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We report a case of advanced gastric carcinoma treated successfully by four courses of neoadjuvant chemotherapy (NAC) with paclitaxel and cisplatin. The patient was a 43-year-old man with advanced gastric cancer, clinically diagnosed as P0H0M0CY0T3N2, which had invaded the upper body of the stomach and esophagus. He was entered into a clinical trial and received the following NAC regimen: paclitaxel 80 mg/m(2), and cisplatin 25 mg/m(2), on days 1, 8, and 15, followed by a rest on day 22, as one course. The lymph nodes had reduced in size to 59% after two courses and to 40% after four courses, with no sign of severe toxicity. Subsequently, he underwent D2 total gastrectomy with pancreatico-splenectomy. On microscopic examinations, no tumor cells were detected in the ulcer scar of the resected stomach or the regional lymph nodes. Thus, we discuss the potential of long-term NAC, especially for responders to two initial courses.

Non-technical skills rating systems, which are designed to support surgical performance, have been introduced worldwide, but not officially in Japan. We performed a pilot study to evaluate the “non-technical skills for surgeons” (NOTSS) rating system in a major Japanese cancer center. Upper gastrointestinal surgeons were selected as trainers or trainees. The trainers attended a master-class on NOTSS, which included simulated demo-videos, to promote consistency across the assessments. The trainers thereafter commenced observing the trainees and whole teams, utilizing the NOTSS and “observational teamwork assessment for surgery” (OTAS) rating systems, before and after their education. Four trainers and six trainees were involved in this study. Test scores for understanding human factors and the NOTSS system were 5.89 ± 1.69 and 8.00 ± 1.32 before and after the e-learning, respectively (mean ± SD, p = 0.010). The OTAS scores for the whole team improved significantly after the trainees’ education in five out of nine stages (p

The role of insulin resistance in the tumor-induced decrease in tissue lipoprotein lipase (LPL) activity was studied in vivo and vitro in methylcholanthrene-induced sarcoma-bearing rats. Intraperitoneal (i.p.) injection of 2U of regular insulin resulted in high-adipose LPL activity in control rats (CTR) of 122.0 +/- 42.4 U/mg tissue, but it had little effect on tumor-bearing rats (TBR), which showed a value of only 9.6 +/- 5.5 U/mg tissue (P = 0.002). When adjusted for serum insulin concentrations, adipose LPL activity remained significantly different between the TBR and CTR at 0.19 +/- 0.17 and 0.78 +/- 0.29 U/mg tissue, respectively (P = 0.02). Following the in vitro incubation with either 1.44 g/l glucose of 1 x 10-8 U insulin of adipose tissue fragments obtained from the TBR and the CTR, measurable LPL activity was maintained in the tissue from the CTR for 2 h but not in that from the TBR. These results suggest that the decreased LPL activities seen in the tumor-bearing state may be mediated by insulin resistance.

The trastuzumab for Gastric Cancer study newly defined tumors that were positive for human epidermal receptor-2 (Her-2) and created a Her-2-oriented treatment strategy that is also applicable in the adjuvant setting for stage 2/3 cancers. However, there is currently no information available on the rate of Her-2 positivity and the relapse-free survival (RFS) stratified by Her-2 status in stage 2/3 patients.The Her-2 status, defined by the current standard method, was examined in 100 gastric cancer patients who underwent curative D2 surgery, who were pathologically diagnosed with stage 2/3 cancer, and received adjuvant S-1 chemotherapy between June 2002 and December 2011.Ten of the 100 patients were Her-2 positive. Her-2-positive status was more frequently seen in tumors with a differentiated histology. The 5-year RFS rate was 56.3 % in Her-2-positive cases, and 48.8 % in Her-2 negative cases, which was not significantly different (P = 0.786).The Her-2-positive rate for stage 2/3 gastric cancer patients was low, at only 10 %. Although the RFS was not significantly different based on the Her-2 status, the low positive rate made interpretation difficult. A multi-center study with a large sample size is necessary to clarify the prognostic impact of Her-2 in stage 2/3 gastric cancer patients.

Adjuvant chemotherapy aims to eradicate micrometastatic tumor cells before and after curative surgery. Many Phase III trials have been conducted to study the efficacy of postoperative adjuvant chemotherapy; however, most trials have failed to show any survival benefit because of their low statistical power and/or poor patient compliance. Since 2000, two pivotal Phase III trials, the ACTS-GC and the CLASSIC, have demonstrated the efficacy of postoperative adjuvant chemotherapy following D2 gastrectomy. Although treatment with S-1 for 1 year or combination therapy with capecitabine and oxaliplatin for 6 months is effective, more intensive chemotherapy is necessary to further improve the survival rates. In Europe, two Phase III trials, the MAGIC and the FNCLCC/FFCD, have produced results that strongly suggest that neoadjuvant chemotherapy is beneficial. The advantages of neoadjuvant chemotherapy include a high rate of R0 resection, tumor regression, high compliance and the avoidance of unnecessary surgery. The disadvantage of neoadjuvant chemotherapy is over-diagnosis. In Japan, the Japan Clinical Oncology Group has conducted several clinical trials using neoadjuvant chemotherapy to target extensive nodal disease and/or scirrhous carcinomas. The optimal courses and regimens of neoadjuvant chemotherapy should, therefore, be clarified in the future.

The effects of multicytokine inducer, OK-432, on tumor-induced metabolic alterations were studied by assessing three key regulatory enzymes of gluconeogenesis, de novo fatty acid synthesis and the triglyceride clearance pathways. Two Klinish Einheit (KE) of OK-432 was subcutaneously injected on alternate days, for 10 days, into Fischer 344 rats with or without methylcholanthrene-induced sarcoma. At the time of sacrifice, the tumors accounted for approximately 23% of their total body weight. The injections of OK-432 did not affect the amount of food intake in either the tumor bearers or the controls. The tissue lipoprotein lipase activities in the epididymal fat pads of the tumor bearers were significantly decreased compared with the controls (P

The long-term effects of gastrectomy on the nutritional and immunologic status were prospectively studied in 79 gastric cancer patients who underwent curative gastrectomy and were followed by us after operation for an average of 5 years and 3 months. The percent of actual weight to pre-illness normal weight was lower than 95% in 80% of all study patients. Retinol binding protein, prealbumin, and albumin were lower than normal in 17%, 26%, and 26% of the patients, respectively. The mean values of the percent normal weight, retinol binding protein, and prealbumin were significantly lower in the totally gastrectomized patients than in the subtotally gastrectomized ones (P < 0.01). The procedures of reconstruction did not affect the nutritional status except for the prealbumin level which was significantly decreased in Roux-en-Y cases than in interposed cases of totally gastrectomized patients. Cell-mediated immunological alterations after gastrectomy were observed in 31%, 37%, and 71% of all patients for OKT3 subpopulation, OKT4/OKT8 ratio, and blastogenesis by phytohemagglutinin, respectively. A multivariate analysis revealed that the long-term immunity of the gastrectomized patients after operation was not affected by the levels of albumin and rapid turnover proteins but by the splenectomy and weight loss they underwent.

Adjacent organ invasion by stomach carcinoma on computed tomography (CT) was studied. CT images of tumors and their adjacent organs, whose invasion was assessed at surgery, were retrospectively analyzed in 51 gastric cancer patients. An absence of fat planes or an irregularity of the border between the tumor and adjacent organs was not found to be significantly related with invasion. The mean densities of the region of interest (ROI) set at the border were greater at the invasion sites (60.0 +/- 38.1) than at noninvasion sites (35.6 +/- 55.5) (P < 0.05). The standard deviation of the densities in the ROI was not affected by invasion. The discriminant function determined invasion to the pancreas, liver, and colon with an accuracy of 75%, 61%, and 78%, respectively. In diagnosing the invasion of stomach cancer on CT, the conventional criteria were not practical, while a quantitative analysis of the density in the ROI with high resolution CT was considered to improve the accuracy.

A patient who had been supported with total parenteral nutrition (TPN) for over 8 years is herein presented, with emphasis on the changes observed in calcium metabolism. The patient was a 31-year-old female, who had undergone a subtotal jejunal and ileal resection for superior mesenteric artery occlusion. TPN was started soon after the surgery. She had been on TPN support for 105 months. Back pain developed at 97 months after the initiation of TPN. During her course, the serum calcium levels were judged to be within the normal ranges, while the 1 alpha, 25(OH)2Vit.D declined. Intermittent hypercalciuria was occasionally observed. Both the serum level of calcium and urinary calcium loss correlated closely to the amount of calcium infused, but they were not influenced by the amount of vitamin D (ergocalciferol) received. The serum level of parathormone and calcitonin were also within the normal ranges. The patient's vertebral bone, which was obtained at autopsy, revealed histopathological changes characteristic of osteoporosis. Based on the above, we conclude that a careful monitoring of the amount of calcium infused is called for to prevent bone disease in patients on long-term parenteral nutrition.