Metastases to the pancreas represent less than 2% of all pancreatic resections; the most common primary malignancy found in this organ is clear renal cell carcinoma. Isolated pancreatic metastases from other organs are exceptional and anecdotal, as evidenced by the published series. Therefore, I will limit my comments to this topic.

Dissemination typically occurs through the hematogenous route and rarely through the lymphatic system. There is no evidence of dissemination from the pancreatic lesion, so a resection of the lesion with clear margins and without lymphadenectomy is sufficient and oncologically appropriate¹.

The paper by Brossuti et al. in this issue of the journal raises several interesting points that merit discussion².

The absence of extrapancreatic disease is crucial because the goal is to leave the patient free of disease through a high-risk surgery that is not free of complications. A recent multicenter Spanish study has shown improvement in survival after pancreatic resection even after a second surgery due to recurrence of pancreatic metastasis³. Currently, tyrosine kinase inhibitors or immunotherapy (pembrolizumab, nivolumab, ipilimumab) offer promising results in patients with extrapancreatic disease or who are not candidates for surgery⁴.

Another factor to consider is that these metastases involve several pancreatic regions in almost 40% of the cases⁵. The biology of these tumors permits the use of conservative techniques. However, the presence of multiple lesions may challenge this approach. Local recurrence of disease following pancreatectomy is likely to be related to this issue⁶. It can be difficult to prove whether it is a persistent or a new metastasis since the late presentation of these lesions (up to more than 25 years)⁷ allows for both possibilities.

To determine the number and location of lesions as accurately as possible, it is important to have highquality imaging tests. The use of computed tomography scanners with more than 16 rows of detectors with dedicated pancreatic protocol is usually effective to detect contrast enhancement during the arterial phase. Magnetic resonance imaging using a 1.5 Tesla scanner or greater with diffusion-weighted imaging to visualize the mobility of water molecules can also be useful. Unfortunately, clear cell renal cell carcinoma metastases are usually not avid for radiotracers in metabolic imaging tests such as PET scan. Endoscopic ultrasound is a highly sensitive technique that allows for biopsies to be taken in doubtful cases. However, it is operator dependent and its images do not provide adequate preoperative planning. Finally, in this context, intraoperative ultrasound could help to detect lesions identified or undetected in preoperative tests⁸.

Surgery can be a classic anatomic resection such as a cephalic pancreaticoduodenectomy, or a distal pancreatectomy, ideally without splenectomy (Kimura technique). Other procedures include extended surgery as total or subtotal pancreaticoduodenectomy, atypical resections, parenchyma-sparing resections (enucleations, central resections, non-anatomic distal resections or uncinatectomies), or combined procedures.

Minimally invasive surgery is feasible for these lesions as they typically do not involve vascular structures and do not require wide surgical margins, resection of other organs, or extensive lymphadenectomy. The complexity of left pancreatectomies or enucleations is not a limitation. Performing a surgery that requires pancreaticojejunostomy, such as cephalic pancreaticoduodenectomy and central pancreatectomy, can be challenging due to the complexity of the reconstruction, soft pancreatic tissue, and thin pancreatic ducts. The correct preparation of the anastomosis is the highest point of the learning curve, which correlates with the highest morbidity and mortality rates in these surgeries.

In our experience, we have performed all surgeries using laparoscopy since 2013. Our patients undergo computed tomography scan, magnetic resonance imaging and bone scintigraphy.

Like the authors of the paper published in this issue², we also had no postoperative mortality. To date, we have not observed recurrence in any of our patients, some of whom have been followed for more than 10 years.

In summary, the preferred treatment for metastases of clear cell renal cell carcinoma in the pancreas is surgical resection, even in cases of second recurrence. This approach has been shown to result in excellent long-term survival rates and low operative mortality. Preoperative or intraoperative identification of the number and location of lesions is essential for planning resection, which in many cases can be done conservatively and minimally invasively by trained teams.