Eradication of intractable malignant ascites by abdominocentesis, reinfusion of concentrated ascites, and adoptive immunotherapy with dendritic cells and activated killer cells in a patient with recurrent lung cancer: a case report

Abstract

Introduction: Malignant ascites is often a sign of a terminal stage in several malignant diseases. To control ascites, drainage and intra-abdominal chemotherapy are often used in those patients but eradication of ascites is difficult and prognosis is poor.

Case presentation: A 55-year-old woman was admitted to our hospital on 26 January 2007 with dyspnea, abdominal distention and oliguria. Abdominocentesis revealed peritoneal carcinomatosis resulting from abdominal recurrence from lung cancer. To alleviate the dyspnea and abdominal distention, we drained the ascites aseptically and infused them intravenously back into the patient after removal of tumor cells by centrifugation, and then concentration by apheresis. After the drainage of ascites, we intraperitoneally infused activated killer cells and dendritic cells from the patient's tumor-draining lymph nodes, together with 4.5 x 105U interleukin-2 in 50 ml saline by 2.1 ml/hour infuser balloon.Drastic decreases in the tumor cell count and in ascite retention were observed after several courses of ascites drainage, intravenous infusion and intraperitoneal immunotherapy. The plasma protein level was maintained during the treatment notwithstanding the repeated drainage of ascites. Cell surface marker analysis, cytotoxic activities against autologous tumor cells and interferon-gamma examination of ascites suggested the possibility that these effects were mediated by immunological responses of activated killer cells and dendritic cells infused intraperitoneally.

Conclusion: Combination of local administration of immune cells and infusion of concentrated cell free ascites may be applicable for patients afflicted with refractory ascites.

Figure 1

Volume of ascites and number of transferred cells: (a) Volume of ascites drained and number of DC+AK cells transferred into the hypogastric area. From 16 February 2007 (day 1), we started to drain 3000 ml of ascites and transferred 5.4 × 10⁹ DC+AK cells on day 8. Drainage and intraperitoneal immunotherapy in the hypogastric area continued for 1 month. A total of 13,222 ml of ascites was aspirated. Black bars indicate the volume of ascites, and white arrows, the date of DC+AK immunotherapy. (b) Volume of ascites drained and number of DC+AK cells transferred into the epigastric area. From 23 March 2007 (day 1), we started to drain 2800 ml of ascites and transferred 9.8 × 10⁹ DC+AK cells on day 5. Drainage and intraperitoneal immunotherapy in the epigastric area continued for 1 month. A total of 6000 ml of ascites was aspirated. Black bars indicate the volume of ascites, and white arrows, the date of DC+AK immunotherapy. The gray arrow indicates the date of TIL immunotherapy.

Figure 2

(a) Number of tumor cells obtained from ascites. From 16 February 2007 (day 1), we started to drain 3000 ml of ascites and counted the number of tumor cells in the hypogastric area. After the second drainage of ascites, we infused DC+AK cells intraperitoneally with IL2. Three days later, 2200 ml of ascites was drained and the number of tumor cells was counted. A drastic decrease in the tumor cell count (1/77) was observed: from 4.6 × 10⁸ cells to 6 × 10⁶ cells. From 23 March (day 36), we initiated drainage from the epigastric area. The number of tumor cells decreased from 6.6 × 10⁸ (day 36) to 0 (day 71) after the fifth immunotherapy with DC+AK cells and TIL. (b) Cytotoxic activity of autologous and allogeneic effector cells. Cytotoxic activity of TIL was examined by the ⁵¹Cr-releasing test. Tumor cells obtained from ascites were labeled with Na₂⁵¹CrO₄, incubated with autologous effector (TIL) cells and allogeneic effector (MT-116) cells. ⁵¹Cr release was counted with a gamma counter. TIL showed a high cytotoxic activity against autologous tumor cells (black filled diamond), but MT-116 did not (black filled square).

Figure 3

Cytological findings of ascites. (a) Papanicolaou stain of ascites on 9 February 2007 (before treatment). Carcinoma cells varying in size with prominent nucleoli form papillary pattern clusters. (b) Papanicolaou stain of ascites on 18 April 2007 (after treatment). Most of the infiltrates are small lymphocytes and carcinoma cells are not present. Cell surface marker analysis indicated that most of the cells were CD4- and CD3-positive T cells (data not shown).