Ridwelski Karsten, Meyer Frank, Hribaschek Arndt, Kasper Udo, Lippert Hans
Division of Oncosurgery/Oncology, Department of Surgery, University Hospital, Otto von Guericke University, Magdeburg, Germany.
J Surg Oncol. 2002 Jan;79(1):10-6. doi: 10.1002/jso.10000.
Malignant tumors of various abdominal organs are blamed to be the cause of death in approximately 40% of cases per year in Western Europe. At the time of death, about half of them show peritoneal carcinomatosis which is considered an unfavorable prognostic factor. In case of peritoneal carcinomatosis, there is no curative treatment available for any of the tumors in the abdominal cavity. The aim of this experimental study was to evaluate the preventive potential of intra-operative or early postoperative local administration of gemcitabine into the abdominal cavity against peritoneal carcinomatosis.
Peritoneal carcinomatosis was induced in male WAG rats (n = 18) by transfer of 5 x 10(6) cells of the adenocarcinoma cell line CC-531 via minilaparotomy carried out in all rats under general anesthesia. Thirty days after cell transfer, rats were sacrificed and peritoneal carcinomatosis was confirmed using histologic investigation in specimens obtained from the peritoneal site. Extension of this carcinomatosis was quantified by (i) counting tumor nodes per square centimeter (mean of several counts) and (ii) determining tumor weight (weight of the greater omentum plus the resected mesentery). Rats were subdivided into three groups (n = 6 per group): group 1 (controls); group 2, simultaneously with tumor cell transfer 24 mg/kg of gemcitabine were administered into the abdominal cavity; group 3, postoperative intraperitoneal irrigation with 24 mg/kg of gemcitabine was achieved via a previously implanted port-a-cath on days(d) 15, 21, and 27.
On the 30th postoperative day, all six animals of the control group showed extensive tumor growth at the peritoneum and greater omentum, indicating carcinomatosis. In contrast, none of the rats of group 2 revealed any traces of intraperitoneal tumor growth. While all rats of group 3 demonstrated intraperitoneal tumor growth, but early postoperative treatment with gemcitabine, however, resulted in a significant reduction of the number of tumor nodes and tumor weight in comparison with group 1 (controls).
Immediate, i.e., simultaneous intraoperative application of a cytostatic agent such as gemcitabine into the abdominal cavity may completely prevent the generation of peritoneal carcinomatosis from occuring tumor cells, whereas early postoperative locoregional chemotherapy into the abdominal cavity can only reduce the severity of the peritoneal carcinomatosis.
在西欧，各种腹部器官的恶性肿瘤每年约导致40%的病例死亡。在死亡时，约一半的病例出现腹膜癌转移，这被认为是一个不良预后因素。对于腹膜癌转移，腹腔内的任何肿瘤都没有有效的治愈性治疗方法。本实验研究的目的是评估术中或术后早期在腹腔内局部给予吉西他滨对腹膜癌转移的预防潜力。
通过在全身麻醉下对所有雄性WAG大鼠（n = 18）进行小切口剖腹术，转移5×10⁶个腺癌细胞系CC - 531的细胞，诱导腹膜癌转移。细胞转移30天后，处死大鼠，并通过对从腹膜部位获取的标本进行组织学检查来确认腹膜癌转移。通过以下方式量化这种癌转移的程度：（i）每平方厘米计数肿瘤结节（多次计数的平均值），（ii）测定肿瘤重量（大网膜加切除的肠系膜的重量）。将大鼠分为三组（每组n = 6）：第1组（对照组）；第2组，在肿瘤细胞转移的同时，将24 mg/kg吉西他滨注入腹腔；第3组，在术后第15、21和27天，通过先前植入的输液港，用24 mg/kg吉西他滨进行腹腔内冲洗。
术后第30天，对照组的所有6只动物在腹膜和大网膜处均显示广泛的肿瘤生长，表明存在癌转移。相比之下，第2组的大鼠均未发现腹腔内肿瘤生长的任何痕迹。虽然第3组的所有大鼠都出现了腹腔内肿瘤生长，但与第1组（对照组）相比，术后早期用吉西他滨治疗导致肿瘤结节数量和肿瘤重量显著减少。
立即，即术中同时在腹腔内应用细胞毒性药物如吉西他滨，可完全防止来自肿瘤细胞的腹膜癌转移的发生，而术后早期在腹腔内进行局部化疗只能减轻腹膜癌转移的严重程度。
