Currently there have been twelve reported cases of PSM after total laparoscopic hysterectomy (TLH). Eight cases had non-isolated PSM and four cases involved isolated PSM, where there was no evidence of an association with peritoneum carcinomatosis [4] [5] . Table 2 summarizes the characteristics of reported PSM after laparoscopic hysterectomy.

Although in the present case there was no carcinomatosis, but because of the presence of several intra-abdo- minal metastasis, we consider this case to be a non-isolated port-site metastasis. Two other cases with high- grade carcinoma (IIIA, IIIC) show an even quicker rate of the PSM-development (1 month) [6] , but they had no recurrence of the first PSM. Only one case of the twelve patients had a double PSM, despite an initial low-grade carcinoma (IA, G2) [7] . In comparison to all the other non-isolated cases, our patient had the lowest grade carcinoma and is the only patient who has both a second recurrence and a quick rate of PSM development.

According to the study of Zivanovic et al. where 1694 patients underwent laparoscopic surgeries for malignant gynecological cancers, our patient would have a bad prognosis because of the rapidity of her disease [2] . Their data showed that the only significant predictor of survival was the interval between laparoscopy and detection. Patients who developed port-site metastases within seven months from the laparoscopic surgery had a median survival of twelve months while patients who developed port-site metastasis after seven months had a median survival of 37 months (P = 0.004). This study also demonstrates that of these 1694 patients, 20 (1.18%)

developed port-site metastasis and 95% of those patients (19 patients) had simultaneously port-site metastasis and metastasis to other sites or carcinomatosis. Their conclusion that PSM is a surrogate for advanced disease [2] .

According to the current data, our patient has three reasons for a poor prognosis. Not only due to her intra-abdonimal metastasis and the occurrence of both PSM in less than 7 months after her TLH, but also due to development of a deep vein thrombosis (DVT) just 1 month after her hysterectomy. DVT is a possible predictor of the presence of an advanced disease in cancer patients [12] . Sorensen et al. concluded that cancer diagnosed in less than one year after an event of venous thromboembolism is associated with an advanced stage of cancer and a poor prognosis [13] .

In 1978, the first case report of a patient with ovarian carcinoma and ascites who developed PSM two weeks after laparoscopic surgery was reported. Current collective experience has demonstrated that PSM in gynecological malignancies occurs mostly in patients with ovarian cancer and in patients with intraperitoneal dissemination such as ascites or carcinomatosis [2] [14] . An explanation might be that the presence and possible leakage of ascites through the small abdominal incision leads to an increased contamination of these abdominal wall incisions by malignant cells [15] . Also, in other disciplines like in General Surgery and Urological Surgery, a patient with ascites or peritoneal carcinomatosis is considered as the high-risk patient for PSM [16] .

There are several benefits of laparoscopic surgery compared to the open approach. These include fewer postoperative complications, reduced risk of morbidity, shorter hospital stays and a quicker recovery which allows the return to normal activities [17] . Also, because of the cosmetic advantage through laparoscopic surgery, more patient satisfaction is achievable.

While the risk of developing a recurrence in the abdominal wall is greater in small incisions of laparoscopic surgery than in open surgery [6] , there have also been reports of recurrences in the laparotomy incision scar [18] [19] . Interestingly, the disease-free interval from the primary treatment in endometrial cancer patients with laparotomy wound recurrence was a mean of five years [18] compared to the port-site metastasis recurrences in patients undergoing a laparoscopic surgery where there is a mean time to PSM of 15.3 months [4] . In general, the risk of wound metastasis in endometrial cancer patients is not thought to be greater in laparoscopic surgeries compared to open procedures [4] [16] and that in both approaches there are no specific risk factors that could predict metastasis [4] .

There are several hypotheses how PSM can occur. These include: wound contamination, pneumoperitoneum, and immunosuppression due to the carbon dioxide (CO₂).

Wound contamination: The extraction of the cancerous specimens through a small port-site incision leads often to a carbon dioxide leakage during the extraction. This can promote free tumor cell movement, which has a high propensity of implantation in the traumatized tissue of the wound [20] . It is also possible that due to the dissection and the extrication of instruments that are contaminated with tumor cells, a wound contamination can occur.

Pneumoperitoneum: To distend the abdomen and visualize the viscera, CO₂ is used as the insufflation gas during the laparoscopy. It is colorless and rapidly absorbable [21] . Unfortunately the high pneumoperitoneal pressure can stimulate movement of free peritoneal tumor cells, or it may dislocate tumor cells from viscera into the peritoneal cavity [22] . The “chimney effect” occurs due to the pressure gradient of the peritoneum. The gradient leads to an outflow of gas with possible floating tumor cells through the trocar or port site [23] . The “chimney effect” stimulates tumor cell implantation at the port site. The subsequent healing process leads to scar formation with the presence of entrapped tumor cells [24] .

Immunosuppression: In a mice model and in a human experiment, it had been shown that in the laparoscopy, using carbon dioxide pneumoperitoneum decreased the immune mediators through TNF-alpha inhibition of the peritoneal macrophage (mice model) [25] . This caused a significant decrease in lymphocytes and cytokines during the early postoperative period before returning to normal levels (human experiment) [26] . This transient immunosuppression may promote the migration of tumor cells to the trocar site wound during laparoscopic surgery.

Even though there is no strategy proven to reduce the risk of PSM, there are several preventive measurements suggested. These include routine irrigation of the port sites [3] [6] [14] [27] [28] suturing of the peritoneum and of the fascia [3] [27] , using a protective extraction bag to prevent wound contamination from resected malignant specimens [27] [29] , occlusion of the fallopian tubes with clips or coagulation to prevent the spreading of tumor cell to the peritoneal cavity [7] [11] , avoiding manipulation of the uterus [7] , preventing high intra-abdominal pressure to avoid the “chimney effect” and deflating slowly [30] before removing the trocars [3] , systematic resection of port-site scars and initiation of adjuvant therapies with no delay [27] .

Even in an early low-grade endometrial cancer where these preventive measures were taken, PSM can occur [5] . In our case, some of the previous recommendations were practiced, including using an extraction bag.

Nevertheless, it was not sufficient to prevent the port-site metastasis. While high-grade histology and advanced stage are risk factors for recurrence, our patient had no surgical or histological risk factors such as high grade, the presence of positive peritoneal cytology, peritoneal studding or carcinomatosis.

Other currently un-measurable risk factors include tumor biology or genetic predisposition. We suspect that even with surgical attention to the prevention of cell spillage, there will always still be some risk of port-site tumor cell implantation from laparoscopy.

Our patient had a history of Hodgkin’s Lymphoma and the possibility of residual immune suppression from her first malignancy. One hypothesis of why the PSM develops is immune suppression related to pneumoperitoneum, which potentially promotes unrestricted implantation of cancer cells. Another possible reason for the PSM occurrence in this patient might be associated with the surgical complications she has had with her hernia, and the widespread abdominal adhesions. The patient’s severe adhesions were most likely a reaction from her splenectomy (associated with her Hodgkin’s Lymphoma 20 years ago). A two hour-long extensive lysis of adhesions was performed to free up the omentum from the anterior abdominal wall. It is possible that the associated prolonged exposure to CO₂ insufflation, causing the “chimney effect”, stimulated tumor entrapment in the port sites.