Kidney autotransplantation after nephrectomy and work bench surgery as an ultimate approach to nephron-sparing surgery.

BACKGROUND: Kidney autotransplantation (KAT) is the ultimate approach for nephron-sparing surgery. It is a rarely used method in renal tumor surgery today as minimal invasive and open techniques for nephron-sparing surgery improve constantly. In this publication, the complication rate and the long-term functional and oncological outcome at a single center are analyzed. METHODS: A prospectively constructed database of patients with renal tumors who underwent renal surgery was retrospectively analyzed to identify patients with KAT and describe surgical and oncological outcomes and to obtain long-term follow-up. Data collection included detailed surgical technique, complications (Clavian-Dindo), and hospital stay, as well as functional and oncological outcome and long-term follow-up. RESULTS: Between 1976 and 2013, 12 patients (median age 50.5 years) underwent KAT for highly complex renal masses: in five cases for complex renal cell carcinoma (RCC), five cases for complex upper urinary tract carcinoma (UTUC), one case for a renal metastasis, and one case for nephroblastoma. The nephrectomy or nephron-ureterectomy was performed open via a flank or transabdominal. The median surgical time was 360 min (range 270-490 min). Intraoperatively, six cases required blood transfusions (50%). Six patients (50%) developed significant postoperative complications (Clavian-Dindo > 2). In two patients, intermittent hemodialysis for delayed graft function (16.6%) was needed, and in six cases (50%), additional blood transfusions postoperatively were necessary. At discharge from hospital, all patients had functioning grafts. The median hospital stay was 29.5 days (range 18-35). At follow-up (median follow-up of 83.5 ± 40.7 months), six patients had died (50%)-all with functioning grafts (free from hemodialysis). In five cases, recurrence of primary tumor or metastatic disease was recorded. In four cases, the recurrent carcinoma could be resected; in detail, UTUC in three cases and one partial nephrectomy of the autotransplanted kidney was performed. One patient suffered from bone and lung metastasis. Two patients died finally tumor-related. Five patients (41.6%) are presently alive, without evidence of tumor relapse. One patient developed terminal renal failure requiring hemodialysis 105 months after autotransplantation. One additional patient was lost to follow-up; after 69 months, this patient had a functioning kidney and no evidence of disease-recurrence at the last follow-up. A cumulative number of 1424 months without hemodialysis was gained for these 12 patients. In the literature to date, most KAT are performed in benign disease, with minor but frequent complication. Here, we report the largest series of KAT for malignant kidney tumors. The complication rates are similar, compared to the recently reported series for benign indications with an improved graft survival rate. Since KAT requires a complex and challenging surgical approach, it should be performed by experienced kidney transplant surgeons. CONCLUSION: In very complex cases involving renal tumors and multi-morbidity, patients should be counseled well before KAT is considered. At the same time, KAT should not be abandoned in these very rare cases, especially when a nephron-sparing approach is otherwise not feasible. KAT can maintain renal function and quality of life and extend expectancy of life.

Robust method for isolation of tumor infiltrating lymphocytes with a high vital cell yield from small samples of renal cell carcinomas by a new collagenase-free mechanical procedure.

BACKGROUND: Tumor-infiltrating lymphocytes (TIL) play an important role in the pathogenesis of renal cell carcinoma. Characterization of TIL requires efficient isolation procedures, especially in early stage disease when the tumor is of small in size. Conventional methods for isolating TIL are based on enzymatic tissue digestion, most frequently with collagenase. Collagenase isolation is limited by poor cell recovery, altered expression of cell-surface molecules, and impaired TIL-functionality. To overcome these limitations, we developed and optimized conditions for a robust collagenase-free mechanical procedure for improved isolation of TIL from renal cell carcinoma samples. METHODS: TIL from tumor samples and T cells from peripheral blood were collected from 12 patients undergoing partial or radical nephrectomy. Samples were subjected to an enzymatic reference protocol and to a newly established mechanical isolation protocol. After viability staining, TIL-subpopulations were quantified and phenotyped by immunohistochemistry and flow-cytometric analysis, and were compared to characteristics of peripheral blood T cells. As a marker for TIL-functionality, T-cell cytokine induction was quantified after polyclonal stimulation. RESULTS: We show that this new technique is rapid and allows identification of CD4 and CD8 T-cell subpopulations including CD4, CD8, and regulatory T cells expressing anergy markers such as programmed death-1 (PD-1) or B- and T-lymphocyte attenuator. When compared to the reference protocol involving collagenase digestion, the yield of TIL after mechanical isolation was higher and the expression of cell-surface markers was better preserved. Moreover, although antitumor activity was not assessed, mechanically isolated TIL are at least equally functional as T cells from peripheral blood, as polyclonal stimulation induced cytokines such as interferon-γ and tumor necrosis factor-α in both TIL and T cells from peripheral blood. CONCLUSION: The mechanical procedure may be applied as a robust and rapid alternative to collagenase digestion for isolation of high amounts of phenotypically and functionally intact TIL from fresh tumor samples.

Successful outcome of kidney transplantation from a HBV-DNA positive donor into recipients with cleared HBV-infection using a pre-emptive therapy approach.

BACKGROUND: Donor-derived transmission of hepatitis B virus (HBV) may cause serious complications after transplantation. To date, transplantation from HBV-infected donors to HBV-infected recipients seems feasible, although this is recommended with prophylaxis with specific drugs and antibodies only, whereas pre-emptive strategies are rarely used. OBJECTIVES: Here, we assessed the success of transplantation of kidneys from a chronically HBV-infected deceased donor (HBs-antigen positive, anti-HBc positive, HBV-DNA positive) to two recipients with cleared HBV-infection (HBs-antigen negative, anti-HBc positive, anti-HBs >100 IU/l) where risk-assessment was performed using a pre-emptive approach in the absence of prophylaxis. STUDY DESIGN: Pre-emptive monitoring included assessment for evidence of infection by analysis of liver enzymes, viral load, and humoral and cellular immunity against HBV and CMV. RESULTS: In line with undetectable HBV-load, HBc-specific T-cell frequencies remained stable (mean 0.46+/-0.10% and 0.06+/-0.03%), whereas CMV-specific T-cell frequencies in one patient showed dynamic changes that coincided with CMV-viremia. Likewise, HBV-specific antibody titres were stable. Liver enzymes demonstrated absence of liver-cell injury and renal function was good (creatinine 1.8 and 0.8 mg/dl at last follow-up after 39 and 38 months, respectively). CONCLUSIONS: When combined with careful HBV-monitoring, kidneys from HBV-infected donors may be transplanted into HBV-immune recipients without the need for specific prophylaxis.

Indocyanine green R15 ratio depends directly on liver perfusion flow rate.

BACKGROUND: Indocyanine green (ICG) is a synthetic dye that is widely used to evaluate liver function in critically ill patients, before liver resection or after liver transplantation. Controversy still exists about the impact exerted on the ICG ratio after 15 min (ICG R15) by differences in liver perfusion rates, hyperdynamic states, or patient cardiac output. We studied the role of different liver perfusion rates on the ICG R15 ratio in a normothermic extracorporeal liver perfusion system under standardized conditions. METHODS: Livers from landrace pigs (40-50 kg) were perfused with fresh porcine blood. Normal and high perfusion rates were defined as 1 ml and 2 ml/g liver/min, respectively. Perfusate pressure of the hepatic artery and portal vein were within the physiological range in both groups. According to manufacturer's instructions, 0.5 mg of ICG per kg was applied and the ICG R15 was calculated. Calculations were based on fifteen experiments in five liver perfusions. Bile production, liver function and histology were analyzed. RESULTS: All perfusions were characterized by physiological bile production, lack of hepatocellular damage and normal histology. ICG R15 ratio in group I, perfused with 1 ml/g liver, was 18.9 +/- 6%. In group II, perfused with 2 ml/g liver, the ICG R15 ratio was 7.2 +/- 3%. The difference between groups 1 and 2 was statistically significant (p < 0.05). CONCLUSION: ICG R15 is reliable within one group at defined perfusion rates. Doubled perfusion rates contribute to higher ICG clearance. For clinical application we would like to suggest considering cardiac output of the patient for interpretation of ICG ratios.