A 57- year-old male, suffering from chronic liver disease arising from non-alcoholic steatohepatitis (NASH), with features of portal hypertension manifesting in the form of gastric varices and hypersplenism, presented at Medanta - Gurugram with an incidentally detected renal mass lesion in the right kidney. The lesion, caught during a routine annual dynamic CT scan, was approximately 2.6cm in size, predominantly exophytic, closely abutting the midpolar calyx and had imaging characteristics of a renal cell carcinoma. In view of multiple co-morbidities, including chronic liver disease (CLD) and very low platelet count (<20,000) as a manifestation of hypersplenism secondary to the portal hypertension, the patient was considered to be at high-risk for surgery. He was advised to consult an interventional radiologist to explore a minimally invasive management strategy with the intention to treat the disease with minimal morbidity in the form of post-procedure recovery and hospital stay. Upon reviewing the patient and his reports, the interventional radiologist found that the lesion was less than 3cm in size, making the patient eligible for thermal ablation with radiofrequency ablation (RFA). However, due to the proximity of vital structures – the mid polar calyx in the vicinity of tentative ablative field – we advised to place a ureteric catheter in the upper ureter so that a continuous flush could be set in place to dissipate the heat in the calyx and prevent or minimise the thermal trauma. However, as RFA antennae constitutes a thicker needle (14G), there is always a risk of bleeding associated with it. This is an important factor to consider, especially in such patients who consistently have a very low platelet count – a component responsible for initiating plug formation essential for formation of clots. To minimise risk, the patient was advised large transfusion of platelets ahead of the procedure. The patient rejected this option owing to personal bias. Despite detailed counselling, he chose to get a trans-arterial embolization done – a procedure that was offered as a relatively safer option in the absence of transfusion. Trans-arterial embolization would limit the disease by cutting off the tumour’s blood supply by selectively entering the blood vessels feeding the tumour through a small access from the femoral artery in the groin. During follow-up after a month, the patient showed good response with no enhancing component. However, after 6 months, a follow-up scan, showed a 7mmx5mm enhancing nodule along the lateral aspect of the embolized lesion, suggestive of recurrence. The patient was again advised ablation as the primary curative strategy. However, this time, instead of thermal, we offered the newly launched technique of irreversible electroporation (IRE). IRE is a newer tissue ablation technique in which micro-to-millisecond electrical pulses are delivered to undesired tissues to produce cell necrosis through irreversible cell membrane permeabilization. This then generates a local and systemic immune response to the tumour cells and destroys it. Crucially, this leaves the collagen- and elastin-rich extracellular matrix unaffected, aiding the regeneration of the treated/ablated tissues. This unique property of IRE spares vital structures, such as blood vessels and the renal collecting system, allowing them to regain function. IRE has an edge over thermal ablation in tumours like the one our patient had – the kind that lie very close to the renal calyces or pelvis wherein heat from thermal ablation may cause trauma to these structures. Moreover, the efficacy of thermal ablation also drops due to proximity of vessels leading to the “heat sink effect” that causes heat dissipation because of the flowing blood. These phenomena are not seen with IRE. The procedure requires placement of 3-4, 19g antennae around the lesion. These antennae are relatively thinner compared to RFA / microwave antennae (MWA). By the virtue of being thinner, they are associated with lower incidence of bleeding – a big limiting factor in our case. As the ablation zone is much more controlled with IRE, and because of its unique property of sparing blood vessels and connective tissue despite the proximity to the calyces, placement of the extremely cumbersome uretric catheter was also not necessary in this case. The patient was again sensitised towards the need for pre-procedure platelet transfusion to make the procedure safer. Despite the risk being considerably lower than the previously offered RFA treatment, the patient consented. The procedure was performed under general anaesthesia and 4 parallel antennae were placed around the lesion under CT guidance to attain a tumour-free margin of 0.5cm. Eighty pulses were given through these antennae combinations in sync with the patient’s heartbeat. Post-procedure, on-table contrast CT showed no evidence of enhancement in the tumour and no evidence of bleeding was noted post procedure. The patient’s recovery in the hospital was uneventful and comfortable. The patient was discharged on Day 2 of the procedure. He has recovered well and has reported significant improvement in his quality of life. In conclusion, IRE surely has emerged as a great ablative strategy for patients with multiple co-morbidities, not fit for surgery. It has an edge over thermal ablative options for tumours proximal to vital structures and vessels; IRE gives similar oncological outcomes with fewer clinically significant adverse effects. Irreversible Electroporation (IRE) IRE, also known as Nanoknife, is a novel, non-thermal ablative therapy used to treat solid cancers. This treatment destroys cancer cells using electricity. It is applied by placing two or more electrodes in and around the tumour. Electrodes can be inserted percutaneously under image guidance, laparoscopically, or using an open approach following a midline laparotomy. Multiple short pulses of high-voltage electrical current are applied between electrode pairs. The application of an electric field across cell membranes is thought to initiate the formation of nanopores in the lipid bilayer of the tumour cell’s plasma membrane, leading to homeostatic disruption and cell death. Unlike other ablative techniques, such as MWA and RFA, IRE is thought to exert its cytotoxic effect without relying on thermal injury, sparing blood vessels and bile ducts. Furthermore, IRE is not susceptible to the “heat sink” effect, a phenomenon where blood flowing in vessels adjacent to the cancer being treated prevents the area of ablation from reaching temperatures effective for cellular damage, leaving viable tumour cells, which is a concern with ablative methods reliant on thermal injury.