Curative Resection Following Neoadjuvant Chemotherapy for Advanced Gastric Cancer With Preservation of a Right Gastroepiploic Artery Coronary Artery Bypass Graft: A Case Report

Recently, the right gastroepiploic artery (RGEA) has been used in coronary artery bypass graft (CABG) as an alternative arterial graft. Because of the improvement of prognosis after CABG, malignant diseases are more common in older patients. However, there is a serious problem in patients with gastric cancer after CABG with RGEA graft. In these patients, an interruption of coronary blood supply through the RGEA may cause a life-threatening myocardial ischemia. Therefore, an appropriate strategy is very important to avoid risk while retaining the curability of the operation. We herein describe a 76-year-old Japanese man with advanced gastric cancer who underwent CABG using the RGEA. Abdominal computed tomography (CT) showed #6 lymph nodes (sub-pyloric lymph nodes) metastases surrounding the RGEA. We concluded that curative resection was impossible while preserving the RGEA and started combination chemotherapy using S-1 and cisplatin. After 2 courses of that, #6 lymph nodes were reduced extremely. Thereafter the patient underwent distal gastrectomy with regional lymph node dissection around the RGEA without excision of the RGEA. Histologically, there were no metastases in #6 lymph nodes. Neoadjuvant chemotherapy may be effective for preserving the RGEA graft in a patient with advanced gastric cancer after CABG.Key words: gastric cancer, CABG, RGEA bypass graft, neoadjuvant chemotherapyThe right gastroepiploic artery (RGEA) has been used in coronary artery bypass graft (CABG) surgery.^1,2 It is recognized as a reliable conduit with superior long-term patency.^3–5 The right gastroepiploic artery is mainly targeted to the right coronary artery because of the limitation of its length. According to the report of a Japanese association for coronary artery surgery, CABG was carried out in more than 0.1 million patients over a period of 7 years that ended in 2004, and the RGEA has been used in more than half of these patients.⁶ After CABG for either triple-vessel or left main disease, patients have a 5-year actual survival rate of 92.9% and a cardiac death-free rate of 97.8%.⁷ Long-term survival increases the opportunity for patients to develop malignant diseases. An increased incidence of gastric cancer after CABG with the use of RGEA has been reported.⁶ In these patients, an interruption of coronary blood supply through the RGEA may cause a life-threatening myocardial ischemia. Therefore, an appropriate strategy is required to avoid risk while retaining the curative potential of the operation. We present a case of gastric cancer after CABG with the RGEA in which neoadjuvant chemotherapy led to curative operation while preserving the RGEA.     

Measurement of the Expiratory Ammonia Concentration and its Clinical Significance

Alghough gaseous ammonia (NH₃) can freely enter cells through the plasma membrane where NH₃ is cyto(neuro)toxic, NH₃ and ionic ammonia (NH₄ ⁺) contents have not been studied in biological materials. We developed a new method for measurement of expiratory NH₃ concentration, which may reflect blood NH₃ concentrations. The method is a sensor tube type-gas assay system. Expiratory NH₃ concentrations in patients with chronic liver diseases increased when their blood ammonia (NH₄ ⁺+NH₃) concentrations increased above 90 μg/dl (normal range; 12–66 μg/dl). However, cirrhotic patients, who had relatively higher expiratory NH₃ concentration compared to blood NH₃ concentrations (calculated from Henderson-Hasselbalch formula), were found to have subclinical encephalopathy. Measurement of experatory NH₃ concentration may be of clinical significance for the diagnosis of encephalopathy associated with hyperammonemia.     

A case of small cell gastric carcinoma with an adenocarcinoma component operated curatively

We present a case of a primary advanced gastric tumor that was composed of 2 different pathological components: small cell carcinoma and moderately-differentiated adenocarcinoma. The patient was still alive four years after the surgery was performed, without recurrence. A large part of the tumor consisted of a diffuse sheet of small cell carcinoma, which transitioned into another small portion consisting of moderately-differentiated tubular adenocarcinoma components. Therefore, this case raised the possibility that small cell gastric carcinoma may originate from totipotential stem cells of the stomach. Although small cell carcinoma progresses aggressively, and patients with it have an extremely poor prognosis, this patient recovered uneventfully after the surgical resection, and has remained in good health, without any recurrences.     

Antisense therapy specific to mutated K-ras gene in hamster pancreatic cancer model. Can it inhibit the growth of 5-FU and MMC-resistant metastatic and remetastatic cell lines?

K-ras point mutation at codon 12 has a relationship greater than 90% with pancreatic cancer. Cancer therapy should also include the treatment of metastatic disease because it is known that the properties of metastatic cells may vary considerably from those of the primary tumor. AIM: To clarify if the same drugs, which can inhibit the tumor growth in the parental cell line, can inhibit the pancreatic metastatic and remetastatic cell lines at the same concentrations and to compare the inhibition with antisense oligonucleotides mismatched to K-ras gene, in Syrian golden hamsters. MATERIALS AND METHODS: HaP-T1, a BHP-induced hamster pancreatic cancer cell line, MS-PaS-1 (a metastatic cell line established from "return trip" metastases from the liver to the pancreas) and MS-PaS-2 named as a "remetastatic cell line", i.e., metastases from MS-PaS-1 were used. MTT and MTT-agarose assays were performed, using 5-Fluorouracil (5-FU), Mitomycin C (MMC) and antisense oligonucleotide specific to K-ras oncogene. RESULTS: The inhibitory concentration (IC50) of 5-FU, which inhibited HaP-T1, had to be increased by 50-fold to inhibit MS-PaS-1 and 100-fold to inhibit MS-PaS-2. MMC had to be increased by 10-fold to inhibit MS-PaS-1 and 50-fold to inhibit MS-PaS-2. However, IC50 was the same when antisense oligonucleotide was tried in these 3 cell lines. CONCLUSION: Antisense oligonucleotide-targeted K-ras gene may be a good choice for therapy because it could inhibit the growth in metastatic and remetastatic cells as well as in primary tumor cells.     

Different pattern of metastasis in liver implanted pancreatic cancer between young and old Syrian golden hamsters

We have previously reported on the "return trip" metastases from the liver to the pancreas in a hamster experimental pancreatic cancer model. Because the pancreas is the main metastatic site of liver-implanted pancreatic tumors, our aim was to clarify whether the metastatic sites differ in young and old tumor-bearing animals. HaP-T1, a continuous tissue-cultured cell line, derived from BHP-induced pancreatic adenocarcinoma, was implanted into the liver. The animals were divided into two groups: A) younger than 26 weeks and B) older than 26 weeks. Three animals from each group were sacrificed on Days 35, 42, 49, 56, 63, 70, 77, 84, 91 and 98, to study the metastatic sites. Survival was also studied. After death, necropsy was performed. Resected and necropsied specimens were analyzed histopathologically and by PCR/RFLP analysis to confirm the presence of K-ras point mutation. The success rate of implantation was 100%. Survival was 102.3+/-2.5 days in group A and 95.3+/-1.5 days in group B. Animals of group A, sacrificed weekly until Day 70, showed metastases only to the pancreas ("return trip"), while this phenomenon happened only in animals sacrificed on Day 35 in group B. In group A, on Days 77, 84, 91 and 98, metastases were also found in the kidneys, lymph nodes, ovary and testis. In hamsters of group B, metastases were found in multiple sites such as the pancreas, vas deferens, ovary and testis ("multiple journeys"). All intra-hepatically-implanted tumor and metastatic sites showed the K-ras point mutation. This homologous implantation model may be helpful for further research into the process of metastasis and its relationship with the immunological response.     

Therapeutic basis of glycyrrhizin on chronic hepatitis B

Glycyrrhizin, a major component of a herb (licorice), has been intravenously used for the treatment of chronic hepatitis B in Japan and improves liver function with occasional complete recovery from hepatitis. This substance modifies the intracellular transport and suppresses sialylation of hepatitis B virus (HBV) surface antigen (HBsAg) in vitro. This study was designed to clarify the pharmacological basis for its effectiveness. The structure-bioactivity relationship of glycyrrhizin, glycyrrhetic acid 3-O-monoglucuronide and glycyrrhetic acid was determined, and glycyrrhetic acid was found to be the most active of them. The amounts of three substances bound to the liver were evaluated in guinea pigs after intravenous administration of glycyrrhizin. Glycyrrhizin and glycyrrhetic acid 3-O-monoglucuronide were detected at concentrations of 31.8-1.3 μg/g of liver, but glycyrrhetic acid was not detected. When glycyrrhizin attained these concentrations in the cellular fraction of the PLC/PRF/5 cell culture, it suppressed the secretion of HBsAg as reported previously. These results indicated that glycyrrhizin administered intravenously might bind to hepatocytes at the concentration at which glycyrrhizin could modify the expression of HBV-related antigens on the hepatocytes and suppress sialylation of HBsAg.     

Habitual food intake and polyunsaturated fatty acid deficiency in liver cirrhosis

OBJECTIVE: We compared the habitual food intake and plasma fatty acid composition in cirrhotic patients living in two different regions in Japan, Okayama and Toyama, and evaluated the effects of dietary polyunsaturated fatty acid and alpha-tocopherol intake on serum alanine aminotransferase (ALT) activity. METHOD: A quantitative food-frequency questionnaire method was used. RESULTS: The significantly higher intake of fish in the patients living in Toyama resulted in higher plasma levels of docosahexaenoic acid and lower levels of arachidonic acid. Serum ALT activity correlated negatively with plasma arachidonic acid (r = -0.456, P < 0.05) and alpha-tocopherol (r = -0.505, P < 0.05) levels. Dietary intakes of vitamin E and polyunsaturated fatty acids (mg/g) correlated negatively with serum ALT (r = -0.377, P < 0.05). Dietary intake of linoleic acid and the ratio of polyunsaturated to saturated fatty acid in dietary fat correlated significantly with serum ALT (r = 0.604, P < 0.01, and r = 0.622, P < 0.01, respectively). The amount of vegetable intake correlated with intake of vitamin E and polyunsaturated fatty acid (r = 0.527, P < 0.02). CONCLUSIONS: These findings suggest that habitual food intake affects the plasma fatty acid profile and that elevated serum ALT may be related to arachidonic acid deficiency and vulnerability to lipid peroxidation in cirrhotic patients with hepatitis B and C viruses.