Influência da terapia neoadjuvante na razão de linfonodos / Influence of neoadjuvant therapy on the ratio of lymph nodes

ABSTRACT Background: To evaluate the relationship between the ratio of affected lymph nodes (LNR) and clinical and anatomopathological variables in patients with rectal adenocarcinoma submitted or not to neoadjuvant chemoradiotherapy. Methods: The LNR was determined by dividing the number of compromised LNR by the total number of LNR dissected in the surgical specimen. Patients were divided into two groups: with QRT and without QRT. In each group, the relationship between LNR and the following variables was evaluated: degree of cell differentiation, depth of invasion in the rectal wall, angiolymphatic /perineural invasion, degree of tumor regression and occurrence of metastases. The LNR was evaluated in patients with more than 1, LNR (LNR >12) or less (LNR<12) in the surgical specimen with overall survival (OS) and disease-free survival (DFS). The results were expressed as the mean with the respective standard deviation. Qualitative variables were analyzed using Fisher's exact test, while quantitative variables were analyzed using the Kruskal -Wallis and Mann-Whitney tests. The significance level was 5%. Results: We evaluated 282 patients with QRT and 114 without QRT, between 1995-2011. In the QRT Group, LNR showed a significant association with mucinous tumors (P=0.007) and degree of tumor regression (P=0.003). In both groups, LNR was associated with poorly differentiated tumors (P=0.001, P=0.02), presence of angiolymphatic invasion (P<0.0001 and P=0.01), perineural (P=0.0007, P=0.02), degree of rectal wall invasion (T3>T2; P<0.0001, P=0.02); Compromised LNR (P<0.0001, P<0.01), metastases (P<0.0001, P<0.01). In patients with QRT, LNR<12 was associated with DFS (5.889; 95%CI1.935-19.687; P=0.018) and LNR>12 with DFS and OS (17.984; 95%CI5.931-54.351; P<0.001 and 10.286; 95%CI 2.654-39.854; P=0.007, respectively). Conclusion: LNR was associated with histological aspects of poor prognosis, regardless of the use of QRT. In the occurrence of less than 12 evaluated LNR, the LNR was associated only with the DFS.

RESUMO Contexto: Avaliar a relação entre a razão de linfonodos (RLA) acometidos e variáveis clínicas e anatomopatológicas em portadores de adenocarcinoma de reto submetidos ou não à quimiorradioterapia neoadjuvante. Métodos: A RLA foi determinada dividindo-se o número total de linfonodos (LFNs) dissecados no espécime cirúrgico pelo número de comprometidos. Os doentes foram divididos em dois grupos: com QRT e sem QRT. Em cada grupo foi avaliada a relação entre a RLA e as seguintes variáveis: grau de diferenciação celular, profundidade de invasão na parede retal, invasão angiolinfática/perineural, grau de regressão tumoral e ocorrência de metástases. Avaliou-se a RLA em pacientes com mais do que 12 LFNs (RLA>12) ou menos (RLA<12) na peça cirúrgica com a sobrevida global (SG) e sobrevida livre de doença (SLD). Os resultados foram expressos pela média com o respectivo desvio padrão. As variáveis qualitativas foram analisadas utilizando-se o teste exato de Fisher, enquanto as quantitativas pelos testes de Kruskal-Wallis e Mann-Whitney. O nível de significância foi de 5%. Resultados: Foram avaliados 282 pacientes com QRT e 114 sem QRT, entre 1995-2011. No Grupo QRT, RLA mostrou associação significativa com os tumores mucinosos (P=0,007) e grau de regressão tumoral (P=0,003). Nos dois grupos, a RLA associou-se com tumores pouco diferenciados (P=0,001 e P=0,02), presença de invasão angiolinfática (P<0,0001 e P=0,01), perineural (P=0,0007 e P=0,02), grau de invasão da parede retal (T3>T2; P<0,0001 e P=0,02); LFNs comprometidos (P<0,0001 e P<0,01), metástases (P<0,0001 e P<0,01). Nos pacientes com QRT, a RLA <12 associou-se com a SLD (5,889; IC95%1,935-19,687; P=0,018) e a RLA >12 com SLD e SG (17,984; IC95%5,931-54,351; P<0,001 e 10,286; IC95%2,654-39,854; P=0,007, respectivamente). Conclusão: A RLA associou-se a aspectos histológicos de mau prognóstico, independentemente do emprego de QRT. Na ocorrência de menos de 12 LFNs avaliados, a RLA associou-se apenas com a SLD.

Complete pathological response in patients with HER2 positive breast cancer treated with neoadjuvant therapy in Colombia / Respuesta patológica completa de pacientes con cáncer de mama HER2 positivo tratadas con quimioterapia neoadyuvante en Colombia

Introduction. Breast cancer is the most common type of cancer and the leading cause of death by cancer in women in Colombia. Approximately 15 to 20% of breast cancers overexpress HER2. Objective. To analyze the relationship between multiple clinical and histological variables and pathological complete response in patients with HER2-positive breast cancer undergoing neoadjuvant therapy in a specialized cancer center in Colombia. Materials and methods. We performed a retrospective analysis of non-metastatic HER2- positive breast cancer patients who received neoadjuvant therapy between 2007 and 2020 at the Instituto de Cancerología Las Americas Auna (Medellín, Colombia). Assessed parameters were tumor grade, proliferation index, estrogen receptor, progesterone receptor, HER2 status, type of neoadjuvant therapy, pathologic complete response rates, and overall survival. Results. Variables associated with low pathologic complete response rates were tumor grades 1-2 (OR = 0.55; 95% CI = 0.37-0.81; p = 0.03), estrogen receptor positivity (OR = 0.65; 95%; CI = 0.43-0.97; p=0.04), and progesterone receptor positivity (OR = 0.44; 95% CI = 0.29-0.65; p = 0.0001). HER2 strong positivity (score 3+) was associated with high pathological complete response rates (OR = 3.3; 95% CI = 1.3-8.35; p=0.013). Five-year overall survival was 91.5% (95% CI = 82.6-95.9) in patients with pathological complete response and 73.6% (95% CI = 66.4-79.6) in patients who did not achieve pathological complete response (p = 0.001). Additionally, the pathological complete response rate was three times higher in patients receiving combined neoadjuvant chemotherapy with anti- HER2 therapy than in those with chemotherapy alone (48% versus 16%). Conclusion. In patients with HER2-positive breast cancer, tumor grade 3, estrogen receptor negativity, progesterone receptor negativity, strong HER2 positivity (score 3+), and the use of the neoadjuvant trastuzumab are associated with higher pathological complete response rates.

Introducción. El adenocarcinoma de seno es el tipo de cáncer más frecuente y con mayor tasa de mortalidad asociada en mujeres en Colombia. Aproximadamente entre el 15 al 20 % de estos cánceres sobreexpresan el gen HER2. Objetivo. Analizar las asociaciones existentes entre múltiples variables clínicas e histológicas con respecto a la respuesta patológica completa en pacientes con cáncer de mama HER2 positivo que fueron tratadas con quimioterapia neoadyuvante en un centro especializado en el tratamiento del cáncer en Colombia. Materiales y métodos. Se realizó un análisis retrospectivo de las pacientes con cáncer de mama HER2 positivo, no metastásicas, que recibieron quimioterapia neoadyuvante entre el 2007 y el 2020 en el Instituto de Cancerología Las Américas Auna (Medellín, Colombia). Se evaluaron los parámetros de grado tumoral, índice de proliferación, estatus de receptores de estrógeno y de progesterona, tipo de quimioterapia neoadyuvante recibida, tasas de respuesta patológica completa y supervivencia global. Resultados. Las variables asociadas con tasas de respuesta patológica completa más bajas fueron grados tumorales 1-2 (OR = 0,55; IC 95% = 0,37-0,81; p= 0,03), positividad de receptores de estrógeno (OR = 0,65; IC 95 % = 0,43-0,97; p = 0,04) y positividad de receptores de progesterona (OR = 0,44; IC 95 % = 0,29-0,65; p = 0,0001). La positividad fuerte para HER2 (puntaje 3+) se asoció a tasas de respuesta patológica completa más altas (OR = 3.3; IC 95 % = 1,3-8,35; p = 0,013). La supervivencia global a cinco años fue del 91,5 % (IC 95 % = 82,6-95,9) en pacientes con respuesta patológica completa y del 73,6 % (IC 95 % = 66.4-79.6) en pacientes sin respuesta patológica completa (p = 0.001). La tasa de respuesta patológica completa fue tres veces mayor en los pacientes que recibieron quimioterapia neoadyuvante con terapia anti-HER2 comparado con aquellos que recibieron quimioterapia sola sin agentes anti-HER2 (48 % versus 16 %). Conclusión. En pacientes con cáncer de mama con sobreexpresión de HER2, grado tumoral tres, receptores de estrógeno y progesterona negativos, positividad fuerte para HER2 (puntaje 3+) y uso de quimioterapia neoadyuvante con trastuzumab se asociaron con mayores tasas de respuesta patológica completa.

Oncological outcomes of visibly complete transurethral resection prior to neoadjuvant chemotherapy for bladder cancer

ABSTRACT Purpose: To evaluate the potential oncologic benefit of a visibly complete transurethral resection of a bladder tumor (TURBT) prior to neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Materials and Methods: We identified patients who received NAC and RC between 2011-2021. Records were reviewed to assess TURBT completeness. The primary outcome was pathologic downstaging (<ypT2N0), with complete pathologic response (ypT0N0) and survival as secondary endpoints. Logistic regression and Cox proportional hazards models were utilized. Results: We identified 153 patients, including 116 (76%) with a complete TURBT. Sixty-four (42%) achieved <ypT2N0 and 43 (28%) achieved ypT0N0. When comparing those with and without a complete TURBT, there was no significant difference in the proportion with <ypT2N0 (43% vs 38%, P=0.57) or ypT0N0 (28% vs 27%, P=0.87). After median follow-up of 3.6 years (IQR 1.5-5.1), 86 patients died, 37 died from bladder cancer, and 61 had recurrence. We did not observe a statistically significant association of complete TURBT with cancer-specific or recurrence-free survival (p≥0.20), although the hazard of death from any cause was significantly higher among those with incomplete TURBT even after adjusting for ECOG and pathologic T stage, HR 1.77 (95% CI 1.04-3.00, P=.034). Conclusions: A visibly complete TURBT was not associated with pathologic downstaging, cancer-specific or recurrence-free survival following NAC and RC. These data do not support the need for repeat TURBT to achieve a visibly complete resection if NAC and RC are planned.

Evaluation of the response rate to neoadjuvant chemoradiotherapy in patients with rectal adenocarcinoma: a retrospective long-term study in two terciary reference centers

Objectives: To evaluate the complete response (CR) rate and surgeries performed in patients with rectal adenocarcinoma who underwent neoadjuvant therapy (NT) at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and at Hospital São Paulo, in Ribeirão Preto, from January 2007 to December 2017. Methods: We evaluated 166 medical records of patients with locally advanced rectal adenocarcinoma (T3, T4 or N+) who underwent NT. The regimen consisted of performing conventional (2D) or conformational (three-dimensional-3D/ radiotherapy with modulated intensity - IMRT) at a dose of 45-50.4Gy associated with capecitabine 1650mg/m2 or 5-fluorouracil (5FU) and leucovorin (LV). The following variables were analyzed: gender, age, pretreatment stage, radiotherapy, CR index, local and distant recurrence rates. Surgical treatment and complications were also evaluated. Results: The CR index was 28.3%. Patients treated with 3D/IMRT radiotherapy had a higher rate of CR (36.3% x 4.8%; p < 0.001), higher rates of clinical follow-up (21% x 0%; p < 0.001), lower surgery rates (79% x 100%; p < 0.001), higher rates of transanal resection (37.1% x 9.5%; p = 0.001), lower rates of abdominal rectosigmoidectomy (25.8% x 50%; p = 0.007) and lower rates of abdominoperineal resection of the rectum (16.1% x 40.5%; p = 0.002), when compared to patients treated with 2D radiotherapy. Conclusion Modern radiotherapy techniques such as 3D conformal and IMRT, by offering greater adequacy and precision of treatment, could result in better local control and less toxicity in organs at risk, enabling organ preservation strategies and less invasive approaches in selected cases. (AU)

Respuesta tumoral a la quimioterapia neoadyuvante en subtipos moleculares de cáncer de mama en Medellín, Colombia. Estudio de cohorte retrospectivo / Tumor response to neoadjuvant chemotherapy in molecular breast cancer subtypes in Medellin, Colombia. Retrospective cohort study

Objetivos: Describir la frecuencia de la respuesta clínica y patológica, entre los diferentes subtipos moleculares de cáncer de mama, en pacientes que previamente recibieron quimioterapia neoadyuvante. Materiales y métodos: Cohorte retrospectiva, descriptiva. Se incluyeron mujeres mayores de 18 años, con diagnóstico histológico de carcinoma invasivo de mama, en estadios IIA, IIB, IIIA, IIIB y IIIC, con clasificación por subtipos moleculares, que hubieran recibido quimioterapia neoadyuvante, atendidas en una clínica de alto nivel de complejidad localizada en Medellín (Colombia), entre el 1 de julio de 2017 y el 30 de julio de 2019. Las variables recolectadas fueron edad, estadio clínico, características histológicas, clasificación molecular y la respuesta clínica y patológica completa por subtipo molecular. Se realizó análisis descriptivo. Resultados: 255 pacientes cumplieron con los criterios de inclusión. La edad media fue de 55,2 años; los estadios clínicos con mayor prevalencia fueron IIIB (28,6 %) y IIB (26,3 %), respecto al grado histológico, los más frecuentes fueron grado 3 (48,2 %) y 2 (37,3 %). La frecuencia por subtipos moleculares fue: luminal A (10,2 %), luminal B HER2 negativo (39,6 %), triple negativo (23,1 %), luminal B HER2 positivo (13,7 %), y HER2 puro (13,3 %). La respuesta clínica completa posquimioterapia por subtipo molecular fue: luminal A (26,9 %), luminal B HER2 negativo (37,6 %), luminal B HER2 positivo (48,6 %), HER2 puro (41,2 %), triple negativo (45,8 %); se logró respuesta patológica completa por subtipo molecular, así: luminal A (19,2 %), luminal B HER2 negativo (32,7 %), luminal B HER2 positivo (54,3 %), HER2 puro (50 %), triple negativo (42,4 %). Conclusiones: En la práctica clínica, la clasificación por subtipos moleculares en cáncer de mama permite hacer una aproximación a la respuesta de la quimioterapia neoadyuvante. Se requieren estudios prospectivos en la región para determinar la capacidad predictiva de la respuesta patológica completa respecto a la sobrevida global y libre de enfermedad.

Objectives: To describe the frequency of clinical and pathological response in different molecular subtypes of breast cancer, in patients receiving prior neoadjuvant chemotherapy. Materials and methods: Descriptive retrospective cohort. The study population consisted of women 18 years of age and older with a histological diagnosis of invasive breast cancer stages IIA, IIB, IIIA, IIIB and IIIC, with a classification by molecular subtypes, who had received prior neoadjuvant chemotherapy, seen at a high complexity clinic in Medellin (Colombia), between July 1, 2017, and July 30, 2019. We measured age clinical stage, histological characteristics, molecular classification, and complete clinical and pathological responses by molecular subtype. A descriptive analysis was conducted. Results: Overall, 255 patients met the inclusion criteria. Mean age was 55.2 years; the clinical stages with the highest prevalence were IIIB (28.6 %) and IIB (26.3 %), and the most frequent by histologic grading were grades 3 (48.2 %) and 2 (37.3 %). Frequency by molecular types was as follows: luminal A (10.2 %), HER2-negative luminal B (39.6 %), triple-negative (23.1%), HER2-positive luminal B (13.7 %), and pure HER2 (13.3 %). Complete clinical response following chemotherapy, by molecular type, was as follows: luminal A (26.9 %), HER2-negative luminal B (37.6 %), HER2-positive luminal B (48.6 %), pure HER2 (41.2 %), triple-negative (45.8 %). Complete pathological response by molecular subtype was achieved in the luminal A (19.2 %), HER2-negative luminal B (32.7 %), HER2-positive luminal B (54.3 %), pure HER2 (50 %) and triple-negative (42.4 %) subtypes. Conclusions: In clinical practice, breast cancer classification by molecular subtypes is a means to approach the assess the to neoadjuvant chemotherapy. Se requieren estudios prospectivos en la región para determinar la capacidad predictiva de la respuesta patológica completa respecto a la sobrevida global y libre de enfermedad.

Perioperative mortality for radical cystectomy in the modern Era: experience from a tertiary referral center

ABSTRACT Purpose To evaluate the perioperative mortality and contributing variables among patients who underwent radical cystectomy (RC) for bladder cancer in recent decades, with comparison between modern (after 2010) and premodern (before 2010) eras. Materials and Methods Using our institutional review board-approved database, we reviewed the records of patients who underwent RC for primary urothelial bladder carcinoma with curative intent from January 2003 to December 2019. The primary and secondary outcomes were 90- and 30-day mortality. Univariate and multivariable logistic regression models were applied to assess the impact of perioperative variables on 90-day mortality. Results A total of 2047 patients with a mean±SD age of 69.6±10.6 years were included. The 30- and 90-day mortality rates were 1.3% and 4.9%, respectively, and consistent during the past two decades. Among 100 deaths within 90 days, 18 occurred during index hospitalization. Infectious, pulmonary, and cardiac complications were the leading mortality causes. Multivariable analysis showed that age (Odds Ratio: OR 1.05), Charlson comorbidity index ≥ 2 (OR 1.82), blood transfusion (OR 1.95), and pathological node disease (OR 2.85) were independently associated with 90-day mortality. Nevertheless, the surgical approach and enhanced recovery protocols had no significant effect on 90-day mortality. Conclusion The 90-day mortality for RC is approaching five percent, with infectious, pulmonary, and cardiac complications as the leading mortality causes. Older age, higher comorbidity, blood transfusion, and pathological lymph node involvement are independently associated with 90-day mortality.

Predicting response to neoadjuvant therapy with glucose transporter-1 in breast cancer

SUMMARY OBJECTIVE: Glucose transporter-1 is a marker involved in energy transport in cancer cells. It has been shown to be a poor prognostic factor in many cancer types, including breast cancer. However, there is no satisfactory parameter predicting treatment in breast cancer patients receiving neoadjuvant therapy. This study investigated the effect of glucose transporter-1 in predicting the treatment response of patients receiving neoadjuvant therapy. METHODS: In this study, glucose transporter-1 immunohistochemistry was applied to tru-cut biopsy of patients who were diagnosed with breast cancer and received neoadjuvant therapy between 2010 and 2021. A built-in scoring system was used to evaluate both the pattern and intensity of glucose transporter-1 immunohistochemistry staining. The relationship between glucose transporter-1 immunohistochemistry staining and other clinicopathological parameters was examined. In addition, the relationship of glucose transporter-1 with response to treatment was investigated. RESULTS: A relationship was found between high glucose transporter-1 expression and other clinicopathological parameters (such as estrogen and progesterone receptor negativity, high Ki-67, triple-negative, and Her2 status). Cases with high glucose transporter-1 expression had either a complete or a partial pathologic response. The result was statistically significant. CONCLUSION: Glucose transporter-1 has the potential to be a biomarker that can be evaluated more objectively as an alternative to Ki-67 labeling index in evaluating the response to treatment in patients receiving neoadjuvant therapy.

A logarithmic model for hormone receptor-positive and breast cancer patients treated with neoadjuvant chemotherapy

SUMMARY OBJECTIVE: The aim of this study was to investigate the predictive importance of the previously validated log(ER)*log(PgR)/Ki-67 predictive model in a larger patient population. METHODS: Patients with hormone receptor positive/HER-2 negative and clinical node positive before chemotherapy were included. Log(ER)*log(PgR)/Ki-67 values of the patients were determined, and the ideal cutoff value was calculated using a receiver operating characteristic curve analysis. It was analyzed with a logistic regression model along with other clinical and pathological characteristics. RESULTS: A total of 181 patients were included in the study. The ideal cutoff value for pathological response was 0.12 (area under the curve=0.585, p=0.032). In the univariate analysis, no statistical correlation was observed between luminal subtype (p=0.294), histological type (p=0.238), clinical t-stage (p=0.927), progesterone receptor level (p=0.261), Ki-67 cutoff value (p=0.425), and pathological complete response. There was a positive relationship between numerical increase in age and residual disease. As the grade of the patients increased, the probability of residual disease decreased. Patients with log(ER)*log(PgR)/Ki-67 above 0.12 had an approximately threefold increased risk of residual disease when compared to patients with 0.12 and below (odds ratio: 3.17, 95% confidence interval: 1.48-6.75, p=0.003). When age, grade, and logarithmic formula were assessed together, the logarithmic formula maintained its statistical significance (odds ratio: 2.47, 95% confidence interval: 1.07-5.69, p=0.034). CONCLUSION: In hormone receptor-positive breast cancer patients receiving neoadjuvant chemotherapy, the logarithmic model has been shown in a larger patient population to be an inexpensive, easy, and rapidly applicable predictive marker that can be used to predict response.

The effect of positron emission tomography/computed tomography in axillary surgery approach after neoadjuvant treatment in breast cancer

SUMMARY OBJECTIVE: The aim of this study was to determine the role of positron emission tomography/computed tomography in the decision to perform axillary surgery by comparing positron emission tomography/computed tomography findings with pathology consistency after neoadjuvant chemotherapy. METHODS: Patients who were diagnosed for T1-4, cN1/2 breast cancer receiving neoadjuvant chemotherapy in our clinic between January 2016 and February 2021 were evaluated. Clinical and radiological responses, axillary surgery, and histopathological results after neoadjuvant chemotherapy were evaluated. RESULTS: Axillary involvement was not detected in positron emission tomography/computed tomography after neoadjuvant chemotherapy in 140 (60.6%) of 231 node-positive patients. In total, 88 (62.8%) of these patients underwent sentinel lymph node biopsy, and axillary lymph node dissection was performed in 29 (33%) of these patients upon detection of 1 or 2 positive lymph nodes. The other 52 (37.1%) patients underwent direct axillary lymph node dissection, and no metastatic lymph nodes were detected in 33 (63.4%) patients. No metastatic lymph node was found pathologically in a total of 92 patients without involvement in positron emission tomography/computed tomography, and the negative predictive value was calculated as 65.7%. Axillary lymph node dissection was performed in 91 (39.4%) patients with axillary involvement in positron emission tomography/computed tomography after neoadjuvant chemotherapy. Metastatic lymph nodes were found pathologically in 83 of these patients, and the positive predictive value was calculated as 91.2%. CONCLUSION: Positron emission tomography/computed tomography was found to be useful in the evaluation of clinical response, but it was not sufficient enough to predict a complete pathological response. When planning axillary surgery, axillary lymph node dissection should not be decided only with a positive positron emission tomography/computed tomography. Other radiological images should also be evaluated, and a positive sentinel lymph node biopsy should be the determinant of axillary lymph node dissection.

Sphincter preservation operation and comprehensive treatment for ultra-low rectal cancer / 中华消化外科杂志

In the past 20 years, the multidisciplinary treatment model based on evidence-based medicine has significantly increased the rate of sphincter-preservation operation for rectal cancer. How to preserve rectum and anal function, avoid permanent colostomy, and improve post-operative quality of life of patients while ensuring radical resection of tumor, remains to be a key and hot topic in surgical treatment of rectal cancer. Based on literatures and clinical experiences, the authors summarize issues of sphincter preservation operation and comprehensive treatment, including intersphincteric resection, conformal sphincter preservation operation, total neoadjuvant therapy and radioimmunotherapy, for ultra-low rectal cancer, in order to provide reference for the colleagues.

The value of immune inflammatory index in predicting the therapeutic efficacy of neoadju-vant chemoradiotherapy for esophageal squamous cell carcinoma / 中华消化外科杂志

Objective:To investigate the value of immune inflammatory index in predic-ting the therapeutic efficacy of neoadjuvant chemoradiotherapy for esophageal squamous cell carci-noma (ESCC).Methods:The retrospective case-control study was conducted. The clinicopatholo-gical data of 163 patients with ESCC who were admitted to Zhongshan Hospital of Fudan University from December 2015 to December 2020 were collected. There were 135 males and 28 females, aged (62±8)years. All 163 patients underwent neoadjuvant chemoradiotherapy and radical resection for ESCC. Observation indicators: (1) relationship between immune inflammatory index and clinical characteristic in patients; (2) relationship between immune inflammatory index and efficacy of neoadjuvant chemoradiotherapy in patients; (3) influencing factor analysis for pathologic complete response and good response of tumor regression grade after neoadjuvant chemoradiotherapy; (4) efficiency of immune inflammatory index in predicting efficacy of neoadjuvant chemoradiotherapy. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers, and comparison between groups was conducted using chi-square test. Comparison of ordinal data was conducted using the rank sum test. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value. Univariate and multi-variate analyses were conducted using the Logistic regression model. The area under the curve (AUC) of ROC curve was used to evaluate the efficiency of predictive model. Results:(1) Relationship between immune inflammatory index and clinical characteristic in patients. ① Optimal cut-off value of systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR), platelet-lympho-cyte ratio (PLR). Results of ROC curve analysis showed that the AUC of SII, NLR, PLR in predicting efficacy of neoadjuvant chemoradiotherapy for patients with ESCC was 0.70(95% confidence interval as 0.61?0.77), 0.78(95% confidence interval as 0.69?0.84), 0.79(95% confidence interval as 0.70?0.85), respectively, with the maximum value of Youden index and the optimal cut-off value as 0.25, 0.32, 0.52 and 446×10 9/L, 2.09, 138. ② Relationship between SII, NLR, PLR and clinical charac-teristic in patients. According to the optimal cut-off value of SII, NLR, PLR, all 163 patients were divided into cases with SII <446×10 9/L as 99, cases with SII ≥446×10 9/L as 64, cases with NLR <2.09 as 107, cases with NLR ≥2.09 as 56, cases with PLR<138 as 88, cases with PLR ≥138 as 75, respectively. There was a significant difference in clinical N staging of tumor in patients with SII <446×10 9/L and SII ≥446×10 9/L ( P<0.05). There were significant differences in clinical N staging and clinical TNM staging of tumor in patients with NLR<2.09 and NLR≥2.09 ( P<0.05). (2) Relationship between immune inflammatory index and efficacy of neoadjuvant chemoradiotherapy in patients. Of 163 patients undergoing neoadjuvant chemoradiotherapy, there were 54 cases with pathologic complete response and 109 cases without pathologic complete response, 94 cases with good response of tumor regression grade and 69 cases with poor response of tumor regression grade. Of the 54 patients with pathologic complete response, cases with SII <446×10 9/L and SII ≥446×10 9/L, cases with NLR <2.09 and NLR ≥2.09, cases with PLR <138 and PLR ≥138 before neoadjuvant chemoradiotherapy were 42 and 12, 47 and 7, 48 and 6, respectively. The above indicators were 57 and 52, 60 and 49, 40 and 69 in the 109 cases without pathologic complete response. There were significant differences in the above indicators between patients with pathologic complete response and without pathologic complete response ( χ2=9.83, 16.39, 39.60, P<0.05). Of the 94 cases with good response of tumor regression grade, cases with SII <446×10 9/L and SII ≥446×10 9/L, cases with NLR <2.09 and NLR ≥2.09, cases with PLR <138 and PLR ≥138 before neoadjuvant chemoradiotherapy were 59 and 35, 78 and 16, 56 and 38, respectively. The above indicators were 40 and 29, 29 and 40, 32 and 37 in the 69 cases with poor response of tumor regression grade. There was no significant difference in the SII and PLR ( χ2=0.38, 2.79, P>0.05) and there was a significant difference in the NLR ( χ2=29.59, P<0.05) between patients with good response of tumor regression grade and poor response of tumor regre-ssion grade. (3) Influencing factor analysis for pathologic complete response and good response of tumor regression grade after neoadjuvant chemoradiotherapy. Results of multivariate analysis showed that PLR <138 before neoadjuvant chemoradiotherapy was an independent protective factor for pathologic complete response in ESCC patients undergoing neoadjuvant chemoradiotherapy ( odds ratio=1.98, 95% confidence interval as 1.56?2.51, P<0.05) and NLR <2.09 before neoadjuvant chemo-radiotherapy was an independent protective factor for good response of tumor regression grade ( odds ratio=2.50, 95% confidence interval as 1.40?4.46, P<0.05). (4) Efficiency of immune inflam-matory index in predicting efficacy of neoadjuvant chemoradio-therapy. The AUC of PLR <138 before neoadjuvant chemoradiotherapy in predicting pathologic complete response of ESCC patients undergoing neoadjuvant chemoradiotherapy was 0.79(95% confidence interval as 0.64?0.87, P<0.05), with the sensitivity, specificity and Youden index as 0.89, 0.63 and 0.52, respectively. The AUC of NLR <2.09 before neoadjuvant chemoradiotherapy in predic-ting good response of tumor regression grade of ESCC patients undergoing neoadjuvant chemoradio-therapy was 0.76 (95% confidence interval as 0.64?0.81, P<0.05), with the sensitivity, specificity and Youden index as 0.83, 0.58 and 0.41, respectively. Conclusion:The PLR<138 and NLR <2.09 before neoadjuvant chemoradiotherapy are independent protective factors for the pathologic complete response and good response of tumor regression grade, respectively, of ESCC patients undergoing neoadjuvant chemoradiotherapy, and both of them can predict the curative effect of neoadjuvant chemoradiotherapy well.

New advances of research in minimally invasive surgery for gastric cancer / 中华消化外科杂志

With the 30 years' development of minimally invasive surgery, the field of gastric cancer surgery is undergoing a paradigm shift from traditional laparotomy to minimally invasive surgery. To chart new trends and directions in the development of gastric surgery, the author briefly reviews the latest advances, mainly focusing on new evidence, new techniques, new models, and new trends in the clinical research of gastric cancer surgery. The long-term non-inferiority outcomes of 5-year overall survival of minimally invasive surgery for locally advanced distal gastric cancer has been confirmed by the CLASS-01 and KLASS-02 trials. Upgrading and innovation of minimally invasive technology, function-preserving surgery, new modes of neoadjuvant therapy, and the application of new technologies are continuing to inject new vitality into minimally invasive surgery for gastric cancer.

Advances in neoadjuvant therapy for hepatocellular carcinoma / 中华消化外科杂志

In recent years, the rapid development of systematic therapy and local therapy, represented by targeted therapy, immunotherapy and vascular interventional therapy, has signifi-cantly improved the therapeutic effects of advanced hepatocellular carcinoma (HCC), and also greatly promoted the development of neoadjuvant therapy of HCC. The main purpose of neoadjuvant therapy is to decrease the size of tumor and the difficulty of surgery, and to reduce the postoperative recurrence rate. But meanwhile it also brings potential risks such as tumor progression and loss of surgical opportunity. At present, most experts recommend that patients with Ⅱb stage and Ⅲa stage HCC according to China Liver Cancer staging system are the preferred target population for neoadjuvant therapy. However, due to the lack of high-quality medical evidence, it is recommended to be cautiously carried out after multidisciplinary discussion. Moreover, it is suggested that neoadjuvant therapy with rapid onset of effect, less and mild side effects, high objective response rate and low probability of disease progression should be carried out. The author expects that neoadjuvant therapy can further improve the prognosis of HCC, and provide more options for clinical practice.

Advances and challenges of conversion therapy and neoadjuvant therapy in hepatocellular carcinoma / 中华消化外科杂志

Hepatocellular carcinoma (HCC) is characterized by a low resection rate and a high postoperative recurrence rate. Conversion therapy and neoadjuvant therapy are effective stra-tegies to improve the long-term prognosis of patients with HCC. With the clinical application of new technologies and methods and the continuous emergence of new anti-tumor drugs, the conversion therapy and neoadjuvant therapy of HCC have ushered in an unprecedented development. At the same time, they are also facing many new challenges. Based on our own clinical experience and the latest progress in conversion therapy and neoadjuvant therapy of HCC, the authors classify and summarize the selection of treatment strategies and the challenges faced in HCC conversion therapy and neoadjuvant therapy.

Prognosis analysis and strategies selection in liver transplantation for intrahepatic cholangio-carcinoma / 中华消化外科杂志

Intrahepatic cholangiocarcinoma (ICC) is a complex malignant tumor with poor prognosis. Historically, the prognosis of ICC patients after liver transplantation is poor, which led to that it is once regarded as a contraindication of liver transplantation. However, in recent years, results of multiple studies challenge the above view. These emerging studies demonstrate that under the condition of reasonable selection of recipients or combined with neoadjuvant therapy, liver trans-plantation has achieved considerable prognosis in patients with ICC. In addition, compared with surgical resection and other treatments, liver transplantation can improve the prognosis of patients with ICC. The factors related to the prognosis of ICC patients who underwent liver transplantation include neoadjuvant therapy, overall tumor burden, tumor biological behavior and comprehensive treatment after transplantation, et al. Based on the results from currently existing clinical studies, the authors make a deep elaboration on the prognosis of ICC patients after liver transplantation, prognosis comparison between liver transplantation and other treatment measures for ICC, factors related to the prognosis of ICC patients who underwent liver transplantation, and the selection strategy of recipient of liver transplantation for ICC, and advance and challenge of liver transplantation for ICC.

Progress in adjuvant therapy of hepatocellular carcinoma complicated with microvascular invasion / 国际肿瘤学杂志

Hepatocellular carcinoma is a highly aggressive malignant tumor. Although the progress of surgical technology has made some achievements in surgical treatment alone, it still fails to significantly improve the long-term survival of patients. Studies have shown that the recurrence rate of hepatocellular carcinoma is extremely high, while microvascular invasion is an important reason for early recurrence and poor prognosis. Therefore, appropriate postoperative adjuvant therapy measures are crucial to improve the survival prognosis of hepatocellular carcinoma patients with microvascular invasion.

Research progress and prospect of surgical treatment of intrahepatic cholangiocarcinoma in the era of liver transplantation / 国际外科学杂志

The incidence of intrahepatic cholangiocarcinoma has been increasing worldwide in recent years. Hepatectomy is the first choice for surgical treatment of intrahepatic cholangiocarcinoma. However, due to high tumor invasion, early lymph node metastasis and other factors, only less than 30% of cases are resectable, and the overall prognosis of patients is very poor. Theoretically, liver transplantation can not only remove the tumor, but also replace the damaged liver. Therefore, many scholars have proposed liver transplantation for the treatment of intrahepatic cholangiocarcinoma in order to obtain better results. Intrahepatic cholangiocarcinoma was once listed as a contraindication of liver transplantation due to limited cases, tumor recurrence, and shortage of donors. However, with the optimization of recipient screening criteria and the development of neoadjuvant therapy, part of patients can also benefit from it, making liver transplantation a potential therapeutic strategy. Based on the literature review and the author′s experience, this article introduced the current situation of surgical treatment of intrahepatic cholangiocarcinoma, the comparison between hepatectomy and liver transplantation, the latest progress of liver transplantation treatment and the future challenges and solutions.

Application and challenge of neoadjuvant immunotherapy on perioperative treatment for locally advanced gastric cancer / 国际外科学杂志

The application of immunotherapy in advanced gastric cancer has become a research hotspot. At the same time, the combination of immunotherapy and neoadjuvant therapy is expected to further achieve tumor downstage, pathological remission, increase the proportion of R0 resection, which enhance the overall therapeutic effect of locally advanced gastric cancer (LAGC). Whether neoadjuvant immunotherapy affects perioperative complications, adverse events, tumor pathological responses, and long-term survival in LAGC is still in the initial stage of clinical exploration, which depends on large-scale prospective phase III clinical studies to demonstrate its clinical value. Meanwhile, the application of new innovative drugs and comprehensive perioperative treatment, screening high-specific biomarkers for therapeutic prediction, and weighing the selection of neoadjuvant cycle and interval of treatment-operation time are helpful to optimize and standardize the rational application of neoadjuvant immunotherapy, and ultimately bring benefits to patients.

Timing of sentinel lymph node biopsy in patients with early breast cancer undergoing neoadjuvant therapy / 国际外科学杂志

Neoadjuvant therapy has been continuously improved the outcomes of early breast cancer patients, and more patients with positive axillary lymph node achieve complete pathological responds. The timing of sentinel lymph node biopsy for patients receiving neoadjuvant therapy has also had a new strategy, especially for the patients with clinical positive axillary lymph node before treatment and become clinical negative after neoadjuvant therapy, sentinel lymph node biopsy after neoadjuvant therapy has gradually become a standard axillary surgery procedure. However, there are still many differences in clinical practice domestic in China and abroad. This article discussed the timing of sentinel lymph node biopsy in patients with early breast cancer undergoing neoadjuvant therapy, in order to draw the attention of domestic surgical colleagues to this issue and promote standardized surgery and multidisciplinary cooperation.

Thoracic SMARCA4-deficient undifferentiated tumor-pathological diagnosis and combined immune checkpoint inhibitor treatment / 北京大学学报(医学版)

We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.