Search

Background and objectives Optimized drug regimens for hyperthermic intraperitoneal chemotherapy (HIPEC) have not been standardized completely in patients with advanced gastric cancer (GC). We evaluated an optimized anti-tumor protocol comprising 5-fluorouracil (5-FU) combined with cisplatin (CDDP) and mitomycin C (MMC) in vitro for clinical use of HIPEC. Methods The sensitivities of 5-FU, CDDP, or MMC, alone or in combination, using different drug concentrations, exposure times, and hyperthermic conditions (42°C) were determined in vitro by the CD-DST method using 3 different differentiated GC cell lines. Results The tumor cell growth-inhibitory effect of 5-FU was concentration-dependent for all cell lines. In addition, 5-FU showed a hyperthermic sensitization effect at all drug concentrations for all cell lines. The appropriate concentration of each drug was 5-FU, 200 µg/mL; CDDP, 10 µg/mL; MMC, 2 µg/mL. Under hyperthermic conditions, most growth-inhibitory effects for each drug at 30 min was equivalent to 60 min of exposure; use of three drugs combined significantly inhibited growth compared with any of the drugs alone. Conclusion An appropriate in vitro intraperitoneal chemotherapy regimen for GC was combined use of 5-FU, CDDP, and MMC at 42°C for 30 min.

Background and Objectives We conducted a dose-finding study for 5-fluorouracil (5-FU) administered with cisplatin (CDDP) and mitomycin C (MMC) to find an improved regimen for hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer (GC). Methods The appropriate HIPEC regimen previously determined in vitro was 5-FU (200 µg/mL), MMC (2 µg/mL), and CDDP (10 µg/mL) at hyperthermic conditions (42°C) for 30 min. This was a clinical study to determine the recommended dose of 5-FU in combination with MMC and CDDP at 42°C for 30 min and to evaluate HIPEC safety in patients at high risk of developing peritoneal metastases following GC surgery. Results Twelve patients were treated with surgery plus HIPEC using 5-FU at 0, 500, 750, and 1000 mg combined with MMC (10 mg) and CDDP (50 mg) in the perfusate (5 L). Dose-limiting toxicities did not develop until 1000 mg 5-FU was reached. Four patients experienced grade 1 or 2 adverse events. The recommended dose was 1000 mg 5-FU/5 L perfusate. Eight (66.7%) patients demonstrated no recurrence of peritoneal metastases; 5-year overall survival rate was 83.3%. Conclusion Gastrectomy and HIPEC with MMC, CDDP, and 5-FU is feasible, safe, and may protect against peritoneal metastasis following surgery for advanced GC.

（目的）成人鼠径部ヘルニアに関する多施設前向き症例登録データを用いて，日本ヘルニア学会「鼠径部ヘルニア分類改訂版」（新分類）の検証と各病型による手術術式を検討した．（方法）2009年５月より10月の期間，滋賀ヘルニア研究会15施設において成人鼠径部ヘルニア327症例を前向き症例登録し，集積したデータを解析した．（結果）初発鼠径部ヘルニア308例について，術者が判定した術者分類（新分類を用いるように依頼）はＩ-１:5.2％，Ｉ-２:46.1％，Ｉ-３:14.0％，II-１:5.2％，II-２:6.2％，II-３:14.0％，III:4.2％，IV:2.6％であった。I型で施設間のばらつきが目立ち，ヘルニア門直径から推測した新分類ではI-１が1.6％となった．Tension free repairが89％を占め，Direct Kugel（DK）法49％，Plug-mesh（PM）法23％，PHS法16％であった．I型ではヘルニア門が大きくなるほどPM法の使用頻度が低下し，DK法とPHS法はPM法と比較してII型で多く採用されていた．（結語）ヘルニア分類とtension free repairに用いられるメッシュの種類・サイズなどに一定の傾向を認めることから，将来，新分類をヘルニア診療ガイドラインに用いることができる可能性が示された．しかし，施設間で分類の病型頻度に差がみられ，新分類の普及やヘルニア門の径判定法の周知などに関して，日本ヘルニア学会およびわれわれ研究会側の努力も必要と考えられる．

To determine the potential role of the transcriptional factor-activating enhancer-binding protein-2beta (TFAP2B) in the regulation of expression of adipokines, adiponectin, leptin, and interleukin-6 (IL-6) in vivo, we quantified the mRNA expression levels of these adipokines and TFAP2B in visceral (omental) and abdominal subcutaneous adipose tissues of 66 individuals with variable degree of adiposity and studied their correlations with BMI and their plasma concentrations. We found that BMI correlated negatively with plasma adiponectin levels and positively with those of leptin. Adiponection mRNA expression in subcutaneous fat correlated negatively with BMI, whereas leptin mRNA levels in the omentum correlated with plasma leptin levels and BMI. In contrast, IL-6 mRNA levels in subcutaneous and omental fat did not correlate with BMI. IL-6 mRNA levels in the omental fat correlated with plasma IL-6 levels. Whereas TFAP2B mRNA expression did not correlate with BMI, it correlated negatively with adiponectin expression in the subcutaneous adipose tissue. Furthermore, TFAP2B mRNA expression correlated negatively with leptin and positively with IL-6 expression in both subcutaneous and omental adipose tissues. These relationships are consistent with our in vitro observations and indicate that TFAP2B seems to regulate the expression of various adipokines in vivo.

Polymyositis is known to amalgamate with malignant tumor. Here, we report a case of successfully resected esophageal carcinoma that amalgamated with polymyositis. Moreover, this is a rare case of squamous cell carcinoma combined with Barrett’s adenocarcinoma. A 47-year-old man was admitted to a hospital because of progressive dysphagia and difficulty in walking. Laboratory data showed creatine phosphokinase (CPK) was elevated, and he was diagnosed with polymyositis. He was treated with steroids, and the symptoms were improved with decreased CPK. Endoscopic and pathological examination showed a squamous cell carcinoma (0-Ipl, SM2-3) combined with Barrett’s adenocarcinoma (0-IIa, M2) of the esophagus. Although we were concerned about postoperative complications associated with polymyositis, the postoperative course was good, with decreased steroid, and he was discharged on the 21st postoperative day. At 1.5 years after surgery, he reports no recurrence of polymyositis or esophageal cancer.

大網裂孔ヘルニアは内ヘルニアの1つで，稀な疾患であり，特徴的な臨床所見に乏しく術前診断は困難とされてきた．2003年から2006年に当科では5例の大網裂孔ヘルニアを経験したが，詳細な画像の検討により全例術前診断が可能であったので報告する．症例は男性3例，女性2例で，平均年齢は79.2歳であった．腹部CTと超音波検査での画像上の特徴として，上行結腸，横行結腸の腹側，外側に位置する拡張した小腸，網嚢腔に嵌入した拡張腸管，腹部CTにおけるヘルニア門に向かう腸間膜の収束像，超音波検査における小腸ループ基部近傍に一塊となった脂肪織が有用な所見であった．開腹歴のないイレウスの診断に際しては，大網裂孔ヘルニアも念頭に置き，腹部CTや超音波検査を行うことが重要と思われた．

In this randomized multicenter Phase III study, patients with curatively resected Stage II/IIIA gastric cancer were assigned to postoperative adjuvant therapy with an oral fluoropyrimidine S-1 alone (2 weeks of treatment and 1 week of rest for 6 months, followed by 2 weeks of treatment and 2 weeks of rest for 6 months) or S-1 combined with an oral biological response modifier PSK (the same regimen of S-1 plus daily PSK for 12 months). The main objective was to evaluate the survival benefit and quality of life (QOL) of combined therapy. The primary end points were the time to relapse and the duration of survival after surgery, i.e. the rates of disease-free survival and overall survival at 3 and 5 years. The secondary end points were the relations of survival rates to drug compliance, QOL, adverse events, postoperative complications, relapse status, and the preoperative expression of immune or tumor markers. The sample size was 140 per treatment arm.

Background: Liver metastases from breast cancer are associated with a poor prognosis, however, local control with microwave thermocoagulation therapy has been used in certain subgroups of these patients in the past decade. In this study, open-configuration magnetic resonance (MR) -guided microwave thermocoagulation therapy was used for metastatic liver tumors from breast cancer, and the efficacy of this treatment was assessed. Methods: Between June 2000 and April 2004, we used MR-guided microwave thermocoagulation ther- apy on 11 nodules in 8 patients with metastatic liver tumors from breast cancer. The procedure was car- ried out under general anesthesia. A 0.5 T open-configuration MR system and a microwave coagulator were used. Near-real-time MR images and real-time temperature images were collected and displayed on the monitor. The MR-compatible thoracoscope was used and combined with MR imaging guidance. Navi- gation software, a 3D Slicer, was installed and customized. Results: The customized navigation software displayed near-real-time MR images. The percutaneous puncture into the tumors was successful in all cases. No mortality or major complications occurred as a result of the procedures. Five of the 8 patients are alive with new metastatic foci with a mean observation period of 25.9 months. Conclusions: We developed several devices to allow safe, easy, and accurate MR-guided microwave thermocoagulation therapy of liver tumors. Open-configuration MR-guided microwave thermocoagulation therapy appears to be a feasible method for tumor ablation of metastatic liver tumors from breast cancer. Breast Cancer 12:26-31, 2005.

A rare case of invasive ductal carcinoma within a fibroadenoma of the breast in a 42-year-old woman is reported. The patient had a well-defined mass, measuring 6.0 × 5.0 cm, in the upper lateral quadrant of the left breast. Physical examination suggested fibroadenoma. Ultraso-nography and mammography revealed some malignant findings. Needle biopsy demonstrated fibroadenoma. Frozen section revealed invasive ductal carcinoma, scirrhous type, arising in a fibroadenoma; muscle-preserving mastectomy was performed. Only 16 cases of carcinoma within a fibroadenoma of the breast have been reported in the literature in Japan. Carcinoma in a fibroadenoma should be treated on the basis of the therapeutic criteria for ordinary carcinoma.

A 5-year-old girl with choledochal cyst (Alonso Lej, type I) and spontaneous perforation of the right hepatic duct during an attack of acute pancreatitis was treated by two-stage surgery. Biliary panperitonitis was diagnosed by abdominal paracentesis, bilirubin and amylase levels in the collected fluid being 41.3 mg/dl and 1812 Somogyi U, respectively. The initial surgery involved simple peritoneal drainage and decompression of the bile duct, followed by removal of a choledochal cyst and the common hepatic bile duct, including the biliary stricture of the left hepatic duct, and biliary reconstruction 5 months later. Cholangiogram after the initial surgery demonstrated pancreaticobiliary maljunction and stricture in the left hepatic duct and the common hepatic duct. Regurgitation of pancreatic juice into the bile duct was shown by the extremely high amylase level (90100 Somogyi U) in the bile drained through a T-tube. The patient is currently well, with normal liver and pancreatic function tests. The experience in this patient is significant in that it should be known that spontaneous perforation of the bile duct may occur at the right hepatic duct in choledochal cyst, causing biliary peritonitis.

Rat and mouse cDNAs for Zn-alpha 2-glycoprotein (Zn alpha 2gp) were isolated from liver libraries (lambda gt11) and compared with the human one. The lengths of cDNA inserts analyzed were 1,233 and 1,273 nucleotides for rat and mouse, respectively. The deduced amino acid sequences suggested that rat and mouse Zn alpha 2gp proteins consist of 279 and 290 amino acid residues in the mature form, respectively. They have 59.4% (rat) and 58.6% (mouse) identities in amino acid sequence with the human counterpart, and between rat and mouse the identity is 88.5%. Among the three domains, domain B is best conserved; the identities are 74.7, 73.6, and 95.6% between human and rat, human and mouse, and rat and mouse, respectively. Four cysteine and eight tryptophan residues are all conserved, and two of the three asparagine residues that carry a glycan in the human protein are conserved. Analysis of rat tissues by Northern blot suggested that its mRNA is expressed in liver, and, to a much lesser extent in submandibular gland, lung, kidney, and stomach. A more detailed study by in situ hybridization demonstrated that some epithelial cells of renal tubules and the isthmus and the neck zone cells of gastric fundic glands express Zn alpha 2gp mRNA.

A 56-year-old female patient was admitted, complaining of hematochezia. She was preoperatively diagnosed with poorly-differentiated carcinoma of anorectum with metastases in the lung and mesorectal lymph nodes, and underwent abdominoperineal resection of the rectum. The immunohistochemistry of the rectal tumor showed positive for vimentin and c-kit, and negative for AE1/AE3, S-100, a-SMA, LCA and CD34, which was compatible with gastrointestinal stromal tumor (GIST). Regardless of the administration of imatinib mesylate, multiple metastases in the brain, bone, adrenal glands and inguinal lymph node proceeded in a short term. An excisional biopsy of the inguinal lymph node was performed and immunohistochemistry of the specimen showed positive for S-100, melan-A, HMB45 and tyrosinase. Therefore, we concluded that amelanotic anorectal melanoma (AMM) metastasized to the lymph node, and rechecked the immuno histochemistry of the anorectal tumor. The anorectal tumor showed positive for melan-A, HMB45 and tyrosinase, but negative for S-100. As far as we know, there are few reports of AMM with S-100 negative and c-kit positive. In such cases, making a differential diagnosis between AMM and GIST of the anorectal region can be very confusing.

解剖学的にほぼ同じ位置より発生する残胃癌 (12例15病変) と胃上部癌 (39例41病変) の相違点を, 臨床病理学的および粘液組織化学的に検討した.組織型では残胃癌は未分化型 (60.0%) が, 胃上部癌は分化型 (82.9%) が多かった.早期癌では残胃癌は隆起型を, 胃上部癌は陥凹型もしくは混合型を, 進行癌になると残胃癌は浸潤型を, 胃上部癌は限局型を呈した.腸上皮化生は残胃癌で75.0%, 胃上部癌で64.1%であったが, gastritis cystica polyposa (GCP) は残胃癌で50.0%, 胃上部癌7.7%と, 残胃癌に高頻度であった.Galactose oxidase-shiff染色, concanavalin-A-paradoxical法III型粘液染色, High iron diamine-alcianblue染色により癌の上皮型を, 胃型, 腸型, 混合型に分類すると, 分化型早期癌において, 残胃癌は胃型 (66.7%) が, 胃上部癌では腸型 (71.4%) が多かった.残胃という特殊な環境での発癌は通常の胃癌発生と機序を異にする可能性が示唆された.

A case of apocrine adenocarcinoma arising in the axilla was experienced, A 66-year-old man was seen at the hospital because of a tumor of the right axilla. The tumor was extirpated and diagnosed as adenocarcinoma. Etiologically it was able to be considered that the tumor was probably originated from (1) the appendages of the skin in the axillary region: (2) accessory breast in the axillary region; (3) axillary lymph node metastasis of breast cancer; and (4) axillary lymph node metastasis from cancer of other organ. As a result of exploration, possibilities (3) and (4) were ruled out and (1) and (2) were considered probable. Extended skin excision and axillary lymph node dissection were performed. Histological examination performed again indicated decapitation which is a pituitary pattern characteristic of normal apocrine gland. The patient was diagnosed as apocrine adenocarcinoma arising in the axilla. Thirteen cases of this disease including this case have been reported in Japan. This disease tended to occur in men. There was no significant difference in the frequency of occurrence between the right and left axillae. Extended excision was performed in 11 cases. Of the 11 cases, 7 cases were added lymph node dissection and positive lymph node was demonstrated in 5 cases. The necessity of lymph node dissection should be emphasized in the treatment of the disease.

We report a patient with advanced gastric cancer with rhabdomyolysis. A 29-year-old man consulted a local doctor complaining of dysphagia and heartburn. He developed rhabdomyolysis that was considered to be caused by administered proton pump inhibitor (PPI). The patient has remained without recurrence for 18 months after operation.

A 57-year-old woman underwent total hysterectomy and bilateral salpingo-oophorectomy for bilateral ovarian tumors (T1b, N0, M0; Stage I b, serous cystoadenocarcinoma) in May 1994. She received 4 courses of CAP (cyclophosphamide 500 mg/m2+epirubicin 50 mg/m2+cisplatin 60 mg/m2) therapy as adjuvant chemotherapy. An increase of the serum CA125 was detected in December 2006, and abdominal CT revealed a mass in the spleen. Since whole-body FDG-PET-CT showed no evidence of local recurrence of the ovarian cancer or multiple organ metastases, a solitary splenic metastasis from ovarian cancer, even though very rare, was strongly suspected. Splenectomy with distal pancreatectomy was undertaken in December 2007. Histopathological examination revealed poorly-differentiated adenocarcinoma, suggesting the final diagnosis of solitary splenic metastasis from ovarian cancer. Periodic CA125 measurements are considered very important even over 10 years after surgery for ovarian cancer. Once solitary splenic metastasis is diagnosed, surgical resection would be the treatment of choice.

We report a case of a 42-year-old female with occult breast cancer presenting axillary nodal metastasis. She complained of a swelling of the right axillary lymph node, but no breast mass was palpable. Biopsy of the lymph node was performed and histological examination showed a metastatic ductal carcinoma with papillotubular formation. Estrogen receptor of the lymph node was positive. No pathological findings were obtained by mammography and ultrasonography and systemic examinations revealed no extramammary primary lesion. All these data suggested an occult carcinoma of the breast and modified radical mastectomy was performed. Pathological findings of the removed specimen failed to find the primary breast cancer lesion. The patient has been treated with hormonal therapy and she is well without evidence of disease 5 years after surgery.

The diagnosis of subacute thyroiditis is not so difficult when it has typical symptoms. But in the case which has no tenderness of thyroid and no acute inflammatory symptoms, it is difficult to distinguish from another thyroid diseases. Recently we have encountered two cases of subacute thyroiditis. At first they were diagnosed as thyroid cancer because of lacking in typical symptoms. Both cases have a tumor in the thyroid, and we could not distinguish them from thyroid cancers by palpation and ultrasonographic findings. It was valuable to establish the diagnosis of subacute thyroiditis be following the changes in palpation and ultrasonographic findings of the tumors.

胆石症158例における術中胆嚢胆汁培養と, T-tubeを留置した48例におけるT-tube胆管胆汁培養について検討した. 術中胆嚢胆汁培養ではE.coli 18例, Klebsiella 12例, Enterococcus faecalis 11例と高頻度に分離された. 胆管結石症, 胆石による症状の既往のある症例, 高齢者 (60歳以上), 術前に肝機能異常や発熱, 白血球数の上昇を認めた症例において細菌の分離頻度が有意に高かった.一方, T-tube胆管胆汁培養ではEnterococcus faecalisの分離される頻度が時間経過とともに増加し, 術中に多かったE.coli, Klebsiellaの分離頻度が減少した. 抗生剤に対しE-coli94.9%, Klebsiella81.9%と良好な感受性を示したのに対し, Enterococcus faecalisは53.3%と低く, このことがT-tube胆管胆汁培養における菌交替現象の原因のひとつと考えられた. 胆石症術後感染は18例で, そのうち13例の起因菌は胆汁からの分離菌と同じであった.

A case of malignant lymphoma of the larynx in a 10-year-old female is reported with a review of literatures. Our case was youngest in the Japanese reports. Biopsy of the right false cord and left ventricle was performed and histological examination revealed malignant lymphoma (diffuse lymphoma, medium sized cell type). The clinical stage of this patient was IE and successfully treated with combined chemotherapy (CHOP) and radiation (40 Gy).

Postprandial hyperglycemia is recognized as an important risk factor for developing type 2 diabetes; it is also common in patients after a gastrectomy and is likely to become exacerbated after a total gastrectomy rather than after a distal gastrectomy. In this study, we investigated the glucose and insulin responses after oral glucose tolerance test (OGTT), and compared the incidence of postchallenge hyperglycemia after OGTT in patients after a distal and total gastrectomy. Forty-six patients, including 18 patients after a distal gastrectomy and 28 after a total gastrectomy, underwent a 75-g OGTT, and the plasma concentrations of glucose and insulin were measured after OGTT. Glucose peaked at 30 min in the distal gastrectomy patients and 60 min in the total gastrectomy patients, and there were significant differences in the 1-h plasma glucose (PG) and 1.5-h PG levels between the distal and total gastrectomy patients. Insulin peaked at 60 min in both the distal and total gastrectomy patients, and there were significant differences in insulin levels at 60 min between the distal and total gastrectomy patients. The incidence of postchallenge hyperglycemia in the patients after a total gastrectomy (57.1%) was higher than in those after distal gastrectomy (27.8%). Moreover, significant positive correlations were found between 1-h PG and hemoglobin antigen HbA1c after a total gastrectomy but not after a distal gastrectomy. These results suggest that postchallenge hyperglycemia after OGTT may become more exacerbated after a total gastrectomy than after a distal gastrectomy. Postprandial hyperglycemia, especially after a total gastrectomy, may therefore be involved in the development of diabetes.

To investigate the prognostic marker for the adjuvant chemotherapy of primary colorectal carcinoma.Primary colorectal cancer tissue from 24 patients was investigated to evaluate the relationship between the mRNA expression level of several 5-fluorouracil (5-FU)-related metabolic enzymes (thymidylate synthase, TS; dihydropyrimidine dehydrogenase, DPD; and thymidine phosphorylase, TP) and chemosensitivity to two different 5-FU doses and duration (1: 5-FU concentration 1.0 microg/mL (7.68 microM), 24 h exposure and 2: 5-FU concentration 0.3 microg/mL (2.30 microM), 144 h exposure). Chemosensitivity and mRNA expression levels were measured using collagen gel droplet embedded culture drug sensitivity tests and real-time quantitative reverse transcription-polymerase chain reaction. Clinicopathological features and chemosensitivity were also compared.The TS mRNA expression level was significantly higher in the 5-FU resistant group (T/C60%) compared with the 5-FU sensitive group (T/C60%) in both 5-FU regimens (1: 5.03 +/- 0.92 vs. 1.58 +/- 0.76, p0.01, 2: 4.88 +/- 0.91 vs. 0.96 +/- 0.20, p0.001). The group with the higher TS mRNA expression level (3.83, the average) were more resistant to both 5-FU regimens than those with lower TS mRNA (3.83) (1: T/C = 80 vs. 66%, p = 0.11, 2: T/C = 89 vs. 64%, p0.005). The TS mRNA expression level inversely correlated with the sensitivity to the latter 5-FU regimen (R = 0.577, p0.01). There were no relationships between chemosensitivity to 5-FU and the mRNA expression level of DPD and TP and clinicopathological factors.The TS mRNA expression level might be a good marker of chemosensitivity to 5-FU in primary colorectal cancer, especially the sensitivity to low dose 5-FU with a long duration.

We previously reported that MUC2 is a useful marker in the detection of lymph node micrometastasis (LMM) in gastric cancer. To improve the detection rate, we focused on a TFF1 gene. We used the duplex reverse transcriptase-polymerase chain reaction (RT-PCR) method with MUC2 and TFF1 genes to detect LMM in histologically node negative (pN0) early gastric cancer (EGC) and evaluated their effectiveness. A total of 310 lymph nodes from 33 patients with pN0 EGC were analyzed. All carcinoma specimens were positive for MUC2 and/or TFF1. The positive rate of TFF1 was significantly higher than MUC2 in the undifferentiated carcinoma specimens (p=0.002). The detection rate of duplex RT-PCR with MUC2 and TFF1 was higher than that of MUC2 or TFF1 alone. In mucosal cancer, 7 cases were positive for duplex RT-PCR. Of these 7 cases, 3 were MUC2-positive/TFF1-negative while 4 were MUC2-negative/TFF1-positive. LMMs were not detected in elevated-type primary mucosal cancers with a 20-30-mm diameter. The duplex RT-PCR assay with both MUC2 and TFF1 provides a higher LMM detection rate than either MUC2 or TFF1 alone, especially in mucosal gastric cancer. LMM detected in this manner may prove useful in broadening the indications for endoscopic mucosal resection in elevated-type cancer.

To investigate retrospectively the clinical and biological features that influence the outcome of infants with neuroblastoma (NB) detected by mass screening (NBMS), and to construct surgical strategies to deal with NBMS, 20 infants diagnosed as having either NB or ganglioneuroblastoma (GNB) between 1986 and 1998 were enrolled in a study. They comprised 15 boys and 5 girls ranging in age from 7 to 14 months. The following factors were analyzed by multivariate analysis: age, stage according to the Japanese staging system at the time of diagnosis, site of the primary tumor, histologic findings, preoperative urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels, VMA/HVA ratio, lactate dehydrogenase, neuron-specific enolase, Shimada's histologic classification, amplification of the N- myc oncogene by Southern blot analysis, nuclear content, and chromosomal abnormality. The 2-year survival was 95.0% (19/20). The site of the primary tumor was the adrenal gland in 12 cases, retroperitoneum in 6, and retrothoracic space in 2. Four infants had stage I, 6 stage II, 3 stage III, 3 stage IVB, and 4 stage IV disease. Complete resection was achieved in all cases except for 1 retroperitoneal GNB. Histologic examination showed that 8 patients had NB. Of the 12 GNBs, 8 were poorly-differentiated and 1 was well-differentiated. Only 1 of the 14 examined tumors showed amplification of N- myc (20 copies). The infant with N- myc-positive NB (stage II) died 23 months after surgery in spite of aggressive postoperative chemotherapy. Multivariate analysis revealed the plasma NSE level to be a significant predictor of survival (p0.0143). This suggests that N- myc amplification and plasma NSE level could be closely related to the survival of infants with NBMS. The N- myc-positive NB case implies that even in locoregional NB detected by NBMS, surgical excision should play a central role in the diagnosis of its oncogenic characteristics and indicate any subsequent therapy.

The extragonadal germ cell tumor are uncommon neoplasms which account for only 1-5% of germ cell tumors, and its prognosis is poor. We report here the use of combination chemotherapy with cisplatin, etoposide, bleomycin, and vinblastine (PVeBV) for the treatment of retroperitoneal germ cell tumor. A 28-year-old male with complaints of abdominal pain and lumbago, without any abnormality in both testes by physical and ultrasonographic examination, showed retroperitoneal tumor by abdominal computed tomography. The serum alpha-fetoprotein and lactate dehydrogenase were elevated. The retroperitoneal tumor was treated surgically. The pathological diagnosis was mixed germ cell tumor. The lung and supraclavicular lymph node metastases disappeared completely after 3 courses of PVeBV chemotherapy with cisplatin (40 mg/m2 per day) and etoposide (100 mg/m2 per day) for 5 consecutive days, with vinblastine (0.2 mg/kg) on day 1, and bleomycin (30 mg/body) given on days 1, 8, and 15. Granulocyte colony-stimulating factor and serotonin receptor antagonist application were available on acute phase toxic effects. The patient is now alive and well, without recurrence, more than 26 months after the operation.

We examined the expression of FGF-2 mRNA in 16 early and 14 advanced gastric cancer by in situ hybridisation to elucidate its role in cancer progression. Anti-sense RNA probes were synthesized by transcribing the subcloned vector with T7 RNA polymerase in the presence of digoxigenin-labeled UTP. FGF-2 mRNA was located mainly in the cytoplasm around the nuclei of endothelial cells, fibroblasts and carcinoma cells. The expression was more frequently in the diffuse type carcinomas (4/7, 57%) than in the intestinal type tumours (5/23, 22%). The survival rates of advanced gastric cancers with FGF-2 mRNA expression were significantly lower than those without FGF-2 mRNA expression (p < 0.01). No significant correlation was seen with other clinicopathological factors. These results suggest that FGF-2 may play an important role for the growth of diffuse type gastric cancers, particularly at their advanced stage.

4092 Background: A large number of advanced gastric cancer patients undergoing curative gastrectomy with D2 lymph node dissection (D2 gastrectomy) show peritoneal metastasis. The source of these metastatic cells and their treatment remain unclear. We examined the mechanism of surgery-induced peritoneal metastasis and determined the appropriate intraoperative treatment. Methods: (1) Curative gastrectomy was performed for 102 gastric cancer patients. Peritoneal lavage fluid was collected before and after gastrectomy. Cytology, RT-PCR, and cell culture were used to determine the presence of cancer cells. Proliferative potential of tumor cells was evaluated using Ki-67 staining. Tumorigenic capacity was assessed by cell injection into the peritoneal cavity of NOD/ShiJic-scid mice. (2) Fifty clinical T3(SE) or T4(SI) advanced gastric cancer patients undergoing curative D2 gastrectomy prospectively received intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) in a phase II trial. HIPEC comprised 50 mg CDDP, 10 mg MMC, and 1000 mg 5-FU in 5 L saline maintained at 42–43C° for 30 min. Results: (1) Of 102 peritoneal lavage fluid samples obtained before gastrectomy, 57 from both early and advanced cancer patients did not contain CEA or CK20 mRNA amplification products or cancer cells. Of these 57 samples, CEA or CK20 mRNA was detected in 35 and viable cancer cells were identified in 24 after gastrectomy. Viable cancer cells in all 24 cases showed Ki-67 positivity, indicating proliferative activity. Cultured viable cancer cells developed into peritoneal tumor nodules after spill over into the peritoneal cavity in NOD/ShiJic-scid mice. (2) Fifty patients were eligible for the phase II clinical trial. The overall 5-year survival rate for all patients was 92.4%. This rate in patients with pT2(ss) (n = 12), pT3(se) (n = 35), and pT4(si) (n = 3) disease was 90.0%, 92.3%, and 100%, respectively. Only 2 patients (4%) showed peritoneal relapse. Conclusions: Viable tumorigenic cancer cells spilled over the peritoneal cavity during curative gastrectomy. Intraoperative HIPEC following curative D2 gastrectomy effectively prevented peritoneal metastasis, thereby potentially improving the prognosis of patients with advanced gastric cancer.

We examined the localization of urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitors (PAI-1 and PAI-2) and plasminogen (plg) in 26 cases of colon cancer by immunohistochemical staining. The u-PA antigen was detected in the cytoplasm of cancer cells (18/26) and stromal cells adjacent to cancer tissues (9/26). The localization of u-PA mRNA examined by in situ hybridization was consistent with that of u-PA antigen. The PAI-1 antigen was detected in fibroblasts and endothelial cells (22/26), while PAI-2 antigen was found in cancer cells (20/26). The plg antigen was seen in the extracellular matrix of the cancer stroma. The u-PA expression in cancer cells was significantly more frequently detected in cases with lymph node metastasis than in cases without metastasis. In either PAI-1- or PAI-2-expressing cases, lymph node metastasis seemed to be restrained. These findings indicate that cancer cells themselves produce u-PA, and suggest that u-PA converts plg into plasmin, which dissolves the extracellular matrix surrounding cancer cells, resulting in cancer invasion and metastasis. PAI-1 and PAI-2 may have inhibitory actions on cancer invasion and metastasis mediated by u-PA.

Background We conducted a multicenter phase II trial to assess the suitability of three types of chemotherapy (docetaxel plus S-1, irinotecan plus S-1, or S-1 alone) for patients with advanced gastric cancer by means of the collagen gel droplet embedded culture-drug sensitivity test (CD-DST). To our knowledge, this is the first multicenter clinical trial that has employed CD-DST to choose anticancer agents for the treatment of advanced gastric cancer. Methods Subjects (n = 64) were patients with advanced or recurrent gastric cancer. Patients were allocated to one of the treatment regimens on the basis of CD-DST results. Outcome of the patients was compared between the groups deemed chemosensitive or chemoresistant by the CD-DST. Results Thirty-three patients showed high sensitivity (T/C ratio