Background: We previously reported that survivin-2B, a splicing variant of survivin, was expressed in various types of tumors and that survivin-2B peptide might serve as a potent immunogenic cancer vaccine. The objective of this study was to examine the toxicity of and to clinically and immunologically evaluate survivin-2B peptide in a phase I clinical study for patients with advanced or recurrent breast cancer.

We reported previously a HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL), recognized by CD8 + CTL. This peptide was derived from survivin protein, an inhibitor of apoptosis proteins, expressed in a variety of tumors, such as adenocarcinoma, squamous cell carcinoma, and malignant melanoma. In this report, we provide further evidence that survivin-2B80-88 peptide might serve as a potent immunogenic cancer vaccine for various cancer patients. Overexpression of survivin was detected in surgically resected primary tumor specimens of most breast and colorectal cancers and some gastric cancers as assessed by immunohistochemical study. HLA-A24/survivin-2B80-88 tetramer analysis revealed that there existed an increased number of CTL precursors in peripheral blood mononuclear cells (PBMC) of HLA-A24 + cancer patients, and in vitro stimulation of PBMCs from six breast cancer patients with survivin-2B80-88 peptide could lead to increases of the CTL precursor frequency. Furthermore, CTLs specific for this peptide were successfully induced from PBMCs in all 7 (100%) patients with breast cancers, 6 of 7 (83%) patients with colorectal cancers, and 4 of 7 (57%) patients with gastric cancers. These data indicate that survivin expressed in tumor tissues is antigenic in cancer patients, and survivin-2B80-88-specific CTLs are present in PBMCs of various cancer patients. Our study raises the possibility that this peptide may be applicable as a general cancer vaccine to a large proportion of HLA-A24 + cancer patients.

Vascular anatomy of the pancreaticoduodenal region has been the subject of numerous studies. However, several essential areas of confusion remain in interpretation of the vascular configuration. We note and discuss three key points in relation to this confusion: (1) a missing vascular arcade, (2) a rearrangement of the arcade by collateral and/or transverse vessels, and (3) a solitary vessel without an accompanying comites vein or artery. In addition, we consider that different interpretations as well as varying reported incidences depend on different "thresholds" when observations are made. Consideration of new aspects of vascular anatomy of the pancreaticoduodenal region is required for further improvement of surgical procedures. In terms of the selection of lymph node resection procedure, we discuss mainly the inferior arterial origin. Special attention should be paid to the ligation of inferior arteries because of the high incidence of the common trunk formation of the upper jejunal and inferior pancreaticoduodenal arteries. With regard to duodenum-preserving pancreatic head resection for benign tumors, our observations are introduced in view of either arterial or venous configuration. First, a communicating artery between the anterior and posterior arterial arcades is noted because of its possible critical role in blood supply to the papilla of Vater. Second, a venous drainage route from the duodenum to the retroperitoneal space in "normal" specimens is described.

This report describes a giant peritoneal loose body in the pelvic cavity. A 63-year-old man who was asymptomatic underwent a routine medical examination, which revealed a tumor in the pelvic space. Computed tomography and magnetic resonance imaging showed a smooth-surfaced mass with two marked calcifications in the central position. Preoperatively, we suspected a calcified leiomyoma originating from the wall of the sigmoid colon; however, at laparoscopic surgery we extracted a hard, egg-shaped mass 5 cm in diameter, with detached appendices epiploicae. Histological examination revealed that this peritoneal loose body was made up of thick layers of fibrous tissue with a few cellular components, and necrotic fat tissue in the central position. Small peritoneal loose bodies are occasionally found during laparotomy or autopsy, but such a large one is very unusual.

Survivin is a member of the inhibitor of apoptosis protein (IAP) family containing a single baculovirus IAP repeat domain. It is expressed during fetal development but becomes undetectable in terminally differentiated normal adult tissues. We previously reported that survivin and its splicing variant survivin-2B was expressed abundantly in various types of tumor tissues as well as tumor cell lines and was suitable as a target antigen for active-specific anti-cancer immunization. Subsequently, we identified an HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL) recognized by CD8+ cytotoxic T lymphocytes (CTLs). We, therefore, started a phase I clinical study assessing the efficacy of survivin-2B peptide vaccination in patients with advanced or recurrent colorectal cancer expressing survivin. Vaccinations with survivin-2B peptide were given subcutaneously six times at 14-day intervals. Of 15 patients who finished receiving the vaccination schedule, three suffered slight toxicities, including anemia (grade 2), general malaise (grade 1), and fever (grade 1). No severe adverse events were observed in any patient. In 6 patients, tumor marker levels (CEA and CA19-9) decreased transiently during the period of vaccination. Slight reduction of the tumor volume was observed in one patient, which was considered a minor responder. No changes were noted in three patients while the remaining eleven patients experienced tumor progression. Analysis of peripheral blood lymphocytes of one patient using HLA-A24/peptide tetramers revealed an increase in peptide-specific CTL frequency from 0.09% to 0.35% of CD8+ T cells after 4 vaccinations. This phase I clinical study indicates that survivin-2B peptide-based vaccination is safe and should be further considered for potential immune and clinical efficacy in HLA-A24-expression patients with colorectal cancer.