Technical Factors

The technical aspects of laparoscopy have received the most attention in the understanding of port site recurrence. Investigators have demonstrated that tumor cells may be deposited at the port site during laparoscopy either directly from contaminated instruments or indirectly via aerosolization of tumor cells in the insufflation gas (51-54). However, "gasless" laparoscopic models also demonstrate variable tumor cell dissemination or port site recurrences when compared to insufflated cases (55-58), potentially further implicating the peritoneal dissemination of malignant cells via the development of a pneumoperitoneum (59). Studies using a CO2-pneumoperitoneum reflect a higher incidence of port site recurrence compared to gasless, or other non-CO2 gas-induced working spaces (60-62). Thomas et al. demonstrated that expelled filtered port site carbon dioxide gas was free from aerosolized malignant cells, but found that every single laparoscopic instrument and trocar themselves had malignant cell contamination, suggesting that direct instrument contamination and not gas dispersion may be the mechanism for port site recurrence (63).

Indeed, contemporary data reflect that direct contamination and seeding are the likely mechanisms (64), as hematogenous and other models (including one renal cell carcinoma model) fail to reflect port site recurrences from pneumoperitoneum creation (65-68).

Tissue manipulation itself may have a significant impact on the rates of port site recurrence. Increased tissue manipulation from laparoscopic-assisted techniques, such as hand-assisted laparoscopic surgery, may also potentiate tumor seeding. The implications on port site recurrence that hand-assisted laparoscopic may demonstrate have been shown in a murine model, where laparoscopic-assisted subcostal splenectomy had a significantly higher port site recurrence rate versus open splenectomy (69). The authors cite increased tissue manipulation as a potential catalyst for wound recurrence. Although not significantly reported in the current literature, one recent renal cell carcinoma port site recurrence was reported at a hand-assisted laparoscopic site (26). Additionally, increased tissue manipulations in concert with "leaking" port sites have promoted implantation and growth of port site recurrences in another murine model (70).

Currently, if a patient with clinically localized renal cell carcinoma is found to have microscopically advanced disease, there is no effective adjunct therapy. As such, morcellation does not alter subsequent follow-up or treatment.

To date, the effects of local wound and peritoneal immunity are poorly understood, but may be a significant variable toward port site recurrence.

The biology of the primary lesion, along with the inoculum size of malignant cells deposited to the trocar site, are also possible sources of port site recurrence.

Inherent with tissue manipulation are entrapment and morcellation. All potentially cancerous tissue should be entrapped in an impermeable sack and the field well draped prior to morcellation or extraction (39,71). Morcellation of specimens for extraction has raised concerns about both accurate pathological staging and its contribution toward port site recurrence. Computed tomography has been proven to be an effective tool for planning surgery and reliably predicting pathological findings. The overall accuracy of computed tomography in staging renal cell carcinoma ranges from 72% to 90% (72-75). In a review of 172 renal tumors treated with open radical nephrectomy, Shalhav et al. correlated the preoperative computed tomography-based clinical stage with the final pathological tumor stage. They found one patient (0.6%) to be understaged and seven (4%) overstaged by preoperative computed tomography. They concluded that clinical computed tomography staging of low-stage renal tumors is reliable and tends to over stage rather than under stage renal tumors (76).

Currently, if a patient with clinically localized renal cell carcinoma is found to have microscopically advanced disease, there is no effective adjunct therapy. As such, morcellation does not alter subsequent follow-up or treatment.

The long-term follow-up in laparoscopic series where kidneys are morcellated compared to open radical nephrectomy shows equivalent cancer free survival (77,78). When pathological staging is required, the specimen may be removed intact through a small, low midline, or Pfannenstiel incision.

Local Wound Factors

Local trocar-induced tissue trauma may itself pose an inherent risk to port site recurrence. Formal excision of laparoscopic port sites has demonstrated an actual increase in wound metastases in one model (79). Notwithstanding, the intact peritoneum seems to provide a barrier to tumor cell implantation. Peritoneal trauma has demonstrated tumor ingrowth at damaged surfaces compared to nontraumatized peritoneal sites (80).

When controlling for anesthesia alone, prolonged (30 minutes), low-pressure (6 mmHg) pneumoperitoneal studies demonstrate not only peritoneal damage (81,82), but also adhesion of cancer cells to the peritoneal basal layer (81). Mathew et al. demonstrated a possible synergistic effect of both peritoneal injury (with port site placement) in concert with pneumoperitoneum (83). Rats undergoing isolated laparotomy after purposeful abdominal malignant cellular dissemination had a statistically less histo-logic wound recurrence when compared to the same model undergoing laparoscopy. These observations may then suggest that obvious peritoneal disruption coupled with creation of a pneumoperitoneum, predispose the potential adhesion and ingrowth of tumor cells.

Immune Response

Various peritoneal immune responses are noted with both open laparotomy and laparoscopic techniques. Authors have suggested that CO2-pneumoperitoneum diminishes macrophage-secreted tumor necrosis factor (84,85), depressing peritoneal cell-mediated immunity and increasing tumor implantation (84). Despite these findings, Lee et al. demonstrated that a full laparotomy performed in a sealed CO2 chamber had similar lymphocyte proliferation suppression when compared to room-air-exposed incisions (86). These findings suggest that the incisional size, and not the CO2 environment, depress peritoneal immunity.

Further work on the importance of peritoneal immunity is demonstrated by Neuhaus et al., where intraperitoneal injection of endotoxin 18 hours prior to laparoscopy decreased tumor growth and port site recurrence. This was challenged against the null effects of systemically injected cyclosporin (87).

To date, the effects of local wound and peritoneal immunity are poorly understood, but may be a significant variable toward port site recurrence.

Tumor Behavior

The biology of the primary lesion, along with the inoculum size of malignant cells deposited to the trocar site, are also possible sources of port site recurrence (88,89).

Cases that support this theory are noted previously in this manuscript. For example, the biologic susceptibility of transitional cell carcinoma to local and ectopic recurrence likely predisposes these tumors to port site recurrence. Squamous cell carcinoma arising from the urothelium is also known to hold aggressive biologic characteristics

TABLE 2 ■ Port Site Recurrence Prevention

Avoid resection and excision of tissue in face of carcinomatosis Ascitic fluid sent for cytology should be isolated from all wounds Minimize direct tumor handling to prevent iatrogenic tumor violation Ensure wide en bloc dissection of tumor and surrounding tissues All tissues should be placed within an impermeable laparoscopic sac prior to morcellation or tissue extraction Redrape port sites at the time of tissue removal All possible contaminated instrumentation should be removed from the newly towel-draped operative field Change the surgeons' and technicians' gloves prior to formal peritoneal closure

(35). Metastatic disease, regardless of etiology, likely demonstrates biologic activity that is more aggressive. For example, chemoresistant cancers, which have metasta-sized, may carry a biologic predilection for tissue implantation and growth (36). This argument is also demonstrated with metastatic lesions to the adrenal, where the only port site recurrence cases from this organ are subsequent to metastatic adrenal lesion excision (36,37).

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