Letter to the Editor
October 2025
Limitations of Using Tumour Grade for Preoperative Lymph Node Metastasis Prediction in GEP-NENs: A Letter to the Editor
By
Mesut Tez
Affiliations
- Department of Surgery, University of Health Sciences, Ankara City Hospital, Cankaya, Ankara, Turkiye
doi: 10.29271/jcpsp.2025.10.1359
Sir,
I read with great interest the article by Ocakli et al. on predictors of lymph node (LN) metastasis in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs).1 This study identifies tumour size, grade, and location as independent risk factors (p = 0.017, 0.008, 0.002). However, the conclusion that these parameters can guide preoperative treatment decisions is misleading. Tumour grade, determined postoperatively through Ki-67 and mitotic rate, cannot inform preoperative planning. Thus, despite statistical significance, its clinical utility remains limited.
Moreover, the focus of the study on pathological and inflam- matory markers (e.g., NLR, LMR) overlooks preoperative radiological tools such as computed tomography (CT) and positron emission tomography (PET) scans, which are critical for the prediction of LN metastasis. Dromain et al.2 reported CT sensitivity of 70-90% for LN detection in GEP-NENs, while Hofman et al.3 found that 68Ga-DOTATATE PET/CT achieved a sensitivity of 90-95%. Geijer et al.4 confirmed a combined CT-PET area under the curve (AUC) of 0.92, highlighting their efficacy. The absence of these parameters restricts the study’s preoperative applicability.
I suggest that future research must integrate the radiological data to enhance preoperative LN prediction, complementing the identified factors for better surgical planning and prognosis in GEP-NENs.
COMPETING INTEREST:
The author declared no conflict of interest.
AUTHOR’S CONTRIBUTION:
MT: Contribution to the conception and design of the work and acquisition, analysis, and interpretation of the data.
The author approved the final version of the manuscript to be published.
REFERENCES
- Ocakli S, Ceylan C, Canlikarakaya F, Goktas A, Kankoc R, Terzioglu SG. Can lymph node metastasis be predicted in gastroenteropancreatic neuroendocrine neoplasms? J Coll Physicians Surg Pak 2025; 35(5):601-6. doi: 10.29271/ jcpsp.2025.05.601.
- Dromain C, Deandreis D, Scoazec JY, Goere D, Ducreux M, Baudin E, et al. Imaging of neuroendocrine tumors of the pancreas. Diagn Interv Imaging 2016; 97(12):1241-57. doi: 10.1016/j.diii.2016.07.012.
- Hofman MS, Lau WF, Hicks RJ. Somatostatin receptor imaging with 68Ga DOTATATE PET/CT: Clinical utility, normal patterns, pearls, and pitfalls in interpretation. Radiographics 2015; 35(2):500-16. doi: 10.1148/rg. 352140164.
- Geijer H, Breimer LH. Somatostatin receptor PET/CT in neuroendocrine tumours: Update on systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 2013; 40(11):1770-80. doi: 10.1007/s00259-013-2482-z.
Authors Reply Section
By
Serhat Ocakli
Affiliations
- Dr. Serhat Ocakli, Department of General Surgery, Ankara Pursaklar State Hospital, Ankara, Turkiye
AUTHOR'S REPLY:
Sir,
We thank the author of the letter for his comment on our article “Can lymph node metastasis be predicted in gastroentero- pancreatic neuroendocrine neoplasias?”.1
While some of the concerns may have merit, we believe they do not entirely align with the primary objective of the study.
It is certainly true that being able to predict whether lymph node metastasis is present or likely to occur is crucial, not only for surgical planning but also for guiding medical treatment and informing prognosis.
The author concurs that CT and PET/CT scans play a significant role in lymph node staging. However, the present study did not aim to develop a preoperative prediction model or compare the parameters investigated with existing models. Consequently, radiological data were not included in this analysis. Also, to clarify, the letter references a study by Hofman et al.2 that reports a sensitivity of 90-95%, which pertains to its accuracy in detecting the primary tumour, not specifically lymph node metastasis.
The letter also suggests that tumour grade, a parameter determined postoperatively, cannot be utilised in the pre- operative setting. While this study does not exclusively focus on a pre- operative prediction model, tumour grade can neverthless be relevant even in the preoperative context. Appendiceal neuroendocrine neoplasms (NENs) are often diagnosed incidentally during or after appendectomies.3,4 In such cases, tumour grade can be used to determine the need for further surgical or medical treatment. Moreover, grade can also be available preoperatively in cases where biopsies are performed before surgery.
The author remains confident that this study contributes valuable insights into the factors influencing lymph node meta- stasis in GEP-NENs, and the author(s) believe it serves as a foundation for future research.
REFERENCES
- Ocakli S, Ceylan C, Canlikarakaya F, Goktas A, Kankoc R, Terzioglu SG. Can lymph node metastasis be predicted in gastroenteropancreatic neuroendocrine neoplasias? J Coll Physicians Surg Pak 2025; 35(5):601-5. doi: 10.29271/ jcpsp.2025.05.601.
- Hofman MS, Lau WF, Hicks RJ. Somatostatin receptor imaging with 68Ga DOTATATE PET/CT: Clinical utility, normal patterns, pearls, and pitfalls in interpretation. Radiographics 2015; 35(2):500-16. doi: 10.1148/rg.352140164.
- Marmor S, Portschy PR, Tuttle TM, Virnig BA. The rise in appendiceal cancer incidence: 2000-2009. J Gastrointest Surg 2015; 19(4):743-50. doi: 10.1007/s11605-014-2726-7.
- Teng TZJ, Thong XR, Lau KY, Balasubramaniam S, Shelat VG. Acute appendicitis-advances and controversies. World J Gastrointest Surg 2021; 13(11):1293-314. doi: 10.4240/ wjgs.v13.i11.1293.