1. Welcome to TODAYS CME

2. Neuroendocrine Tumor(carcinoid) of stomach : A case report and update
Dr. Md. Rashedul Islam
MD(Thesis Part Student)
Department of Medical Oncology
National Institute of Cancer Research & Hospital

4. Chief complains:
1.Upper abdominal pain for 0ne and half year.
2.Anorexia and nausea for one year
3.Weight loss for 6 months
On examination
Mildly anemic (Hb%-9 gm/dl)
Epigastric tenderness without clinically palpable mass
USG of whole abdomen-normal(10/7/2017)
Endoscopy report-Peptic ulcer disease (17/7 /2017).

5. She was treated conservatively by local physician
She was treated conservatively by local physician. symptomatic improvement lasted for 6 months, then she again visited with same complains and evaluated properly.
Upper GI endoscopy- Gastropathy (07/9/2018)
2nd endoscopy revealed -Polypoid,ulcerated& mobile growth seen at the lower end of oesophagus involving the cardiac part of stomach (24/10/2018) and biopsy was taken

6. Digital barium swallow of esophagus: no organic lesion
Digital barium swallow of esophagus: no organic lesion. (out side the NICRH) Spiral CT scan of whole abdomen-Thickening of the wall of lower end of esophagus .post contrast scan revealed enhancement of the thickened wall. (16/10/2018) HPR: -suggestive of poorly differentiated adenocarcinoma(27/10/2018)

7. After proper investigations and evaluation she was diagnosed as a case of Ca- esophagus involving the cardiac part of stomach and admitted at NIDCH for surgical management. Oesophagogastostomy with feeding jejunostomy was done 13/12/2018. HPR :- CARCINOID TUMOR with lymphnode metastasis (pT3N3Mx) (15/12/2018)

8. Patient was advised for IHC but due to financial issues, patient denied, so we advised for slide review. Slide Review:- Small cell neuroendocrine carcinoma (17/02/19)

9. Patient admitted at medical Oncology department of NICRH for further management. We evaluated the patient properly and advised for palliative systemic chemotherapy with Cisplatin and Etoposide.

13. Neuroendocrine Tumor
Neuroendocrine tumors (NET) of the gastrointestinal tract (carcinoid tumors) are uncommon
The incidence of gastrointestinal (GI) NETs is 6.2 per 100,000
Small bowel NETs (midgut carcinoids) are more common than both foregut and hindgut & also can remain small (<1 cm) and still metastasize to regional lymph nodes and liver
Risk factors for the development of midgut carcinoid tumors include age , male sex, increased body mass index, and menopausal hormone therapy

14. These tumors are indolent and patients survive a long time
The prevalence is quite high, making them the second most prevalent GI tract tumor, second only to colon cancer
Some are clinically silent and have been detected only at autopsy (incidence 8%)
In 1907, Oberndorfer first used the term carcinoid, meaning “cancer-like,” to describe a rare ileal tumor with less malignant behavior than the large bowel carcinomas

15. They are derived from the diffuse neuroendocrine system that is composed of peptide- and amine-producing cells that may secrete different hormones depending on the site of origin
There is currently no single system for staging for NETs at all anatomic site
Critical factors in NET pathology include key features are
Embryologic site of origin (foregut, midgut, hindgut),
Functional status (defined as hormone secretion associated with symptoms of hormone excess), and
Grade

16. The recent 2010 World Health Organization pathology classification relies mainly on proliferation rates as measured by Ki67 antibody staining or mitotic index.
Low-grade tumors (grade 1) are the most common and have a mitotic index of fewer than two mitoses/10 high power field (hpf) and a Ki67 <3%
Intermediate-grade tumors (grade 2) have a mitotic index of 2 to 20 mitoses/10 hpf and a Ki67 3% to 20%
High-grade tumors (grade 3) have a mitotic index >20 mitoses/10 hpf and a Ki67 >20%.

17. General Diagnostic Principle
Diagnosis of GI and pulmonary NET is often incidental
Patient with functional tumor can present with symptoms of hormone excess
Elevated serum hormone markers can be a surrogate marker of symptoms of hormone excess or tumor growth
Chromogranin A levels are elevated in approximately 80% of patients with GI NETs
Urine 5-hydroxyindoleacetic acid (5-HIAA), the primary metabolite of serotonin, is elevated in carcinoid syndrome.

18. Abnormal levels (>5 mg/24 hours) of 5-HIAA are diagnostic of carcinoid syndrome
Less common NETs may also be identified by the specific hormone and syndrome that is produced
Imaging play an important role in diagnostic evaluation of GI and pulmonary NET like CT scan, MRI, SRS
Ga-68 DOTATATE is a newer somatostatin-based scintrigraphy that is thought to be more sensitive than octreoscan

19. PET-CT with FDG has poor sensitivity for well differentiated NETs
¹³¹I-meta-iodobenzylguanidine scan in patients with small intestine is useful in patients whose tumors secrete catecholamines
CT-enteroclysis is a newer imaging modality designed to image tumors of the small bowel

20. Staging and Grading

22. Management

23. Oncological principles of management in patients with NETs depend on many factors and require a multidisciplinary approach
Treatment often requires individualization
Surgery is the only definitive cure but is rarely possible in patients with metastatic disease, and other approaches are therefore necessary
Anti-proliferative treatment decisions depend on:
Origin of the primary tumour
Histological differentiation
Tumour grade (or proliferative capacity)

24. Evaluation and treatment of Local gastric NETs

25. Resect primary Gastrinoma
Primary gastrinoma not resected
Metastatic disease
Endoscopic resection of prominent tumor
EGD
Gastric biopsy
Serum Gastrin level
Consider gastric Pᴴ
Hypergastrinemic/type 1
(atropic gastritis, or High gastric Pᴴ
Hypergastrinemic/type2
Zollinger-Ellison syndrome,no atropic gastritis,low gastric Pᴴ
Vit B12 level
EUS as clinically indicated
Abdominal multiphasic CT/MRI
Somatostatin receptor based imaging(68 Ga-dotatate or SRS
EUS as clinically indicated
Other biochemical evaluation as clinically indicaed
Consider testing for inherited genetic syndromes
Normal gastrin/ type 3
EUS
Somatostatin receptor based Imaging
Radical resection with lymphadenectomy Or
Endoscopic surgical wedge resection

26. Consider endoscopic Surveillence and endoscopic resection of prominent tumor
and/or
Consider Octreotide or Lanreotide
And
Manage gastric hypersecretion with high dose PPI
Primary gastrinoma not resected

27. Management of Locoregional advance disease And/or distant metastasis of GI tract NETs

28. Multiphasic CT/MRI of abdomen and pelvis
Chest CT as clinically indicated
Somatostatin based Imaging or Somatostatin receptor scintigraphy
Biochemical evaluation as clinically indicated
If complete resection possible
Resect primary+ metastasis
Refer for surveillance
Asymptomatic low tumor burden
Observe with imaging or
Octreotide/Lanreotide
Locally symptomatic primary tumor
Consider resection of primary tumor
Clinically significant tumor burden Or
Alternative frontline therapy
Every mo

29. Multiphasic CT/MRI of abdomen and pelvis
Every mo
Chest CT as clinically indicated
Clinically significant tumor burden
If disease progression on Octreotide or Lanreotide
If disease progression
Everolimus(10mg/d) or
PRRT with 177 lu-dotatate(if somatostatin receptor positive and progression on octreotide) Or
Hepatic directed therapy for hepatic predominant disease
Arterial embolization or
Hepatic chemoembolization or
Radioembolization or
Cytoreductive therapy
Interferon alpha-2B
Cytotoxic chemotherapy If no other option is feasible

30. Systemic therapy for well differentiated NETs
Streptozocin based
Combination chemotherapy with either 5 FU or Doxorubicin
Molecular targeted therapy
Either with Everolimus Or
Sunitinib
Temozolamide based
Oxaliplatin based
Combination chemotherapy with capcetabine
Combination chemotherapy with FOLFOX/ CapOx

31. Systemic therapy for poorly differentiated NETs
Cisplatin based
Combination chemotherapy with Etoposide
Irinotecan based
Combination with leucovorin and 5 FU(FOLFIRI)
Temozolamide based
Oxaliplatin based
Combination chemotherapy with capcetabine
Combination chemotherapy with FOLFOX/ CapOx