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Lateral lymph nodes in
rectal cancer
Pushpa Lal Bhadel
Department of Surgical oncology
BCH
Surgical anatomy
 Lymph nodes draining the rectum below
the peritoneal reflection:
o Along superior rectal artery & inferior
mesenteric artery into para-aortic nodes
o Along middle and inferior rectal artery into
obturator, internal iliac and external iliac
nodes
 TNM:
o Involvement of internal iliac LN: regional
disease
o External iliac nodes : metastatic disease
 Japanese classification: all lateral LN as
regional nodes Figure 1. Lymphatic drainage of the rectum highlighting the lateral LN
Fig. Lymphatic drainage system and LLNs in low rectal cancer
Incidence
 Pre-operative LLN involvement (Based on MRI)
Dharmarajan S et al 57 %
Ishibe et al 19.9%
MERCURY study group 11.7%
Ishihara et al 8.1%
 Incidence based on post-operative histopathology
Akiyoshi et al 40.3%
Moriya Y 23%
Ueno et at 17.3%
Quadros et al 17%
Significance of LLN metastasis
 Synchronous LLN disease in locally advanced tumors: 10-25% 1
 According to Japanese society- incidence of LLN in tumors below peritoneal
reflection: 27% 2
1 Wei M, Wu Q, Fan C, Li Y, Chen X, et al. (2016) Lateral pelvic lymph node dissection after neoadjuvant chemo-radiation for preoperative enlarged lateral nodes in advanced low rectal cancer: study
protocol for a randomized controlled trial. Trials17: 561
2 Watanabe T, Muro K, Ajioka Y, Hashiguchi Y, Ito Y, et al. (2018) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol 23: 1-34
Diagnosis of LN mets in rectal cancer
 MRI as primary staging tool:1
o Sensitivity: 55% and specificity: 78%
 Morphologic criteria: irregular border, heterogeneous signal intensity and round
shape in combination with size: 2
o Sensitivity (36%-85%) and specificity (95%-100%)
 Cutoff for LPLN size varies from 4 mm to 12 mm 3
 Diffusion weighted MR-imaging (DWI-MRI) for LLNs: LLN have high DWI signal 4
1 Lahaye MJ, Engelen SME, Nelemans PJ, et al. Imaging for predicting the risk factors—the circumferential resection margin and nodal disease—of local recurrence in rectal cancer: a meta-analysis. Seminars in
Ultrasound, CT and MRI. 2005;26(4):259-268
2 Kim JH, Beets GL, Kim MJ, Kessels AGH, Beets-Tan RGH. High-resolution MR imaging for nodal staging in rectal cancer: are there any criteria in addition to the size? European Journal of Radiology.
2004;52(1):78-83
4 Ogawa S, Itabashi M, Hirosawa T, Hashimoto T, Bamba Y, Okamoto T. Diagnosis of lateral pelvic lymph node metastasis of T1 lower rectal cancer using diffusion-weighted magnetic resonance imaging: A case
report with lateral pelvic lymph node dissection of lower rectal cancer. Molecular and Clinical Oncology. 2016;4(5):817-820
3 Kawai K, Shiratori H, Hata K, Nozawa H, Tanaka T, Nishikawa T, Murono K, Ishihara S. Optimal Size Criteria for Lateral Lymph Node Dissection After Neoadjuvant Chemoradiotherapy for Rectal Cancer. Dis
Colon Rectum. 2021;64:274–283
Managing the LLNs
Advantage of LLND: 1
 Decrease the intra-pelvic recurrence by 50%
 Improve the 5-year survival by 8%-9%
Western concept Japanese concept
Regional nodes Internal iliac nodes Internal, external and
common iliac and obturator
nodes
Metastatic nodes Common iliac, external iliac and
obturator nodes
Not applicable
Management nCRT with RT boost to involved nodes LLN dissection
1 Watanabe T, Muro K, Ajioka Y, Hashiguchi Y, Ito Y, et al. (2018) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol 23: 1-34
AJCC: combination of TME with radiation therapy (RT) and
Chemoradiation therapy (CRT) – standard treatment for advanced
lower rectal cancer
 Preoperative RT and CRT: partial local control effect
 Reduce local recurrence to ≤10%
NCCN: recommends TME after CRT with concomitant fluorouracil
for cStage II-III rectal cancer
 No specific description for LPLD
 Extended dissection of LNs located outside resection region to which LPLNs
correspond is indicated for resectable LNs with suspected mets
ESMO: preoperative RT and CRT recommended depending on the
risk
 LPLN mets is classified as advanced: preoperative CRT f/b surgery (TME +
extensive surgery) OR preoperative short-course RT + Folinic acid _
Fluorouracil + oxaliplatin (FOLFOX) regimen
Reassessment and preoperative treatment
 Restaging to be performed after neoadjuvant treatment
 Discussed during MDT meeting
 Surgical decisions based on response of LLNs
oCurrent evidence infers: Internal iliac LLNs >4mm (SA) and obturator LLNs >6
mm (SA) after CRT benefit from LLND
 Pt. with LLNs with complete clinical remission of both primary tumor
and LLNs after chemoradiation: careful assessment with MRI and
frequent f/u
Fig. Modified lithotomy (Lloyd-Davies) position
Complications
Intraoperative complications:
oLong operative time
oLarge volume blood loss
oInjury to ureter, gonadal vessels
Post-operative complications:
oUrinary and sexual dysfunction
LPLD and CRT for cLPLN(-) cases
 JCOG0212 randomized controlled trial :
o Outcomes of prophylactic LPLD in cLPLN(-) cases without suspected metastasis
o Examined TME alone compared to TME + LPLD
o 5-year relapse-free survival (RFS) was 73.4% in the LPLD group and 73.3% in the ME
group
o 5-year OS was 92.6% in the LPLD group and 90.2% in the ME group
o 5-year local recurrence-free rates were 87.7% in the LPLD group and 82.4% in the
ME group
o Local recurrence rate 26 cases (7.4%) vs 44 cases (12.6%) was significantly lower in
the LPLD group
o LPLD is effective for reduction of recurrence in this lateral pelvis region
LPLD and CRT for cLPLN(+) cases
 Kim et al:
o Local recurrence in 29 (7.9%) of 366 cases treated with TME alone without LPLD
after preoperative CRT.
o Recurrence in the lateral pelvis was found in 24 (82.7%) of these cases
o Local recurrence rates according to pretreatment LPLN size were 2.3%, 12.5% and
68.8% in cases with sizes < 5 mm, 5-10 mm and > 10 mm, showing that this rate was
high in cases with LPLN enlargement
 Akiyoshi et al: 127 CRT treated cases
o Performed TME alone in 89 cases without suspected LPLN metastasis before
treatment (the TME group) and TME + LPLD in 38 suspected cases (LPLD group)
o LPLN metastasis: 25 (65.8%) cases in the LPLD group, but local recurrence: 7 (7.9%)
cases in the TME group and 1 (2.6%) case in the LPLD group.
o Lateral pelvic recurrence was found in only 3 cases (3.4%) in the TME group and
none in the LPLD group
Yang et al:
oFound no difference in overall local recurrence in cases
with suspected LPLN metastasis
oIncidence of local recurrence in the lateral pelvic region
was significantly lower in the TME + CRT + LPLD group
than in the TME + CRT group
Conclusion
 Although the role of prophylactic LLND is unclear, it may have a role in
clinically positive lateral nodes and those that are resistant to CRT
 The major question that remains still unanswered is whether routine
TME + LLND post CRT in stage II and stage III rectal cancer needs to be
advocated globally based on the oriental experience
 The results from ongoing RCTs might provide an answer
Reference
 Bailey short practice of surgery, 27th edition
 Sabiston textbook of surgery, 20th edition
 Internet sources
Thank You

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Lateral lymph nodes in rectal cancer.pptx

  • 1. Lateral lymph nodes in rectal cancer Pushpa Lal Bhadel Department of Surgical oncology BCH
  • 2. Surgical anatomy  Lymph nodes draining the rectum below the peritoneal reflection: o Along superior rectal artery & inferior mesenteric artery into para-aortic nodes o Along middle and inferior rectal artery into obturator, internal iliac and external iliac nodes  TNM: o Involvement of internal iliac LN: regional disease o External iliac nodes : metastatic disease  Japanese classification: all lateral LN as regional nodes Figure 1. Lymphatic drainage of the rectum highlighting the lateral LN
  • 3. Fig. Lymphatic drainage system and LLNs in low rectal cancer
  • 4. Incidence  Pre-operative LLN involvement (Based on MRI) Dharmarajan S et al 57 % Ishibe et al 19.9% MERCURY study group 11.7% Ishihara et al 8.1%  Incidence based on post-operative histopathology Akiyoshi et al 40.3% Moriya Y 23% Ueno et at 17.3% Quadros et al 17% Significance of LLN metastasis  Synchronous LLN disease in locally advanced tumors: 10-25% 1  According to Japanese society- incidence of LLN in tumors below peritoneal reflection: 27% 2 1 Wei M, Wu Q, Fan C, Li Y, Chen X, et al. (2016) Lateral pelvic lymph node dissection after neoadjuvant chemo-radiation for preoperative enlarged lateral nodes in advanced low rectal cancer: study protocol for a randomized controlled trial. Trials17: 561 2 Watanabe T, Muro K, Ajioka Y, Hashiguchi Y, Ito Y, et al. (2018) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol 23: 1-34
  • 5. Diagnosis of LN mets in rectal cancer  MRI as primary staging tool:1 o Sensitivity: 55% and specificity: 78%  Morphologic criteria: irregular border, heterogeneous signal intensity and round shape in combination with size: 2 o Sensitivity (36%-85%) and specificity (95%-100%)  Cutoff for LPLN size varies from 4 mm to 12 mm 3  Diffusion weighted MR-imaging (DWI-MRI) for LLNs: LLN have high DWI signal 4 1 Lahaye MJ, Engelen SME, Nelemans PJ, et al. Imaging for predicting the risk factors—the circumferential resection margin and nodal disease—of local recurrence in rectal cancer: a meta-analysis. Seminars in Ultrasound, CT and MRI. 2005;26(4):259-268 2 Kim JH, Beets GL, Kim MJ, Kessels AGH, Beets-Tan RGH. High-resolution MR imaging for nodal staging in rectal cancer: are there any criteria in addition to the size? European Journal of Radiology. 2004;52(1):78-83 4 Ogawa S, Itabashi M, Hirosawa T, Hashimoto T, Bamba Y, Okamoto T. Diagnosis of lateral pelvic lymph node metastasis of T1 lower rectal cancer using diffusion-weighted magnetic resonance imaging: A case report with lateral pelvic lymph node dissection of lower rectal cancer. Molecular and Clinical Oncology. 2016;4(5):817-820 3 Kawai K, Shiratori H, Hata K, Nozawa H, Tanaka T, Nishikawa T, Murono K, Ishihara S. Optimal Size Criteria for Lateral Lymph Node Dissection After Neoadjuvant Chemoradiotherapy for Rectal Cancer. Dis Colon Rectum. 2021;64:274–283
  • 6. Managing the LLNs Advantage of LLND: 1  Decrease the intra-pelvic recurrence by 50%  Improve the 5-year survival by 8%-9% Western concept Japanese concept Regional nodes Internal iliac nodes Internal, external and common iliac and obturator nodes Metastatic nodes Common iliac, external iliac and obturator nodes Not applicable Management nCRT with RT boost to involved nodes LLN dissection 1 Watanabe T, Muro K, Ajioka Y, Hashiguchi Y, Ito Y, et al. (2018) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol 23: 1-34
  • 7. AJCC: combination of TME with radiation therapy (RT) and Chemoradiation therapy (CRT) – standard treatment for advanced lower rectal cancer  Preoperative RT and CRT: partial local control effect  Reduce local recurrence to ≤10% NCCN: recommends TME after CRT with concomitant fluorouracil for cStage II-III rectal cancer  No specific description for LPLD  Extended dissection of LNs located outside resection region to which LPLNs correspond is indicated for resectable LNs with suspected mets ESMO: preoperative RT and CRT recommended depending on the risk  LPLN mets is classified as advanced: preoperative CRT f/b surgery (TME + extensive surgery) OR preoperative short-course RT + Folinic acid _ Fluorouracil + oxaliplatin (FOLFOX) regimen
  • 8. Reassessment and preoperative treatment  Restaging to be performed after neoadjuvant treatment  Discussed during MDT meeting  Surgical decisions based on response of LLNs oCurrent evidence infers: Internal iliac LLNs >4mm (SA) and obturator LLNs >6 mm (SA) after CRT benefit from LLND  Pt. with LLNs with complete clinical remission of both primary tumor and LLNs after chemoradiation: careful assessment with MRI and frequent f/u
  • 9. Fig. Modified lithotomy (Lloyd-Davies) position
  • 10.
  • 11. Complications Intraoperative complications: oLong operative time oLarge volume blood loss oInjury to ureter, gonadal vessels Post-operative complications: oUrinary and sexual dysfunction
  • 12. LPLD and CRT for cLPLN(-) cases  JCOG0212 randomized controlled trial : o Outcomes of prophylactic LPLD in cLPLN(-) cases without suspected metastasis o Examined TME alone compared to TME + LPLD o 5-year relapse-free survival (RFS) was 73.4% in the LPLD group and 73.3% in the ME group o 5-year OS was 92.6% in the LPLD group and 90.2% in the ME group o 5-year local recurrence-free rates were 87.7% in the LPLD group and 82.4% in the ME group o Local recurrence rate 26 cases (7.4%) vs 44 cases (12.6%) was significantly lower in the LPLD group o LPLD is effective for reduction of recurrence in this lateral pelvis region
  • 13. LPLD and CRT for cLPLN(+) cases  Kim et al: o Local recurrence in 29 (7.9%) of 366 cases treated with TME alone without LPLD after preoperative CRT. o Recurrence in the lateral pelvis was found in 24 (82.7%) of these cases o Local recurrence rates according to pretreatment LPLN size were 2.3%, 12.5% and 68.8% in cases with sizes < 5 mm, 5-10 mm and > 10 mm, showing that this rate was high in cases with LPLN enlargement  Akiyoshi et al: 127 CRT treated cases o Performed TME alone in 89 cases without suspected LPLN metastasis before treatment (the TME group) and TME + LPLD in 38 suspected cases (LPLD group) o LPLN metastasis: 25 (65.8%) cases in the LPLD group, but local recurrence: 7 (7.9%) cases in the TME group and 1 (2.6%) case in the LPLD group. o Lateral pelvic recurrence was found in only 3 cases (3.4%) in the TME group and none in the LPLD group
  • 14. Yang et al: oFound no difference in overall local recurrence in cases with suspected LPLN metastasis oIncidence of local recurrence in the lateral pelvic region was significantly lower in the TME + CRT + LPLD group than in the TME + CRT group
  • 15. Conclusion  Although the role of prophylactic LLND is unclear, it may have a role in clinically positive lateral nodes and those that are resistant to CRT  The major question that remains still unanswered is whether routine TME + LLND post CRT in stage II and stage III rectal cancer needs to be advocated globally based on the oriental experience  The results from ongoing RCTs might provide an answer
  • 16. Reference  Bailey short practice of surgery, 27th edition  Sabiston textbook of surgery, 20th edition  Internet sources

Editor's Notes

  1. The majority of the first group of nodes are resected as a part of Total Mesorectal Excision (TME) The second group of nodes, the lateral pelvic nodes, albeit being recognised long before, have triggered a significant interest in the field of rectal cancer surgery on the approach, recurrence and survival. According to the TNM staging, involvement of the internal iliac group of nodes is considered as regional disease whereas the external and common iliac nodes are treated as metastatic disease. In contrast, the Japanese classification considers all of the lateral lymph node groups as regional nodes. The Japanese guidelines for colorectal cancer (2016) recommend Lateral Lymph Node Dissection (LLND) for all tumors below the peritoneal reflection
  2. Internal iliac compartment: Cranial: bifurcation of common iliac artery Caudal: internal iliac artery exiting the pelvis via sciatic foramen Medial: mesorectal fascia Lateral: lateral border of internal iliac artery Posterior: piriformis muscle, sacrum Obturator compartment: Cranial: bifurcation of common iliac artery Caudal: lateral lymphatic tissue meeting pelvic side-wall Medial: lateral border of internal iliac artery Lateral: internal obturator muscle and pelvis side-wall Posterior: piriformis muscle
  3. - LLN involvement in stage II-III rectal cancer - LLNs are also reported to be the major cause for local recurrence following curative resection. About 50% of the local recurrences occur in the LLN basin without evidence of distant metastasis
  4.  European Society of Gastrointestinal and Abdominal Radiology (ESGAR) stated: “there is to date no solid evidence regarding specific or alternative (size) criteria for extra-mesorectal nodes and as such it was not deemed feasible to recommend any specific criteria for these nodes MRI: large Field of view(FOV) thus broad assessment of all compartment Increased sen and spe in determining malignancy in mesorectal lymph nodes Diffusion-weighted MRI, Gadofosveset-enhanced MRI, and LN-specific contrast medium ultrasmall superparamagnetic iron oxide contrast agent (i.e. ‘USPIO’)-enhanced MRI have been examined for improvement of diagnosis of LN metastasis of rectal cancer
  5. The AJCC classifies LLN involvement as metastatic disease except for the internal iliac nodes. As the LLNs apart from the internal iliac group are considered as metastatic disease, they were dealt with less aggressively. However, radiation oncologists in the US nowadays are preferring to deal with the non-regional nodes with treatment intensification, either Radiotherapy (RT) boost or Surgical LLND The Japanese classification, on the other hand, considers all LLN involvement as regional disease, irrespective of the site. As a result, LLN dissection is routinely performed in this part of the world.
  6. - The ESMO guidelines also do not particularly recommend prophylactic dissection for LPLNs without suspected metastasis, similar to the NCCN guidelines, and LPLD is not routinely performed in Western countries.
  7. Current evidence supports LLND to be the most effective treatment strategy for persistently enlarged LLNs after (C)RT A Ureter is dissected and taped. B After the expose of the common iliac artery, the common iliac vein, and the hypogastric nerve, the lymph nodes in region 273 with adipose tissues located among them can be seen Other institutions may only remove individual LLNs, without removing the entire compartment, known as “node-picking.” This approach does not follow general oncological principles, ignoring potential micro-metastatic involvement, extracapsular growth or (lympho-)vascular invasion that may result in tumor spillage or residual disease.
  8. C The obturator nerve and vessels are exposed after dissecting anterior aspect of external iliac vein. The lymph nodes in region 283 with adipose tissues can be seen. D After severing the obturator vessels, obturator LLNs of region 283 are removed with the obturator nerve being preserved. E Umbilical artery is dissected and taped. F The lymph nodes in region 263 are resected along the inner side of internal iliac artery using the superior vesical artery as a boundary
  9. - 5-year relapse-free survival (RFS) was 73.4% in the LPLD group and 73.3% in the ME group, which did not demonstrate non-inferiority of TME alone; moreover, the Kaplan-Meier curve for RFS was consistent, showing no superiority of LPLD. The secondary endpoint of 5-year OS was 92.6% in the LPLD group and 90.2% in the ME group, again showing no significant difference. The 5-year local recurrence-free rates were 87.7% in the LPLD group and 82.4% in the ME group, with no significant difference, but the local recurrence rate was significantly lower in the LPLD group