Superexpressão do receptor de Inositol 1,4, 5-trifosfato isoforma 3 (ITPR3) em colangiocarcinoma e sua correlação com a proteína dependente de cálcio S100A4 / Inositol 1,4, 5-triphosphate receptor isoform 3 (ITPR3) overexpression in cholangiocarcinoma and its correlation with calcium-dependent protein S100A4

O colangiocarcinoma (CCA) é a segunda neoplasia mais maligna do fígado que surge na árvore biliar. O CCA está associado com mau prognóstico e os principais fatores envolvidos em sua patogênese não são bem compreendidos. Os receptores tirosina quinases (RTKs), como o receptor do fator de crescimento epidérmico (EGFR), podem mediar as vias de sinalização de cálcio intracelular (Ca 2+ ), via inositol 1,4,5-trifosfato (InsP3). Eles ativam os receptores 1,4,5-trifosfato (ITPRs) e regulam o crescimento tumoral. ITPR isoforma 3 é o principal canal de liberação intracelular de Ca 2+ em colangiócitos. Os efeitos do Ca 2+ intracelular, por sua vez são mediados por proteínas de ligação de cálcio, como calmodulina e proteína A4 de ligação de cálcio S100 (S100A4). No entanto, o significado clínico patológico e biológico de EGFR, ITPR3 e S100A4 no CCA permanece obscuro. Assim, o presente trabalho investiga a imuno exprepressão dessas três proteínas em 59 pacientes diagnosticados com CCA, submetidos a tratamento cirúrgico curativo e correlaciona os dados com características clínico-patológicas e sobrevida. A alta expressão de ITPR3 foi correlacionada com os níveis de CA 19-9, estágio TNM e metástases em linfonodos (N). Além disso, a expressão de ITPR3 foi aumentada em CCA distal em comparação com ductos biliares de controle e CCAs intra-hepáticos e peri-hilares. Os escores clínicos ITPR3 e S100A4 foram significativamente correlacionados. Em resumo, a super expressão de ITPR3 pode contribuir para a progressão da CCA e pode representar um potencial alvo terapêutico. Palavras-chave: ITPRs; ITPR3; S100A4; Colangiocarcinoma; Fígado; Câncer

Cholangiocarcinoma (CCA) is the second most malignant neoplasm in the liver that arises from the biliary tree. CCA is associated with a poor prognosis, and the key players involved in its pathogenesis are still not well understood. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), can mediate intracellular calcium (Ca2+) signaling pathways via inositol 1,4,5trisphosphate (InsP3), activating inositol 1,4,5-trisphosphate receptors (ITPRs) and regulating tumor growth. ITPR isoform 3 (ITPR3) is the main intracellular Ca2+ release channel in cholangiocytes. The effects of intracellular Ca2+ are mediated by calciumbinding proteins such as Calmodulin and S100 calcium-binding protein A4 (S100A4). However, the clinicopathological and biological significance of EGFR, ITPR3 and S100A4 in CCA remains unclear. Thus, the present work investigates the immunoexpression of these three proteins in 59 CCAs from patients who underwent curative surgical treatment and correlates the data with clinicopathological features and survival. High ITPR3 expression was correlated with CA 19-9 levels, TNM stage and lymph node metastasis (N). Furthermore, ITPR3 expression was increased in distal CCA compared to control bile ducts and intrahepatic and perihilar CCAs. In summary, ITPR3 overexpression could contribute to CCA progression and it may represent a potential therapeutic target.

Estadiaje ganglionar en el adenocarcinoma gástrico / Lymph node stage in gastric adenocarcinoma

Resumen Objetivos: El sistema linfático del estómago es complejo y multidireccional, siendo difícil predecir el patrón de diseminación linfática en el adenocarcinoma (ADC) gástrico. Los objetivos de este trabajo son determinar si el analizar los grupos ganglionares de la pieza quirúrgica por separado tiene implicaciones en el estadiaje, además estudiar la afectación de diferentes grupos ganglionares. Materials y Método: Estudio observacional retrospectivo de pacientes intervenidos de gastrectomía y linfadenectomía con intención curativa por ADC en un hospital de referencia (2017-2021).,_Se han comparado aquellos pacientes cuya pieza quirúrgica se estudió en su totalidad (grupo A) con aquellos en los que se separaron los grupos ganglionares para su análisis (grupo B). En el grupo B, se ha analizado la afectación ganglionar de diferentes grupos ganglionares en base a la localización tumoral y el estadio pT. Resultados: Se incluyeron 150 pacientes. La media de ganglios analizados fue significativamente mayor cuando se separaron los grupos ganglionares (grupo B) (24,01 respecto a 20,49). La afectación ganglionar fue del 45,8%, 58,3% y 55,5% en los tumores de tercio superior, medio e inferior respectivamente, y los grupos difirieron en base a la localización tumoral. El riesgo de afectación ganglionar fue significativamente mayor y hubo más grupos ganglionares perigástricos afectos cuanto mayor era el estadio pT. Conclusiones: Separar los grupos ganglionares previo a su análisis aumenta el número de ganglios analizados mejorando el estadiaje ganglionar. Existen diferentes rutas de drenaje linfático dependiendo de la localización tumoral y la afectación ganglionar aumenta de forma paralela al estadio pT.

Objectives: The lymphatic system of the stomach is complex and multidirectional, making it difficult to predict the pattern of lymphatic spread in gastric adenocarcinoma (GAC). The aim of this paper is to determine if analyzing the lymph node groups of the surgical specimen separately has implications in the pathological staging, as well as to study the involvement rate of different lymph node groups. Material and Method: Retrospective observational study of patients who underwent curative intent gastrectomy and lymphadenectomy for GAC in a reference hospital (2017-2021). Those patients whose surgical specimen was studied as a whole (group A) were compared with those in whom the lymph node groups were separated by surgeons before analysis (group B). In group B, the involvement of different lymph node groups was analyzed based on tumor location and pT stage. Results: 150 patients were included. The mean number of lymph nodes analyzed was significantly higher when the lymph node groups were separately analyzed (group B) (24.01 compared to 20.49). Lymph node involvement was 45.8%, 58.3%, and 55.5% in tumors of the upper, middle, and lower third, respectively, and the involved groups differed depending on the tumor location. The higher the pT stage was, the risk of lymph node involvement was significantly higher and there were more perigastric lymph node groups affected. Conclusions: Separating lymph node groups prior to their analysis increases the number of lymph nodes analyzed and therefore improves lymph node staging. There are different lymphatic drainage routes depending on the tumor location and lymph node involvement increases in parallel with the pT stage.

Surgical roles in the management of metachronus para-aortic lymph node recurrence and synchronous para-aortic lymph node metastasis in colorectal cancer patients

Background: The relative rarity of synchronous para-aortic lymph node (PALN) metastasis (SPM) and metachronous PALN recurrence (MPR) in colorectal carcinoma (CRC) patients leads to a limited number of studies on patient management, and no treatment guidelines have been established to date. Objective: To assess the prognostic, predictive roles, and long-term outcomes of different management strategies for isolated MPR and SPM in CRC patients to establish the best one. Materials and Methods: We included 35 CRC patients with isolated MPR and 25 patients with isolated SPM who underwent curative R0 resection. We performed PALN dissection (PALND) in 15 cases in MPR group and in 10 cases in the SPM group; all remaining patients in both groups underwent chemoradiotherapy (CRT) without further surgical intervention. During the study period of about 5 years, we compared the patients who underwent PALND and those who underwent CRT. Results: The overall survival and recurrence-free survival rates were significantly longer in patients who underwent PALND (p = 0.049 and 0.036 respectively). (AU)

Analysis of the related risk factors of inguinal lymph node metastasis in patients with penile cancer: A cross-sectional study

ABSTRACT Purpose: To determine independent predictors of inguinal lymph node (ILN) metastasis in patients with penile cancer. Patients and methods: We retrospectively analyzed all patients with penile cancer who underwent surgery at our medical center in the last ten years (n=157). Using univariate and multivariate logistic-regression models, we assessed associations with age, medical-history, phimosis, onset-time, number and maximum diameter of involved ILNs measured by imaging, pathological T stage, degree of tumor differentiation and/or cornification, lymphatic vascular infiltration (LVI), nerve infiltration, and ILN metastases. Interaction and stratified analyses were used to assess age, phimosis, onset time, number of ILNs, cornification, and nerve infiltration. Results: A total of 110 patients were included in the study. Multiple logistic regression analysis showed that the following factors were significantly correlated with ILN metastasis: maximum diameter of enlarged ILNs, T stage, pathological differentiation, and LVI. Among patients with a maximum ILN diameter ≥1.5cm, 50% had lymph node metastasis whereas 30.6% patients with a maximum ILN diameter <1.5cm showed LNM. Among 44 patients with stage Ta/T1, 10 showed ILN metastases, while 47.0% patients with stage T2 showed ILN metastases. Among 40 patients with highly differentiated penile-cancer, eight showed ILN metastasis, while 47.1% patients with low-to-middle differentiation showed ILN metastases. The rate of LNM was 33.3% in the LVI-free group and 64.3% in the LVI group. Conclusion: Our single-center results suggested that maximum ILN diameter, pathological T stage, pathological differentiation, and LVI were independent risk factors for ILN metastases.

Hidradenoma nodular maligno / Malignant Nodular Hidradenoma

Introducción: El hidradenoma nodular maligno es un tumor maligno de glándula sudorípara ecrinas, poco común, considerada una lesión de diferenciación anexial ecrinas, que generalmente surge de nuevo, aunque se han descrito unos pocos casos surgidos sobre un hidradenoma nodular. Es decir, representa la contrapartida maligna del hidradenoma nodular. Objetivo: Dar a conocer la presentación de un caso, dada la inusual aparición de esta entidad, con revisión de los criterios para su diagnóstico. Caso clínico: Se informa el caso de un hombre de 74 años de edad con una neo formación en la región parietal derecha del cuero cabelludo. Conclusiones: Debemos pensar en un hidradenoma nodular maligno ante un tumor solitario, firme o fluctuante, infrecuente en el cuero cabelludo, con curso agresivo, recurrencias y metástasis ganglionares y confirmar su diagnóstico con el estudio inmunohistoquímico(AU)

Introduction: Malignant nodular hidradenoma is a rare malignant eccrine sweat gland tumor considered a lesion of eccrine adnexal differentiation, which usually arises again, although a few arising cases on nodular hidradenoma have been described. In other words, it represents the malignant counterpart of nodular hidradenoma. Objective: To report a case, given the unusual occurrence of this entity, with a review of the criteria for its diagnosis. Case report: We report the case of a 74-year-old man with a neoformation in the right parietal region of the scalp. Conclusions: We should consider a malignant nodular hidradenoma when faced with a solitary, firm or fluctuant tumor, rare in the scalp, with aggressive evolution, recurrences and lymph node metastasis, and confirm its diagnosis with immunohistochemical study(AU)

An easy and practical prognostic parameter: tumor-stroma ratio in Luminal, Her2, and triple-negative breast cancers

SUMMARY OBJECTIVE: The stroma surrounding the tumor cells is important in tumor progression and treatment resistance, besides the properties of tumor cells. Studies on the tumor stroma characteristics will contribute to the knowledge for new treatment approaches. METHODS: A total of 363 breast cancer patients were evaluated for the tumor-stroma ratio. The percentage of stroma was visually assessed on hematoxylin-eosin stained slides. The cases of tumor-stroma ratio more than 50% were categorized as tumor-stroma ratio high, and those less than 50% and below were categorized as tumor-stroma ratio low. RESULTS: Tumor-stroma ratio-high tumors had shorter overall survival (p=0.002). Disease-free survival tended to be shorter in tumor-stroma ratio-high tumors (p=0.082) compared with tumor-stroma ratio-low tumors. Tumor-stroma ratio was an independent prognostic parameter for the total group of patients (p=0.003) and also axillary lymph node metastasis and tumor-stroma ratio was statistically associated (p=0.004). Also, tumor-stroma ratio was an independent prognostic parameter in node-positive Luminal A and B subgroups for overall survival (p<0.001). CONCLUSION: Tumor-stroma ratio is an independent prognostic parameter that can be evaluated quite easily in all molecular subtypes of all breast cancers and does not require extra cost and time to evaluate.

Construction of a nomogram prediction model for pathological complete response (pCR) of ipsilateral supraclavicular lymph node after neoadjuvant chemotherapy for breast cancer with first diagnosis of ipsilateral supraclavicular lymph node metastasis / 中华肿瘤杂志

Objective: To develop a predictive model for pathologic complete response (pCR) of ipsilateral supraclavicular lymph nodes (ISLN) after neoadjuvant chemotherapy for breast cancer and guide the local treatment. Methods: Two hundred and eleven consecutive breast cancer patients with first diagnosis of ipsilateral supraclavicular lymph node metastasis who underwent ipsilateral supraclavicular lymph node dissection and treated in the Breast Department of Henan Cancer Hospital from September 2012 to May 2019 were included. One hundred and forty two cases were divided into the training set while other 69 cases into the validation set. The factors affecting ipsilateral supraclavicular lymph node pCR (ispCR)of breast cancer after neoadjuvant chemotherapy were analyzed by univariate and multivariate logistic regression analyses, and a nomogram prediction model of ispCR was established. Internal and external validation evaluation of the nomogram prediction model were conducted by receiver operating characteristic (ROC) curve analysis and plotting calibration curves. Results: Univariate logistic regression analysis showed that Ki-67 index, number of axillary lymph node metastases, breast pCR, axillary pCR, and ISLN size after neoadjuvant chemotherapy were associated with ispCR of breast cancerafter neoadjuvant chemotherapy (P<0.05). Multivariate logistic regression analysis showed that the number of axillary lymph node metastases (OR=5.035, 95%CI: 1.722-14.721, P=0.003), breast pCR (OR=4.662, 95%CI: 1.456-14.922, P=0.010) and ISLN size after neoadjuvant chemotherapy (OR=4.231, 95%CI: 1.194-14.985, P=0.025) were independent predictors of ispCR of breast cancer after neoadjuvant chemotherapy. A nomogram prediction model of ispCR of breast cancer after neoadjuvant chemotherapy was constructed using five factors: number of axillary lymph node metastases, Ki-67 index, breast pCR, axillary pCR and size of ISLN after neoadjuvant chemotherapy. The areas under the ROC curve for the nomogram prediction model in the training and validation sets were 0.855 and 0.838, respectively, and the difference was not statistically significant (P=0.755). The 3-year disease-free survival rates of patients in the ispCR and non-ispCR groups after neoadjuvant chemotherapy were 64.3% and 54.8%, respectively, with statistically significant differences (P=0.024), the 3-year overall survival rates were 83.8% and 70.2%, respectively, without statistically significant difference (P=0.087). Conclusions: Disease free survival is significantly improved in breast cancer patients with ispCR after neoadjuvant chemotherapy. The constructed nomogram prediction model of ispCR of breast cancer patients after neoadjuvant chemotherapy is well fitted. Application of this prediction model can assist the development of local management strategies for the ipsilateral supraclavicular region after neoadjuvant chemotherapy and predict the long-term prognosis of breast cancer patients.

Impact of the examined number of lymph nodes at N1 station on the prognosis of patients with pT1-3N0M0 non-small cell lung cancer / 中华肿瘤杂志

Objective: To investigate the relationship between the examined number of lymph nodes at the N1 station and the clinicopathological characteristics and prognosis of patients with pT1-3N0M0 non-small cell lung cancer (NSCLC). Methods: A total of 337 patients with pT1-3N0M0 NSCLC who underwent radical lung cancer surgery at the Provincial Hospital Affiliated to Anhui Medical University from January 2013 to March 2015 were selected. The receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off value for predicting 5-year survival in pT1-3N0M0 NSCLC patients by the examined number of lymph nodes at the N1 station. The relationships between the examined number of lymph nodes at the N1 station and the clinicopathological characteristics and prognosis of patients with pT1-3N0M0 NSCLC were analyzed according to the optimal cut-off group. Results: A total of 1 321 lymph nodes at N1 station were examined in 337 patients, with a mean of 3.9 nodes per patient. The median survival time was 42.0 months, with 1-, 3- and 5-year survival rates of 82.2%, 57.1% and 24.9%, respectively. ROC curve analysis showed that the optimal cut-off value of 4.5 lymph nodes examined at the N1 station was used to predict 5-year survival in patients with pT1-3N0M0 NSCLC. After rounding off the number, the number of lymph nodes examined at the N1 station was 5 as the cut-off value, and the patients were divided into the group with <5 lymph nodes examined (212 cases) and the group with ≥5 lymph nodes examined (125 cases). The proportion of patients received adjuvant chemotherapy was 19.2% in the group with ≥5 lymph nodes examined, which was higher than 9.0% in the group with <5 lymph nodes examined (P=0.007), and the differences in other clinicopathological characteristics between the two groups were not statistically significant (P>0.05). The median survival time for patients in the group with <5 lymph nodes examined was 38.0 months, with 1-, 3- and 5-year survival rates of 80.1%, 52.5% and 15.6%, respectively. The median survival time for patients in the group with ≥5 lymph nodes examined was 48.0 months, and the 1-, 3- and 5-year survival rates were 85.6%, 64.0% and 36.0%, respectively. The survival rate of patients in the group with ≥5 lymph nodes examined was better than that in the group with <5 lymph nodes examined (P=0.002). Multifactorial Cox regression analysis showed that T stage (OR=1.408, 95% CI: 1.118-1.670) and the examined number of lymph nodes at N1 station (OR=0.670, 95% CI: 0.526-0.853) were independent influence factors for the prognosis of pT1-3N0M0 NSCLC patients. Conclusion: The examined number of lymph nodes at the N1 station is associated with the prognosis of patients with pT1-3N0M0 NSCLC, and the examination of at least 5 lymph nodes at N1 station at the time of postoperative pathological examination improves the 5-year survival rate of patients.

Biochemical Relapse in Low-risk Prostate Cancer Treated with Radical Prostatectomy and Bilateral Pelvic Lymphadenectomy / Recaída bioquímica en cáncer de próstata de bajo riesgo tratado con prostatectomía radical y linfadenectomía pélvica bilateral

Introduction For low-risk prostate cancer (PCa), curative treatment with radical prostatectomy (RP) can be performed, reporting a biochemical relapse-free survival rate (bRFS) at 5 and 7 years of 90.1% and 88.3%, respectively. Prostatic specific antigen (PSA), pathological stage (pT), and positive margins (R1) are significant predictors of biochemical relapse (BR). Even though pelvic lymphadenectomy is not recommended during RP, in the literature, it is performed in 34% of these patients, finding 0.37% of positive lymph nodes (N1). In this study, we aim to evaluate the 10-year bRFS in patients with low-risk PCa who underwent RP and extended pelvic lymph node dissection (ePLND). Methodology All low-risk patients who underwent RP plus bilateral ePLND at the National Cancer Institute of Colombia between 2006 and 2019 were reviewed. Biochemical relapse was defined as 2 consecutive increasing levels of PSA > 0.2 ng/mL. A descriptive analysis was performed using the STATA 15 software (Stata Corp., College Station, TX, USA), and the Kaplan-Meier curves and uni and multivariate Cox proportional hazard models were used for the survival outcome analysis. The related regression coefficients were used for the hazard ratio (HR), and, for all comparisons, a two-sided p-value ˂ 0.05 was used to define statistical significance. Results Two hundred and two patients met the study criteria. The 10-year bRFS for the general population was 82.5%, statistically related to stage pT3 (p = 0.047), higher Gleason grade group (GG) (p ≤ 0.001), and R1 (p ≤ 0.001), but not with N1. A total of 3.9% of the patients had N1; of these, 75% had R1, 25% GG2, and 37% GG3. Among the N0 (non-lymph node metástasis in prostate cáncer) patients, 31% of the patients had R1, 41% GG2, and 13% GG3. Conclusions Our bRFS was 82.5% in low-risk patients who underwent RP and ePLND. With higher pT, GG, and presence of R1, the probability of BR increased. Those with pN1 (pathologicaly confirmed positive lymph nodes) were not associated with bRFS, with a pN1 detection rate of 3.9%. Details: In low-risk PCa, curative treatment with RP can be performed, reporting a bRFS rate at 5 and 7 years of 90.1% and 88.3%, respectively. Despite the fact that pelvic lymphadenectomy is not recommended during RP in clinical guidelines, in the literature, it is performed in 34% of these patients, finding 0.37% of N1. In this study, we report the 10-year bRFS in patients with low-risk PCa who underwent surgery.

Introducción En el cáncer de próstata (CaP) de bajo riesgo se puede realizar un tratamiento curativo mediante prostatectomía radical (PR), con una tasa de supervivencia libre de recaída bioquímica (SLRb) a 5 y 7 años del 90,1% y el 88,3%, respectivamente. El antígeno prostático específico (PSA), el estadio patológico (pT) y los márgenes positivos (R1) son predictores significativos de recaída bioquímica (BR). Aunque la linfadenectomía pélvica no está recomendada durante la PR, en la literatura se realiza en el 34% de estos pacientes, encontrándose un 0,37% de ganglios linfáticos positivos (N1). En este estudio, nuestro objetivo es evaluar la SLB a 10 años en pacientes con CaP de bajo riesgo sometidos a PR y disección ganglionar pélvica extendida (DGLPe). Metodología Se revisaron todos los pacientes de bajo riesgo sometidos a PR más ePLND bilateral en el Instituto Nacional de Cancerología de Colombia entre 2006 y 2019. La recaída bioquímica se definió como 2 niveles crecientes consecutivos de PSA > 0,2 ng/mL. Se realizó un análisis descriptivo utilizando el software STATA 15 (Stata Corp., College Station, TX, USA), y se utilizaron las curvas de Kaplan-Meier y los modelos uni y multivariados de riesgos proporcionales de Cox para el análisis de resultados de supervivencia. Los coeficientes de regresión relacionados se utilizaron para la hazard ratio (HR), y, para todas las comparaciones, se utilizó un valor p de dos caras ˂ 0,05 para definir la significación estadística. Resultados Doscientos dos pacientes cumplieron los criterios del estudio. La bRFS a 10 años para la población general fue del 82,5%, estadísticamente relacionada con el estadio pT3 (p = 0,047), mayor grupo de grado Gleason (GG) (p ≤ 0,001), y R1 (p ≤ 0,001), pero no con N1. Un total del 3,9% de los pacientes tenían N1; de ellos, el 75% tenían R1, el 25% GG2, y el 37% GG3. Entre los pacientes N0 (metástasis no ganglionar en el cáncer de próstata), el 31% de los pacientes tenían R1, el 41% GG2 y el 13% GG3. Conclusiones Nuestra SSEb fue del 82,5% en los pacientes de bajo riesgo que se sometieron a RP y ePLND. A mayor pT, GG y presencia de R1, mayor probabilidad de RB. Aquellos con pN1 (ganglios linfáticos patológicamente confirmados como positivos) no se asociaron con la SSEb, con una tasa de detección de pN1 del 3,9%. Detalles: En el CaP de bajo riesgo se puede realizar tratamiento curativo con PR, reportando una tasa de SSEb a 5 y 7 años de 90,1% y 88,3%, respectivamente. A pesar de que la linfadenectomía pélvica no está recomendada durante la PR en las guías clínicas, en la literatura se realiza en el 34% de estos pacientes, encontrando un 0,37% de N1. En este estudio, reportamos la SLB a 10 años en pacientes con CaP de bajo riesgo sometidos a cirugía.

Metástasis cervical de cáncer papilar oculto de tiroides: reporte de casos / Cervical metastasis from occult papillary thyroid cancer: case report

El microcarcinoma papilar de tiroides es definido como un tumor de un cm o menos de diámetro mayor. La mayoría permanecen ocultos clínicamente, siendo un hallazgo en autopsias hasta en 36%. La presentación oculta ocurre hasta en un 10 a 26% de todas las neoplasias malignas de tiroides y se define como la presencia de ganglios metastásicos de carcinoma papilar de tiroides en ausencia de lesión primitiva tiroidea evidente durante la exploración clínica y ecográfica. El objetivo de este trabajo es el reporte de dos casos donde el diagnóstico de cáncer de tiroides se realizó a través de su presentación metastásica cervical, siendo el estudio anatomopatológico de la pieza de resección quirúrgica el que devela la presencia de un microcarcinoma papilar. Si bien el tratamiento del de estas lesiones es controversial, existen elementos que sellan la necesidad de resolución quirúrgica. En el debut metastásico ganglionar cervical, está indicada la tiroidectomía total con el vaciamiento ganglionar cervical radical modificado ipsilateral y central. El raidioyodo postquirúrgico será empleado en forma complementaria ante la persistencia, recurrencia o elementos de alto riesgo.

Papillary thyroid microcarcinoma is defined as a tumor one cm or less in diameter. Most remain clinically hidden, being an autopsy finding in up to 36%. Occult presentation occurs in up to 10% to 26% of all thyroid malignancies and is defined as the presence of metastatic nodes from papillary thyroid carcinoma in the absence of a primitive thyroid lesion evident on clinical and ultrasound examination. The objective of this work is the report of two cases where the diagnosis of thyroid cancer was made through its cervical metastatic presentation, being the pathological study of the surgical resection specimen that reveals the presence of a papillary microcarcinoma. Although the treatment of these lesions is controversial, there are elements that seal the need for surgical resolution. In cervical lymph node metastatic debut, total thyroidectomy with modified ipsilateral and central radical cervical lymph node dissection is indicated. Post-surgical radiation iodine will be used in a complementary way in the event of persistence, recurrence or high-risk elements.

Effect of PAIP1 on the metastatic potential and prognostic significance in oral squamous cell carcinoma / 国际口腔科学杂志·英文版

Poly Adenylate Binding Protein Interacting protein 1 (PAIP1) plays a critical role in translation initiation and is associated with the several cancer types. However, its function and clinical significance have not yet been described in oral squamous cell carcinoma (OSCC) and its associated features like lymph node metastasis (LNM). Here, we used the data available from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) to analyze PAIP1 expression in oral cancer. The publicly available data suggests that PAIP1 mRNA and protein levels were increased in OSCC. The high PAIP1 expression was more evident in samples with advanced stage, LNM, and worse pattern of invasion. Moreover, the in vitro experiments revealed that PAIP1 knockdown attenuated colony forming, the aggressiveness of OSCC cell lines, decreasing MMP9 activity and SRC phosphorylation. Importantly, we found a correlation between PAIP1 and pSRC through the analysis of the IHC scores and CPTAC data in patient samples. Our findings suggest that PAIP1 could be an independent prognostic factor in OSCC with LNM and a suitable therapeutic target to improve OSCC patient outcomes.

68Ga-PSMA ligand PET/CT integrating indocyanine green-guided salvage lymph node dissection for lymph node metastasis after radical prostatectomy / 亚洲男科学杂志(英文版)

To efficiently remove all recurrent lymph nodes (rLNs) and minimize complications, we developed a combination approach that consisted of 68Gallium prostate-specific membrane antigen (PSMA) ligand positron emission tomography (PET)/computed tomography (CT) and integrated indocyanine green (ICG)-guided salvage lymph node dissection (sLND) for rLNs after radical prostatectomy (RP). Nineteen patients were enrolled to receive such treatment. 68Ga-PSMA ligand PET/CT was used to identify rLNs, and 5 mg of ICG was injected into the space between the rectum and bladder before surgery. Fluorescent laparoscopy was used to perform sLND. While extensive LN dissection was performed at level I, another 5 mg of ICG was injected via the intravenous route to intensify the fluorescent signal, and laparoscopy was introduced to intensively target stained LNs along levels I and II, specifically around suspicious LNs, with 68Ga-PSMA ligand PET/CT. Next, both lateral peritonea were exposed longitudinally to facilitate the removal of fluorescently stained LNs at levels III and IV. In total, pathological analysis confirmed that 42 nodes were rLNs. Among 145 positive LNs stained with ICG, 24 suspicious LNs identified with 68Ga-PSMA ligand PET/CT were included. The sensitivity and specificity of 68Ga-PSMA ligand PET/CT for detecting rLNs were 42.9% and 96.6%, respectively. For ICG, the sensitivity was 92.8% and the specificity was 39.1%. At a median follow-up of 15 (interquartile range [IQR]: 6-31) months, 15 patients experienced complete biochemical remission (BR, prostate-specific antigen [PSA] <0.2 ng ml-1), and 4 patients had a decline in the PSA level, but it remained >0.2 ng ml-1. Therefore, 68Ga-PSMA ligand PET/CT integrating ICG-guided sLND provides efficient sLND with few complications for patients with rLNs after RP.

Pan-cancer analysis of the expression pattern of long non-coding RNA MIR22HG / 南方医科大学学报

OBJECTIVE@#To conduct a pan-cancer analysis of the expression of long non-coding RNA (lncRNA) MIR22HG and explore its association with clinical characteristics.@*METHODS@#We analyzed the expression of MIR22HG in different tumors and its association with clinical staging, lymph node metastasis, tumor mutation burden (TMB) and microsatellite instability (MSI) using R package based on the Cancer Genome Atlas (TCGA) datasets. The relationship between MIR22HG expression and infiltrating immune cells was analyzed using TIMER algorithm. The association of MIR22HG gene alteration frequency with the clinical outcomes was examined using cBioPortal online software. Data form Genomics of Drug Sensitivity in Cancer (GDSC) were used to analyze the relationship between MIR22HG and the sensitivity of chemotherapy drugs. We specifically analyzed MIR22HG expression in hepatocellular carcinoma (HCC) and its correlation with sorafenib treatment using GEO database and verified the results in 12 pairs of HCC specimens. Kaplan-Meier analysis was performed to analyze the correlation of MIR22HG with the outcomes of sorafenib treatment. We also tested the effects of MIR22HG overexpression and knockdown on IC50 of sorafenib in HCC cells.@*RESULTS@#MIR22HG was downregulated in most tumors (P < 0.05), where its deletion mutations were frequent, and associated with a poor prognosis (P < 0.05). In many tumors, MIR22HG expression level was correlated with clinical stage, lymph node metastasis, TMB, MSI, immune cell infiltration, immune checkpoint-related genes, and sensitivity to common chemotherapeutic drugs (P < 0.05). Among the 6 common infiltrating immune cells in cancers, neutrophil infiltration had the strongest correlation with MIR22HG expression level, especially in breast cancer, rectal cancer and kidney renal papillary cell carcinoma (P < 0.05). MIR22HG was downregulated in HCC in association with HCC progression (P < 0.05). In HCC patients, a low MIR22HG expression was associated with a favorable outcome after sorafenib treatment (HR=2.94, P=0.075) and was capable of predicting the response to sorafenib treatment (AUC=0.8095). Compared with the negative control, MIR22HG overexpression obviously reduced sorafenib sensitivity (with IC50 of 7.731 vs 15.61) while MIR22HG knockdown increased sorafenib sensitivity of HCC cells (with IC50 of 7.986 vs 5.085).@*CONCLUSION@#MIR22HG expression level is correlated with clinical stage, lymph node metastasis, TMB, MSI, immune cell infiltration, and chemosensitivity in most cancer, suggesting its potential as an immunotherapeutic target and also a prognostic biomarker for tumors.

Clinical features and prognostic influences of retropharyngeal lymph node metastasis in oropharyngeal and hypopharyngeal squamous cell carcinoma: a meta analysis / 中华耳鼻咽喉头颈外科杂志

Objective: To compare the clinical features and prognoses of patients with oropharyngeal or hypopharyngeal squamous cell carcinoma (SCC) with and without retropharyngeal lymph node metastases. Methods: PubMed, Cochrane, Web of Science, CNKI, VIP and Wanfang databases were searched for published literatures on retropharyngeal lymph node metastasis of oropharyngeal or hypopharyngeal squamous cell carcinoma (1900, 2021), and outcome indicators such as survival rate and related clinical features were extracted. The quality evaluation of the included literatures was carried out. RevMan 5.4 and Stata 16.0 software were used for data analysis. Results: A total of 18 literatures were included. Meta analysis showed that 3-year and 5-year survival rates and 5-year disease-specific survival rate of patients with oropharyngeal or hypopharyngeal squamous cell carcinoma with retropharyngeal lymph node metastases were lower than those without metastases, 46.1% vs. 53.0%, 40.8% vs. 62.5% and 35.9% vs. 53.1%, respectively, and the differences were statistically significant (OR values were 0.26, 0.38, 0.38, and 95%CI were 0.10-0.69, 0.28-0.51, 0.23-0.65, respectively, all P values<0.05). There were statistically significant differences in clinical stage (III-IV), T stage (T3+T4), N stage (N2), positive cervical lymph node metastases and number of lymph node metastases (≥3) between the two groups (OR values were 4.28, 2.20, 2.88, 10.83, 6.53, and 95%CI were 1.70-10.74, 1.35-3.58, 1.90-4.34, 3.57-32.95, 1.75-24.38, respectively, all P<0.05). The sensitivity and specificity of preoperative imaging for diagnosing retropharyngeal lymph nodes metastases were respectively 0.72 (95%CI=0.54-0.85) and 0.98 (95%CI=0.74-1.00), and the area under curve (AUC) of summary receiver operating characteristic curve (SROC) was 0.84 (95%CI=0.80-0.87). Conclusions: The survival rate of patients with oropharyngeal or hypopharyngeal squamous cell carcinoma with retropharyngeal lymph node metastasis is significantly reduced, the clinical stage and T stage are late, and the cervical lymph node metastasis rate is high. Retropharyngeal lymph node metastasis is more insidious, the sensitivity of preoperative imaging diagnosis is not high.

Clinical controversy and research thoughts on lymphadenectomy of gastric cancer / 中华胃肠外科杂志

Lymphadenectomy, as one of the controversial foci in clinic, is an extremely important part of radical surgery for gastric cancer. So far, the preliminary consensus has been reached on the scope and number of lymph node dissection, based on the etiological mechanism, disease progression, diagnosis and treatment prognosis of gastric cancer. At present, some clinical issues of lymphadenectomy in curative gastrectomy are still need to be addressed. Firstly, standardized procedure in lymph node dissection for gastric cancer is a prerequisite to decrease the incidence of postoperative complications and to improve the prognosis of gastric cancer patients. Furthermore, the plausible treatment strategy in perioperative phase is also deemed as the other key method to offer a benefit of survival rate for advanced stage patients after lymphadenectomy. Last but not least, the technologies for enhancement the prediction accuracy of lymph node metastasis preoperatively or intraoperatively should be worthy in-depth study.

Clinical significance of No.11p posterior lymph nodes dissection in gastric cancer surgery / 中华胃肠外科杂志

Objective: To analyze the association of No.11p posterior lymph node metastasis with clinicopathological features and its prognostic significance in gastric cancer. Methods: A single-center retrospective cohort study was conducted. Clinicopathological data of patients with primary gastric cancers undergoing No.11p posterior lymph node dissection from January 2016 to December 2020 were retrieved from the Database of Gastric Cancer, West China Hospital, Sichuan University. Case inclusion criteria: (1) gastric cancer proved by pathology; (2) radical resection with intraoperative No.11p posterior lymph node dissection; (3) operations performed by the same surgical team; (4) no previous history of other malignant tumors and no concurrent malignant tumors. Those with stump gastric cancer, history of gastrectomy, neoadjuvant chemotherapy, incomplete clinicopathological data and lost to follow-up were excluded. During the operation, the upper edge of the pancreas was retracted forward to expose the area between the upper edge of the pancreas and the splenic vessels. The proximal segment of the splenic artery was skeletonized to remove lymphatic tissue anterior and superior to the splenic artery for No.11p lymph node dissection. For patients with lymphadenopathy in the area between the splenic artery and the splenic vein, dissection was performed. The enlarged lymph nodes were labeled with titanium clips and named as No.11p posterior lymph node. Pathological examination was performed separately after the specimen was isolated. Statistical analysis was performed using R software. Results: A total of 127 gastric cancer patients, who underwent No.11p posterior lymph nodes dissection were included in this study, of which 120 patients without No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes negative) and 7 patients with No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes positive). A total of 8 metastatic No.11p posterior lymph nodes were detected in 7 patients, metastasis rate and with a ratio of 5.5% (7/127) and 6.8% (8/127), respectively. In the subgroup analysis of T3-4 stage patients, the metastasis rate and ratio of No.11p posterior lymph nodes were 9.0% (7/78) and 10.7% (8/75), respectively. Compared to negative cases, patients with No.11p posterior lymph nodes metastasis had larger tumor (P=0.002), higher proportion of Borrmann type Ⅲ and Ⅳ tumors (P=0.005), more metastatic lymph nodes (P<0.001), more advanced T stage (P=0.043), N stage (P=0.004) and TNM stage (P=0.015). In survival analysis, patients with No.11p posterior lymph node metastasis had a significantly worse prognosis than those without metastasis after adjusting for TNM stage (hazard ratio=3.009, 95% confidence interval: 1.824-4.964, P<0.001). Conclusions: The No.11p posterior lymph node metastasis in gastric cancer is associated with worse prognosis. For patients of T3-4 stage gastric cancer, No.11p posterior lymph node dissection should be emphasized during radical operation.

Establishment of artificial neural network model for predicting lymph node metastasis in patients with stage Ⅱ-Ⅲ gastric cancer / 中华胃肠外科杂志

Objective: To establish a neural network model for predicting lymph node metastasis in patients with stage II-III gastric cancer. Methods: Case inclusion criteria: (1) gastric adenocarcinoma diagnosed by pathology as stage II-III (the 8th edition of AJCC staging); (2) no distant metastasis of liver, lung and abdominal cavity in preoperative chest film, abdominal ultrasound and upper abdominal CT; (3) undergoing R0 resection. Case exclusion criteria: (1) receiving preoperative neoadjuvant chemotherapy or radiotherapy; (2) incomplete clinical data; (3) gastric stump cancer.Clinicopathological data of 1231 patients with stage II-III gastric cancer who underwent radical surgery at the Fujian Medical University Union Hospital from January 2010 to August 2014 were retrospectively analyzed. A total of 1035 patients with lymph node metastasis were confirmed after operation, and 196 patients had no lymph node metastasis. According to the postoperative pathologic staging. 416 patients (33.8%) were stage Ⅱ and 815 patients (66.2%) were stage III. Patients were randomly divided into training group (861/1231, 69.9%) and validation group (370/1231, 30.1%) to establish an artificial neural network model (N+-ANN) for the prediction of lymph node metastasis. Firstly, the Logistic univariate analysis method was used to retrospectively analyze the case samples of the training group, screen the variables affecting lymph node metastasis, determine the variable items of the input point of the artificial neural network, and then the multi-layer perceptron (MLP) to train N+-ANN. The input layer of N+-ANN was composed of the variables screened by Logistic univariate analysis. Artificial intelligence analyzed the status of lymph node metastasis according to the input data and compared it with the real value. The accuracy of the model was evaluated by drawing the receiver operating characteristic (ROC) curve and obtaining the area under the curve (AUC). The ability of N+-ANN was evaluated by sensitivity, specificity, positive predictive values, negative predictive values, and AUC values. Results: There were no significant differences in baseline data between the training group and validation group (all P>0.05). Univariate analysis of the training group showed that preoperative platelet to lymphocyte ratio (PLR), preoperative systemic immune inflammation index (SII), tumor size, clinical N (cN) stage were closely related to postoperative lymph node metastasis. The N+-ANN was constructed based on the above variables as the input layer variables. In the training group, the accuracy of N+-ANN for predicting postoperative lymph node metastasis was 88.4% (761/861), the sensitivity was 98.9% (717/725), the specificity was 32.4% (44/136), the positive predictive value was 88.6% (717/809), the negative predictive value was 84.6% (44/52), and the AUC value was 0.748 (95%CI: 0.717-0.776). In the validation group, N+-ANN had a prediction accuracy of 88.4% (327/370) with a sensitivity of 99.7% (309/310), specificity of 30.0% (18/60), positive predictive value of 88.0% (309/351), negative predictive value of 94.7% (18/19), and an AUC of 0.717 (95%CI:0.668-0.763). According to the individualized lymph node metastasis probability output by N+-ANN, the cut-off values of 0-50%, >50%-75%, >75%-90% and >90%-100% were applied and patients were divided into N0 group, N1 group, N2 group and N3 group. The overall prediction accuracy of N+-ANN for pN staging in the training group and the validation group was 53.7% and 54.1% respectively, while the overall prediction accuracy of cN staging for pN staging in the training group and the validation group was 30.1% and 33.2% respectively, indicating that N+-ANN had a better prediction than cN stage. Conclusions: The N+-ANN constructed in this study can accurately predict postoperative lymph node metastasis in patients with stage Ⅱ-Ⅲ gastric cancer. The N+-ANN based on individualized lymph node metastasis probability has better accurate prediction for pN staging as compared to cN staging.

A nomogram for predicting lymph node metastasis in early gastric cancer / 中华胃肠外科杂志

Objective: To explore the independent risk factors of lymph node metastasis (LNM) in early gastric cancer, and to use nomogram to construct a prediction model for above LNM. Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) primary early gastric cancer as stage pT1 confirmed by postoperative pathology; (2) complete clinicopathological data. Exclusion criteria: (1) patients with advanced gastric cancer, stump gastric cancer or history of gastrectomy; (2) early gastric cancer patients confirmed by pathology after neoadjuvant chemotherapy; (3) other types of gastric tumors, such as lymphoma, neuroendocrine tumor, stromal tumor, etc.; (4) primary tumors of other organs with gastric metastasis. According to the above criteria, 1633 patients with early gastric cancer who underwent radical gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital First Medical Center from December 2005 to December 2020 were enrolled as training set, meanwhile 239 patients with early gastric cancer who underwent gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital Fourth Medical Center from December 2015 to December 2020 were enrolled as external validation set. Risk factors of LNM in early gastric cancer were identified by using univariate and multivariate logistic regression analyses. A nomogram prediction model was established with significant factors screened by multivariate analysis. Area under the receiver operating characteristic curve (AUC) was used for assessing the predictive value of the model. Calibration curve was drawn for external validation. Results: Among 1633 patients in training set, the mean number of retrieved lymph nodes was 20 (13-28), and 209 patients (12.8%) had lymph node metastasis. Univariate analysis showed that gender, resection range, tumor location, tumor morphology, lymph node clearance, vascular invasion, lymphatic cancer thrombus, tumor length, tumor differentiation, microscopic presence of signet ring cells and depth of tumor invasion were associated with LNM (all P<0.05). Multivariate analysis revealed that females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa, and poor differentiation were independent risk factors for LNM in early gastric cancers (all P<0.05). Receiver operating characteristic curve indicated that AUC of training set was 0.818 (95%CI: 0.790-0.847) and AUC of external validation set was 0.765 (95%CI: 0.688-0.843). The calibration curve showed that the LNM probability predicted by nomogram was consistent with the actual situation (C-index: 0.818 in training set and 0.765 in external validation set). Conclusions: Females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa and poor differentiation are independent risk factors for LNM of early gastric cancer. The establishment of a nomogram prediction model for LNM in early gastric cancer has great diagnostic value and can provide reference for treatment selection.

The effect of prealbumin on the long-term prognosis of hilar cholangiocarcinoma following radical surgery / 中华外科杂志

Objective: To investigate the association between prealbumin and the long-term prognosis of patients with hilar cholangiocarcinoma(HCCA) following radical surgery. Methods: The clinical data of 262 HCCA patients who underwent radical surgery admitted from January 2010 to January 2017 at the First Affiliated Hospital of Army Medical University were collected,retrospectively. There were 158 males and 104 females; aged (57.6±9.9)years old(range:32 to 78 years). According to the preoperative serum prealbumin level(170 mg/L),the patients were divided into low prealbumin group(n=143) and normal prealbumin group(n=119). Follow-up until September 2020,the main research indicator was overall survival(OS), and the secondary research indicator was recurrence-free survival(RFS). The measurement data conforming to the normal distribution adopted the t test,the measurement data not conforming to the normal distribution adopted the Mann-Whitney U test,and the count data adopted the χ2 test. The Kaplan-Meier method was used to calculate the cumulative survival rate. The Log-rank test was used for univariate analysis of the cumulative survival rate. Variables with P<0.10 in univariate analysis were included in the Cox proportional hazards model for multivariate analysis. Results: The 1-, 3-, and 5-year OS rate of the 262 patients was 73.4%, 32.1%, and 24.0%, respectively, and the 1-, 3-, and 5-year RFS rate was 54.6%, 25.2%, and 16.2%, respectively. Median OS and RFS were 21 months and 12 months for patients with low prealbumin and 25 months and 19 months for patients with normal prealbumin. The OS rate and RFS rate of patients in the low prealbumin group were lower than those in the normal prealbumin group, and the difference was statistically significant (both P<0.05). The results of univariate analysis indicated that low prealbumin, CA19-9>150 U/L, tumor infiltration length>3 cm, preoperative jaundice, macrovascular invasion, microvascular invasion, lymph node metastasis, and poor differentiation maybe the risk factors of OS,and low prealbumin,tumor invasion length>3 cm,macrovascular invasion, microvascular invasion,lymph node metastasis,and poor differentiation maybe the risk factors of RFS for postoperative for radical resection in patients with HCCA (all P<0.10). Multivariate results suggested that low prealbumin,tumor invasion length>3 cm,microvascular invasion,lymph node metastasis,and poor differentiation were independent risk factors affecting OS and RFS in patients with HCCA after radical operation (all P<0.05). Conclusion: Preoperative prealbumin level can predict the long-term prognosis of patients with hilar cholangiocarcinoma following radical surgery.