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ORIGINAL RESEARCH |
From the Department of Gynecology, Cancer Institute Hospital, Tokyo, Japan.
Address reprint requests to: Yasuo Hirai, MD Department of Gynecology Cancer Institute Hospital 1-37-1 Kami-Ikebukuro Toshima-ku Tokyo 170-8455 Japan E-mail: yhirai{at}jfcr.or.jp
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Abstract |
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Methods: Fifty patients with clinical stage I–II endometrial cancer in whom the disease was completely surgically resected and positive peritoneal smears were found at surgery formed the study population. In these patients, a tube for cytologic analyses was inserted into the peritoneal cavity when closing the abdomen. The peritoneal cavity was irrigated with physiologic saline, and washings were obtained through the tube 7 and 14 days after the operation.
Results: Persistence of positive peritoneal cytology was observed in four of seven patients with adnexal metastasis, zero of nine patients with nodal disease, and one of 34 patients with disease confined to the uterus, for a total of 10% (5 of 50). In the remaining 45 (90%) patients, no malignant cells were found in any of the washings.
Conclusion: The current series suggests that endometrial cancer cells found in the peritoneal cavity usually disappear within a short time and seem to have a low malignant potential. It also seems that only malignant cells from special cases, such as adnexal metastasis, may be capable of independent growth, and are possibly associated with intraperitoneal recurrence.
Obtaining peritoneal washings is now an accepted part of the evaluation of patients with endometrial cancer. The presence of malignant cells in these washings has been related to significant association with survival in a number of studies,1–4 so this test could be used to guide decisions regarding adjuvant therapy. However, other authors5–9 have concluded malignant cytology is not a prognostic indicator and is only of limited value.
Meanwhile, the manner in which malignant cells appear in the peritoneal cavity in the absence of uterine serosal involvement also continues to be debated. Migration through the fallopian tubes has received the greatest attention because of the obvious anatomic continuity, and the presence of endometrial carcinoma cells within the fallopian tube has been confirmed in several cases.10,11 The presence of alternative pathways is supported by the fact that in a patient with previous bilateral salpingectomy, adenocarcinoma appeared in the peritoneal cavity.10
In addition to these discussions, it is of interest whether these malignant cells are viable or capable of independent growth in the peritoneal cavity. This study was undertaken to investigate the malignant potential of positive peritoneal cytology in endometrial cancer.
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Materials and Methods |
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Peritoneal fluid retained in the cul-de-sac was aspirated completely by syringe immediately upon opening the peritoneal cavity. In cases with no ascites, 20–30 mL of saline was instilled into the cul-de-sac. After being centrifuged, the specimens were immediately investigated by at least two cytopathologists. The results were disclosed to the surgeons during the operation.
In 55 patients, the peritoneal smears were diagnosed as positive for malignant cells. In an additional five patients, the washings were judged as being suspicious, but these patients were excluded from the study. In the 55 patients, a tube for cytologic analyses was inserted into the abdominal cavity when closing the abdomen. Informed consent was obtained from each patient before the operation. In five patients, the tubes for cytologic analyses were not accessible after the operation because of accidental loss or obstruction. The remaining 50 patients formed the study population. In these patients, the peritoneal cavity was irrigated with 500 mL of physiologic saline, and washings were obtained through the tube 7 and 14 days after the operation (Figure 1
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shows the profile of the 50 patients in this study. In all patients, the standard operation was completed, and no macroscopic residual disease was found at the end of the surgery. All patients except five had received preoperative hysteroscopy. This procedure was usually performed 7 days before the operation. No adjuvant therapy was provided for any patients until the cytologic collection was completed.
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Results |
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Table 2 shows the details of five patients in whom the positive peritoneal cytology persisted. Four of the five had adnexal metastasis. There were seven patients with adnexal metastasis in this study, thus positive peritoneal cytology persisted in 57% (four of seven) of the patients with adnexal metastasis, and in 2.3% (one of 43) of patients without adnexal metastasis. The difference is significant (P < .001, 95% confidence interval 4.7–671). Conversely, there were nine patients with nodal disease in this study, and none of them showed positive cytology after the operation. In 34 patients with the disease confined to the uterus, only one (3%) patient showed positive peritoneal cytology after surgery.
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Discussion |
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Concern has often been expressed that the increase in intrauterine pressure during hysteroscopy may lead to dissemination of malignant cells into the abdominal cavity. An increasing number of case reports12,13 assume abdominal dissemination of malignant cells during hysteroscopy, and Egarter et al14 have actually demonstrated this phenomenon using intraoperative hysteroscopy. Another study15 compared the incidence of positive peritoneal washings in patients with endometrial cancer who underwent fluid hysteroscopy plus dilatation and curettage with that in patients who underwent only dilatation and curettage before surgical staging. The results strongly suggested that dissemination of endometrial cancer cells occurred during hysteroscopy. Thus, hysteroscopy appears to be responsible for the transport of malignant endometrial cells into the peritoneal cavity. However, based on the findings from our study, we believe that the malignant cells disseminated by hysteroscopy have little potential for implantation and little influence on clinical course.
Although a number of reports that deny the prognostic significance of positive peritoneal cytology have been published, some reports7–9 agree with its impact on survival in cases of extrauterine spread. Kadar et al16 stressed the importance of the concomitant presence or absence of extrauterine spread when evaluating the prognostic impact of positive peritoneal cytology. They found that positive peritoneal cytology had an adverse effect only if the endometrial cancer had spread to the adnexa, peritoneum, or lymph nodes, but not if disease was otherwise confined to the uterus. Similar findings were reported in other studies.8,9 These reports9,16,17 have also demonstrated a significant survival disadvantage in lymph node-positive patients with positive peritoneal washings when compared with those who showed negative cytology. Our findings seem to be linked to these previous reports regarding patients with disease confined to the uterus as well as patients with adnexal metastasis. However, in our nine patients with nodal disease, no malignant cells were found in any of the washings obtained 7 and 14 days after the operation. This finding suggests that these malignant cells associated with nodal disease are unrelated to intraperitoneal recurrence, even if the prognostic significance of positive peritoneal cytology is justified in node-positive patients.
It is interesting that most of our patients in whom positive peritoneal cytology persisted after surgery had adnexal metastases. The reason why malignant cells in patients with adnexal metastases persist and those in patients with nodal disease disappear quickly is unclear. However, we propose the difference may result from the presence or absence of adjacent occult metastatic lesions. Micrometastases in the peritoneal cavity are probably more easily born during the process of metastases to the tubes or ovaries when compared with that of lymph node metastases.
A significant proportion of recurrent disease in cytology-positive patients is extraperitoneal, despite the observation of positive washings.6 Obviously, the current study does not deny the prognostic significance of positive peritoneal cytology in endometrial cancer because positive peritoneal cytology may be a marker of tumor aggressiveness rather than metastatic spread. Nonetheless, we believe this series has provided an additional insight into the relationship between positive peritoneal washings and intraperitoneal recurrence. It seems that only malignant cells from special cases, such as adnexal metastasis, are capable of independent growth, and may be associated with intraperitoneal recurrence.
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Footnotes |
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Received August 31, 2000. Received in revised form December 12, 2000. Accepted January 12, 2001.
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References |
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2. Mazurka JL, Krepart GV, Lotocki RJ. Prognostic significance of positive peritoneal cytology in endometrial carcinoma. Am J Obstet Gynecol 1988;158:303–6.[Medline]
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6. Lurain JR, Rumsey NK, Schink JC, Wallemark CB, Chmiel JS. Prognostic significance of positive peritoneal cytology in clinical stage I adenocarcinoma of the endometrium. Obstet Gynecol 1989;74:175–9.
7. Hirai Y, Fujimoto I, Yamauchi K, Hasumi K, Masubuchi K, Sano Y. Peritoneal fluid cytology and prognosis in patients with endometrial carcinoma. Obstet Gynecol 1989;73:335–8.
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10. Creasman WT, Lukeman J. Role of the fallopian tube in dissemination of malignant cells in corpus cancer. Cancer 1972;29:456–7.[Medline]
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12. Schmitz MJ, Nahhas WA. Hysteroscopy may transport malignant cells into the peritoneal cavity: Case report. Eur J Gynecol Oncol 1994;15:121–4.
13. Rose PG, Mendelsohn G, Kornbluth I. Hysteroscopic dissemination of endometrial carcinoma. Gynecol Oncol 1998;71:145–6.[Medline]
14. Egarter C, Krestan C, Kurz C. Abdominal dissemination of malignant cells with hysteroscopy. Gynecol Oncol 1996;63:143–4.[Medline]
15. Obermair A, Geramou M, Gucer F, Denison U, Graf AH, Kapshammer E, et al. Does hysteroscopy facilitate tumor cell dissemination? Cancer 2000;88:139–43.[Medline]
16. Kadar N, Homesley HD, Malfetano JH. Positive peritoneal cytology is an adverse factor in endometrial cancer only if there is other evidence of extrauterine disease. Gynecol Oncol 1992;46:145–9.[Medline]
17. Kadar N, Homesley HD, Malfetano JH. Prognostic factors in surgical stage III and IV carcinoma of the endometrium. Obstet Gynecol 1994;84:983–6.
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