Junji Kawada

NY-ESO-1 antibody as a novel tumour marker of gastric cancer.

Background:NY-ESO-1 antibodies are specifically observed in patients with NY-ESO-1-expressing tumours. We analysed whether the NY-ESO-1 humoral immune response is a useful tumour marker of gastric cancer.Methods:Sera from 363 gastric cancer patients were screened by enzyme-linked immunosorbent assay (ELISA) to detect NY-ESO-1 antibodies. Serial serum samples were obtained from 25 NY-ESO-1 antibody-positive patients, including 16 patients with curative resection and 9 patients who received chemotherapy alone.Results:NY-ESO-1 antibodies were detected in 3.4% of stage I, 4.4% of stage II, 25.3% of stage III, and 20.0% of stage IV patients. The frequency of antibody positivity increased with disease progression. When the NY-ESO-1 antibody was used in combination with carcinoembryonic antigen and CA19-9 to detect gastric cancer, information gains of 11.2% in stages III and IV, and 5.8% in all patients were observed. The NY-ESO-1 immune response levels of the patients without recurrence fell below the cutoff level after surgery. Two of the patients with recurrence displayed incomplete decreases. The nine patients who received chemotherapy alone continued to display NY-ESO-1 immune responses.Conclusion:When combined with conventional tumour markers, the NY-ESO-1 humoral immune response could be a useful tumour marker for detecting advanced gastric cancer and inferring the post-treatment tumour load in seropositive patients.

Heteroclitic serological response in esophageal and prostate cancer patients after NY-ESO-1 protein vaccination.

NY‐ESO‐1 is a prototypic cancer/testis antigen. In a recent phase I clinical trial, we vaccinated 13 patients bearing NY‐ESO‐1‐expressing tumors with a complex of cholesterol‐bearing hydrophobized pullulan (CHP) and NY‐ESO‐1 protein (CHP‐NY‐ESO‐1) and showed efficient induction of NY‐ESO‐1 antibody, and CD4 and CD8 T cell responses using peripheral blood from the patients. In our study, we analyzed heteroclitic serological responses in those patients after vaccination. Serological response against 11 tumor antigens including MAGE‐A1, MAGE‐A3, MAGE‐A4, CT7/MAGEC1, CT10/MAGEC2, CT45, CT46/HORMAD1, SOX2, SSX2, XAGE1B and p53 was examined by enzyme‐linked immunosorbent assay (ELISA) using sera from ten vaccinated patients. Expression of tumor antigens was determined by reverse transcription‐polymerase chain reaction or immunohistochemistry. Eight of nine patients who showed antibody responses against NY‐ESO‐1 also showed an antibody response against at least 1 of these 11 tumor antigens after vaccination. In one patient, seven tumor antigens were recognized. Specificity analysis of the antibody response by ELISA using control recombinant proteins and synthetic peptides and by Western blot showed that the response was not against His6‐tag and/or bacterial products included in a preparation of CHP‐NY‐ESO‐1 used for vaccination. Thus, heteroclitic serological responses appear to be indicative of the overall immune response against the tumor, and their analysis could be useful for immune monitoring in cancer vaccine.

Clinical Trial of the Intratumoral Administration of Labeled DC Combined With Systemic Chemotherapy for Esophageal Cancer

Esophageal cancer is a highly aggressive disease, and improved modalities for its treatment are needed. We performed chemoimmunotherapy involving the intratumoral administration of 111In-labeled dendritic cells (DC) in combination with preoperative chemotherapy in 5 esophageal cancer patients. Mature DC were generated and traced by scintigraphy after their administration. No adverse events that were directly related to the intratumoral DC administration were observed. Delayed-type hypersensitivity skin tests against keyhole limpet hemocyanin, which was added to the culture medium, detected a positive response in 3 patients, and keyhole limpet hemocyanin antibody production was observed in 4 patients, suggesting that intratumorally administered DC migrate to the lymph nodes, where they function as antigen-presenting cells. However, scintigraphic images obtained after the DC administration demonstrated that the DC remained at the esophageal tumor injection sites in all cases, and no DC accumulation was observed elsewhere. The accumulation of CD83+ cells in the primary tumor was also observed in 2 out of 4 patients in an immunohistochemical analysis using surgically resected specimens. Although the induction of tumor-specific immune responses during chemoimmunotherapy was also analyzed in enzyme-linked immunosorbent assay against 28 tumor antigens, none of the antibodies against the antigens displayed enhanced titers. No changes of NY-ESO-1-specific cellular immune response was observed in a patient who displayed NY-ESO-1 antibody production before the DC administration. These results suggest that the intratumoral administration of 111In-labeled mature DC during chemotherapy does not lead to detectable DC migration from the primary tumor to the draining lymph nodes, and therefore, might not achieve an optimal clinical response.

Subcuticular sutures versus staples for skin closure after open gastrointestinal surgery: a phase 3, multicentre, open-label, randomised controlled trial

BACKGROUND Staples have been widely used for skin closure after open gastrointestinal surgery. The potential advantages of subcuticular sutures compared with staples have not been assessed. We assessed the differences in the frequency of wound complications, including superficial incisional surgical site infection and hypertrophic scar formation, depending on whether subcuticular sutures or staples are used. METHODS We did a multicentre, open-label, randomised controlled trial at 24 institutions between June 1, 2009, and Feb 28, 2012. Eligible patients aged 20 years or older, with adequate organ function and undergoing elective open upper or lower gastrointestinal surgery, were randomly assigned preoperatively to either staples or subcuticular sutures for skin closure. Randomisation was done via a computer-generated permuted-block sequence, and was stratified by institution, sex, and type of surgery (ie, upper or lower gastrointestinal surgery). Our primary endpoint was the incidence of wound complications within 30 days of surgery. Analysis was done by intention to treat. This study is registered with UMINCTR, UMIN000002480. FINDINGS 1080 patients were enrolled and randomly assigned in a one to one ratio: 562 to subcuticular sutures and 518 to staples. 1072 were eligible for the primary endpoint and 1058 for the secondary endpoint. Of the 558 patients who received subcuticular sutures, 382 underwent upper gastrointestinal surgery and 176 underwent lower gastrointestinal surgery. Wound complications occurred in 47 of 558 patients (8·4%, 95% CI 6·3-11·0). Of the 514 who received staples, 413 underwent upper gastrointestinal surgery and 101 underwent lower gastrointestinal surgery. Wound complications occurred in 59 of 514 (11·5%, 95% CI 8·9-14·6). Overall, the rate of wound complications did not differ significantly between the subcuticular sutures and staples groups (odds ratio 0·709, 95% CI 0·474-1·062; p=0·12). INTERPRETATION The efficacy of subcuticular sutures was not validated as an improvement over a standard procedure for skin closure to reduce the incidence of wound complications after open gastrointestinal surgery. FUNDING Johnson & Johnson.

Appropriate Follow-Up Strategies for Gastrointestinal Stromal Tumor Patients Based on the Analysis of Recurrent Interval and Patterns

Background/Aims: Previous studies have proposed risk classifications for patients with gastrointestinal stromal tumor (GIST) after resection and have contributed to the prediction of its prognosis. However, optimal postoperative surveillance has not yet been established. Methods: We retrospectively analyzed data from 115 GIST patients who experienced recurrence after complete resection. The relationships between clinicopathological characteristics and the first recurrence sites, or time to recurrence (TTR), were investigated. We also compared the characteristics between 2 subgroups based on a TTR of ≤5 or >5 years. Results: The first recurrence occurred in the abdomen in 114 of 115 patients (99.1%); one case of esophageal GIST recurred in the lung. Gastric and small intestinal GISTs recurred most frequently in the liver or peritoneum, while the most common recurrences of colorectal GISTs were found to be local. Fourteen patients (12.2%) experienced recurrence after >5 years. Smaller tumors and those categorized as lower risk were significantly more frequent in the TTR >5 years group than in the TTR ≤5 years group. In the TTR >5 years group, local recurrence was the most frequent type of recurrence (42.9%). Conclusion: Based on abdominal examination, postoperative surveillance after complete resection for primary GISTs may be recommended for >5 years.

Evaluation of blood flow on the remnant distal bowel during left-sided colectomy

Adequate blood flow in anastomosis is of paramount importance to prevent anastomotic leakage. However, it is sometimes difficult to predict the viability of the intestine during surgery. During left-sided colectomy, blood flow on the remnant distal bowel is supplied only from the middle and inferior rectal arteries. The blood backflow after the root ligation of the inferior mesenteric artery is often said to be kept up to promontorium levels; however, this premise is actually based on experience, without reliable evidence. Here, we introduce the intraoperative evaluation of blood flow on the remnant distal bowel during left-sided colectomy using an indocyanine green fluorescence technique.

Well-leg compartment syndrome after laparoscopic low anterior resection for lower rectal cancer in the lithotomy position: A case report

A 64‐year‐old man underwent laparoscopic low anterior resection for lower rectal cancer. Because he was overweight (BMI, 28.1 kg/m2) with rich visceral fat and a narrow pelvic cavity, the operation was technically difficult and the operation time was 686 min. Postoperatively, the patient immediately complained of pain and swelling of the left lower limb. Laboratory examination showed that serum creatinine kinase was markedly increased and urine myoglobin was positive on postoperative day 1. He was diagnosed with well‐leg compartment syndrome and was transported to the trauma and critical care center for emergency fasciotomy. After initial treatment, he was transferred to our hospital on postoperative day 7. He completely recovered after 2 months. Although well‐leg compartment syndrome is rare, it is necessary to consider it as a potential complication when performing a long colorectal cancer surgery with the patient in the lithotomy position, particularly when laparoscopic surgery is planned.

Evaluation of the effects of postoperative oral nutrition support on body weight in gastric cancer patients by using an elemental diet: A randomized study.

110 Background: Postoperative weight loss causes deterioration in the patient’s quality of life and influences long-term prognosis in gastric cancer patients who have undergone gastrectomy. Moreover, recent retrospective studies indicated postoperative weight loss as a risk factor for premature interruption of S-1 adjuvant chemotherapy. We conducted a prospective randomized controlled study to examine whether the early institution of nutritional support comprising an oral elemental diet (ED) prepared for post-gastrectomy patients with depressed digestive/absorptive function would help prevent postoperative weight loss. Methods: After surgery, patients were randomly assigned to the ED or control groups. The groups were divided according to the surgical methods used (total/distal gastrectomy), clinical stage (≤Ia/>Ia), and patients’ body mass index ( 18.5). In patients assigned to the ED group (Elental, 300 kcal) was provided in addition to the regular diet from the day starting soft rice diet or equi...