[A case of unresectable gastric cancer with poor ingestion].

We encountered cases of unresectable gastric cancer in which patients had difficulty with ingestion because of pyloric stenosis and diffuse invasion. We examined the improvement in the quality of life(QOL)of patients and the effect and usefulness of S-1 treatment in such cases. The median survival time(MST; 310 days)of patients who received S-1 as primary treatment was significantly longer than that(105 days)of patients who did not receive S-1 treatment(p=0.0001). Of the 25 patients who underwent gastrojejunostomy, S-1 was administered to 10 patients(MST: 384 days). The MST of patients who received drugs other than S-1 was 121 days. Thus, the MST of patients who did receive S-1 was significantly longer than that of patients who did not receive S-1. In univariate analysis, oral ingestion, performance status(PS), best supportive care(BSC), and S-1 administration were prognostic factors. Of these factors, oral ingestion(p=0.0278, hazard ratio[HR]: 2.992)and S- 1 administration(p=0.0002, HR: 14.956)were prognostic factors in multivariate analysis. Gastrojejunostomy is desirable for the treatment of cases of unresectable gastric cancer with poor ingestion. In addition, the use of postoperative chemotherapy with S-1 alone or with S-1 as combination therapy may help improve prognosis.

Clinical outcomes of Roux-en-Y and Billroth I reconstruction after a distal gastrectomy for gastric cancer: What is the optimal reconstructive procedure?

BACKGROUND/AIMS: The aim of this study was to evaluate the clinical advantages of Roux-en-Y (R-Y) and Billroth-I (B-I) reconstruction after distal gastrectomy for gastric cancer by examining the postoperative symptoms based on a patient questionnaire and patient nutrition. In addition, this study determined which of the R-Y or B-I procedures is preferable following distal gastrectomy. METHODOLOGY: Fifty-one patients who had undergone R-Y reconstruction and 50 patients who had undergone B-I reconstruction were retrospectively enrolled in this study. The operative and postoperative findings such as operating time, blood loss, complications, and postoperative hospital stay were evaluated as short-term clinical outcomes. Postoperative serum nutrition parameters, transition of body weight, incidence of residual gastritis, and clinical symptoms were evaluated as mid-term clinical outcomes. An assessment of symptoms was based on a questionnaire concerning dumping symptoms, reflux symptoms, food intake, and satisfaction with the operation. RESULTS: No significant differences were observed in the operative and postoperative clinical parameters without stage grouping. The transition of serum nutrition parameters revealed no significant differences between the two groups for the preoperative and postoperative states. Dumping symptoms, reflux symptoms, and abdominal symptoms were less frequent in R-Y patients, but there were no significant differences between the two groups. Moreover, the differences in body weight recovery rates were not found to be statistically significant between two groups. However, the incidence of residual gastritis was significantly less in R-Y patients (21.2%) than in B-I patients (68.8%) (p < 0.05). The questionnaire results regarding food intake and surgery satisfaction were not significantly different between the two groups. CONCLUSIONS: Definite clinical advantages were not recognized in patients with R-Y reconstruction. B-I and R-Y reconstructive procedures should be selected according to the condition of each patient. However, the advantages of these reconstruction procedures following distal gastrectomy would only be revealed in large randomized controlled trials.

Targeting of interleukin-2 to human MK-1-expressing carcinoma by fusion with a single-chain Fv of anti-MK-1 antibody.

BACKGROUND: Targeting of cytokines into the tumor sites using antibody-cytokine fission proteins represents a novel approach in cancer immunotherapy. We previously reported a novel monoclonal antibody, FU-MK-1, which recognizes a glycoprotein antigen (termed MK-1 antigen) that is overexpressed on the surface of a majority of carcinomas. MATERIALS AND METHODS: To target IL-2 and cytotoxicity of effector cells to MK-1-expressing tumor cells, we genetically fused recombinant human interleukin-2 (rhIL-2) to a single chain variable fragment (scFv) antibody derived from FU-MK-1. The resulting fission protein, designated FUscFv/IL-2 was expressed in Pichia pastoris, purified by Ni-affinity chromatography, and characterized for the MK-1-binding specificity and the IL-2 biological activity. RESULTS: The FUscFv/IL-2 fusion protein effectively introduced a specific cytotoxicity of lymphokine-activated killer cells to the tumor cells and consequently suppressed the tumor growth in a SCID mouse xenograft model. CONCLUSION: This approach may be used for in vivo administration to localize IL-2 to tumor tissues, enhancing the immune response to human MK-1-expressing tumors while reducing systemic side-effects.

T-cell immunotherapy for human MK-1-expressing tumors using a fusion protein of the superantigen SEA and anti-MK-1 scFv antibody.

BACKGROUND: The bacterial superantigen staphylococcal enterotoxin A (SEA) is an extremely potent activator of T lymphocytes when presented on major histocompatibility complex (MHC) class II molecules. To develop a tumor-specific superantigen for cancer therapy, we constructed a recombinant fusion protein of SEA and the single-chain variable fragment (scFv) of the FU-MK-1 antibody, which recognizes a glycoprotein antigen (termed MK-1 antigen) present on most carcinomas. MATERIALS AND METHODS: We employed recombinant DNA techniques to fuse recombinant mutant SEA to an scFv antibody derived from FU-MK-1 and the resulting fusion protein (SEA/FUscFv) was produced by a bacterial expression system, purified with a metal-affinity column, and characterized for its MK-1-binding specificity and its antitumor activity. RESULTS: The SEA/FUscFv fusion protein retained the reactivity with MK-1-expressing tumor cells, introduced a specific cytotoxicity of lymphokine-activated killer T-cells to the tumor cells, and consequently suppressed the tumor growth in a SCID mouse xenograft model. CONCLUSION: This genetically engineered SEA/FUscFv fusion protein may serve as a potentially useful immunotherapeutic reagent for human MK-1-expressing tumors.

Targeted sonodynamic therapy of cancer using a photosensitizer conjugated with antibody against carcinoembryonic antigen.

The goal of this study was to develop a strategy for the selective destruction of cancer cells by ultrasonic irradiation in the presence of an antibody-conjugated photosensitizer. To this end, a photoimmunoconjugate (PIC) was prepared between ATX-70, a photosensitizer of a gallium-porphyrin analogue, and F11-39, a high affinity monoclonal antibody (MAb) against carcinoembryonic antigen (CEA), which is often overexpressed in various carcinoma cells. This conjugate, designated F39/ATX-70, retained immunoreactivity against purified CEA and CEA-expressing cells as determined by enzyme-linked immunosorbent assay, flow cytometry and immunofluorescence microscopic analysis. The cytotoxicity of F39/ATX-70 against CEA-expressing human gastric carcinoma cells in vitro was found to be greater than that of ATX-70 when applied in combination with ultrasound irradiation. When in vivo anti-tumor effects in a mouse xenograft model were assessed, intravenous administration of F39/ATX-70 followed by ultrasonic irradiation produced a marked growth inhibition of tumor compared with irradiation alone or irradiation after administration of ATX-70. These results suggest that the PIC between anti-CEA MAb and ATX-70 may have applications in sonodynamic therapy where destruction of CEA-expressing tumor is required.

Significance of tumor-associated antigens in the diagnosis and therapy of cancer: an overview.

An enormous effort using a wide variety of approaches has been undertaken over the last three decades to transform both basic and clinical research into improved diagnoses and therapies of cancer. This brief overview summarizes the significance of tumor-associated antigens (TAAs) in the diagnosis and therapy of cancer. Current data suggest that immunotherapy and gene therapy using antibody-recognized TAAs as their targets are promising, whereas those using T cell-recognized peptide epitopes of TAAs as their targets remain controversial regarding their efficacy, mainly due to general losses of HLA molecules in tumor cells.

Necrotizing enteritis with hepatic portal venous gas and pneumatosis intestinalis: report of a case.

A 73-year-old woman visited our hospital because of increasing abdominal distension and lower abdominal pain. On abdominal computed tomography (CT), hepatic portal venous gas (HPVG) and pneumatosis intestinalis of the small intestine were found. HPVG caused by intestinal necrosis was diagnosed, and an emergency laparotomy was thus performed. Necrosis of the small intestine over a 40-cm area from the ileocaecal region toward the mouth was found, and the lesion was resected. Histopathologically, haemorrhagic necrotic enteritis was diagnosed. The patient is alive as of the seventieth day after operation. The prognosis of intestinal necrosis accompanied by HPVG and pneumatosis intestinalis is poor. The presence of HPVG suggests the occurrence of a serious lesion in the abdominal cavity. Therefore, appropriate treatment should be performed immediately.

A dose-volume analysis of magnetic resonance imaging-aided high-dose-rate image-based interstitial brachytherapy for uterine cervical cancer.

PURPOSE: To investigate the feasibility of our novel image-based high-dose-rate interstitial brachytherapy (HDR-ISBT) for uterine cervical cancer, we evaluated the dose-volume histogram (DVH) according to the recommendations of the Gynecological GEC-ESTRO Working Group for image-based intracavitary brachytherapy (ICBT). METHODS AND MATERIALS: Between June 2005 and June 2007, 18 previously untreated cervical cancer patients were enrolled. We implanted magnetic resonance imaging (MRI)-available plastic applicators by our unique ambulatory technique. Total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy (EBRT). Treatment plans were created based on planning computed tomography with MRI as a reference. DVHs of the high-risk clinical target volume (HR CTV), intermediate-risk CTV (IR CTV), and the bladder and rectum were calculated. Dose values were biologically normalized to equivalent doses in 2-Gy fractions (EQD(2)). RESULTS: The median D90 (HR CTV) and D90 (IR CTV) per fraction were 6.8 Gy (range, 5.5-7.5) and 5.4 Gy (range, 4.2-6.3), respectively. The median V100 (HR CTV) and V100 (IR CTV) were 98.4% (range, 83-100) and 81.8% (range, 64-93.8), respectively. When the dose of EBRT was added, the median D90 and D100 of HR CTV were 80.6 Gy (range, 65.5-96.6) and 62.4 Gy (range, 49-83.2). The D(2cc) of the bladder was 62 Gy (range, 51.4-89) and of the rectum was 65.9 Gy (range, 48.9-76). CONCLUSIONS: Although the targets were advanced and difficult to treat effectively by ICBT, MRI-aided image-based ISBT showed favorable results for CTV and organs at risk compared with previously reported image-based ICBT results.

Small bowel obstruction caused by anisakiasis of the small intestine: report of a case.

Enteric anisakiasis is a relatively rare disease that is difficult to diagnose preoperatively. We report a case of small bowel obstruction caused by enteric anisakiasis in a 59-year-old Japanese man who presented with abdominal pain a few hours after eating sliced, raw fish. Because of signs of an intestinal obstruction, a laparotomy was performed. Focal thickening and stenosis of the ileocecal region were seen about 100 cm from the end of the ileum and the lesion was excised. We found a moving anisakis thrusting its head into the mucosa of the excised small intestine. Histopathological examination revealed the infiltration of eosinophils in all layers of the intestinal wall and severe edema. Enteric anisakiasis is very rare, and its diagnosis is usually only made after laparotomy. Nevertheless, when signs of acute abdomen develop after the ingestion of raw fish, such as sushi or sashimi, the possibility of enteric anisakiasis should be borne in mind.