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Intraperitoneal Photodynamic Therapy: complications.

Romeo Giuli MD, resident.
School of General and Emergency Surgery.
University of Siena.   Italy.

December 2002.     Review Article.      To previous article

Peritoneal carcinomatosis and sarcomatosis are generally incurable diseases for which few effective treatment options exist. However, because of their tendency to remain as regional diseases, as well as the significant attendant patient morbidity, an aggressive approach to these conditions is indicated.
In an effort to better treat this group of patients, several management strategies have evolved, including aggressive debulking combined with systemic chemotherapy (principally for ovarian cancer), debulking with continuous hyperthermic peritoneal perfusion (CHPP), immunotherapy, and photodynamic therapy (PDT).
Introduced clinically in 1985, PDT is an anticancer treatment that combines a photosensitizer drug, oxygen, and laser light to produce cytotoxic reactive oxygen species. Photosensitizing agents are thought to accumulate preferentially in tumor cells, thereby making PDT-induced damage selective for malignant cells. Debulking is an important component of this therapy, because light penetration with currently available sensitizers is limited to < 5 mm.
A phase II trial of surgery and intraoperative PDT for diffuse peritoneal cancers is under investigation at University of Pennsylvania, Philadelphia, Pennsylvania. Although the trial is ongoing and follow-up is limited, preliminary results have been encouraging, with an overall median survival to date of 21 months and several patients who continue to have prolonged disease-free survival. It has become apparent, however, that patients who undergo this treatment develop a significant inflammatory response syndrome after surgery that necessitates massive fluid resuscitation, careful intensive care unit (ICU) monitoring, and, frequently, mechanical ventilation of several days' duration, all in excess of what would be expected from major abdominal surgery alone.

SIRS ( systemic inflammatory response syndrome ) has become a well-recognized, albeit poorly defined, entity that occurs in many clinical settings, including burns, sepsis, pancreatitis, and after cardiopulmonary bypass. It is typically characterized by increased vascular permeability, which simultaneously leads to intravascular volume depletion and tissue edema. In severe cases, it can progress to ARDS, shock, and multiorgan failure.
Although a consensus has not emerged to explain the sequence of events at the molecular and cellular levels, SIRS is believed to occur when proinflammatory mediators, such as tumor necrosis factor alpha, interleukin-1, and interleukin-8, stimulate an exaggerated response from immune effector cells, such as neutrophils, dendritic cells, and macrophages. Ongoing proinflammatory cytokine production from these effector cells then presumably leads to propagation and amplification of this inflammatory cascade, with resultant end-organ manifestations. Ischemia/reperfusion and host-cell apoptosis, particularly of lymphocytes and intestinal epithelial cells, are considered important mediators of the SIRS pathway because the release of oxidants and cellular degradative enzymes likely contributes to end-organ injury.
The variability in the development and expression of SIRS among patients reflects the complexity of the interaction between the various exogenous inflammatory insults that initiate SIRS and the host's response to these stimuli ( 1, 2, 3 ) .


1) Robert J. Canter, Rosemarie Mick, et al. Intraperitoneal Photodynamic Therapy Causes a Capillary-Leak Syndrome. Annals of Surgical Oncology, 10(5):514-524. Pub Med

2) Hendren SK, Hahn SM, Spitz FR, et al. Phase II trial of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors. Ann Surg Oncol 2001;8:65-71. Pub Med

3) TW Bauer, S Hahn, F R Spitz, A Kachur, E Glatstein, DL Fraker. Preliminary report of photodynamic therapy for intraperitoneal sarcomatosis. Annals of Surgical Oncology 2001, 8 (3): 254-259. Pub Med

4) Dougherty TJ, Gomer CJ, Henderson BW, et al. Photodynamic therapy. J Natl Cancer Inst 1998;90:889 -905. Pub Med

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