Seiya Susumu

Cross-presentation of NY-ESO-1 cytotoxic T lymphocyte epitope fused to human heat shock cognate protein 70 by dendritic cells.

The cancer–testis antigen NY‐ESO‐1 has been implicated as one of the most attractive candidates for a cancer vaccine. However, a protein vaccine generally meets inefficient antigen presentation to CD8+ T cells, which could be overcome by combination with an appropriate adjuvant. Heat shock protein is a natural adjuvant and activates the antigen‐presenting cells to channel exogenous antigens into the classical major histocompatibility complex class I antigen‐processing pathway (cross‐presentation). Therefore, we genetically fused a minigene encompassing the NY‐ESO‐1 cytotoxic T lymphocyte (CTL) epitope 157‐165 (ESO p157‐165) to the human heat shock cognate protein 70 (hsc70) and expressed the resulting fusion proteins in Escherichia coli. By using a human leukocyte antigen‐A*0201‐restricted NY‐ESO‐1‐specific CTL clone, the cross‐presentation of ESO p157‐165 by monocyte‐derived dendritic cells (mo‐DC) pulsed with the fusion protein was evaluated. The fusion protein‐pulsed mo‐DC activates the CTL clone much more efficiently than the free NY‐ESO‐1 protein‐pulsed mo‐DC. Moreover, the magnitude of the CTL activity was comparable between ESO p157‐165 and the fusion protein of hsc70 and ESO p157‐165 (hsc70–ESO p157‐165 fusion protein). In addition, the CTL activation induced by the fusion protein, but not by the epitope, was inhibited by paraformaldehyde fixation of the mo‐DC and by treatment with lactacystin, a specific inhibitor for the proteasome. Finally, the hsc70–ESO p157‐165 fusion protein‐pulsed DC was able to induce an antigen‐specific T‐cell response. These results suggest that the hsc70–ESO p157‐165 fusion protein is therefore considered to be a promising candidate as a cancer vaccine. (Cancer Sci 2008; 99: 107–112)

Tetanus After a Resection for a Gangrenous Perforated Small Intestine: Report of a Case

We report herein the case of a 75-year-old man who developed severe tetanus 24h after the resection of a gangrenous perforated small intestine. It seemed that the tetanus was caused by a spillage of the intestinal contents harboringClostridium tetani; however, this was not identified by a culture. The diagnosis of tetanus was made only when opisthotonus in this patient became evident and normal tetanus treatment proved to be successful

Prediction and management of a low-lying costal arch which restricts the operative working space during laparoscopic cholecystectomy.

Background/purposeLaparoscopic cholecystectomy is difficult to perform in patients with a low-lying costal arch that entirely covers the liver. We conducted this study to clarify the factors related to a low-lying costal arch and establish countermeasures to circumvent this characteristic.MethodsThe study included 103 consecutive patients who underwent a laparoscopic cholecystectomy. The possible clinical factors associated with a low-lying costal arch restricting the operative working space were analyzed. The position of the liver against the costal arch and the presumed surgical visual angle for laparoscopic cholecystectomy, comprising the hepatic porta, umbilicus, and costal arch, were estimated with abdominal multidetector computed tomography (MDCT).ResultsSeven (7%) patients had a low-lying costal arch presenting an inadequate exposure of Calot’s triangle and restricted instrument mobility during laparoscopic cholecystectomy, and three patients required conversion to a laparotomy. A low-lying costal arch was significantly associated with advanced age, shorter stature, lighter body weight, coexisting kyphoscoliosis, gallbladder pathology, laparotomy conversion, and most of all, the liver edge lying above the costal arch and a narrow surgical visual angle upon MDCT. Of the seven patients with a critical low-lying costal arch, four underwent a successful laparoscopic cholecystectomy, this being done by lifting the right costal arch to create a workable surgical field; the rib-lifting procedure was planned as part of the scheduled procedure in the other three patients because the preoperative MDCT examination indicated a poor working space for a laparoscopic cholecystectomy.ConclusionsA low-lying costal arch is a substantial risk factor for conversion to a laparotomy when performing a laparoscopic cholecystectomy. However, the operative difficulty related to a low-lying costal arch can be predicted by using preoperative MDCT images and can be managed with proper planning and the appropriate use of the rib-lifting technique.

Inflammatory Polyp of the Gallbladder Mimicking Early Polypoid Carcinoma

We treated a 69-year-old male with a 16-mm polyp of the gallbladder. Enhanced computed tomography demonstrated marked enhancement. With a tentative diagnosis of early polypoid cancer of the gallbladder, open cholecystectomy was performed. Intraoperative ultrasound showed hyperechoic spots on the surface of the polyp with an inner echopenic area. The histological diagnosis was an inflammatory polyp that manifested nonneoplastic, edematous stroma, and infiltration of lymphcytes and plasmacytes.

Hand-assisted laparoscopic subtotal colectomy with cecorectal anastomosis for chronic idiopathic colonic pseudo-obstruction: report of a case

Chronic idiopathic colonic pseudo-obstruction (CICP) is characterized by the chronic disturbance of colonic motility without mechanical obstruction, any underlying disease or medication. Currently, there are no established medical treatments for CICP. A 62-year-old female who had undergone right hemicolectomy for splenic flexure syndrome caused by idiopathic megacolon was referred to our hospital with relapse, experiencing palpitation and abdominal fullness. She was diagnosed with CICP according to findings of marked dilation of the colon without mechanical obstruction, dilation of other parts of the gastrointestinal tract, or underlying disease. The dilated colon was surgically removed by hand-assisted laparoscopic subtotal colectomy, followed by cecorectal anastomosis. Histopathologically, there was no degeneration or lack of ganglion cells in Auerbach’s plexus. The patient has experienced no severe symptoms after undergoing the present operation.

Immunological milieu in the peritoneal cavity at laparotomy for gastric cancer

AIM To investigate the immunological repertoire in the peritoneal cavity of gastric cancer patients. METHODS The peritoneal cavity is a compartment in which immunological host-tumor interactions can occur. However, the role of lymphocytes in the peritoneal cavity of gastric cancer patients is unclear. We observed 64 patients who underwent gastrectomy for gastric cancer and 11 patients who underwent laparoscopic cholecystectomy for gallstones and acted as controls. Lymphocytes isolated from both peripheral blood and peritoneal lavage were analyzed for surface markers of lymphocytes and their cytokine production by flow cytometry. CD4(+)CD25(high) T cells isolated from the patients peripheral blood were co-cultivated for 4 d with the intra-peritoneal lymphocytes, and a cytokine assay was performed. RESULTS At gastrectomy, CCR7(-) CD45RA(-) CD8(+) effector memory T cells were observed in the peritoneal cavity. The frequency of CD4(+) CD25 (high) T cells in both the peripheral blood and peritoneal cavity was elevated in patients at advanced stage [control vs stage IV in the peripheral blood: 6.89 (3.39-10.4) vs 15.34 (11.37-19.31), P < 0.05, control vs stage IV in the peritoneal cavity: 8.65 (5.28-12.0) vs 19.56 (14.81-24.32), P < 0.05]. On the other hand, the suppression was restored with CD4(+) CD25(high) T cells from their own peripheral blood. This study is the first to analyze lymphocyte and cytokine production in the peritoneal cavity in patients with gastric cancer. Immune regulation at advanced stage is reversible at the point of gastrectomy. CONCLUSION The immunological milieu in the peritoneal cavity of patients with advanced gastric cancer elicited a Th2 response even at gastrectomy, but this response was reversible.