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1
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Chen Z, Zhu D. Risk factors for lateral pelvic lymph node metastasis in patients with rectal neuroendocrine tumors: a systematic review and meta-analysis. Front Oncol 2025; 15:1500623. [PMID: 39959663 PMCID: PMC11825347 DOI: 10.3389/fonc.2025.1500623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 01/06/2025] [Indexed: 02/18/2025] Open
Abstract
Background and objective Lateral pelvic lymph node (LPLN) metastasis is one of the prominent reasons for local recurrence in patients with rectal neuroendocrine tumors (RNETs). The evaluation criteria of lateral lymph node metastasis for patients and the indications and value of lateral pelvic lymph node dissection (LPLD) have been controversial. Total mesorectal excision (TME), a conventional surgical treatment for RNETs, excluding lateral lymph nodes, may be one of the reasons for postoperative local recurrence. This study aimed to analyze the risk factors for LPLN metastasis in patients with RNETs in order to guide surgical methods. Methods We searched relevant databases (PubMed, Embase, Medline, Cochrane Library, and Web of Science) for articles published between 1 January 2000 and 1 April 2024 to evaluate the risk factors for LPLN metastasis in patients with RNETs in this meta-analysis. Results A total of seven articles with 433 patients were included in this study. The overall results showed that a WHO grade > G1, tumor invasion of the muscularis propria or deeper, lymphovascular invasion (LVI), mesorectal lymph node metastasis (MLNM), and distant metastasis (M1) were significant risk factors for LPLN metastasis in patients with RNETs (P <0.05). Conclusion This study identified key risk factors for LPLN metastasis in patients with RNETs, providing guidance for treatment strategies. A comprehensive evaluation of these risk factors and imaging findings is recommended to tailor personalized treatment strategies that optimize survival outcomes and improve quality of life. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42024581891.
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Affiliation(s)
| | - Dajian Zhu
- Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, Guangdong, China
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2
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Lucas K, Melling N, Giannou AD, Reeh M, Mann O, Hackert T, Izbicki JR, Perez D, Grass JK. Lymphatic Mapping in Colon Cancer Depending on Injection Time and Tracing Agent: A Systematic Review and Meta-Analysis of Prospective Designed Studies. Cancers (Basel) 2023; 15:3196. [PMID: 37370806 PMCID: PMC10296374 DOI: 10.3390/cancers15123196] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 06/08/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
An optimized lymph node yield leads to better survival in colon cancer, but extended lymphadenectomy is not associated with survival benefits. Lymphatic mapping shows several colon cancers feature aberrant drainage pathways inducing local recurrence when not resected. Currently, different protocols exist for lymphatic mapping procedures. This meta-analysis assessed which protocol has the best capacity to detect tumor-draining and possibly metastatic lymph nodes. A systematic review was conducted according to PRISMA guidelines, including prospective trials with in vivo tracer application. The risk of bias was evaluated using the QUADAS-2 tool. Traced lymph nodes, total resected lymph nodes, and aberrant drainage detection rate were analyzed. Fifty-eight studies met the inclusion criteria, of which 42 searched for aberrant drainage. While a preoperative tracer injection significantly increased the traced lymph node rates compared to intraoperative tracing (30.1% (15.4, 47.3) vs. 14.1% (11.9, 16.5), p = 0.03), no effect was shown for the tracer used (p = 0.740) or the application sites comparing submucosal and subserosal injection (22.9% (14.1, 33.1) vs. 14.3% (12.1, 16.8), p = 0.07). Preoperative tracer injection resulted in a significantly higher rate of detected aberrant lymph nodes compared to intraoperative injection (26.3% [95% CI 11.5, 44.0] vs. 2.5% [95% CI 0.8, 4.7], p < 0.001). Analyzing 112 individual patient datasets from eight studies revealed a significant impact on aberrant drainage detection for injection timing, favoring preoperative over intraoperative injection (OR 0.050 [95% CI 0.010-0.176], p < 0.001) while indocyanine green presented itself as the superior tracer (OR 0.127 [95% CI 0.018-0.528], p = 0.012). Optimized lymphatic mapping techniques result in significantly higher detection of aberrant lymphatic drainage patterns and thus enable a personalized approach to reducing local recurrence.
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Affiliation(s)
- Katharina Lucas
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
- Department of Visceral, Thoracic, Vascular Surgery and Angiology, City Hospital Triemli, Birmensdorferstrasse 497, 8063 Zürich, Switzerland
| | - Nathaniel Melling
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Anastasios D. Giannou
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Matthias Reeh
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Oliver Mann
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Thilo Hackert
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Jakob R. Izbicki
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Daniel Perez
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
- Department of General and Visceral Surgery, Asklepios Hospital Altona, Paul-Ehrlich-Straße 1, 22763 Hamburg, Germany
| | - Julia K. Grass
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
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Livadaru C, Morarasu S, Bargaoanu R, Iacob S, Frunza T, Musina AM, Velenciuc N, Roata CE, Zugun-Eloae F, Ferariu D, Lunca S, Dimofte MG. The mesocolic apical fragment in complete mesocolic excision colectomies: Should it be analysed separately? A proof-of-concept study. Colorectal Dis 2023; 25:234-242. [PMID: 36227063 DOI: 10.1111/codi.16362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 06/15/2022] [Accepted: 09/29/2022] [Indexed: 02/08/2023]
Abstract
AIM The aim of this work is to describe a protocol and assess the feasibility of harvesting and analysing the mesocolic apical fragment (MAF) for the presence of central lymph node (LN) metastasis and extra lymphatic free tumour cells in a random subgroup extracted from a cohort of complete mesocolic excision colectomies with central vascular ligation. METHOD Forty-seven patients diagnosed with colorectal cancer were included. A 2/2 cm pyramid of tissue was cut around the central tie and sent for pathological examination. The MAF was sectioned into 16 slices. High-definition images were taken from the slices which were merged into a panoramic three-dimensional image of the MAF. The distribution of LNs in the MAF was quantified. Immunohistochemistry staining for cytokeratin 14 was used to identify isolated tumour cells and micrometastases in the extranodal tissue. RESULTS No tumoural cells migrating through the apical zone, outside of the LNs, were identified. Margins of resection, mesocolic tissue and LNs were all negative in the subgroup of ultrastaged MAFs. The number of examined central LNs varied between 0 and 24, with positive MAF LNs being identified only in pN2 stages. The rate of positive apical LNs in our cohort was 4.2% (n = 2). CONCLUSIONS The MAF can be easily extracted from standard specimens, allowing for accurate analysis of lymphatic and extra-nodal tumour cells on the central resection margins, in central LNs and in the apical mesocolic tissue. Future research on larger cohorts is required to establish if analysing the MAF has an impact on patient staging, prognosis and management.
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Affiliation(s)
- Cristian Livadaru
- Radiology and Medical Imaging Department, St Spiridon University Hospital, Iași, Romania.,Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania
| | - Stefan Morarasu
- Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania.,2nd Department of Surgical Oncology, Regional Institute of Oncology (IRO), Iași, Romania
| | - Roxana Bargaoanu
- 2nd Department of Surgical Oncology, Regional Institute of Oncology (IRO), Iași, Romania
| | - Stefan Iacob
- Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania.,2nd Department of Surgical Oncology, Regional Institute of Oncology (IRO), Iași, Romania
| | - Tudor Frunza
- Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania.,2nd Department of Surgical Oncology, Regional Institute of Oncology (IRO), Iași, Romania
| | - Ana Maria Musina
- Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania.,2nd Department of Surgical Oncology, Regional Institute of Oncology (IRO), Iași, Romania
| | - Natalia Velenciuc
- Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania.,2nd Department of Surgical Oncology, Regional Institute of Oncology (IRO), Iași, Romania
| | - Cristian Ene Roata
- Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania.,2nd Department of Surgical Oncology, Regional Institute of Oncology (IRO), Iași, Romania
| | - Florin Zugun-Eloae
- Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania.,Center of Fundamental Research and Experimental Development in Translational Medicine at Regional Institute of Oncology, Regional Institute of Oncology (IRO), Iasi, Romania
| | - Dan Ferariu
- Department of Pathology, Regional Institute of Oncology (IRO), Iasi, Romania
| | - Sorinel Lunca
- Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania.,2nd Department of Surgical Oncology, Regional Institute of Oncology (IRO), Iași, Romania
| | - Mihail-Gabriel Dimofte
- Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania.,2nd Department of Surgical Oncology, Regional Institute of Oncology (IRO), Iași, Romania
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Serrano Del Moral Á, Pérez Viejo E, Castaño Pascual Á, Llorente Herrero E, Rodríguez Caravaca G, Duran Poveda M, Pereira Pérez F. Usefulness of histological superstudy of sentinel lymph nodes detected with radioisotopes in colon cancer. Rev Esp Med Nucl Imagen Mol 2021; 40:358-366. [PMID: 34752369 DOI: 10.1016/j.remnie.2021.03.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 12/16/2020] [Indexed: 11/29/2022]
Abstract
INTRODUCTION Adjuvant chemotherapy (CT) significally reduces the rate of relapse in +pN (stage III) colon cancer (CC) and in some pN0 (stage II) with risk factors such as pT4, vascular invasion V1, perineural invasion Pn1, and complicated tumors. However, unexpectedly, 20%-30% of pN0 present a relapse in the follow-up, which may suggest that the lymph node involvement was not discovered in the conventional histological study (CS), and its finding with a superstudy (SS) could increase the number of patients who would benefit from neoadjuvant CT. It is not possible to perform this SS in every lymph node (LN) from the specimen, but it is possible in a small group of LN which are representative of the N status (definition of sentinel node SN). The aim of our work is to state the representativeness of the SN and to analyze de number of patients who are suprastaged after the SS of the SN. MATERIAL AND METHODS Prospective study of a series of patients who have undergone curative surgery for CC, to whom we perform selective biopsy of sentinel node (SBDN). Identification of SN was carried out with in vivo injection of the radiotracer, with ex vivo isolation of SN. Once the specimen is out, we take pictures of the surgical bed to rule out the presence of aberrant drainage routes, out of the routine oncological resection area. We performed the histological CS (Hematoxilin-Eosin stain (H-E) in conventional sections) in the rest of the LN from the mesocolon. In the SN we performed the CS and a SS with H-E in serial sections, immunohistochemistry (IHC) and molecular study with OSNA® (One Step Nucleic Acid Amplification). Diagnostic validity study od SBSN was carried out, defining the false negative (FN) as the negativity of the SN while other LN are positive (N+), as well as a valuation of the suprastaging due to the SS of the SN. RESULTS We performed lymphatic map in 72 patients, finding the SN in 62 of them (87.3%). The 9 identification failures happened in the first 17 cases. We have not found aberrant drainage routes. A total of 1.164 LN were studied in the 62 patients (18.8 LN/patient), from which 145 are SN (2,34 SN/patient), having found 103 positive LN with the CS and 112 positive with the SS of SN (9+ LN more in 8 patients than detected with the CS). Positivity after CS in the SN group is 17.24% (25/145), while it is 8.53% in the rest (87/1.019) (P < .001). With the CS, 50% of the patients (31/62) were pN+ (4 are N+ exclusively in the SN), and after the SS of the SN, only 1 of the 31 pN0 patients (3.2%) becomes pN1a, with a definitive 51.6% of N+ in the whole series (32 N+ in the 62 patients) (5 are N+ exclusively in the SN). Exclusively with the SS of the SN, FN rate ("-SN, +others", meaning patients who are N+ having -SN) is 54.8% (17/31). With the SS of the SN, 8 of the 62 patients (12.9%) increase their total number of +LN: apart from the patient who turns from pN0 to pN1a, suprastaging from IIA to IIIB (and therefore increasing the total number of pN+ to 32), 5 of the 17 FN in the CS turns into positive (2 change the pN subindex and one is suprastaged from IIIB to IIIC), decreasing FN to 37.5% (12/32 cases). Besides, 2 patients whose SN is already positive in the CS increase the number of +SN after the SS of the SN, therefore both changing their pN subindex and one of them suprastaging from IIIB to IIIC. In summary, 8 patients increase the total number of positive SN after the SS (8/62, 12.9%), 5 of them changing the pN subindex (5/62, 12.9%), even if only 3 of them get suprastaged (3/62, 4.8%), among them the one who turns from pN0 to pN1a. CONCLUSION Technique is valid and reproducible, with a high detection rate even with a high learning curve. It globally increases the number of affected LN in 12.9% of patients, having prognostic implications in 4.8% (suprastaging rate). Only 3.2% of pN0 patients in the CS turn to be +pN after the SS of the SN, with its therapeutic implications (prescription of adjuvant CT), which could be relevant when extrapolated to a big number of patients. The high FN rate (37.5%) prevents us from accepting the representativeness of SN as the global N status, but it is not clinically relevant in CC, as its aim is not to avoid lymphadenectomy, which remains mandatory (opposite to breast cancer or melanoma in which SN detection decides upon whether to perform or not the lymphadenectomy), but to decide which patients would benefit from adjuvant CT.
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Affiliation(s)
- Á Serrano Del Moral
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain.
| | - E Pérez Viejo
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain
| | - Á Castaño Pascual
- Servicio de Anatomía Patológica, Hospital Universitario de Fuenlabrada, Madrid, Spain
| | - E Llorente Herrero
- Unidad de Medicina Nuclear, Hospital Universitario de Fuenlabrada, Madrid, Spain
| | - G Rodríguez Caravaca
- Unidad de Medicina Preventiva, Hospital Universitario Fundación de Alcorcón, Madrid, Spain
| | - M Duran Poveda
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Rey Juan Carlos de Móstoles, Madrid, Spain
| | - F Pereira Pérez
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain
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5
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Serrano Del Moral Á, Pérez Viejo E, Castaño Pascual Á, Llorente Herrero E, Rodríguez Caravaca G, Durán Poveda M, Pereira Pérez F. Usefulness of histological superstudy of sentinel node detected with radioisotope in colon cancer. Rev Esp Med Nucl Imagen Mol 2021; 40:S2253-654X(21)00017-2. [PMID: 33642258 DOI: 10.1016/j.remn.2020.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 12/12/2020] [Accepted: 12/16/2020] [Indexed: 11/21/2022]
Abstract
INTRODUCTION Adjuvant chemotherapy (CT) significally reduces the rate of relapse in +pN (stage III) colon cancer and in some pN0 (stage II) with risk factors such as pT4, vascular invasion V1, perineural invasion Pn1, and complicated tumors. However, unexpectedly, 20-30% of pN0 present a relapse in the follow-up, which may suggest that the lymph node involvement was not discovered in the conventional histological study (CS), and its finding with a superstudy (SS) could increase the number of patients who would benefit from neoadjuvant CT. It is not possible to perform this SS in every lymph node (LN) from the specimen, but it is possible in a small group of LN which are representative of the N status (definition of sentinel node SN). The aim of our work is to state the representativeness of the SN and to analyze de number of patients who are suprastaged after the SS of the SN. MATERIAL AND METHODS Prospective study of a series of patients who have undergone curative surgery for colon cancer, to whom we perform selective biopsy of sentinel node. Identification of SN was carried out with in vivo injection of the radiotracer, with ex vivo isolation of SN. Once the specimen is out, we take pictures of the surgical bed to rule out the presence of aberrant drainage routes, out of the routine oncological resection area. We performed the histological CS (hematoxilin-eosin stain in conventional sections) in the rest of the LN from the mesocolon. In the SN we performed the CS and a SS with hematoxilin-eosin in serial sections, immunohistochemistry (IHC) and molecular study with One Step Nucleic Acid Amplification (OSNA®). Diagnostic validity study od selective biopsy of sentinel node was carried out, defining the false negative (FN) as the negativity of the SN while other LN are positive (N+), as well as a valuation of the suprastaging due to the SS of the SN. RESULTS We performed lymphatic map in 72 patients, finding the SN in 62 of them (87.3%). The 9 identification failures happened in the first 17 cases. We have not found aberrant drainage routes. A total of 1.164 LN were studied in the 62 patients (18.8 LN/ patient), from which 145 are SN (2,34 SN/ patient), having found 103 positive LN with the CS and 112 positive with the SS of SN (9 +LN more in 8 patients than detected with the CS). Positivity after CS in the SN group is 17.24% (25/145), while it is 8.53% in the rest (87/1.019) (p<.001). With the CS, 50% of the patients (31/62) were pN+ (4 are N+ exclusively in the SN), and after the SS of the SN, only 1 of the 31 pN0 patients (3.2%) becomes pN1a, with a definitive 51.6% of N+ in the whole series (32 N+ in the 62 patients) (5 are N+ exclusively in the SN). Exclusively with the SS of the SN, FN rate ("-SN, +others", meaning patients who are N+ having -SN) is 54.8% (17/31). With the SS of the SN, 8 of the 62 patients (12.9%) increase their total number of +LN: apart from the patient who turns from pN0 to pN1a, suprastaging from IIA to IIIB (and therefore increasing the total number of pN+ to 32), 5 of the 17 FN in the CS turns into positive (2 change the pN subindex and one is suprastaged from IIIB to IIIC), decreasing FN to 37.5% (12/32 cases). Besides, 2 patients whose SN is already positive in the CS increase the number of +SN after the SS of the SN, therefore both changing their pN subindex and one of them suprastaging from IIIB to IIIC. In summary, 8 patients increase the total number of positive SN after the SS (8/62, 12.9%), 5 of them changing the pN subindex (5/62, 12.9%), even if only 3 of them get suprastaged (3/62, 4.8%), among them the one who turns from pN0 to pN1a. CONCLUSION Technique is valid and reproducible, with a high detection rate even with a high learning curve. It globally increases the number of affected LN in 12.9% of patients, having prognostic implications in 4.8% (suprastaging rate). Only 3.2% of pN0 patients in the CS turn to be +pN after the SS of the SN, with its therapeutic implications (prescription of adjuvant CT), which could be relevant when extrapolated to a big number of patients. The high FN rate (37.5%) prevents us from accepting the representativeness of SN as the global N status, but it is not clinically relevant in colon cancer, as its aim is not to avoid lymphadenectomy, which remains mandatory (opposite to breast cancer or melanoma in which SN detection decides upon whether to perform or not the lymphadenectomy), but to decide which patients would benefit from adjuvant CT.
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Affiliation(s)
- Á Serrano Del Moral
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España.
| | - E Pérez Viejo
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España
| | - Á Castaño Pascual
- Servicio de Anatomía Patológica, Hospital Universitario de Fuenlabrada, Madrid, España
| | - E Llorente Herrero
- Unidad de Medicina Nuclear, Hospital Universitario de Fuenlabrada, Madrid, España
| | - G Rodríguez Caravaca
- Unidad de Medicina Preventiva, Hospital Universitario Fundación de Alcorcón, Madrid, España
| | - M Durán Poveda
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Rey Juan Carlos de Móstoles, Madrid, España
| | - F Pereira Pérez
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España
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6
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Bao F, Deng ZG, Wang D, Xian-yu JB, Li GQ, Xiang CH, Xiang RC, Zhi X. Factors influencing lymph node skip metastasis in colorectal cancer: a retrospective study. ANZ J Surg 2017; 88:770-774. [PMID: 29194915 DOI: 10.1111/ans.14268] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Revised: 09/07/2017] [Accepted: 09/09/2017] [Indexed: 01/16/2023]
Affiliation(s)
- Feng Bao
- Department of General Surgery; Mianyang Central Hospital; Mianyang, Sichuan China
| | - Zhi-gang Deng
- Department of General Surgery; Mianyang Central Hospital; Mianyang, Sichuan China
| | - Dong Wang
- Department of General Surgery; Mianyang Central Hospital; Mianyang, Sichuan China
| | - Jian-bo Xian-yu
- Department of General Surgery; Mianyang Central Hospital; Mianyang, Sichuan China
| | - Guo-qiang Li
- Department of General Surgery; Mianyang Central Hospital; Mianyang, Sichuan China
| | - Chun-hua Xiang
- Department of General Surgery; Mianyang Central Hospital; Mianyang, Sichuan China
| | - Rong-chao Xiang
- Department of General Surgery; Mianyang Central Hospital; Mianyang, Sichuan China
| | - Xing Zhi
- Department of General Surgery; Mianyang Central Hospital; Mianyang, Sichuan China
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7
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Bao F, Zhao LY, Balde AI, Liu H, Yan J, Li TT, Chen H, Li GX. Prognostic impact of lymph node skip metastasis in Stage III colorectal cancer. Colorectal Dis 2016; 18:O322-O329. [PMID: 27438774 DOI: 10.1111/codi.13465] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Accepted: 05/29/2016] [Indexed: 12/12/2022]
Abstract
AIM The aim of this study was to evaluate the prognostic impact of lymph node skip metastasis (LNSM) in patients with Stage III colorectal cancer. METHOD Between April 2003 and December 2014, a total of 41 patients with lymph node skip metastasis (skip+) were compared with 86 patients with pericolic lymph node metastases [lymph node distribution (LND)1] and 57 patients with intermediate and/or main lymph node metastasis (LND2+3). All patients had radical D3 lymphadenectomy, performed either laparoscopically or as open surgery. RESULTS The frequency of pT1-2 stage cancer was significantly higher in the skip+ group than in the LND1 group (26.8% vs 5.8%, P = 0.001). The number of metastatic lymph nodes in the skip+ group was lower than in the LND2+3 group (1.9 ± 1.5 vs 6.5 ± 6.0, P < 0.001). The 3-year disease-free survival (DFS) of the skip+, LND1 and LND2+3 groups was 64.8%, 69.7% and 40.1%, respectively (P = 0.008). The 3-year systemic recurrence rates of the skip+, LND1 and LND2+3 groups were 30.2%, 20.3% and 48.1%, respectively; (P = 0.002). Cox regression analysis revealed that preoperative carcinoembryonic antigen (CEA) of ≥ 5 ng/ml [hazard ratio (HR) = 2.2, P = 0.029], poor differentiation (HR = 3.8, P = 0.001) and skip+ (HR = 0.2, P = 0.021) were independently prognostic factors for DFS. CONCLUSION The prognosis for the LND1-negative lymph node skip metastasis group was better than for the LND2+3 group and was comparable with that of the LND1 group after radical D3 lymphadenectomy.
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Affiliation(s)
- F Bao
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Department of General Surgery, Mianyang Central Hospital, Mianyang, China
| | - L-Y Zhao
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - A I Balde
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - H Liu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - J Yan
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - T-T Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - H Chen
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - G-X Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Beppu N, Niki M, Kimura F, Matsubara N, Tomita N, Yanagi H, Yamanaka N. A case of rectal carcinoid, 7 mm in diameter, with skip metastasis to the lateral lymph node. Mol Clin Oncol 2016; 4:549-552. [PMID: 27073660 DOI: 10.3892/mco.2016.761] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2015] [Accepted: 12/17/2015] [Indexed: 01/12/2023] Open
Abstract
The present case study presented a 59-year-old man with a 7 mm submucosal tumor in the lower rectum and swelling in a 7 mm lateral lymph node (the obturator lymph node). No swelling of the lymph nodes within the mesorectum was observed. The patient underwent laparoscopic intersphincteric resection with left side lateral lymphadenectomy. At the pathological examination, the patient was diagnosed with a rectal neuroendocrine tumor (Grade 1; carcinoid), which had invaded the perirectal tissues and exhibited lateral lymph node metastasis; however, mesorectal lymph node metastasis was not observed, therefore, the definitive diagnosis was rectal carcinoid with skip metastasis to the lateral lymph node. No sign of recurrence was observed at the 3 year follow-up. The treatment algorithm of rectal carcinoid was decided by the risk of lymph node metastasis. The present study confirmed skip metastasis to the lateral lymph node from the rectal carcinoid, which is typically very slow growing and has a low grade malignant potential.
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Affiliation(s)
- Naohito Beppu
- Department of Surgery, Meiwa Hospital, Nishinomiya, Hyogo 663-8186, Japan
| | - Masami Niki
- Department of Gastroenterology, Niki Clinic, Nishinomiya, Hyogo 663-8245, Japan
| | - Fumihiko Kimura
- Department of Surgery, Meiwa Hospital, Nishinomiya, Hyogo 663-8186, Japan
| | - Nagahide Matsubara
- Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Naohiro Tomita
- Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Hidenori Yanagi
- Department of Surgery, Meiwa Hospital, Nishinomiya, Hyogo 663-8186, Japan
| | - Naoki Yamanaka
- Department of Surgery, Meiwa Hospital, Nishinomiya, Hyogo 663-8186, Japan
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Pedrazzani C, Lauka L, Sforza S, Ruzzenente A, Nifosì F, Delaini G, Guglielmi A. Management of nodal disease from colon cancer in the laparoscopic era. Int J Colorectal Dis 2015; 30:303-14. [PMID: 25416529 DOI: 10.1007/s00384-014-2075-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/12/2014] [Indexed: 02/06/2023]
Abstract
PURPOSE In colon cancer (CC), nodal involvement is the main prognostic factor following potentially curative (R0) resection. The purpose of this study was to examine data from the literature to provide an up-to-date analysis of the management of nodal disease with special reference to laparoscopic treatment. METHODS MEDLINE and EMBASE databases were searched for potentially eligible studies published in English up to July 15, 2014. RESULTS In CC, nodal involvement is a frequent event and represents the main risk of cancer recurrence. Node negative patients recur in 10-30 % of cases most likely due to underdiagnosed or undertreated nodal disease. Extended colonic resections (complete mesocolic excision with central vascular ligation; D3 lymphadenectomy) provides a survival benefit and better local control. Sentinel lymph node mapping in addition to standard surgical resection represents an option for improving staging of clinical node negative patients. Both extended resection and sentinel lymph node mapping are feasible in a laparoscopic setting. CONCLUSIONS Both extended colonic resection and sentinel lymph node mapping should play a role in the laparoscopic treatment of CC with the purpose of improving control and staging of nodal disease.
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Affiliation(s)
- Corrado Pedrazzani
- Department of Surgery, Chirurgia Generale e Epatobiliare, G.B. Rossi University Hospital, University of Verona, Verona, Italy,
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Can MF, Yagci G, Cetiner S. Systematic Review of Studies Investigating Sentinel Node Navigation Surgery and Lymphatic Mapping for Gastric Cancer. J Laparoendosc Adv Surg Tech A 2013; 23:651-62. [DOI: 10.1089/lap.2012.0311] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Affiliation(s)
- Mehmet Fatih Can
- Division of Gastrointestinal Surgery, Department of Surgery, Gulhane School of Medicine, Etlik, Ankara, Turkey
| | - Gokhan Yagci
- Division of Gastrointestinal Surgery, Department of Surgery, Gulhane School of Medicine, Etlik, Ankara, Turkey
| | - Sadettin Cetiner
- Division of Gastrointestinal Surgery, Department of Surgery, Gulhane School of Medicine, Etlik, Ankara, Turkey
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Lezoche E, Fabiani B, D’Ambrosio G, Ursi P, Balla A, Lezoche G, Monteleone F, Paganini AM. Nucleotide-guided mesorectal excision combined with endoluminal locoregional resection by transanal endoscopic microsurgery in the treatment of rectal tumors: technique and preliminary results. Surg Endosc 2013; 27:4136-41. [DOI: 10.1007/s00464-013-3012-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2012] [Accepted: 05/03/2013] [Indexed: 10/26/2022]
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Sardón Ramos JD, Errasti Alustiza J, Campo Cimarras E, Cermeño Toral B, Romeo Ramírez JA, Sáenz de Ugarte Sobrón J, Atares Pueyo B, Moreno Nieto V, Cuadra Cestafe M, Miranda Serrano E. [Sentinel lymph node biopsy technique in colon cancer. Experience in 125 cases]. Cir Esp 2013; 91:366-71. [PMID: 23415815 DOI: 10.1016/j.ciresp.2012.11.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2012] [Revised: 11/01/2012] [Accepted: 11/04/2012] [Indexed: 01/23/2023]
Abstract
INTRODUCTION The level of lymph node involvement is the most important factor in staging colorectal cancer without metastasis. Sentinel lymph node mapping identifies the node(s) that most accurately reflect the lymph node status of patients, and intensive techniques that improve staging can be focused on these nodes. The aim of this study was to assess the efficacy of ex vivo sentinel lymph node mapping in the staging of colon cancer. MATERIALS AND METHODS A prospective study was conducted on 125 patients from the Alava-Txagorritxu University Hospital Health Region (Alava), who were diagnosed prior to surgery with colon cancer without distant metastasis from September 2009 to December 2011. Ex vivo sentinel lymph node mapping with methylene blue was use in these patients to study the sentinel nodes with multiple slices using immunohistochemical techniques and haematoxylin-eosin staining. A comparative study was also performed based on a control group of 170 patients staged with conventional techniques, and involving a single slice and haematoxylin-eosin staining. RESULTS The sentinel lymph node identification rate was 98%, with 5.6% false negatives. Upstaging occurred in 14.2% of cases compared to the group studied using conventional techniques (P=.006). CONCLUSIONS Ex vivo sentinel lymph node mapping with methylene blue accurately reflects the lymph node status of patients with colon cancer. This approach upstages patients classified as stages i and ii by conventional techniques to stage iii, indicating chemotherapy that may improve their prognosis.
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Affiliation(s)
- José Domingo Sardón Ramos
- Servicio de Cirugía General, Hospital Universitario de Álava - Txagorritxu, Vitoria-Gasteiz, España.
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van der Zaag ES, Bouma WH, Tanis PJ, Ubbink DT, Bemelman WA, Buskens CJ. Systematic review of sentinel lymph node mapping procedure in colorectal cancer. Ann Surg Oncol 2012; 19:3449-59. [PMID: 22644513 DOI: 10.1245/s10434-012-2417-0] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2011] [Indexed: 12/21/2022]
Abstract
BACKGROUND The clinical impact of sentinel lymph node (SN) biopsy in colorectal cancer is still controversial. The aim of our study was to determine the accuracy of this procedure from published data and to identify factors that contribute to the conflicting reports. METHODS A systematic search of the Medline, Embase, and Cochrane databases up to July 2011 revealed 98 potentially eligible studies, of which 57 were analyzed including 3,934 patients (3,944 specimens). RESULTS The pooled SN identification rate was 90.7% (95% CI 88.2-93.3), with a significant higher identification rate in studies including more than 100 patients or studies using the ex vivo SN technique. The pooled sensitivity of the SN procedure was 69.6% (95% CI 64.7-74.6). Including the immunohistochemical findings increased the pooled sensitivity of SN procedure to 80.2% (95% CI 4.7-10.7). Subgroups with significantly higher sensitivity could be identified: ≥4 SNs versus <4 SNs (85.2 vs. 66.3%, p = 0.003), colon versus rectal cancer (77.6 vs. 65.7%, p = 0.04), early T1 or T2 versus advanced T3 or T4 carcinomas (93.4 vs. 58.8%, p = 0.01). Serial sectioning and immunohistochemistry resulted in a mean upstaging of 18.9% (range 0-50%). True upstaging defined as micrometastases (pN1mi+) rather than isolated tumor cells (pN0itc+) was 7.7%. CONCLUSIONS The SN procedure in colorectal cancer has an overall sensitivity of 70%, with increased sensitivity and refined staging in early-stage colon cancer. Because the ex vivo SN mapping is an easy technique it should be considered in addition to conventional resection in colon cancer.
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Rivet EB, Mutch MG, Ritter JH, Khan AA, Lewis JS, Winslow E, Fleshman JW. Ex vivo sentinel lymph node mapping in laparoscopic resection of colon cancer. Colorectal Dis 2011; 13:1249-55. [PMID: 21083799 DOI: 10.1111/j.1463-1318.2010.02450.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM The study examined the feasibility and potential benefit of ex vivo sentinel lymph node (SLN) mapping, including multilevel sectioning (MLS) and immunohistochemistry (IHC) in colon cancer patients undergoing laparoscopic colectomy. The secondary goals were (i) to identify patient and tumour characteristics that might influence the success of the SLN technique, (ii) to investigate the extent of lymphadenectomy required to encompass tumour-positive nonsentinel lymph nodes (NSLN) and (iii) to ascertain the association of SLN status with oncological outcomes. METHOD SLN mapping was performed after specimen extraction using 1% Isosulfan blue. The SLNs were analysed with H&E staining after MLS, and if negative, IHC was performed. NSLNs were grouped by distance either greater than or less than 4 cm from the tumour. RESULTS Seventy-one patients completed the study between 2003 and 2007. Using H&E with MLS, the accuracy of SLN mapping was 76%, sensitivity was 52% and the false-negative rate was 48%. Excluding patients with clinically positive lymph nodes resulted in a significant improvement in accuracy to 81% and decreased the false-negative rate to 30%. Furthermore, as the only positive NSLN > 4 cm from the tumour was grossly positive, SLN mapping with a 4-cm mesenteric cuff would have given 100% sensitivity in patients without macroscopically involved nodes. CONCLUSIONS SLN mapping may be of value in selected patients. It may be possible to accurately stage patients with a 4-cm cuff of mesentery, although further validation of this proposal is required.
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Affiliation(s)
- E B Rivet
- Bon Secours Hampton Roads Health System, Suffolk, Virginia, USA
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Can MF, Yagci G, Cetiner S. Sentinel lymph node biopsy for gastric cancer: Where do we stand? World J Gastrointest Surg 2011; 3:131-7. [PMID: 22007282 PMCID: PMC3192223 DOI: 10.4240/wjgs.v3.i9.131] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2011] [Revised: 08/27/2011] [Accepted: 09/12/2011] [Indexed: 02/06/2023] Open
Abstract
Development of sentinel node navigation surgery (SNNS) and advances in minimally invasive surgical techniques have greatly shaped the modern day approach to gastric cancer surgery. An extensive body of knowledge now exists on this type of clinical application but is principally composed of single institute studies. Certain dye tracers, such as isosulfan blue or patent blue violet, have been widely utilized with a notable amount of success; however, indocyanine green is gaining popularity. The double tracer method, a synchronized use of dye and radio-isotope tracers, appears to be superior to any of the dyes alone. In the meantime, the concepts of infrared ray electronic endoscopy, florescence imaging, nanoparticles and near-infrared technology are emerging as particularly promising alternative techniques. Hematoxylin and eosin staining remains the main method for the detection of sentinel lymph node (SLN) metastases. Several specialized centers have begun to employ immunohistochemical staining for this type of clinical analysis but the equipment costs involving the associated ultra-rapid processing systems is limiting its widespread application. Laparoscopic function-preserving resection of primary tumor from the stomach in conjunction with lymphatic basin dissection navigated by SLN identification represents the current paramount of SNNS for early gastric cancer. Patients with cT3 stage or higher still require standard D2 dissection.
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Affiliation(s)
- Mehmet Fatih Can
- Mehmet Fatih Can, Gokhan Yagci, Sadettin Cetiner, Division of Gastrointestinal Surgery, Department of Surgery, Gulhane School of Medicine, 06018, Etlik, Ankara, Turkey
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Sentinel-lymph-node procedure in colon and rectal cancer: a systematic review and meta-analysis. Lancet Oncol 2011; 12:540-50. [PMID: 21549638 DOI: 10.1016/s1470-2045(11)70075-4] [Citation(s) in RCA: 93] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND No consensus exists on the validity of the sentinel-lymph-node procedure for assessment of nodal status in patients with colorectal cancer. We aimed to assess the diagnostic performance of this procedure. METHODS We searched Embase and PubMed databases for studies published before March 20, 2010. Eligible studies had a prospective design, a sample size of at least 20 patients, and reported the rate of sentinel-lymph-node positivity. Individual patient data were requested for localisation and T-stage stratification. A subset of reports with high methodological quality was selected and analysed. FINDINGS We identified 52 eligible studies, which included 3767 sentinel-lymph-node procedures (2961 [78·6%] colon and 806 [21·4%] rectal carcinomas). Most tumours 2339 (62·1%) were stage T3 or T4. 1887 (50·1%) of patients were male, 1880 (49·9%) female. Mean overall weighted-detection rate was 0·94 (95% CI 0·92-0·95), at a pooled sensitivity of 0·76 (0·72-0·80) with limited heterogeneity (χ(2)=286·08, degrees of freedom=51; p=0·003). A mean weighted upstaging of 0·15 (95% CI 0·12-0·19) was noted. Individual patient data were available from 19 studies that included 1168 patients. Analysis of these data showed no significant difference in sensitivity between colon (0·86 [95% CI 0·83-0·90]) and rectal cancer (0·82 [0·77-0·88]; p=0·23). Also, there was no dependency of sensitivity on T stage for both colon (pT1: 0·79 [95% CI 0·73-0·84], pT2: 0·76 [0·62-0·90], pT3: 0·73 [0·59-0·87], pT4: 0·73 [0·53-0·93]) and rectal cancer (T1 or T2: 0·81 [0·52-0·94] vs T3 or T4: 0·80 [0·51-0·93]). The subgroup of eight studies with high methodological quality showed a mean detection rate of 0·96 (95% CI 0·90-0·99) for colonic tumours and 0·95 (0·75-0·99) for rectal tumours, and a mean sensitivity of 0·90 (95% CI 0·86-0·93) for colonic tumours and 0·82 (0·60-0·93) for rectal tumours. INTERPRETATION The sentinel-lymph-node procedure shows a low sensitivity, regardless of T stage, localisation, or pathological technique. For every patient diagnosed with colon or rectal cancer without clinical evidence of lymph-node involvement or metastatic disease, this procedure in addition to conventional resection should be considered, since the prognostic information provided by this technique could be clinically significant. FUNDING Cancer Center Amsterdam Foundation, Amsterdam, Netherlands.
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Märkl B, Arnholdt HM, Jähnig H, Spatz H, Anthuber M, Oruzio DV, Kerwel TG. A new concept for the role of ex vivo sentinel lymph nodes in node-negative colorectal cancer. Ann Surg Oncol 2010; 17:2647-55. [PMID: 20333553 DOI: 10.1245/s10434-010-1030-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2009] [Indexed: 12/13/2022]
Abstract
BACKGROUND We recently introduced ex vivo, intra-arterial methylene blue injection as a simple method to improve the lymph node (LN) harvest in gastrointestinal cancer. We now combined it with a novel ex vivo sentinel lymph node (evSLN) mapping technique. METHODS evSLN mapping was performed by subserosal (n = 20) or submucosal (n = 30) India ink injection. Subsequently, methylene blue was injected intra-arterially to enhance visibility of all LNs to improve the overall LN harvest. Manual LN dissection was carried out after fixing overnight. evSLNs nodes were identified by detecting carbon particles during histological examination. In primary node-negative cases, all detected LNs were step sectioned and immunohistochemically stained for pan-cytokeratin. RESULTS India ink injection was easy to perform. Methylene blue injection failed in 1 case. The mean lymph node harvest was 42 ± 18 LNs, and the SLN detection rate was 78%. The sensitivity for detecting metastases was 75%. The mean SLN number was 3 ± 1. LN metastases were found in 20 of 47 malignant cases (43%). Skip metastases occurred in 4 cases. Of these cases, 3 showed involvement of at least 1 entire LN. True upstaging (N0 → N1mi) was found in 1 of 23 cases (4%) within a SLN after advanced evaluation. CONCLUSIONS Combination of methylene blue technique and ex vivo sentinel mapping is feasible, easy to perform, and cost effective. It guarantees an optimal LN harvest and has the potential to heighten the sensitivity of metastasis detection.
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Affiliation(s)
- Bruno Märkl
- Institute of Pathology, Klinikum Augsburg, Augsburg, Germany.
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Abstract
PURPOSE Controversy exists over the utility of sentinel lymph node mapping in the treatment of rectal cancer. The purpose of this study was to evaluate the use of ex vivo sentinel lymph node mapping in the setting of proctectomy for rectal cancer, with and without multilevel sectioning and immunohistochemistry. METHODS A prospective phase 2 clinical study of subjects undergoing proctectomy for rectal cancer from 2003 to 2008 was conducted. Sentinel lymph node mapping was performed with ex vivo injection of isosulfan blue. Sentinel lymph nodes were examined by hematoxylin and eosin evaluation, and when the results were negative, they were examined by multilevel sectioning and immunohistochemistry. RESULTS The study population consisted of 58 subjects; 88% received neoadjuvant therapy. Tumors were downstaged in 25 (49%) subjects receiving neoadjuvant therapy, 24% were clinical complete responders, and 20% were pathologic complete responders. The mean total lymph node harvest was 12.1 nodes per patient. Twenty-five subjects had positive nodal disease on final pathology. The sentinel lymph node detection rate was 85%, with a mean sentinel lymph node harvest of 2.2 nodes per subject. Fifteen (26%) subjects had sentinel lymph node nodal metastasis on routine hematoxylin and eosin examination. Neither multilevel sectioning nor immunohistochemistry evaluation improved detection of sentinel lymph node positivity. The accuracy of sentinel lymph node mapping was 71%, the sensitivity was 53%, the negative predictive value was 79%, and the false negative rate was 47%. Seven subjects were determined to have nodal disease only in the sentinel lymph node. CONCLUSION Ex vivo sentinel lymph node mapping is feasible after proctectomy for rectal cancer but did not improve staging. Neither multilevel sectioning nor immunohistochemistry improved the sensitivity of sentinel lymph node mapping.
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van der Zaag ES, Kooij N, van de Vijver MJ, Bemelman WA, Peters HM, Buskens CJ. Diagnosing occult tumour cells and their predictive value in sentinel nodes of histologically negative patients with colorectal cancer. Eur J Surg Oncol 2010; 36:350-7. [PMID: 20163930 DOI: 10.1016/j.ejso.2009.11.008] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2009] [Revised: 11/11/2009] [Accepted: 11/16/2009] [Indexed: 12/13/2022] Open
Abstract
PURPOSE Most studies on the sentinel node (SN) procedure in patients with colorectal cancer include immunohistochemical analysis of the SN only. To evaluate the real diagnostic accuracy of the SN procedure with immunohistochemical analysis, the presence of occult tumour cells in all histologically negative lymph nodes was compared to the presence of these cells in SNs. Also the reproducibility of diagnosing occult tumour cells (OTC) and the sensitivity of three different antibodies was assessed. METHODS Between November 2006 en July 2007, an ex vivo SN procedure was performed in 58 histologically N0 patients with colorectal cancer. All lymph nodes (n = 908, mean 15.7) were step-sectioned and immunohistochemistry was performed using two antibodies against cytokeratins (Cam5.2, and CK 20) and one antibody against BerEp-4. RESULTS OTC were identified in 19 of 58 patients, with micrometastases (0.2-2 mm) in 7 and isolated tumour cells (ITC)(<0.2 mm) in 12 patients. The overall agreement in diagnosing OTC between two independent pathologists was 86%. An SN was identified in 53 of 58 patients. All micrometastases were found in SNs. In two patients with negative SNs, ITC's were demonstrated in non-SNs (sensitivity 88%, and overall accuracy 96%). CONCLUSION Additional immunohistochemical analysis of histologically negative lymph nodes demonstrates occult tumour cells in 33% of the patients resulting in an upstaging rate of 12%. Occult tumour cells are predominantly found in the SN, therefore SN mapping has the potential to refine the staging system for patients with colorectal cancer.
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Affiliation(s)
- E S van der Zaag
- Department of Surgery, Gelre Ziekenhuizen, Albert Schweitzerlaan 31, 7334 DZ Apeldoorn, The Netherlands.
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Park JS, Chang IT, Park SJ, Kim BG, Choi YS, Cha SJ, Park ES, Kwon GY. Comparison of ex vivo and in vivo injection of blue dye in sentinel lymph node mapping for colorectal cancer. World J Surg 2010; 33:539-46. [PMID: 19132443 DOI: 10.1007/s00268-008-9872-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The technique of sentinel lymph node (SLN) mapping in patients with colorectal cancer varies between reports, and the optimal method has not been established. The purpose of this study was to determine the optimal injection technique for SLN mapping. METHODS Sixty-nine consecutive patients who underwent curative surgery for colorectal cancer were enrolled. The SLNs was identified intraoperatively by subserosal blue dye injection (in vivo) or by submucosal injection after standard colectomy (ex vivo). If negative by conventional hematoxylin and eosin staining analysis, all lymph nodes, SLNs and non-SLNs, were subjected to further analysis by multi-level section and immunohistochemical examination. RESULTS The in vivo and ex vivo injected groups were similar in demographic character, tumor size, and histological grade. The mean number of SLNs identified was 2.3 in the in vivo group and 2.6 in the ex vivo group (p = 0.192). The detection rate of SLNs by blue dye injection was somewhat higher in the ex vivo group than in the in vivo group: 90.6 vs. 81.1% (p = 0.219). The false-negative rate was 23.5% for the in vivo group and 13.3% for the ex vivo group (p = 0.392). The upstaging rate, which was 18.5% overall, was similar in both groups (p = 0.538). CONCLUSIONS These findings suggest that ex vivo blue dye injection is an effective alternative to in vivo injection for identifying SLNs in patients with colorectal cancer. Because of its simplicity and applicability in routine clinical settings, further investigation of the ex vivo mapping technique is warranted.
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Affiliation(s)
- Jun Seok Park
- Department of Surgery, Chung-Ang University, College of Medicine, 224-1 Heukseok_Dong, Dongjak-Gu, Seoul 156-755, South Korea
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CpG-island methylation of the ER promoter in colorectal cancer: analysis of micrometastases in lymph nodes from UICC stage I and II patients. Br J Cancer 2009; 100:360-5. [PMID: 19142184 PMCID: PMC2634714 DOI: 10.1038/sj.bjc.6604859] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Patients with UICC stage II colorectal cancer (CRC) have a risk of approximately 20% to develop disease recurrence after tumour resection. The presence and significance of micrometastases for locoregional recurrence in these patients lacking histopathological lymph node involvement on routine stained HE sections is undefined. Oestrogen receptor (ER) promoter methylation has earlier been identified in CRC. Therefore, we evaluated the methylation status of the ER promoter in lymph nodes from 49 patients with CRC UICC stage I and II as a molecular marker of micrometastases and predictor of local recurrence. DNA from 574 paraffin-embedded lymph nodes was isolated and treated with bisulphite. For the detection of methylated ER promoter sequences, quantitative real-time methylation-specific PCR was used. Of the 49 patients tested, 15 (31%) had ER methylation-positive lymph nodes. Thirteen of those (86%) remained disease free and two (14%) developed local recurrence. In the resected lymph nodes of 34 of the 49 patients (69%), no ER promoter methylation could be detected and none of these patients experienced a local relapse. The methylation status of the ER promoter in lymph nodes of UICC stage I and II CRC patients may be a useful marker for the identification of patients at a high risk for local recurrence.
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Cahill RA, Leroy J, Marescaux J. Could lymphatic mapping and sentinel node biopsy provide oncological providence for local resectional techniques for colon cancer? A review of the literature. BMC Surg 2008; 8:17. [PMID: 18816403 PMCID: PMC2565653 DOI: 10.1186/1471-2482-8-17] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2008] [Accepted: 09/24/2008] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Endoscopic resectional techniques for colon cancer are undermined by their inability to determine lymph node status. This limits their application to only those lesions at the most minimal risk of lymphatic dissemination whereas their technical capacity could allow intraluminal or even transluminal address of larger lesions. Sentinel node biopsy may theoretically address this breach although the variability of its reported results for this disease is worrisome. METHODS Medline, EMBASE and Cochrane databases were interrogated back to 1999 to identify all publications concerning lymphatic mapping for colon cancer with reference cross-checking for completeness. All reports were examined from the perspective of in vivo technique accuracy selectively in early stage disease (i.e. lesions potentially within the technical capacity of endoscopic resection). RESULTS Fifty-two studies detailing the experiences of 3390 patients were identified. Considerable variation in patient characteristics as well as in surgical and histological quality assurances were however evident among the studies identified. In addition, considerable contamination of the studies by inclusion of rectal cancer without subgroup separation was frequent. Indeed such is the heterogeneity of the publications to date, formal meta-analysis to pool patient cohorts in order to definitively ascertain technique accuracy in those with T1 and/or T2 cancer is not possible. Although lymphatic mapping in early stage neoplasia alone has rarely been specifically studied, those studies that included examination of false negative rates identified high T3/4 patient proportions and larger tumor size as being important confounders. Under selected circumstances however the technique seems to perform sufficiently reliably to allow it prompt consideration of its use to tailor operative extent. CONCLUSION The specific question of whether sentinel node biopsy can augment the oncological propriety for endoscopic resective techniques (including Natural Orifice Transluminal Endoscopic Surgery [NOTES]) cannot be definitively answered at present. Study heterogeneity may account for the variability evident in the results from different centers. Enhanced capacity (perhaps to the level necessary to consider selective avoidance of en bloc mesenteric resection) by its confinement to only early stage disease is plausible although not proven. Specific study of the technique in early stage tumors is clearly essential before proffering this approach.
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Affiliation(s)
| | - Joel Leroy
- Department of Surgery, IRCAD/EITS, Strasbourg, France
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Bembenek A, String A, Gretschel S, Schlag PM. Technique and clinical consequences of sentinel lymph node biopsy in colorectal cancer. Surg Oncol 2008; 17:183-93. [PMID: 18571920 DOI: 10.1016/j.suronc.2008.05.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Sentinel lymph node biopsy (SLNB) in colorectal cancer (CRC) is a controversial issue. Different detection techniques, various protocols for the histopathological work-up of the SLN and a greatly differing experience between the investigators make the comparison of the available studies problematic. Nevertheless, it is clear, that the successful clinical application of SLNB in breast cancer and melanoma cannot simply be transferred into colorectal cancer treatment. In this paper we try to define the current status of clinical application of this technique in CRC by means of a literature review and our own experience. Moreover, the background and the potential clinical implications of additionally small tumor deposits in the SLN (so-called "upstaging") is critically reviewed. Summarizing the results, it is clear, that the value of SLNB in CRC is still unclear. If current techniques are to be applied outside a study protocol and no patient selection is performed the correct identification of macrometastases needs further investigation. Although still under debate, there is otherwise growing evidence, that -at least if RT-PCR-techniques are used- the detection of small tumor deposits in the SLN may be of prognostic and therefore clinical value. Future studies should focus on two subjects: First, alternative detection techniques and careful patient selection may clarify, if an improvement of the sensitivity to detect macrometastases is feasible. Second, large prospective trials using a standardized histopathological lymph node assessment should compare SLN and Non-SLN for its incidence to bear small tumor deposits. If SLNB proves to be sensitive, the prognostic and predictive value of these additional findings should be clarified.
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Affiliation(s)
- Andreas Bembenek
- Department of Surgery and Surgical Oncology, Robert-Rössle-Klinik, Charité, Universitätsmedizin Berlin Campus Buch im Helios Klinikum Berlin, Schwanebecker Chaussee 50, 13125 Berlin, Germany.
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Pirro N, Pignodel C, Cathala P, Fabbro-Peray P, Godlewski G, Prudhomme M. The number of lymph nodes is correlated with mesorectal morphometry. Surg Radiol Anat 2008; 30:297-302. [PMID: 18309450 DOI: 10.1007/s00276-008-0322-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2007] [Accepted: 02/04/2008] [Indexed: 01/14/2023]
Abstract
BACKGROUND Lymph node involvement is one of the most significant prognostic factors of patients with rectal cancer. However, the distribution of mesorectal lymph nodes is not well known. This study was designed to assess lymph nodes in the mesorectum and to evaluate the correlation between the volume and weight of the mesorectum and the number of lymph nodes. METHODS The mesorectums of 20 human cadavers were studied. The volume and weight of the superior rectal mesentery, superior mesorectum and inferior mesorectum were measured. Lymph nodes were sought by manual dissection and were submitted for histological examination. The correlation between the number of lymph nodes and the volume and weight of the mesorectum was evaluated by non-parametric Spearman test. RESULTS A total of 178 lymph nodes were identified. The mean number of lymph nodes per specimen was 9.2 +/- 4.5. The lymph nodes were mostly smaller than 3 mm and located in the superior and posterior parts of the mesorectum. A positive correlation was found between the number of mesorectal lymph nodes and the volume and weight of the mesorectum. The number of lymph nodes in the superior rectal mesentery was independent of its volume and its weight. CONCLUSIONS Mesorectal lymph nodes are mainly located above the peritoneal reflection within the posterior mesorectum. The positive correlation between the volume or the weight of the mesorectum and the number of mesorectal lymph nodes should be considered as a possible means to determine the minimum number of mesorectal lymph nodes required for histological examination.
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Affiliation(s)
- N Pirro
- Department of Digestive Surgery, Hôpital La Timone, 264 rue Saint Pierre, 13385 Marseille Cedex 5, France.
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Abstract
Despite near-universal embrace of the concept and clinical relevance of lymphatic mapping for sentinel node identification and analysis for cancers of the breast and integument, the same technique has struggled to a find a role in gastrointestinal cancers in general and, perhaps, in colon cancer in particular. Despite many studies demonstrating its feasibility in malignancies of the large bowel, concern is continually aroused by the variable and often unacceptably low sensitivity rates. Additionally, many confess uncertainty as to what benefit it could ever confer to patients even if it were proven sufficiently accurate given that standard surgical resection incorporates mesenteric resection anyway. However, the huge impact sentinel node mapping has had on clinical practice in certain cancers means that each of these aspects merit careful reconsideration, from very first principles.
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Bembenek A, Gretschel S, Schlag PM. Sentinel lymph node biopsy for gastrointestinal cancers. J Surg Oncol 2007; 96:342-52. [PMID: 17726666 DOI: 10.1002/jso.20863] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Sentinel lymph node biopsy (SLNB) in gastrointestinal-(GI)-tract cancer is not yet of clinical relevance. Nevertheless, the results in the upper GI-tract promise to be helpful to individualize the indication for surgical therapy. SLNB in colon cancer still fails to show high validity to predict the nodal status, but may be helpful to clarify the prognostic role of micrometastases/isolated tumor cells. In anal cancer SLNB is able to guide the indication for groin irradiation.
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Affiliation(s)
- A Bembenek
- Department of Surgery and Surgical Oncology, Robert-Rössle-Klinik, Charité Universitätsmedizin Berlin, Campus Buch, Lindenberger, Berlin, Germany
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