Journal club on Intraaortocaval lymphnodes metastatic or not in CA GB. Includes 2 Indian studies from prestigious institutions.

1. PRESENTER : DR. PAYAL KAW
Impact factor : 2.58
Impact factor : 2.4

2. Introduction
Gall bladder cancer (GBC) has a very high prevalence in northern and northeastern states of Uttar
Pradesh, Bihar, Orissa, West Bengal and Assam.
Incidence rates in India - 14/100,000.
Source: National cancer Registry program: consolidated report of population-based cancer registries. 2012−2014. ICMR publication

3. Regional lymph nodes of the gallbladder
Charles H.C., Pilgrim, Val Usatoff and Peter Evans.Consideration of anatomical structures relevant to the surgical strategy for managing
gallbladder carcinoma.European Journal of Surgical Oncology, 2009-11-01, Volume 35, Issue 11, Pages 1131-1136, Copyright © 2009.
Shirai Y, Wakai T, Sakata J, Hatakeyama K. Regional lymphadenectomy for gallbladder cancer: rational extent, technical details and patient
outcomes. World J Gastroenterol. 2012;18:2775–83. https://doi.org/10.3748/wjg.v18.i22.2775

4. Introduction
Complete surgical resection of the tumor with regional lymphadenectomy is the treatment of
choice.
Traditionally Regional lymphadenectomy involves removal of 1st and 2nd echelon nodes.
Involvement of 3rd echelon nodes i.e., para-aortic or interaortocaval lymph nodes (IACLN)
is a contraindication to resection.
Shirai Y, Wakai T, Sakata J, Hatakeyama K. Regional lymphadenectomy for gallbladder cancer: rational extent, technical details and patient
outcomes. World J Gastroenterol. 2012;18:2775–83. https://doi.org/10.3748/wjg.v18.i22.2775

5. Few authors have reported that survival after resection in patients with IACLN was similar to unresectable
patients.
But in a subsequent study by the same group, it was reported that resection improved survival in patients
with microscopic IACLN metastasis.
Nishio H, Nagino M, Ebata T, et al. Aggressive surgery for stage IV gallbladder carcinoma; what are the contraindications? J Hepatobiliary Pancreat Surg. 2007;14:351–7. Murakami Y, Uemura K, Sudo T, et al.
Is para-aortic lymph node metastasis a contraindication for radical resection in biliary carcinoma? World J Surg. 2011;35:1085–93.
Kondo S, Nimura Y, Hayakawa N, et al. Regional and para-aortic lymphadenectomy in radical surgery for advanced gallbladder carcinoma. Br J Surg. 2000;87:418–22.
Miyazaki M, Itoh H, Ambiru S, et al. Radical surgery for advanced gallbladder carcinoma. Br J Surg. 1996;83:478–81.

6. AIM
To study the long-term outcomes after radical resection in GBC patients with
IACLN metastasis in the era of adjuvant and neoadjuvant chemotherapy.

7. Methodology
Retrospective study
Conducted at Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India
Time period - January 2012 to December 2019.
Data was retrieved from a prospectively maintained electronic database.

8. Inclusion Criteria
All patients taken up for radical surgery for suspected gall bladder cancer.

9. Exclusion Criteria
Locally unresectable diseases;
Metastases other than IACLN or multiple site metastases;
Regional nodes negative (N0) on final histopathology;
Benign disease on final histopathology;
Isolated IACLN metastases—but did not undergo radical surgery.

10. Suspected
CA GB
Preoperative evaluation
CECT abdomen and pelvis
CEA and CA 19–9
Jaundice : MRCP and a biliary drainage procedure as indicated
Resectable Locally advanced
18-FDG
PET scan
Incidental CA GB
Gemcitabine-based NACT for 3 cycles
CECT abdomen and pelvis
CEA/ CA 19.9
NO PET SCAN
Staging laparoscopy to rule out distant metastasis followed by exploratory laparotomy and IACLN sampling
for frozen section

11. Positive IACLN
found on table
Abandoned
Selected Cases as per surgeon’s discretion underwent Radical surgery.
• Isolated IACLN involvement,
• Good performance score,
• Not requiring multi-visceral resection or major hepatectomy.
Positive IACLN
found
preoperatively
Neoadjuvant therapy and
reassessed for surgery
after chemotherapy.
Curative surgery radical cholecystectomy which included en-bloc resection of the gall bladder with a non-
anatomical liver wedge (2-cm liver margin) or segment IVB/V resection with regional lymphadenectomy including
retropancreatic lymph nodes (station 13) and common hepatic artery node (station 8) along with all the soft tissue
around and in between hilar structures (station 12).

12. Follow-up
Every 3 months for the first 2 years and 6 months for the next 3 years.
At each visit, physical examination and tumour markers were done (CA 19–9
and CEA).
CECT whole abdomen was done every 6 months.
In case of suspicious or equivocal findings, a PET-CT was also done.
All recurrences were confirmed by histopathological examination and patients
were taken up for palliative therapy as indicated.

13. Statistical Analysis
Categorical variables expressed as frequency (percentages) – comparison done
using chi-square test.
Continuous variables expressed as mean/median - comparison done using t-test.
Overall survival (OS) and disease-free survival (DFS) were calculated using
Kaplan–Meier curves and compared using log rank test.
Univariate and multivariate analysis was done.
Factors significant in univariate analysis were used for multivariable analysis.

14. Results

18. Follow-up and Survival
Whole cohort RLN group IACLN
group
Locally unresecetable
and metastatic group
Median
DFS
(months)
13.4 18.7 13 -
Median
OS
(months)
26 27 20 14
p value –0.06
Majority (21 out of 39) of the patients developed recurrence at a distant site
followed by loco-regional site in 11 and multiple sites in 7 patients.

19. Factors Affecting Survival

20. Discussion
Positive IACLN was seen in 9.4% patients.
The median number of lymph nodes resected was 9.5 and 87.5% of the patients had 6 or more
regional lymph nodes resected, indicating adequate regional lymphadenectomy.
The median and 5-year survival was similar in node-positive patients without (14.3 months and 32%)
or with para-aortic lymph node metastasis (14.7 months and 24%).

21. Discussion
The median survival for IACLN-positive group was 20 months, which is significantly higher than the
previously reported results. One possible explanation for this can be that a large number of patients
who received adjuvant therapy in this study.
IACLN patients who received palliative therapy only (n = 14) had a median overall survival
of 11 months.
The role of adjuvant chemotherapy would have been better elucidated by comparing the patients who
have not received adjuvant chemotherapy. Such a comparison was not feasible in this study as most of
the patients in the IACLN group (15 out of 17) have received adjuvant therapy

22. This study suggested that IACLN are neither regional node nor metastatic
diseases and probably a separate entity which needs more evaluation.
IACLN involvement should not be considered an absolute contraindication to
resection in era of multimodality management.

23. Conclusion
The median OS in GBC patients with IACLN metastasis undergoing resection and
adjuvant therapy was 20 months.
The survival was inferior to the RLN group but was better than the metastatic or
unresectable patients.
Moreover, IACLN metastasis was not a significant prognostic factor for disease-free or
overall survival in the cohort of node-positive gall bladder cancer patients. So it may not
be considered a metastatic disease in the era of multimodality management.

24. Limitation
Retrospective study.
Small cohort.
Selection bias to select only good risk patients in the IACLN group.
To evaluate the role of curative resection in IACLN group, the ideal method
would have been to prospectively compare the patients undergoing resection with
patients who were not resected and received palliative chemotherapy. But due to
retrospective nature, heterogeneous study population and selection bias, such a
comparison was not possible in this study.

25. Our institution study…

26. South Asian J Cancer 2022;11(3):195–200.
 Retrospective study
 Time period : January 2013 and December 2018
 Database analyzed : patients of GBC with RLNM (interaortocaval and paraaortic) or DM on frozen section
biopsy at surgery.
 Survival in these two groups (RLNM and DM) was compared with log-rank test.

28. 50% patients in the RLNM group received palliative treatment as compared with 22% in the DM
group; the difference was statistically significant (p = 0.04).
In majority of the cases, the patients opted against chemotherapy either due to logistic issues
or the nihilism associated with disseminated disease.

30. Conclusion
Due to similar poor survival in presence of RLNM or DM, RLNM should be
considered as the equivalent of DM.
This study strengthens evidence to avoid curative surgery in patients with RLNM.
These lymph nodes should be sampled preoperatively, if suspicious on imaging, for
fine-needle aspiration cytology and at surgery, as a routine for frozen section histological
examination before initiating curative resection to avert a futile exercise.

31. Thank you