Response to letter to the editor on emergency surgery influences oncological outcome in small intestinal neuroendocrine tumors

Dear Editor,

We wish to thank Ahmad and colleagues for their interest in our article. ¹ In their letter, the authors raised four constructive points, which we believe may enrich the discussion about challenges in managing small intestinal neuroendocrine tumors (siNETs) in emergency situations.

First, we agree that the retrospective design of our study poses limitations due to a potential selection bias. Our analysis included adjustments for various known and established confounding factors to reduce baseline bias. However, the retrospective study design cannot eliminate all potential confounders. Unfortunately, prospective randomized trials are difficult to implement in emergency care as emergency cases require immediate treatment and cannot be planned. Therefore, we would like to highlight the need and encourage the realization of future multicenter trials. For example, prospectively collected registry data may help to investigate and differentiate the impact of emergency surgery in siNET on oncological outcome. Especially in rare diseases such as siNET, registries will enable larger amounts of data with higher standardization and quality for statistical matching methods such as propensity score matching.

In their second point, the authors address pre- and perioperative factors as possible influencing factors on outcome including delay to emergency surgery. We recognize that preoperative delays and perioperative management play an essential role in peri- and postoperative outcomes and the development of complications. Patients in our emergency surgery group underwent highly urgent or emergency operations within a maximum of 24 h after presentation with acute symptoms. However, the exact time span from initial presentation in the emergency department to surgery was not analyzed, nor was the perioperative intensive care that patients received. Nonetheless, 30-day morbidity and 30-day mortality did not differ between the two groups, suggesting that both groups received similar perioperative care.

We very much appreciate Ahmad and colleagues’ suggestion to consider the effect of tumor biology and aggressiveness on oncological outcome. They refer to Manguso et al. ² who postulated that siNET patients with tumor recurrence present more often with lymphovascular and perineural invasion. Indeed, we have previously shown that lymphatic, microvascular, and perineural invasion is characteristics of more advanced tumors and is associated with worse prognosis in siNETs. ³ We encourage complete histopathological assessment of siNET specimen and consideration for adjuvant treatment and follow-up decisions after both elective and emergency surgeries.

Finally, the authors propose the implementation of enhanced recovery after surgery (ERAS) protocols for siNET patients. While ERAS after emergency laparotomy has been shown to reduce postoperative length of hospital stay, 30-day morbidity and mortality, no effect on long-term oncological outcomes has been demonstrated in other cancer entities.^4–6

In conclusion, addressing these questions in multicenter studies and large registries will contribute to a more comprehensive and global understanding of siNET treatment and improve patient care further on.