different malignant conditions of stomach

1. Malignant Neoplasms of
Stomach
Pushpa Lal Bhadel
FCPS Resident
Department of Surgery
Kathmandu Model Hospital
Moderator:
Dr. Udaya Koirala
HOD
Department of General Surgery

2. Introduction
 GLOBOCAN 2018: globally 5th most common cancer
 3rd leading cause of cancer death
 Disease of older individual affecting 7th decade of life (6th-8th)
 Outlook is generally poor, owing to the advanced stage of tumor at
presentation
 Better results in Japan; higher incidence, better screening programs
and high-quality surgical treatments
 Early gastric cancer has higher cure rates; earlier diagnosis better the
results

3. Basic anatomy
Fig. The peristaltic ejection waves of the stomach

5. lesser
curvature
short gastric
left
gastroepiploic
right
gastroepiploic
Suprapyloric
Infrapyloric
common hepatic
Left
paracardial
Right
paracardial
left gastric
artery
CELIAC

6. Splenic
hilum
Proximal & distal
splenic
Hepatoduodenal ligament
-Hepatic artery
-Portal vein
-Bile duct
Posterior of
pancreatic
head
superior mesenteric vein
superior mesenteric artery
15
middle colic
artery and vein
Mesentric
root
Transverse mesocolon

7. Epidemiology
 In US 12th most common cancer and cause of cancer death
 At first more prevalent in developed countries, but now increasingly
common in developing countries
 Among developed countries: Japan and Korea has highest incidence
 Males are at higher risk of developing cancer (60%)
 Twice common in Blacks, Hispanics as in Whites
 Younger pt.: tumors are diffuse variety and tend to be large,
aggressive and more poorly differentiated

8. High risk: 1
 Elderly males
 Smoked meat
consumption in
Gurung community
 Smoking history from
Brahmin family
1 Ghosh A, Sathian B, Ghartimagar D, Narasimhan R, Talwar OP. Epidemiologic analysis of gastric carcinoma in the western region of nepal. Nepal J
Epidemiology. 1970;1(1):26-32.

9. Risk Factors
Nutritional:
 Low fat/protein consumption
 Salter meat/fish
 High nitrate consumption
 High complex CHO consumption
Environmental:
 Poor food preparation (smoked/salted)
 Lack of refrigeration
 Poor drinking water (contaminated well
water)
 Smoking
Medical:
 Prior gastric surgery
 H. pylori infection
 Gastric atrophy and chronic gastritis
 Adenomatous polyps
Social:
 Low social class

10. Etiology
Helicobacter pylori infection:
 In 1994: labelled as potent carcinogen
 Primary mechanism involved:
oChronic inflammation leading to chronic gastritis progressing to intestinal
metaplasia and dysplasia(potent risk factor)
 Got genetic linkup with transcription factors, microsatellite instability
and others (COX-2 and Cyclin D2 overexpression, p53 mutation,
decreased p27 expression, CDX1 and CDX2 alteration)

11.  Regional variances d/t prevalence and virulence of H. pylori
 Cag a positive H. Pylori infection – associated with development of ca
stomach.
Antral mucosa
showing colonization
with Helicobacter
pylori

13. Dietary factors:
 High salted food containing higher levels of nitrates
 Main mechanism: conversion of nitrates in food to N-nitroso
compounds by help of bacteria
 Low fruit and vegetable intake
 Synergism between diet, H. pylori and carcinoma of stomach
 Decline of gastric cancer in last 70 years d/t increase in refrigeration

15. Hereditary and genetic factors:
Hereditary factors:
 Hereditary diffuse gastric cancer: mutation in E-cadherin, 80% lifetime
incidence
 Li-Fraumeni syndrome: autosomal dominant, p53 mutation
 Lynch syndrome: microsatellite instability
Genetic factors:
 Activation of oncogenes:
o c-met proto-oncogene
o k-sam and c-erbB2 oncogene
 Inactivation of tumor suppressor gene:
o P53, p16, APC, DCC

16. Pernicious anemia: achlorhydria
Polyps:
 Adenomatous polyp: frequent mucosal atypia; risk 10-20%
 Fundic gland polyps: strongly associated with PPI use
Proton pump inhibitors:
 Block the H+/K+ pump within parietal cells
 Develop hypergastrinemia
 Relationship between PPPI use, H. pylori and gastric ca development
Blood group A
Previous gastric surgery (gastroenterostomy)
Chronic gastritis (rarely)

17. Pathology
Borrmann classification(1926):
 Based on endoscopic findings
 Five types based on macroscopic appearance
Lauren classification(1965):
 Most useful clinicopathological classification
 Based on histology
Intestinal type
Diffuse type

20. Mainly divided into
 Early Gastric cancer:

21. Japanese classification
sub-mucosa
mucosa

22.  Advanced gastric
cancer:

23. WHO classification
 Adenocarcinoma [based on growth pattern]
 Papillary
 Tubular
 Mucinous
 Signet ring
 Adenosquamous cell carcinoma
 Squamous cell carcinoma
 Small cell carcinoma
 Undifferentiated carcinoma
 Unclassified carcinoma

24. Siewert-stein classification of GEJ
 Type I: adenoca of the distal
esophagus (epicenter of lesion 1-5 cm
above GEJ)
 Type II: adenoca of the cardia
(epicenter of lesion up to 1 cm above
and 2cm below GEJ)
 Type III: sub-cardial type adenoca
(epicenter of lesion 2-5 cm below GEJ)

25. Clinical features
 Main symptoms:
oEpigastric pain
oEarly satiety
oWeight loss
oDysphagia
 Advanced disease: bloating, distention, obstruction, GI bleeding and
anemia
 Paraneoplastic syndromes:
oTrousseau’s syndrome (thrombophlebitis)
oAcanthosis nigricans (hyperpigmentation of axilla/groin)
oPeripheral neuropath (rare)

26. Fig. Trousseau’s syndrome Fig. Acanthosis nigricans

27. Alarming features suggestive of gastric cancer
 New onset dyspepsia in patients >55 years of age
 Family history of UGI cancer
 Unintentional weight loss
 Upper or lower GI bleeding
 Progressive dysphagia
 Iron deficiency anemia
 Persistent vomiting
 Palpable mass
 Palpable lymph nodes
 Jaundice

28. Physical examination
 Typically normal
 Signs of weight loss
 Cervical, supraclavicular (left referred to as Virchow’s node/Troisier sign),
axillary LN enlarged (Irish nodule)
 Metastatic pleural effusion/ aspiration pneumonitis
 Abdominal mass(usually T4)/ malignant ascites
 Carcinomatosis (including Krukenberg’s tumor or ovary)
 Sister Joseph’s nodule: palpable umbilical nodule
 Rectal examination: heme positive stool and hard nodularity extraluminally
and anteriorly, indicating drop metastases or rectal shelf or Blumer in
pouch of Douglas

29. Fig. Sister Mary Joseph nodule
Fig. Blumer shelf

30. Sites involved

31. Routes of spread
 Distant spread is unusual before the disease spreads locally and
distant metastases are uncommon in the absence of LN metastases
 Diffuse type cancer spreads via submucosal and subserosal lymphatic
plexus and it penetrates gastric wall at an early stage
 Different ways of spreading:
oDirect spread
oLymphatic (both by permeation and emboli)
oBlood-borne metastases
oTransperitoneal spread

32. Diagnosis
 Suspected in patient with abdominal pain or weight loss and history
of gastric ulcer
 Histologic examination of tumor tissue is required
 Routine investigations: CBC, LFT and coagulation studies
 Barium meal x-ray
 Endoscopy and EUS: diagnostic and therapeutic
 CT: evaluation of metastasis
 PET CT: +ve patient have advanced disease
 Laparoscopy

33. Fig. A view of the
normal stomach
during endoscopy
Fig. Endoscopic view of
intestinal-type
adenocarcinoma of
the gastric cardia.
Fig. A video-gastroscope
(courtesy of Keymed (Medical
and Industrial Equipment Ltd)).
(a) The camera stack.
(b) The gastroscope, and biopsy
forceps, in the working channel.
A
B

34. Intestinal-type adenocarcinoma
consisting of an elevated mass with
heaped-up borders and central
ulceration.
Linitis plastica. The gastric
wall is markedly thickened,
and rugal folds are partially
lost
Gastric adenocarcinoma

35. Fig. Barium meal scan showing
extensive gastric carcinoma with
narrowing of lumen (arrows)
Fig. A computed tomography scan of
the abdomen, showing a gastric
cancer arising in the body of the
stomach.

36. Fig. Computed tomography/positron emission
tomography of a patient with gastric cancer. The
middle pair of images shows the primary tumor. The
two images on the left show unsuspected liver
metastases, whereas the two on the right show a left
cervical node positive for metastases.
Fig. Endoscopic ultrasound of the
stomach. Five layers can be identified in
the normal stomach. A gastric cancer is
shown invading the muscle of the gastric
wall.

37. Fig. General staging and
treatment strategy for gastric
adenocarcinoma.

38. Staging
 Advantages:
oGain information on prognosis
oDetermine extent of disease
 Most widely used AJCC TNM staging system
 Prior to 1997, nodal stage was determined by anatomical location of
nodes with respect to primary tumor rather than number of nodes
 In current staging: minimum of 15 nodes must be evaluated for
accurate staging
 Disadvantage of AJCC system: not specific for nodal location

39. Before AJCC, UICC (Union for International Cancer Control)
Defined nodal system as location of LN mets relative to
primary site
oPn1: <3 cm from primary
oPn2: >3cm from primary
R status (Hermanck 1994)
To know the status of tumor after resection in order to
determine the adequacy of surgery
oR0: microscopically margin negative resection
oR1: macroscopically absent, microscopically present
oR3: Gross residual disease

40. Japanese classification for Gastric Cancer (JCGC)
 Designed to describe the anatomical location of nodes to be removed
during gastrectomy
 Total 16 nodes considered
 Each LN further classified as LN station or echelons
 These echelons mainly reflect the likelihood of harboring metastases
 JCGC not accepted by AJCC

44. Management
 Surgical therapy
 Endoscopic resection
 Lymph node dissection
 Adjuvant and neoadjuvant therapy
 Palliative therapy and systemic therapy
 3 main treatment modalities:
o Resection (with/without adjuvant therapy)
o Neoadjuvant therapy f/b resection
o Treatment of systemic disease without resection

45. Surgical therapy
 Complete resection with a wide margin
 Cancers of distal stomach including body and antrum: distal
gastrectomy
 Possibility of recurrence in tumor bed suggests a Bilroth II
reconstruction rather than a Bilroth I
 Patient with small area of stomach proximal to the area of resection:
Roux-en-Y reconstruction
 Cancers of fundus or cardia: total gastrectomy with Roux-en-Y
esophagojejunostomy or Proximal gastrectomy

46. Based on the amount of stomach
removed:
 Total
 Near total > 90%
 Subtotal 80-90%
 Partial 65-75%
 Hemigastrectomy 50%
 Antrectomy(distal gastrectomy) 35-
50%

47. Proximal 1/3rd tumor
 Proximal esophago-gastrectomy (if R0 resection is possible)
 Total gastrectomy

48. Middle 1/3rd tumor
 Subtotal gastrectomy
 Total gastrectomy
Distal 1/3rd tumor
 Distal gastrectomy
 Hemigastrectomy
 Subtotal gastrectomy

49. Gastrectomy
Based on amount of
stomach resected
Partial
Proximal Distal
Antrectomy
Std. Partial
Sub-total
Total
Based on method of
resection
Bilroth TypeⅠ
Roux-en-Y Loop
Bilroth TypeⅡ
Radicality of
Lymphadenectomy
D0 , D1
D2
D3

50. Bilroth Type Ⅱ
Bilroth TypeⅠ Roux-en-Y loop

51. Endoscopic resection
 For early gastric cancer with limited penetration of gastric wall and no
e/o LN metastases
 General guidelines:
oTumor limited to mucosa
oNo lymphovascular invasion
oTumor smaller than 2 cm
oNo ulceration
oWell/moderately differentiated histopathology
 Major disadvantage: incomplete resection

52.  Can be performed using either EMR or EMD
 Basic principle:
o Elevate the tumor using saline injection
o Encircling the affected mucosa using a snare device
o Excise with electrocautery
 Complication: perforation and bleeding
 Proposed extended criteria:
o All intramucosal tumors without ulceration
o Differentiated mucosal tumors smaller than 3 cm regardless of ulceration status
o Tumors with limited submucosal invasion that were < 3cm and without ulceration

53. ADC

55. Lymph node dissection
 Area of ongoing debate
Extent of LN dissection
 D1:
o Peri gastric nodes (station 1-6)
o Conservative node dissection
 D2:
o D1 + left gastric, common hepatic, celiac & splenic LN (7-11)
o Extended node dissection
 D3:
o D2 + Hepato-duodenal ligament, retro pancreatic & mesenteric root (12-16)
o Super-extended lymphadenectomy
 D4:
o D3 + para-aortic and para colic LN dissection

56.  Extended lymphadenectomy (D2 to D4)
 Performed by most of Japanese surgeons
 Removal of larger number of nodes
–Greater the probability of positive nodes
–More accurately stages disease extent
–Minimize stage migration (the “Okie phenomenon”, described
by Will Rodgers)
–Explain better survival results in Asian patients
Bunt AM et al. J Clin Oncol 1995; 13:19.37
de Manzoni G et al. Br J Cancer 2002; 87:171

57.  Two main arguments against the routine use of an extended
lymphadenectomy
o Higher morbidity and mortality
o Lack of a survival benefit in most large randomized trials
 Medical Research Council (MRC) trial
o Prospective randomized trial
o 400 pts undergoing curative resection to D1 or D2
lymphadenectomy
o Conclusion
–Postoperative morbidity was significantly greater in the D2 group -
46 vs 28%, operative mortality - 13 vs 6%
–Due to splenectomy and distal pancreatectomy to achieve complete
node dissection
Cuschieri A et al. Lancet 1996; 347:995

58. Extent of nodal dissection D1 v/s D2 most
controversial area in gastric cancer management
Japanese literature
 Increased survival in patients undergoing a D2 dissection, with no increased or
minimal increase in morbidity.
Non japanese literature
 D2 lymphadenectomy, when compared with a D1 dissection, has increased surgical
morbidity, without a benefit in survival.
 One criticism of the Western data is that although randomized, the D2 group did not
differentiate between patients who had a splenectomy and those who did not.
 Subsequent subgroup analysis of the D2 without splenectomy group has shown
results similar to the Japanese studies, with increased survival and no significant
increase in morbidity.

59. Adjuvant and neoadjuvant therapy
Southwest Oncology Group (9008/INT-0116)
 RCT of 556 patients who had undergone gastrectomy alone or
combined with adjuvant 5-FU and radiotherapy
 Significant benefit for adjuvant therapy for
oOverall survival (41 vs 50%)
oRecurrence free survival (41 vs 64%)

60. Peri-operative Chemotherapy
MAGIC trial:
 RCT of 503 pts
 With stage II or higher gastric cancer that compared perioperative chemotherapy
with surgery alone.
CEF (Cisplatin, Epirubicin, 5-FU) - 3 cycles as neo-adjuvant CT
- 3 cycles as adjuvant CT
 5-yr survival, rate of local recurrence & distant metastasis were improved in CT
group
UK National Cancer Institute trial:
OEX (Oxaliplatin, Epirubicin, Capecitabine)
 Longer overall survival than with CEF and decreased incidence of thromboembolic
phenomenon by substituting oxaliplatin for cisplatin

61. Intraperitoneal Chemotherapy (IPC)
 Recurrence following curative resection is likely due to peritoneal
carcinomatosis.
 Systemic CT : blood-peritoneal barrier prevents the chemotherapeutic
agents from achieving their cytotoxic effect.
 IPC : administering high doses of chemotherapy directly to the
peritoneum whilst reducing the systemic effects.
 HIPEC (Hyperthermic Intraperitoneal Chemotherapy)
 Increased risk of neutropenia and intra-abdominal abscesses.

62. Adjuvant Radiotherapy
 INT(0116) trial demonstrates improvement in DFS and OS with
post-operative chemoradiation than with surgery alone.
 Radiotherapy is limited, due to its position near vital organs like
kidney spinal cord, pancreas, liver & bowel.
 Stomach itself is highly sensitive, tends to bleed and ulcerate with
EBRT.

63. Intraoperative radiotherapy (IORT)
 Takahashi & Abe in 1986, Japan randomized 211 patient IORT (25- 40
Gy) Vs surgery alone claims ↑ in 5-yr SR with IORT.
 Chen & Song 1994, China randomized stage 3 & 4 patients for surgery
with IORT Vs surgery alone claims ↑ in SR only in stage 3.
 Sindelar & Tepper et al in 1993 , NCI (National Cancer institute) claims no
survival benefit with IORT, but improvement in local recurrence (44% Vs
92%, p < 0.001).
 Still it needs to define the role of IORT in gastric carcinoma.

64. Palliative and systemic therapy
 Unresectable or metastatic gastric cancer: 50%
 Chemotherapy improves survival in unresectable tumors
 2006 meta-analysis showed triple therapy (5-FU, Cisplatin and
anthracycline based compound Epirubicin) superior to single/double
therapy
 Directed therapy:
o Epidermal growth factor receptor inhibitor Cetuximab
o Human epidermal growth factor receptor 2(HER2) antagonist Transtuzumab

65. Outcomes
 Overall mortality rate 3.7 deaths/100,000 people
 Overall 5-year survival <25%
 Those with curative resection
o 5-year survival: 24% to 57%
 Early gastric cancer: cure rate of 80%
 Patient with distant disease: long term survival is 4%

66. Recurrence
 High: 40-80%
 Most within first 3 years
 Locoregional failure rate: 38-45%
 Peritoneal dissemination: 54%

67. References
 Sabiston Textbook pf Surgery, 20th edition
 Schwartz’s Principles of Surgery. 10th edition
 Bailey & Love’s Short practice of Surgery, 27th edition

68. Thank you