2, respectively. Every cell of normal and inflammatory mucosa, and T1 cancers had the polarized pattern. The depolarized pattern was dominant in cancer cells from the advanced tumours of T2, T3 and T4. That is, (45/74) of cancer cells from the mucosal layer and (58/74) of penetrating cancer cells in submucosal layer had the depolarized pattern. There was no significant correlation of MUC 1 expression rate and staining pattern with cancer differentiation and microscopic venous invasion. On the other hand, lymphatic vessel invasion was significantly correlated with the staining pattern but not with expression rate. CONCLUSION: MUC 1 core protein expression rate and pattern are suggesting that MUC 1 core protein would be a marker of malignant transformation of gallbladder epithelium and its depolarized expression would also be a marker of invasion of gallbladder cancer.     

Chemopreventive and therapeutic efficacy of orally active tyrosine kinase inhibitors in a transgenic mouse model of gallbladder carcinoma.

Biliary tract cancer (BTC) is the second most common primary hepatobiliary cancer after hepatocellular cancer. At the time of diagnosis, most BTC are at an advanced stage and are unresectable. There is presently no effective curative treatment of the advanced disease nor is there any effective clinical therapy that will prevent the development of BTC. All of these factors render gallbladder cancer nearly incurable with a poor survival rate. The aim of our study was to provide a better understanding of the mechanisms involved in the development of gallbladder carcinoma as the advancement of more effective treatment options would significantly improve prognosis. In the present study, we examined the effect of gefitinib, a selective epidermal growth factor receptor/tyrosine kinase inhibitor (EGFR/TKI), on the development of gallbladder carcinoma in BK5.erbB2 mice. In addition, we examined the effect of another quinazoline derivative, GW2974, which is able to block the activation of both the EGFR and erbB2, in this model. Animals were treated with either 400 ppm gefitinib or 200 ppm GW2974 as a supplement in the diet using either a chemopreventive or therapeutic protocol. The results show that both compounds were potent chemopreventive and therapeutic agents in this mouse model of human BTC. The results also suggest that activation of the EGFR plays an important role in development of BTC in this model and that targeting both the EGFR and erbB2 may be an effective strategy for treatment of this disease.