This document provides an overview and recent updates on the treatment of esophageal and gastric cancers. It discusses testing and biomarkers that can guide targeted therapies, such as MSI, HER2, and NTRK testing. It also reviews staging assessments including endoscopy, EUS, PET/CT, and liquid biopsy. Principles of surgery are covered, including acceptable approaches, conduits, lymph node dissections, and minimally invasive options. Palliative endoscopic treatments and nutrition management are also summarized.

1. Recent update on
Oesophageal and primary gastric Malignancy
Presented By:
Dr.Emran Murshed
Phase B Resident, Surgical oncology ,BSMMU

2. Recent update on
Oesophageal malignancy

4. Microsatellite Instability (MSI) or Mismatch
Repair (MMR) Testing
 Testing for MSI by polymerase chain reaction (PCR)/NGS or
MMR by IHC should be considered on locally advanced,
recurrent, or metastatic esophageal and EGJ cancers in patients
who are candidates for treatment with programmed cell death
protein 1 (PD-1) inhibitors.
 Patients with MSI-H or dMMR tumors should be referred to a
genetics counselor for further assessment in the appropriate
clinical context.

5. PD-L1 testing may be considered on locally advanced, recurrent,
or metastatic esophageal and EGJ cancers in patients who are
candidates for treatment with PD-1 inhibitors.
PD-L1 Testing

6. KEYNOTE-158 (ClinicalTrials.gov identifier NCT02628067) was a
phase 2 trial that enrolled patients with treatment-refractory,
noncolorectal MSI-H/dMMR cancers to receive
pembrolizumab. Of the 24 patients with oesophageal cancer,
there were 11 responses (including 4 complete responses), and
the median PFS was 11 months.

7. Next-Generation Sequencing (NGS)
Comprehensive genomic profiling via a validated NGS assay
performed in a CLIA (clinical lab improvement amendments )-
approved laboratory may be used for the identification of HER2
amplification, MSI status, MMR deficiency, TMB(high tumor
mutational burden ), NTRK(neurotropic tyrosine receptor kinase)
gene fusions, RET gene fusions, and BRAF V600E mutations.

8. The FDA granted approval for the use of select TRK inhibitors for NTRK gene fusion-
positive solid tumors, and selpercatinib for RET gene fusion-positive tumors.
Dabrafenib/trametinib has been approved for tumors with BRAF V600E mutations.
Trastuzumab is based on testing for HER2 overexpression. Pembrolizumab/nivolumab
are based on testing for MSI by PCR or NGS/MMR by IHC, PD-L1 immunohistochemical
expression, or high tumor mutational burden (TMB) by NGS.

9. Recent randomized trials have demonstrated the value of
anti-PD1 and anti-PDL1 in the treatment of advanced or
metastatic EC and as adjuvant treatment after R0 resection .

10. Liquid Biopsy
The genomic alterations of solid cancers may be identified by
evaluating circulating tumor DNA (ctDNA) in the blood, hence a
form of “liquid biopsy.’’
For patients who have metastatic or advanced
esophageal/esophagogastric cancers who may be unable to
undergo a traditional biopsy or for disease progression
monitoring, testing using a validated NGS-based comprehensive
genomic profiling assay performed in a CLIA-approved laboratory
may be considered. A negative result should be interpreted with
caution, as this does not exclude the presence of tumor mutations
or amplifications

11. PRINCIPLES OF ENDOSCOPIC STAGING AND
THERAPY
The location of the tumor relative to the teeth and EGJ, the
length of the tumor, the extent of circumferential involvement,
and the degree of obstruction should be carefully recorded to
assist with treatment planning.

12. Multiple biopsies, six to eight, using standard size endoscopy forceps
should be performed to provide sufficient material for histologic and
molecular interpretation.Larger forceps are recommended during
surveillance endoscopy of Barrett esophagus for the detection of
dysplasia.

13.  EUS performed prior to any treatment is important in the initial
clinical staging of neoplastic disease. Careful attention to
ultrasound images provides evidence of depth of tumor invasion
(T designation), presence of abnormal or enlarged lymph nodes
likely to harbor cancer (N designation), and occasionally signs of
distant spread, such as lesions in surrounding organs (M
designation).

14. The goal of endoscopic therapy [by endoscopic mucosal resection
(EMR), endoscopic submucosal dissection (ESD), and/or ablation] is
the complete removal or eradication of early-stage disease (pTis,
pT1a, selected superficial pT1b without LVI) and pre-neoplastic
tissue (Barrett esophagus)

15.  Laparoscopy may be useful in select patients in detecting
radiographically occult metastatic disease, especially in patients
with Siewert II and III tumors.

16. Positive peritoneal cytology (performed in the absence of visible
peritoneal implants) is associated with poor prognosis and is
defined as M1 disease. In patients with advanced tumors, clinical
T3 or N+ disease should be considered for laparoscopic staging with
peritoneal washings.

17. Siewert Classification
Siewert tumor type should be assessed in all patients with adenocarcinomas involving the EGJ
Siewert Type I: adenocarcinoma of the lower esophagus (often associated with Barrett
esophagus) with the epicenter located within 1 cm to 5 cm above the anatomic EGJ.
 Siewert Type II: true carcinoma of the cardia at the EGJ, with the tumor epicenter within 1
cm above and 2 cm below the EGJ.
Siewert Type III: subcardial carcinoma with the tumor epicenter between 2 cm and 5 cm
below the EGJ, which infiltrates the EGJ and lower esophagus from below.
The treatment of Siewert types I and II is as described in the NCCN Guidelines for Esophageal
and Esophagogastric Junction Cancers.
Siewert type III lesions are considered gastric cancers, and thus should be treated as
described in the NCCN Guidelines for Gastric Cancer. In some cases additional esophageal
resection may be needed in order to obtain adequate margins.

19. Esophageal resection should be considered for all patients who
are physiologically fit with resectable esophageal cancer.
T1a tumors, defined as tumors involving the mucosa but not invading the
submucosa, may be considered for EMR + ablation or esophagectomy in experienced
centers.
Tumors in the submucosa (T1b) or deeper may be treated with esophagectomy.
 T1–T3 tumors are resectable even with regional nodal metastases (N+), although
bulky; multi-station lymphatic involvement is a relative contraindication to surgery, to
be considered in conjunction with age and performance status.
T4a tumors with involvement of pericardium, pleura, or diaphragm are resectable.
Resectable esophageal or EGJ cancer

20. Unresectable esophageal cancer
 cT4b tumors with involvement of the heart, great vessels, trachea, or
adjacent organs including liver, pancreas, lung, and spleen are
unresectable.
 Most patients with multi-station, bulky lymphadenopathy should be
considered unresectable, although lymph node involvement should be
considered in conjunction with other factors, including age,
performance status, and response to therapy.
Patients with EGJ and supraclavicular lymph node involvement should
be considered unresectable.
 Patients with distant (including nonregional lymph nodes) metastases
(stage IV) are unresectable.

21. PRINCIPLES OF SURGERY
The type of esophageal resection is dictated by the location of
the tumor, the available choices for conduit, as well as by the
surgeon's experience and preference and the patient's
preference.
 In patients who are unable to swallow well enough to maintain
nutrition during induction therapy, esophageal dilatation or a
feeding jejunostomy tube (J-tube) are preferred to a gastrostomy
(which may compromise the integrity of gastric conduit for
reconstruction).

22. Acceptable operative approaches for resectable
esophageal or EGJ cancer
 Ivor Lewis esophagogastrectomy (laparotomy + right thoracotomy)
 McKeown esophagogastrectomy (right thoracotomy + laparotomy + cervical
anastomosis)
 Minimally invasive Ivor Lewis esophagogastrectomy (laparoscopy + limited right
thoracotomy)
 Minimally invasive McKeown esophagogastrectomy (right thoracoscopy +
limited laparotomy/laparoscopy + cervical anastomosis)
Transhiatal esophagogastrectomy (laparotomy + cervical anastomosis)
 Robotic minimally invasive esophagogastrectomy
 Left transthoracic or thoracoabdominal approaches with anastomosis in chest
or neck

23. The Robot-Assisted Minimally Invasive Thoracolaparoscopic
Esophagectomy Versus Open Transthoracic Esophagectomy for
Resectable Esophageal Cancer (ROBOT) randomized controlled trial
compared the open route with the totally minimally invasive robot-
assisted route with manual cervical anastomosis .
A decrease in global and pulmonary complications was
demonstrated in the robot-assisted group.

25. Acceptable conduits
 Gastric (preferred)
 Colon
 Jejunum
Acceptable lymph node dissections
Standard
Extended (en-bloc)
In patients undergoing esophagectomy without induction
chemoradiation, at least 15 lymph nodes should be removed and
assessed to achieve adequate nodal staging. The optimum number of
nodes after preoperative chemoradiation is unknown, although similar
lymph node resection is recommended.

26. One stage- 35 cm and below
Two stage- 25- 35 cm
Three stage- less than 25 cm
Surgical approach

27. Results: Vagal-sparing esophagectomy preserved the function of the vagi, as evident by an
increase in gastric acid output, a rise in serum pancreatic polypeptide following sham feeding,
and preservation of normal postoperative gastric emptying in 70% of the patients. After vagal-
sparing esophagectomy, patients were free of dumping and diarrhea and were analogous to
normal subjects in meal capacity but had a slight reduction in the speed of eating.
Conclusions: Vagal-sparing esophagectomy preserves gastric secretory, motor, and reservoir
function. Postoperatively, patients have normal alimentation, bowel regulation, and no weight
loss. It is an ideal procedure for patients with end-stage benign disease, Barrett's esophagus
with high-grade dysplasia, or esophageal carcinoma limited to the lamina propria.

28. Treatment of Symptoms or palliation
• Esophageal dilation can be performed with the use of dilating balloons or bougies to
temporarily relieve obstruction from tumors, or treatment-related strictures. Caution should
be exercised to avoid overdilation, to minimize the risk of perforation.
• Long-term palliation of dysphagia can be achieved with endoscopic tumor ablation by
Nd:YAG laser, PDT and cryoablation, or endoscopic and radiographic-assisted insertion of
expandable metal or plastic stents.
• Long-term palliation of anorexia, dysphagia, or malnutrition may be achieved with
endoscopic or radiographic-assisted placement of feeding gastrostomy or jejunostomy. The
placement of a gastrostomy in the preoperative setting may compromise the gastric
vasculature, thereby interfering with the creation of the gastric conduit in the
reconstruction during esophagectomy and should be avoided.

30. Recent update on
Carcinoma
stomach

32. Criteria of Unresectability for Cure
• Locoregionally advanced
 Disease infiltration of the root of the mesentery or para-aortic lymph node highly
suspicious on imaging or confirmed by biopsy
 Invasion or encasement of major vascular structures (excluding the splenic vessels)
• Distant metastasis or peritoneal seeding (including positive peritoneal cytology)

35. PRINCIPLES OF SURGERY
• Tis or T1 tumors limited to mucosa (T1a) may be candidates for EMR
or ESD if they meet appropriate criteria (in experienced centers).
• T1b–T3: Adequate gastric resection to achieve negative microscopic
margins along with lymphadenectomy.
Distal gastrectomy
Subtotal gastrectomy
Total gastrectomy
• T4b tumors require en bloc resection of involved structures.

36. N1 lymph nodes are defined as the
perigastric lymph nodes in stations
#1, 3, 5 (lesser curvature) and
stations #2, 4, 6 (greater curvature),
N2 lymph nodes are defined as left
gastric (#7), common hepatic artery (#8),
celiac artery (#9), splenic artery (#11),
and splenic hilum lymph nodes (#10)
• Gastric resection should include the regional lymphatics—perigastric lymph nodes (D1) and
those along the named vessels of the celiac axis (D2), with a goal of examining at least 16 or
greater lymph nodes

37. The Extent of Lymph Node Dissection in Advanced Gastric Cancer
The current standard of care for curative surgery for gastric cancer is
for D2 gastrectomy. Lymph node dissection is performed to
determine the extent of lymph node involvement with metastases
and to improve outcome from surgery. The benefit of lymph node
dissection beyond D2 gastrectomy for advanced gastric remains
controversial.

38. Japanese surgeons now suggest that D2 gastrectomy plus para-
aortic lymph node dissection after neoadjuvant chemotherapy
may improve outcome in advanced gastric cancer with positive
lymph nodes or extensive metastasis of N2 lymph nodes .

39. Aim of lymphadenectomy in gastric cancer
The AJCC staging guidelines for accurate staging, suggesting that at least 16 regional
lymph nodes be removed and assessed pathologically.
1. Adequate therapy
2. Extended lymphadenectomy have superior results in terms of decrease
recurrence.
3. Extended lymph node dissection, including celiac and hepatic artery
lymph nodes, was associated with improved survival in patients with
gastric cancer.

40. • Routine splenectomy is not indicated unless the spleen is involved or extensive hilar
adenopathy is noted.
• Minimally invasive surgical approaches may be considered for selected cases based on
the following criteria:
The surgeon has experience performing laparoscopic or robotic foregut procedures and
has experience in lymphadenectomy.
Both early and locally advanced gastric cancers can be considered for laparoscopic or
robotic gastrectomy given evidence that supports equivalent oncologic outcomes from
the East and West.
Minimally invasive approaches are generally not recommended for T4b or N2 bulky
gastric cancer

41. Laparoscopic Surgery for Advanced Gastric Cancer
Laparoscopic surgery for the treatment of early gastric cancer is performed routinely
worldwide and is recommended as a standard treatment in Japan and South Korea. The
results from two prospective trials (KLASS 01 and JCOG 0703) have further confirmed the
safety and feasibility of laparoscopic surgery for early gastric cancer . There have been
further studies that have supported the use of laparoscopy-assisted gastrectomy for
advanced gastric cancer, but this type of surgery requires training and experience .
However, the use of minimally invasive techniques remains controversial for the treatment
of advanced-stage tumors, mainly because of concerns about the adequacy of surgical
resection and the ability to adequately perform surgical lymph node dissection .

42.  Hyperthermic intraperitoneal chemotherapy (HIPEC) or laparoscopic HIPEC may be a
therapeutic alternative for carefully selected stage IV patients in the setting of ongoing
clinical trials and is under further clinical investigation.

44. • Hyperthermic intraperitoneal chemotherapy (HIPEC) or
laparoscopic HIPEC may be a therapeutic alternative for carefully
selected stage IV patients in the setting of ongoing clinical trials and
is under further clinical investigation.

45. REFERENCES