[Present condition and new vista of the future in robotic-assisted laparoscopic surgeries].

The introduction of robotic surgical system is one of the most exciting topic in the field of the surgery. In this symposium, we presented and explained the present condition of robotic-assisted laparoscopic surgeries performed in the department of Urology, Gastroenterology and Gynecology of the Hokkaido University Hospital. By using this surgical system, laparoscopic surgery, which is generally considered to be difficult, can be safely performed by surgeons. Especially in radical prostatectomy against localized prostate cancer, this surgical approach brought the decrease in peri- and postoperative problems including blood loss and postoperative urinary incontinence in comparison with open or laparoscopic radical prostatectomy. We wish that this symposium would help the audience to understand the present condition and new vista of the future in robotic-assisted laparoscopic surgeries.

[Carcinoma of the gallbladder which progress on the mucosa of choledochocolonic fistula].

A 70-year-old man was admitted to our hospital for further examination of pneumobilia and atrophy in the gallbladder. Abdominal CT scan and EUS revealed that the atrophic gallbladder was occupied by a tumor lesion. In addition, ERCP showed choledochocolonic fistula. Colonoscopy revealed an elevated lesion in the colonic side of fistula, and biopsy of the elevated lesion revealed adenocarcinoma. Cholecystectomy and right hemicolectomy was performed under a preoperative diagnosis of gallbladder carcinoma with choledochocolonic fistula. Pathologically, most of the tumor was localized in the gallbladder, and grew along the mucosa of choledchocolonic fistula. This case was of interest with regard to the relationship between the choledochocolonic fistula and gallbladder carcinoma.

Laparoscopic gastrectomy for early gastric cancer targeting as a less invasive procedure.

BACKGROUND: Since only a few extensive reports are available on the less invasive nature of laparoscopic gastrectomy, we compared postoperative changes over time in vital signs and hematological parameters between this surgery and laparotomic gastrectomy. METHODS: Of 188 patients who underwent distal gastrectomy for preoperatively diagnosed early gastric cancer between January 2004 and September 2006, 87 underwent laparoscopy-assisted distal gastrectomy (LADG) and 101 underwent laparotomic distal gastrectomy (DG). The invasiveness of the two procedures was evaluated in 164 patients with no postoperative complications (82 cases of LADG and 82 cases of DG by measuing vital signs daily and performing hematological examination on postoperative days (POD) 1, 4, 7, and 10. RESULTS: For body temperature, heart rate, and blood pressure, significantly lower values were obtained with LADG on 3 and 4 POD, 4 POD, and 3 and 4 POD, respectively. For white blood cell counts (WBC) and C-reactive protein (CRP), significantly lower values were obtained with LADG on 7 and 10 POD, and 10 POD, respectively. For serum protein levels and lymphocyte counts, significantly higher values were obtained with LADG on 1, 4, 7, and 10 POD, and 4 and 10 POD, respectively. Body temperature, WBC, and CRP showed no significant difference immediately after surgery but earlier recovery occurred with LADG. For protein levels and lymphocyte counts, higher values were obtained immediately after surgery. There seemed to be two patterns of less invasiveness in the parameters: the early recovery found for body temperature, WBC and CRP, and the smaller shift immediately after surgery in protein level and lymphocyte count, and probably, heart rate and blood pressure. The complication rate was 18.8% for DG and 5.7% for LADG. CONCLUSIONS: LADG is a less-invasive surgical procedure as it produces early normalization or smaller shifts in various parameters and exhibits a low prevalence of complications.

Phase I trial of personalized peptide vaccination for cytokine-refractory metastatic renal cell carcinoma patients.

The aim of this clinical trial was to investigate the toxicity and immunological responses of personalized peptide vaccination for cytokine-refractory metastatic renal cell carcinoma patients. Patients were confirmed to be human leukocyte antigen (HLA)-A24 or HLA-A2 positive and had histologically confirmed renal cell carcinoma. Ten patients were enrolled in the present study. The peptides to be administered were determined based on the presence of peptide-specific cytotoxic T lymphocyte precursors in peripheral blood mononuclear cells (PBMC) and peptide-specific IgG in the plasma of cancer patients. Patients received subcutaneous injections of four different peptides (3 mg/peptide) every 2 weeks. Vaccinations were well tolerated without any major adverse events. A minimal increase in peptide-specific interferon-gamma production in postvaccination PBMC was observed, regardless of higher levels of cytotoxic T lymphocyte activity in prevaccination PBMC. In contrast, an increase in peptide-specific IgG levels of postvaccination (sixth) plasma was observed in the majority of patients. After progression, five patients received interleukin-2 therapy and continuous vaccination, with survival of 31, 25, 23, 17, and 15 months, but interleukin-2 did not impede humoral responses boosted by the vaccination. These results encourage further clinical trials of personalized peptide vaccinations.

[Efficacy and safety of novel oral fluoropyrimidine anticancer drug, TS-1 for advanced and recurrent gastric cancer patients].

The efficacy and safety of the oral fluoropyrimidine TS-1, which contains a dihydropyrimidine dehydrogenase (DPD) inhibitor, were examined in fifty-five patients with gastric cancer. The patients were divided into 28 with measurable cancer lesions (TUM group) and 27 without them (ADJ group). The total number of courses was 164 (mean: 5.9 courses) in the TUM group and 146 (mean; 5.4 courses) in the ADJ group. The response rate in the TUM group, excluding three patients who could not be evaluated because of incomplete administration, was 40% (CR: 4, PR: 6, NC: 6, PD: 9). Among responders, the mean number of courses to response was 2.2 and the median survival time (MST) was 21.7 months. In terms of safety, adverse reactions appeared in forty-five patients (82%) and the incidence was higher in the ADJ group. Major toxicities were leukopenia (38%), anorexia (27%), increased total bilirubin concentration (25%) and diarrhea (24%). Adverse reaction of grade 3 was found in only three patients (5.5%) and there were no drug-related deaths. In conclusion, TS-1 is safe and effective if attention is given to biweekly examinations for the development of adverse reactions.

[A patient with recurrent gastric cancer who developed TS-1 induced hand-foot syndrome].

Hand-foot syndrome (HFS) is a rare adverse reaction to oral fluoropyrimidine TS-1, which contains the dihydropyrimidine dehydrogenase (DPD) inhibitor. We treated a recurrent gastric cancer patient with chronic renal failure who developed grade 2 HFS, grade 2 conjunctivitis and grade 3 stomatitis soon after TS-1 administration. Those symptoms improved with the administration of vitamin B6, topical emollient therapy, and so on. We thought that the continuous elevation of serum 5-FU concentration, due to the accumulation of DPD inhibitor from the renal dysfunction, led to the development of HFS, although the participation of 5-FU metabolites such as F-beta-alanine cannot be ruled out.

[Rules to carry out hepatic arterial infusion chemotherapy at home for patients with liver metastasis of colorectal cancer].

We analyzed the effectiveness and adverse effects of hepatic arterial infusion chemotherapy (HAI) for patients with liver metastasis of colorectal cancer in order to clarify the rules of HAI. We provided HAI to 72 patients after hepatic resection and to 119 patients with unresectable liver metastases. The preventive effect on hepatic recurrence was recognized in the group administered more than 15 g of 5-FU (total dose). The response rate of patients with unresectable metastases was 60.3%. Adverse effects were observed in 65.8% of the patients. It is important to establish a follow-up system in each hospital to treat the patients as soon as possible when patients develop an adverse reaction.

[Prevention of side effects in the chemotherapy at home].

The chemotherapy at home is most different from the conventional chemotherapy because of the condition not to watch patients all the time. In order to avoid serious side effect it is necessary to administrate some drugs continuously or together. It is useful to use portable pump system. It is also important to educate patients about the chemotherapy at home and to establish the observation system against the trouble from the chemotherapy at home. As the chemotherapy at home is safe if we know the side effect well, this type of chemotherapy will become the one of main branch in the chemotherapy of colorectal cancer.

Immunological evaluation of personalized peptide vaccination with gemcitabine for pancreatic cancer.

The aim of the present study was to investigate the safety and immune responses of personalized peptide vaccination when administered with gemcitabine (GEM) in advanced pancreatic cancer (APC) patients. Thirteen patients with APC were enrolled. Pre-vaccination with peripheral blood mononuclear cells and plasma was carried out to examine cellular and humoral responses to 25 or 23 peptides in human leukocyte antigen A24+(+) or A2++(+) patients, respectively. Only the reactive peptides (maximum of four) were then administered weekly at three different dose settings: 1, 2 and 3 mg of peptide. GEM was administered at 1000 mg/m(2) per week for 3 weeks, followed by 1 week of rest. The combination therapy was well tolerated. Grade 3 toxicities were: anemia (three patients), neutropenia (two patients) and thrombocytopenia (two patients). Of these 13 patients, 11 (85%) showed clinical responses, such as reduction in tumor size and/or level of tumor markers. Augmentation of peptide-specific cytotoxic T lymphocyte activity against pancreatic cancer cells was observed at each dose level, whereas the increment of peptide-specific IgG antibodies was dependent on peptide dose. GEM did not inhibit the immune responses induced by personalized peptide vaccinations, and this new type of immunochemotherapy combination is recommended for further clinical study in APC patients.