Approximately 4 h after surgery, the patient developed archorrhagia (dark red blood and clots per rectum), and the amount of blood loss increased up to 200 mL within 1 h. After exploration per anus, a bleeding wound near the anastomosis was identified and the control of hemorrhage was performed timely. There was no recurrence of archorrhagia ever since. The further postoperative course was uneventful. Graft function stayed well, and serum creatinine levels were always within the normal limits, ranging from 80 to 104 μmol/L. The ostomy was opened on the third postoperative day, and flatus was passed then. The patient went on a liquid diet 4 days after surgery and made a recovery soon. He stayed in hospital for 9 days after surgery, and drainage tubes were removed at discharge.
During 4 months of follow-up period, immunosuppressive therapy with tacrolimus 2.5 mg/d, mycophenolate mofetil 1.5 g/d, and prednisolone 10 mg/d continued, no allograft rejection and complications were observed. Considering his tumor stage, he received adjuvant chemotherapy with a regimen of FOLFOX (oxaliplatin/5-fluorouracil/calcium folinate). After 8 cycles of chemotherapy, repeated CT scan indicated no evidences of local recurrence and distant metastasis. To date, the patient was in a good condition.
We have reported the detailed case of a patient after kidney transplantation, in whom laparoscopic surgery for advanced rectal cancer had been performed. Our case demonstrates that laparoscopic assisted surgery for advanced rectal cancer can be tolerated by kidney transplant recipients, and its short as well as long-term outcomes are acceptable and encouraging.
Kidney transplantation is a definite treatment for patients with ESRD. As surgical techniques, organ procurement, immunosuppression regimen, and postoperative monitoring have improved, kidney transplant recipients have a higher treatment success rate and a longer life span. However, the development of de novo malignancy has become a major cause of late mortality in these patients.
The increased risk of CRC after kidney transplantation has been well documented.[10–12] Moreover, compared with the general population, CRC that are diagnosed in kidney transplant patients often display a more aggressive behavior, and the aggressive behavior is characterized by an earlier age of cancer diagnosis, a more advanced cancer stage (American joint committee on cancer stage > II), and a lower 5-year survival.[13,15] Interestingly, a significantly reduced risk of rectal cancer was observed in the transplant recipients when separated from colon cancer,[16,17] and it seems that the elevated risk of CRC was driven by excess of proximal colon cancer. One possible explanation to these results might be that transplant recipients were screened more frequently than the general population primarily through sigmoidoscopy, which did not reach the proximal colon, highlighting the importance of colonoscopy for CRC screening. There have been strong evidences that long-term immunosuppression increases the risk of CRC after kidney transplantation. The use of some specific immunosuppressive agents like azathioprine and calcineurin inhibitor (CNI) including tacrolimus and cyclosporine were also proposed to be associated with higher incidence of post-transplant malignancy.[17,18] The patient in our report developed advanced rectal cancer (pT3N1M0) 4 years after kidney transplantation at an age of 50 years. Based on the general rule, tumors detected within the first 12 months after transplantation are correlated with pre-existed condition. Despite the fact that he had not received colonoscopic surveillance before or at the time of transplantation, we considered the diagnosed rectal cancer as the de novo malignancy. While, long-term exposure to CNI-based triple immunosuppressive agents together with an absence of colonscopic surveillance are speculated to be the 2 major hazard factors for occurrence of rectal cancer in our case.
It is generally accepted that surgery plays a role in the treatment for CRC after transplantation. Several studies found surgeries exerted a positive effect on survival of transplant patients with CRC.[14,19] Theoretically, these patients were supposed to be more susceptible to perioperative complications. However, Krysa assessed the outcome of 21 kidney transplant recipients undergoing elective colorectal surgery, and suggested the results were favorable, with no transplant rejection, low morbidity and mortality. Wisam also compared postoperative morbidity and oncologic outcome between patients with CRC in chronic immunosuppressive therapy and control groups. No significant difference was observed in wound infection, intra-abdominal abscess, anastomotic leak, urinary tract infection, or pneumonia, but lower in 3- and 5-year overall and disease-free survival. Consistently, several other reports demonstrated standard surgical treatment for CRC could be done safely in transplant recipients as long as the general condition and graft function were allowable.[22,23]
Regarding the relationship between option for timing of surgery and surgical outcomes, Lee found kidney transplant recipients undergoing colorectal resection <1 year of transplant had a higher perioperative mortality rate than those with grafts >1 year, likely due to more emergent surgeries in the early post-transplant period. Emergent colorectal surgery in kidney transplant patients was reported to have a significant risk of anastomotic leak; moreover, the overall major complication rate after emergent surgery was 81%, much higher than 19% of that after elective surgery. Therefore, emergent surgery for CRC in transplant recipients is not recommended considering its worse surgical outcomes.
Compared with conventional open surgery, laparoscopic surgery for rectal cancer possesses comparable oncologic outcomes, and remarkable short-term advantages, particularly, a lower intra-postoperative complication rate.[2,3] Immunosuppression is known to delay wound healing, increase infection risk, and lead to hemorrhage, anemia, as well as renal failure, which may be a bigger problem to open surgery. Therefore, transplant recipients seem to benefit more from the minimal access approach. Alasari evaluated short- and long-term outcomes of minimally invasive (laparoscopic and robotic) colorectal resection in 10 kidney transplant recipients with CRC between May 2007 and August 2012. Having observed a favorable result in operative time (192.5 ± 15 min), blood loss (30 ± 50 mL), and postoperative complication (2/10 minor complications), they proposed minimally invasive colorectal procedures could be considered as safe and feasible alternatives to open colorectal resection in kidney transplant patients. In our report, the patient underwent laparoscopic assisted low anterior resection and prophylactic loop transverse colostomy. We evaluate the outcome of surgery from 3 respects as follows.
3.1 Short-term outcomes
Laparoscopic resection for CRC in kidney transplant patients is technically feasible. Duration of our surgery was <2 h, and intraoperative blood loss was little. Analgesia pump was not used postoperatively. Except for the anastomotic hemorrhage, no complications occurred including wound or urinary tract infections, pneumonia, anastomotic leakage, and prolonged ileus. Passing flatus began early represented a fast recovery of intestinal function. The favorable outcome in our case provided a powerful support for the advantages of laparoscopic surgery in the treatment of transplant patients with CRC. Most concerns about the use of laparoscopic surgery in CRC focused on technical complexity and longer operative time. However, it was shown that duration of laparoscopic surgery decreased significantly with the number of interventions performed, accompanied with a significant reduction in postoperative morbidity as the surgeon gained more experience. Having performed 148 laparoscopic surgery for CRC in the high-risk elderly patients including 3 kidney and 1 heart transplant recipients from 2010 to 2012 in our institution, we accumulated abundant experience that wound complication was 3.3%, and no case of anastomotic leakage was identified. To prevent anastomotic leakage, temporary diverting ostomy has been recommended for those patients at high risks such as transplant recipients on immunosuppressive therapy, which is our routine method to protect anastomosis. The most common stoma options are the loop transverse colostomy or loop ileostomy. For our patient, his graft was located in the right lower quadrant with severe adhesions from previous surgery around, which may easily get injured during the loop ileostomy. In addition, much more fluid loss after loop ileostomy than loop transverse colostomy leads to a higher incidence of renal insufficiency. For these reasons, loop transverse colostomy seemed to be a better option in this case. Anastomotic bleeding after laparoscopic rectal surgery is not rare. The use of a circular side stapling technique in laparoscopic low anterior resection for rectal cancer proved to be safe and did not increase the risk of anastomotic complications. Possible reason for bleeding in our case was likely to be attributed to the lower location of tumor.
3.2 Long-term oncologic outcome
Laparoscopic resection for CRC in kidney transplant patients is oncologically safe. Oncologic outcome is usually measured by the extent of resection, disease-free survival and overall survival. Curative extent of resection represents radical tumor removal with negative margins, TME, and a sufficient number of lymph nodes (>12). During our surgery, resection achieved adequate range of intestinal segment and total mesorectum. In addition, 14 lymph nodes were harvested, which fulfilled the standard of radical operation. Similar outcomes could be achieved by Rivas during the laparoscopic resection for colon cancer in transplant patients, as long as the allograft was placed in the contralateral side of the colon resection. As for disease-free survival and overall survival, our patient was alive without recurrence and metastasis after 4 months of follow-up. Further follow-up is needed to evaluate his long-term survival.
3.3 Graft function and immunosuppression modification
In this case, 2 trocars were placed away from the incision scar of the transplant surgery and the position of graft. Slightly lower pneumoperitoneum pressure during the surgery was maintained to preserving an adequate allograft function. Immunosuppressive therapy was not stopped perioperatively to avoid danger of rejection, and postoperative serum creatinine levels stayed within the normal limits. In recent years, immunosuppressive medication modification including CNI-free regimens, substitution by mammalian target of rapamycin inhibitors or reduction in dosage of immunosuppression has been utilized as a treatment after cancer diagnosis in some transplant patients.[34,35] It has been speculated that the use of rapamycin, instead of CNI might reduce the recurrence of cancer in transplant patients. In a case of adenocarcinoma in the stage of III B, as in our patient, switching immunosuppression regimen from cyclosporin to rapamycin might be helpful for his survival after surgery.
Based on the favorable oncologic outcome and low operative complications, laparoscopic assisted resection might be a preferred option for transplant patients with CRC. Indeed, decisions regarding surgical approach should also take into consideration of surgeon experience, tumor stage, potential contraindications, and patient expectations.
In summary, we have reported a case of a patient after kidney transplantation, in whom laparoscopic assisted low anterior resection for advanced rectal cancer had been performed successfully. The de novo rectal cancer was speculated to associate with long-term exposure to CNI-based immunosuppressive agents and an absence of colonscopic surveillance. We believe laparoscopic surgery for CRC in transplant recipients is technically feasible and oncologically safe, which could be a preferred option of surgical procedure in the near future.
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Keywords:Copyright © 2016 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
case report; kidney transplantation; laparoscopic surgery; low anterior resection; rectal cancer