Un reto multidisciplinar: tratamiento con fósforo-32 en el carcinoma de páncreas localmente avanzado / A multidisciplinary challenge: Therapy with phosphorus-32 for locally advanced pancreatic cancer

El cáncer de páncreas es una enfermedad de pronóstico precario, siendo su supervivencia global la que menos ha mejorado en los últimos 40 años entre todos los cánceres. El adenocarcinoma de páncreas localmente avanzado, sin metástasis a distancia, pero con una afectación vascular limitante, constituye casi un tercio de estos pacientes. En este grupo se concentran gran parte de los esfuerzos investigadores para introducir tratamientos que permitan un aumento de las tasas de rescate quirúrgico y/o de la supervivencia, con 2 objetivos fundamentales: el del control local y el de la prevención de la progresión sistémica. El tratamiento intratumoral con micropartículas de fósforo-32, guiado por ecoendoscopia y combinado con quimioterapia estándar puede tener beneficios significativos y clínicamente relevantes en estos pacientes y, por tanto, una opción valiosa de tratamiento en una enfermedad en la que existe una necesidad urgente de desarrollar nuevas terapias que nos ayuden a mejorar los resultados (AU)

Pancreatic cancer is a disease with a poor prognosis, and overall survival has improved the least in the last 40 years of all cancers. Locally advanced pancreatic adenocarcinoma, without distant metastasis but with limiting vascular involvement, constitutes almost one third of these patients. This group is the focus of most research efforts to introduce treatments to increase surgical salvage rates and/or survival, with two main objectives: local control and prevention of systemic progression. Intratumoural treatment with phosphorus-32 microparticles, guided by echoendoscopy and combined with standard chemotherapy may have significant and clinically relevant benefits in these patients, and therefore a valuable treatment option in a disease where there is an urgent need to develop new therapies to help improve outcomes (AU)

A multidisciplinary challenge: Therapy with phosphorus-32 for locally advanced pancreatic cancer.

Pancreatic cancer is a disease with a poor prognosis, and overall survival has improved the least in the last 40 years of all cancers. Locally advanced pancreatic adenocarcinoma, without distant metastasis but with limiting vascular involvement, constitutes almost one third of these patients. This group is the focus of most research efforts to introduce treatments to increase surgical salvage rates and/or survival, with two main objectives: local control and prevention of systemic progression. Intratumoural treatment with phosphorus-32 microparticles, guided by echoendoscopy and combined with standard chemotherapy may have significant and clinically relevant benefits in these patients, and therefore a valuable treatment option in a disease where there is an urgent need to develop new therapies to help improve outcomes.

Usefulness of histological superstudy of sentinel lymph nodes detected with radioisotopes in colon cancer.

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.

Usefulness of histological superstudy of sentinel node detected with radioisotope in colon cancer. / Utilidad del superestudio anatomopatológico de ganglio centinela detectado con radioisótopos en el cáncer de colon.

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.

Carcinoma de Merkel nasal con biopsia del ganglio centinela y reconstrucción con colgajo frontal / Merkel cell carcinoma of the nose with sentinel lymph node biopsy and reconstruction with frontal flap

El carcinoma de células de Merkel (CM) es una neoplasia neuroendocrina agresiva, en la que está indicada la biopsia del ganglio centinela (BGC) para una correcta estadificación ganglionar regional. El tratamiento habitual del CM es la resección quirúrgica amplia con radioterapia adyuvante, reservandola quimioterapia para casos recurrentes o diseminados. Presentamos el caso de un varón de 83 años con un CM nasal, al que se realizó una BGC, una resección nasal subtotal y reconstrucción con colgajo frontal para mediano (AU)

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine neoplasm in which sentinel lymph node biopsy (SLNB) is indicated to perform the correctregional staging. The usual treatment is surgery with wide margins and adjuvant radiation therapy, while systemic chemotherapy is reserved for recurrentor disseminated disease. We present the case of an 83 year old man with a MCC of the nose, in which a SLNB, subtotal excision of the nose and reconstruction with a paramedian forehead flap was done (AU)

[An ACTH-secreting carcinoid tumor of the thymus. A report of a new case]. / Tumor carcinoide de timo secretor de ACTH. Presentación de un nuevo caso.

Carcinoid tumour of the thymus is a rare condition, with less than a hundred cases reported in the literature. Diagnosis is complex as they are usually asymptomatic. We describe a case of a severe Cushing syndrome developed in a 51-year-old man. The diagnosis of a thymic carcinoid was established. Three years ago, the patient was treated by surgical resection of an anterior mediastinal mass. A massive tumour dissemination was detected by MIBG and CT image techniques. Both techniques are currently considered useful for this kind of diagnosis. ACTH secretion was detected immunohistochemically. Although the treatment with SMS-201-995 octreotide was effective in controlling the clinical symptoms, the patient died three months later with extensive metastases. The carcinoid tumours of the thymus associated to Cushing syndrome are aggressive tumours and usually produce local and distant metastases.