Isolated Liver and Limb Perfusion in Preclinical and Clinical Studies: gene therapy and biochemotherapeutic strategies

__Abstract__ The liver is the major site of metastatic spread of primary colorectal cancer, whereas 3% of all patients with colorectal cancer will develop resectable liver metastases. If a resection with curative intent is done, a five year survival rate of 25-30% has been demonstrated in a large number of studies. The natural history of untreated patients with comparable liver involvement shows a five year survival rate of 0-3% (8). As noted above, the majority of patients with evidence of liver metastases are irresectable, because of extra-hepatic disease or excessive liver involvement. There is no standard treatment for unresectable hepatic metastases confined to the liver, so novel treatment modalities have to be developed. In order to achieve a better control of intrahepatic disease and to reduce systemic toxicity of the applied therapy, locoregional therapies have been developed. These therapies include hepatic arterial embolization (9), intratumoral injections of ethanol, acetic acid, biological agents, stereotactic or intra-arterial radiotherapy, intralesional laser therapy, cryotherapy, radiofrequency ablation and regional infusion or perfusion of chemotherapeutic drugs

Fifty tumor necrosis factor-based isolated limb perfusions for limb salvage in patients older than 75 years with limb-threatening soft tissue sarcomas and other extremity tumors

BACKGROUND: Isolated limb perfusion (ILP) with tumor necrosis factor (TNF) and melphalan is highly effective in treating limb-threatening soft tissue sarcoma (STS) and other bulky tumors. Because of fear of TNF-associated toxicity, ILP with TNF is not offered to older patients in some cancer centers, although especially in older patients, every attempt to avoid an amputation that may end their independence must be considered. METHODS: Out of 306 TNF-based ILPs, 50 ILPs were performed for limb salvage in 43 patients >75 years old (range, 75-91 years): 29 STS and 14 melanoma patients. RESULTS: In the STS patients, a response rate of 76% and a limb-salvage rate of 76% were achieved; in the melanoma patients, a 100% response rate and a 93% limb-salvage rate were achieved. Local toxicity was mild. The three postoperative deaths that occurred in the total series of 306 TNF-based ILPs in Rotterdam (75 years old after leakage-free perfusions and were not related to TNF but to extremely high-risk profiles in these three patients. CONCLUSIONS: Older patients should not be withheld a TNF-based ILP for limb salvage, because the procedure is safe and highly effective in these patients

A low incidence of perineal hernia when using a biological mesh after extralevator abdominoperineal excision with or without pelvic exenteration or distal sacral resection in locally advanced rectal cancer patients

Background Extralevator abdominoperineal excision (ELAPE), abdominoperineal excision (APE) or pelvic exenteration (PE) with or without sacral resection (SR) for locally advanced rectal cancer leaves a significant defect in the pelvic floor. At first, this defect was closed primarily. To prevent perineal hernias, the use of a biological mesh to restore the pelvic floor has been increasing. The aim of this study, was to evaluate the outcome of the use of a biological mesh after ELAPE, APE or PE with/without SR. Methods A retrospective study was conducted on patients who had ELAPE, APE or PE with/without SR with a biological mesh (Permacol™) for pelvic reconstruction in rectal cancer in our center between January 2012 and April 2015. The endpoints were the incidence of perineal herniation and wound healing complications. Results Data of 35 consecutive patients [22 men, 13 women; mean age 62 years (range 31–77 years)] were reviewed. Median follow-up was 24 months (range 0.4–64 months). Perineal hernia was reported in 3 patients (8.6%), and was asymptomatic in 2 of them. The perineal wound healed within 3 months in 37.1% (n = 13), within 6 months in 51.4% (n = 18) and within 1 year in 62.9% (n = 22). In 17.1% (n = 6), the wound healed after 1 year. It was not possible to confirm perineal wound healing in the remaining 7 patients (20.0%) due to death or loss to follow-up. Wound dehiscence was reported in 18 patients (51.4%), 9 of whom needed vacuum-assisted closure therapy, surgical closure or a flap reconstruction. Conclusions Closure of the perineal wound after (EL)APE with a biological mesh is associated with a low incidence of perineal hernia. Wound healing complications in this high-risk group of patients are comparable to those reported in the literature

Primary Leiomyosarcoma of the Adrenal Gland

We report a rare case of a primary leiomyosarcoma of the adrenal gland. A 73-year-old woman presented with an inferior vena cava syndrome. MR imaging was suggestive of a large tumour originating from the right adrenal gland. Angiography revealed a tumour vascularised by the right adrenal artery. At explorative laparotomy a tumour of 27 cm in diameter was found which was completely fixed to the liver; the tumour was therefore considered unresectable. As a consequence of the mechanical problems caused by this large tumour, the patient died 3 weeks after the operation. Autopsy revealed no distant metastases or other primary tumour site

Quality of Life, Sexual Functioning, and Physical Functioning Following Perineal Reconstruction with the Lotus Petal Flap

BACKGROUND: Lotus petal flaps (LPF) may be used for the reconstruction of extralevator abdominoperineal defects that cannot be closed primarily. Limited data are available on how perineal reconstruction with the LPF impacts on patients' quality of life (QoL), sexual functioning, and physical functioning. METHODS: A cross-sectional study was performed following perineal reconstruction with the LPF. The QoL of patients having undergone LPF reconstruction was compared with a control group in which perineal defects were closed without flaps. Sexual and physical functioning (presence of perineal herniation and range of motion [ROM] of the hip joints) could only be evaluated in the LPF group. Psychometrically sound questionnaires were used. Physical functioning was evaluated subjectively with binary questions and objectively by physical examination. RESULTS: Of the 23 patients asked to participate, 15 (65%) completed the questionnaires and 11 (47%) underwent physical examination. In the control group, 16 patients were included. There were no significant differences in QoL between the LPF and control groups. Within the LPF group, 33% of patients were sexually active postoperatively compared with 87% preoperatively. No perineal herniation was found. The ROM of the hip joints was bilaterally smaller compared with the generally accepted values. CONCLUSIONS: Conclusions should be made with care given the small sample size. Despite a supposedly larger resection area in the LPF group, QoL was comparable in both groups. Nonetheless, reconstruction seemed to affect sexual function and physical function, not hampering overall satisfaction

Re-Irradiation in Patients with Recurrent Rectal Cancer is Safe and Feasible

BACKGROUND: There is no consensus yet for the best treatment regimen in patients with recurrent rectal cancer (RRC). This study aims to evaluate toxicity and oncological outcomes after re-irradiation in patients with RRC in our center. Clinical (cCR) and pathological complete response (pCR) rates and radicality were also studied. METHODS: Between January 2010 and December 2018, 61 locally advanced RRC patients were treated and analyzed retrospectively. Patients received radiotherapy at a dose of 30.0-30.6 Gy (reCRT) or 50.0-50.4 Gy chemoradiotherapy (CRT) in cases of no prior irradiation because of low-risk primary rectal cancer. In both groups, patients received capecitabine concomitantly. RESULTS: In total, 60 patients received the prescribed neoadjuvant (chemo)radiotherapy followed by surgery, 35 patients (58.3%) in the reRCT group and 25 patients (41.7%) in the long-course CRT group. There were no significant differences in overall survival (p = 0.82), disease-free survival (p = 0.63), and local recurrence-free survival (p = 0.17) between the groups. Patients in the long-course CRT group reported more skin toxicity after radiotherapy (p = 0.040). No differences were observed in late toxicity. In the long-course CRT group, a significantly higher cCR rate was observed (p = 0.029); however, there was no difference in the pCR rate (p = 0.66). CONCLUSIONS: The treatment of RRC patients with re-irradiation is comparable to treatment with long-course CRT regarding toxicity and oncological outcomes. In the reCRT group, less cCR was observed, although there was no difference in pCR. The findings in this study suggest that it is safe and feasible to re-irradiate RRC patients