Information about Treatment of Pancreatic Neuroendocrine Neoplasms in clinical practice guidelines, management and tumors, practice changing study, Gastric NETs etc. by Dr Dhaval Mangukiya. Details of Low Anterior Resection(LAR), Arterial Supply, Venous Drainage, Ports, Position, Modified Lithotomy, Vessel Ligation, Lymph Nodes, Nerves Anatomy, Superior Hypogastric Plexus, Lateral Pelvic Nerves, Correct TME, Anastomosis etc. https://drdhavalmangukiya.com/ http://www.youtube.com/c/DrDhavalMangukiyaGastrosurgeonSurat https://gastrosurgerysurat.blogspot.com/

1. Journal Club
13/02/2016
Dr Dhaval Mangukiya

2. Update on surgical treatment of
pancreatic neuroendocrine neoplasms
Jan G D’Haese, Chiara Tosolini, Güralp O Ceyhan, Bo Kong, Irene Esposito,
Christoph W Michalski, Jörg Kleeff
World J Gastroenterol
2014 October 14; 20(38): 13893-13898
• Pancreatic Neuroendocrine Neoplasms
• G1 [mitotic count < 2/10 high power fields(HPF) and a Ki-67 index < 3 %]
• G2 (mitotic count of 2-20/10 HPF and a Ki67 index of 3%-20%)
• G3 (mitotic count > 20/10 HPF and/or a KI-67 index > 20%)
• Well differentiated PNENs are either low or intermediate grade (G1 + G2)
and are termed neuroendocrine tumors (PNETs)
• Poorly differentiated PNENs are considered high grade (G3) and are
called neuroendocrine carcinomas (PNECs)

3. • Although parenchyma-preserving techniques
have slightly increased morbidities (76%) and
pancreatic fistula (69%) compared to standard
resections (58% and 42%), the patients do
clearly benefit in terms of pancreatic endo-
and exocrine function
• Cherif R , Gaujoux S, Couvelard A, Dokmak S, Vuillerme MP, Ruszniewski P, Belghiti J,
Sauvanet A. Parenchyma- sparing resections for pancreatic neuroendocrine tumors. J
Gastrointest Surg 2012; 16: 2045-2055

4. • a margin-positive resection in locally ad-
vanced PNETs seems to offer a similar overall
survival compared to margin-negative
resections
• Pomianowska E, Gladhaug IP, Grzyb K, Røsok BI, Edwin B, Bergestuen DS, Mathisen O.
Survival following resection of pancreatic endocrine tumors: importance of R-status and the
WHO and TNM classification systems. Scand J Gastroenterol 2010; 45: 971-979

5. • In patients with PNEN liver metastasis,
debulking of > 90% of the macroscopically
visible tumor mass - if technically feasible -
seems to extend overall survival
• Falconi M, Bartsch DK, Eriksson B, Klöppel G, Lopes JM, O’Connor JM, Salazar R, Taal BG, Vullierme MP, O’Toole D. ENETS Consensus
Guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: well differentiated
pancreatic nonfunctioning tumors. Neuroendocrinology 2012; 95:120-134
• Mayo SC, de Jong MC, Pulitano C, Clary BM, Reddy SK, Gamblin TC, Celinksi SA, Kooby DA, Staley CA, Stokes JB, Chu CK, Ferrero A,
Schulick RD, Choti MA, Mentha G, Strub J, Bauer TW, Adams RB, Aldrighetti L, Capussotti L, Pawlik TM. Surgical management of hepatic
neuroendocrine tumor metastasis: results from an international multi institutional analysis. Ann Surg Oncol 2010; 17: 3129-3136
• Cusati D, Zhang L, Harmsen WS, Hu A, Farnell MB, Nagorney DM, Donohue JH, Que FG, Reid Lombardo KM, Kendrick ML. Metastatic
nonfunctioning pancreatic neuroendocrine carcinoma to liver: surgical treatment and outcomes. J Am Coll Surg 2012; 215: 117-124;
discussion 124-125

8. Rindi G, Arnold R, Bosman FT et al. Nomenclature and classification of
neuroendocrine neoplasms of the digestive system. In Bosman FT, Hruban RH,
Theise ND (eds), WHO Classification of Tumours of the Digestive System. Lyon:
IARC 2010; 13–14.

9. The European Neuroendocrine Tumor Society has
proposed a tumor–node–metastasis staging and
grading system for various types of GEP-NETs
Pape UF, Jann H, Muller-Nordhorn J et al. Prognostic relevance of a novel TNM
classification system for upper gastroenteropancreatic neuroendocrine tumors.
Cancer 2008; 113: 256–265.

17. Eight tables were created to define treatment and
workup recommendations
(1) Pathology
(2) NETs of the thorax
(3) Gastric NETs
(4)Pancreatic NETs
(5) NETs of the small bowel and cecum (‘‘midgut’’)
(6) NETs of the colon and rectum (‘‘hindgut’’)
(7)Pheochromocytoma, paraganglioma, and medullary
thyroid cancer
(8) High-grade neuroendocrine carcinoma

18. Practice changing study
•The RAD001 in Advanced Neuroendocrine Tumors-3 (RADIANT-3) study
• published in 2011
•randomized phase 3 study evaluating the efficacy of everolimus in advanced
pancreatic NETs
•international multisite study
•410 patients
•with low- or intermediate-grade, progressive, advanced pancreatic NETs were
randomized to receive everolimus, 10 mg oral daily, or placebo.
•The median progression-free survival (PFS) was 11.0 months with everolimus
compared with 4.6 months with placebo (hazard ratio, 0.35; 95% confidence
interval, 0.27Y0.45; P G 0.001)
•The response rate was 5% in the everolimus arm compared with 2% in the
placebo arm. The median overall survival has not been reached.
Yao JC, Shah MH, Ito T, et al. Everolimus for
advanced pancreatic neuroendocrine tumors.
N Engl J Med. 2011;364(6):514Y523.

19. Phase 3 study
• published in 2011
• 171 patients
• with advanced, well-differentiated, progressive pancreatic NETs
• randomized to receive sunitinib, 37.5 mg orally daily, or placebo.9
• The study was discontinued prematurely after an independent data
and safety monitoring committee observed more serious adverse
events and deaths in the placebo arm and a difference in PFS that
favored the sunitinib arm during an unplanned interim analysis
• The median PFS was 11.4 months in the sunitinib arm compared
with 5.5 months in the placebo arm (hazard ratio, 0.42; 95%
confidence interval, 0.26Y0.66; P G 0.001)
• Response rates in the sunitinib and placebo arms were 9.3% and
0%, respectively
Raymond E, Dahan L, Raoul JL, et al. Sunitinib
malate for the treatment of pancreatic
neuroendocrine tumors. N Engl J Med.
2011;364(6):501Y513

20. Klimstra DS, Modlin IR, Coppola D, et al. The
pathologic classification of neuroendocrine
tumors: a review of nomenclature, grading,
and staging systems. Pancreas.
2010;39(6):707Y712.
Klimstra DS, Modlin IR, Adsay NV, et al.
Pathology reporting of neuroendocrine
tumors: application of the Delphic consensus
process to the development of a minimum
pathology data set. Am J Surg Pathol.
2010;34(3):300Y313

24. Gastric NETs
3 distinct groups
•those associated with chronic atrophic
gastritis/ pernicious anemia (type 1; 70%–80%)
•those associated with Zollinger-Ellison
syndrome (ZES) with multiple endocrine
neoplasia type I (MEN I) (type 2; 5%)
•sporadic NETs of the stomach (type 3; 15%–
20%)

26. Gastric NET

28. Panc NET

29. Panc NET

30. Panc NET

31. Panc NET

32. Neuroendocrine Tumors of the
Jejunum, Ileum, Appendix, and Cecum

33. Advanced DiseaseVOncologic Control Generally for NETs, lines of therapy have not
been established. When multiple options are listed, order of listing does not imply
order of therapy.
Surgical resection should be considered if most (approximately 90%) of gross disease
can be resected safely. Clinical trials should always be considered.
Neuroendocrine Tumors of the
Jejunum, Ileum, Appendix, and Cecum

34. Neuroendocrine Tumors of the Distal
Colon and Rectum

35. Treatment Algorithm (ESMO)