Surgical resection and lymphadenectomy are the mainstay of curative treatment for oesophagogastric cancer. In this study we evaluate the results of intravascular methylene blue injection into oesophagectomy and gastrectomy specimens as a tool to increase lymph node detection.
A prospective and descriptive study was run on 24 patients (11 oesophagus, 13 stomach cases). The most frequent histological type was adenocarcinoma (oesophagus 29.2%, stomach 90.9%). All patients with oesophageal cancer received neoadjuvant treatment, compared to 8 with gastric cancer. The anatomopathological analysis of oesophagectomies showed a median of 42 isolated nodes, compared to 46 in gastrectomies. In oesophageal cancer, a total of 8 (72.7%) patients did not show lymphatic involvement, whereas, in gastric cancer patients, 76.9% of patients had lymph nodes, with a median number of positive nodes of 3 (RIC = 0.5–7).
Instillation of methylene blue enables a large number of nodes to be analysed and could therefore improve staging, treatment and prognosis for patients with oesophagogastric cancer.
La resección quirúrgica y la linfadenectomía son la base del tratamiento curativo del cáncer de esófagogástrico. En este estudio evaluamos los resultados de la inyección intravascular de azul de metileno en muestras de esofagectomía y gastrectomía como herramienta para aumentar la detección de ganglios linfáticos.
Se realizó un estudio prospectivo y descriptivo en 24 pacientes (11 casos de esófago, 13 de estómago). El tipo histológico más frecuente fue el adenocarcinoma (esófago 29,2%, estómago 90,9%). Todos los pacientes con cáncer de esófago recibieron tratamiento neoadyuvante, frente a 8 con cáncer gástrico. El análisis anatomopatológico de las esofagectomías mostró una mediana de 42 ganglios aislados, frente a 46 en las gastrectomías. En el cáncer de esófago, un total de 8 (72,7%) pacientes no presentaron afectación linfática, mientras que, en los pacientes con cáncer gástrico, el 76,9% de los pacientes presentaban ganglios linfáticos, con una mediana de ganglios positivos de 3 (RIC = 0,5–7).
La instilación de azul de metileno permite analizar un gran número de ganglios y, por tanto, podría mejorar la estadificación, el tratamiento y el pronóstico de los pacientes con cáncer de esófagogástrico.
The treatment of esophageal and stomach cancer must be approached from a multidisciplinary approach, with surgical resection associated with a correct lymphadenectomy being the pillar of curative treatment. Currently, there are certain recommendations for the extent of lymphadenectomy and the minimum number of nodes that should be surgically removed depending on the stage of this type of tumor,1–5 with the removal and analysis of a greater number of nodes having been related to better tumor staging and survival.6–8
In order to achieve a correct staging and more appropriate treatment, different techniques have been proposed to achieve a more exhaustive study of the surgical specimens and increase the performance of the histopathological study.5,9 In the present study, the results of the intravascular injection are presented of ex vivo methylene blue in the surgical specimen of esophagectomy and gastrectomy as a tool to improve the detection of lymph nodes for their anatomopathological study.
Surgical techniqueA prospective and descriptive study was carried out on 24 patients operated on for oesophageal cancer (n = 11) and stomach cancer (n = 13) during the period from June 2022 to March 2024 at the Hospital Politècnic i Universitari La Fe.
Prior to surgery, all patients were informed of the aim of the project and the possibility of their inclusion, while respecting their confidentiality. One of the criteria for inclusion in the present study was the acceptance and signing of the informed consent prior to surgery.
The median age was 68.5 years (63–74). Regarding cardiovascular risk factors, 19 (57.6%) patients had at least one factor, the most frequent being smoking (n = 14), followed by arterial hypertension (n = 12) and diabetes (n = 7).
The most frequent histological type diagnosed was adenocarcinoma, both in oesophageal cancer (29.2%) and gastric cancer (90.9%).
All patients diagnosed with oesophageal neoplasia received neoadjuvant treatment (QT n = 4; QT-RT n = 7), while of the patients with gastric neoplasia, 5 did not require this.
The surgical approach was by minimally invasive surgery in 83.3% (n = 20) of the cases, with a switch to open surgery being necessary in 4 of them. In the oesophageal cancer group, the most commonly used surgical technique was McKeown-type oesophagectomy (n = 8) accompanied by standard lymphadenectomy in 1 case, extended (including right recurrent nodes) in 4 cases, and total lymphadenectomy (including left recurrent nodes) in 6 patients. Considering the patients who underwent gastrectomy, 6 underwent subtotal gastrectomy and 7 underwent total gastrectomy. The lymphadenectomy performed in this group of patients was the D1+ type in 10 cases, with D1 lymphadenectomy in the remaining 3.
Once the surgical specimen had been removed en bloc, a dilution of 50 mg of methylene blue in 30 ml of saline solution was used for the instillation of the dye through a 16fr intravascular catheter, proceeding, after instillation, to ligate the vessel to prevent any loss once 10 ml of this solution had been injected.
The dye was instilled through the left gastric vein and artery in most cases (n = 17 (70.8%) and n = 14 (58.3%), respectively). In 5 of the patients who underwent gastrectomy, the dye was also injected through the right gastroepiploic vein and artery, with no significant differences between the two groups.
The instillation of the dye was performed immediately after the removal of the surgical specimen by one of the surgeons and always before the separation of the lymph nodes, which is why, in the oesophageal cancer group, despite performing the instillation of the dye through the coronary vein, this enabled the detection of paratracheal and infracarinal nodes.
All the specimens were subsequently fixed with 10% formaldehyde and sent for anatomopathological study, processing and obtaining 3 mm samples stained with haematoxylin-eosin. One single pathologist was in charge of reviewing each of the samples, confirming the staining of all the lymph node groups under study.
Overall, the median number of isolated and positive nodes after analysis (N+) was 43 (21–67) and 1 (0–17), respectively.
After performing a differential analysis depending on the tumour location and lymphadenectomy performed, in the gastric cancer group, the median number of isolated nodes was 47 (25–65) in D1+ lymphadenectomy versus 27 (25–67) in D1 lymphadenectomy. In the oesophageal cancer group, the median was 41 (27–60) in extended lymphadenectomy and 36 (21–48) in total lymphadenectomy.
We were able to observe that in all our patients there was an analysis of more than 12–15 lymph nodes, thus following the recommendations of clinical guidelines, which stipulate the need to analyse at least 12–15 nodes to carry out an adequate histopathological study.
When performing a comparative analysis with a retrospective cohort from the period between 2020 and 2022 in patients operated on for gastric and oesophageal cancer, whose surgical specimens had not been treated with methylene blue, we observed a higher median of nodes analysed in our experimental group (Table 1).
Within oesophageal neoplasms, a total of 8 (72.7%) patients did not demonstrate lymphatic involvement after histopathological analysis. Regarding patients with gastric cancer, 10 (76.9%) were found to have affected lymph nodes, with the median number of positive nodes being 3 (0–17).
Based on the Ryan score to assess the pathological response after neoadjuvant treatment in patients with oesophageal cancer, 54.5% (n = 6) showed a grade 2 response (minimal response) in the surgical specimen. In the gastric cancer group, in those who received neoadjuvant treatment (69.2% n = 8), an absence of response (grade 3) was observed in up to 50% of cases (n = 4).
With regard to adjuvant treatment, 16 patients received adjuvant therapy, while 6 did not receive any type of postoperative treatment, with 2 patients currently awaiting assessment by the oncology unit to decide on the need for adjuvant therapy.
During follow-up, 1 death occurred due to progression of gastric tumour disease.
DiscussionThe high rate of relapse and recurrence of oesophageal and stomach cancers makes a correct and accurate assessment of surgical specimens essential. Consequently, dissection and exhaustive analysis of the excised nodes takes on major importance as regards correct pathological staging, administration of treatments and calculation of the prognosis. Currently, the NCCN guidelines recommend excision of at least 15 lymph nodes for better oncological outcomes in esophagogastric cancer. However, in the recommendations of the literature reviewed, the number of nodes varies from 10 (pN0) to 30 (pN+).1,2,5,6,8,10,11
Understaging of the disease sometimes leads to inadequate treatment, thereby increasing the risk of metastasis and recurrence, so the effective removal and analysis of surgical specimens is essential. Thus, the lymphatic extraction rate can be affected by factors such as neoadjuvant therapy, lymph node size, tumour location, immunological reaction or surgical technique.7,8,11
Over the last few years, new methods have been developed to increase the performance of lymphadenectomy. These include polymerase chain reaction, (PCR) adipose tissue cleaning, sentinel lymph node or immunohistochemical study. However, all of these involve high cost, a long learning curve and lengthy execution time.6,7
As an alternative, methylene blue injection into the surgical specimen is proposed, considered a simpler technique that could enable the detection of a greater number of lymph nodes. The injection of this dye through the vessels increases its concentration in the lymph nodes, making it easier for the pathologist to identify them, as other studies in colorectal surgery have suggested.7,8
However, this technique can be more complex in oesophagogastric surgery due to the calibre of the vessels, the anatomy and vascular variants and the characteristics of the mesenteries.6 In this area, some groups have studied gastrectomy specimens with statistically significant results in favour of a greater number of nodes analysed after the use of the dye, especially in small nodes (1–6 mm) without any side effects or greater risk for patients.6,11
In the present study, despite its purely descriptive design on a small sample size, it is shown that with intravascular instillation of methylene blue in the ex-vivo specimens, a high number of lymph nodes were obtained for histopathological analysis. Currently, a prospective and comparative study with a control cohort is being carried out at our centre to assess the real usefulness of this procedure, its impact on histopathological analysis and the application of adjuvant treatments, as well as its possible involvement in the prognosis and survival of these patients.
FundingNo organisations funded the study.
After writing this article, I would like to recognise my colleagues for their involvement and dedication, especially the residents who assisted and collaborated in the study, as well as the Esophagogastric Surgery Unit for their professionalism and assistance in the development of this research.
