Atsuo Oka

Administration in a Hypotonic Solution Is Preferable to Dose Escalation in Intraperitoneal Cisplatin Chemotherapy for Peritoneal Carcinomatosis in Rats

An animal model of intraperitoneal (i.p.) cisplatin chemotherapy using hypotonic solutions of sodium chloride has been developed as a treatment for peritoneal carcinomatosis. The concentrations of platinum in the plasma and in the i.p. fluid of Donryu rats were measured after i.p. injection of hypotonic (103 or 154 mosm/l) and isotonic (308 mosm/l) solutions that contained an equal amount of cisplatin. The maximum concentration (Cmax) and the area under the curve of concentration versus time (AUC) of platinum in the plasma increased proportionately with increases in the dose of cisplatin and they were significantly higher in rats given cisplatin in hypotonic solutions than in those given the drug in isotonic solution. The Cmax and AUC of total platinum were similar for the solution of 103 mosm/l with 2.5 mg/kg cisplatin and the isotonic solution with 5.0 mg/kg cisplatin. The Cmax and AUC of free platinum in the plasma did not increase with increases in the dose of cisplatin in isotonic solution but did increase after hypotonic injection. However, the solutions of lower osmolarity gave a decreased AUC of platinum in the i.p. fluid. Hypotonic conditions continued for 30 min at most after i.p. injection of hypotonic solutions. When the same dose of cisplatin was given to rats with tumors derived from AH100B carcinoma cells, the amount of platinum taken by i.p. solid tumors from the solution of 103 mosm/l was about twice that from the isotonic solution and was much the same as that taken up from the isotonic solution with twice the amount of cisplatin. These results indicate that hypotonic i.p. cisplatin chemotherapy might be preferable to escalation of the dose of i.p. cisplatin in the treatment of peritoneal carcinomatosis.

Infiltration of dendritic cells into regional lymph nodes in gastric cancer.

Background. Dendritic cells (DC), including epidermal Langerhans cells, are potent antigen‐presenting cells that can carry and present tumor antigens to helper T‐cells. An immunohistochemical study was performed to clarify the relationship between the extent of infiltration by DCs in primary gastric cancer and that in the regional lymph nodes.

Long-term Survival of 5 Years Following Initial Surgery for Gastric Cancer and Simultaneous Disseminated Peritoneal Metastasis : Report of a Case

We report herein the rare case of a patient who survived for 5 years and 10 months after commencing treatment for gastric cancer with simultaneous disseminated peritoneal metastasis. A 45-year-old man was diagnosed as having advanced gastric cancer following the discovery of numerous nodules in the peritoneal cavity at laparotomy. The patient was treated by palliative gastrectomy and continuous hyperthermic peritoneal perfusion (CHPP) immediately after surgery on November 11, 1987. Postoperatively, he underwent radiofrequency (RF) hyperthermia with intraperitoneal cisplatin a total of seven times. He continued on a combination of uracil and tegafur (UFT) administered orally with a protein-bound β-d-glucan extracted from the mycelia ofCariolus versicolor(PSK). Long-term survival was achieved following the initial palliative gastrectomy despite simultaneous disseminated peritoneal metastasis.

Are argyrophilic nucleolar organizer regions good prognostic indicators of survival of patients with esophageal cancer with lymph node metastasis

Argyrophilic nucleolar organizer regions (AgNORs) were evaluated in 95 samples from primary esophageal squamous cell carcinomas and 75 samples from metastatic lymph nodes. The number of AgNORs per nucleus in primary tumors with positive nodes (n = 53, 6.1 ± 1.8) was greater than that in primary tumors with negative nodes (n = 42, 3.8 ± 1.1, P < 0.001). In 39 of 53 patients with positive nodes, the numbers of AgNORs per nucleus in metastatic lymph nodes were lower than those in primary tumors. The 5‐year survival rate of these patients was 23.7%. However, the numbers of AgNORs per nucleus in metastatic lymph nodes were greater than those of primary tumors in 14 of 53 patients with positive nodes, and 11 of these 14 patients died from recurrence of cancer within 3 years after surgery. These observations suggest that the proliferative activity of cancer cells might be suppressed in the regional lymph nodes. However, cancer cells with higher proliferative activity in the regional lymph nodes than in the primary tumors might overcome immunological defenses and subsequent further metastasis might occur.

Flow Cytometric Analysis of the DNA Content of Tumor Cells in Cases of Gastric Cancer in the Upper Third of the Stomach and in the Remnant Stomach

Thirteen samples of gastric tumors that had developed in the remnant stomach (remnant gastric cancer) were compared with 63 samples of primary gastric tumors located in the upper third of the stomach (primary gastric cancer) by both clinicopathologic and flow cytometric analysis. The depths of invasion of all these tumors corresponded to the mucosa, submucosa, or muscularis propria layers and the histological stages were stages I, II, or III. There was no significant difference between the two groups of samples either histopathologically or clinically (the 5-year survival rates were 74.6% for patients with remnant gastric cancer and 90.4% for patients with primary gastric cancer). DNA aneuploidy was encountered in 23.1% of the cases of remnant gastric cancer and in 33.3% of the cases of primary gastric cancer. Little difference was found in the S-phase fractions between tumors and normal gastric mucosa of the upper third of the stomach and the remnant stomach. Thus, while the environments in the upper third of the stomach and in the remnant stomach are very different, histopathological and biological characteristics of adenocarcinomas that developed in the remnant stomach are very similar to those of adenocarcinomas in the upper third of the stomach.

Number of argyrophilic nucleolar organizer regions is a good indicator of lymph node metastasis in patients with esophageal carcinoma

The number of argyrophilic nucleolar organizer regions (AgNORs) was evaluated as a predictor of lymph node metastasis in 45 patients who had undergone resection of advanced squamous cell carcinoma of the esophagus. The mean AgNOR score of carcinomas was 5.0 ± 1.8, and it was greater than that of normal esophageal epithelium adjacent to a carcinoma (2.3 ± 0.5, P<0.001). The AgNOR score of tumors from 26 patients with lymph node metastasis was 6.1 ± 1.6, and it was greater than that of tumors from 19 patients without lymph node metastasis (3.7 ± 1.0, P<0.001). The AgNOR scores of metastatic lymph nodes (4.9 ± 1.5) from 26 patients with lymph node metastasis were closely related to the number of metastatic lymph nodes of individual patients (r =0.582, P<0.001). The 3-year survival rate in patients with low AgNOR scores (AgNOR score <5, n=22) was 56.2%. By contrast, that in patients with high AgNOR scores (AgNOR score ≥5, n=20) was only 13.1%. There was a statistically significant difference between the two survival curves (P<0.05). These results indicate that the AgNOR score is a good indicator of lymph node metastasis and suggest that it might also be a useful prognostic marker in patients with esophageal cancer.ZusammenfassungDie Anzahl der AgNOR wurde als Indikator für Lymphknotenmetastasen (LKM) bei 45 Patienten mit reseziertem Plattenepithelkarzinom des Ösophagus untersucht. Der mittlere AgNOR-Karzinomscore betrug 5,0 ± 1,8 und war damit höher als bei normalem Ösophagealepithel in der Nachbarschaft des Karzi noms (2,3 ± 0,5, p<0,001). Der AgNOR-Tumorscore betrug bei 26 Patienten mit LKM 6,1 ± 1,6 und war damit höher als bei 19 Patienten ohne LKM (3,7 ± 1,0, p< 0,001). Die AgNOR-Scores der metastatischen Lymphknoten (4,9 ± 1,5) bei 26 Patienten mit LKM wiesen eine enge Korrelation zur Anzahl metastatischer Lymphknoten bei einzelnen Patienten auf (r=0,582, p<0,001). Die Dreijahresüberlebensrate mit niedrigen AgNOR-Scores (AgNOR-Score <5, n=22) betrug 56,2%, hingegen bei Patienten mit hohen AgNOR-Scores (AgNOR-Score ≥ 5, n=20) nur 13,1%. Es gab einen statistischen signifikanten Unterschied zwischen beiden Überlebenskurven (p< 0,05). Nach diesen Resultaten ist der AgNOR-Score ein guter LKM-Indikator und könnte auch gut zur Prognose bei Patienten mit Ösophaguskarzinom verwendet werden.

A CASE OF NEUROFIBROMATOSIS I (VON RECKLINGHAUSEN DISEASE) ASSOCIATED WITH BREAST CANCER AND LEIOMYOSARCOMA OF THE SMALL INTESTINE

神経線維腫症1型(neurofibromatosis 1: NF 1,von Recklinghausen病)に乳腺アポクリン癌と小腸平滑筋肉腫を異時性に合併した稀な症例を経験した.症例は42歳,女性.右乳房腫瘤を主訴に来院.右乳腺円状部分切除術後,広範な乳管内進展による断端陽性のため,右胸筋温存乳房切除術施行(t2nO, stage I). follow up中の9カ月後,下腹部超音波検査を受け,径約8cmの右卵巣腫瘤が疑われた.開腹術中,空腸壁外性に発生した平滑筋肉腫と診断された. NF lは,神経原性悪性腫瘍との関連はよく知られているが,上皮性悪性腫瘍との関連はまだ明らかでない.NF 1に合併した乳腺アポクリン癌および空腸平滑筋肉腫は,それぞれ本邦報告例がまだ50例に満たない稀なものであるが, NF 1の本体がgenetic disorderと思われる以上,悪性腫瘍との関連は濃厚であると考えられる.本症患者は潜在的悪性腫瘍患者と考え,計画的な全身検索が必要と思われた.